General lectures (II

Proceedings of the 59th Annual Meeting, 1973-Kagoshima 185

Genera l Lectures (II)

(101) THE EFFECT OF CALCIUM ON HUMAN GASTRIC

SECRETION K. Segawa, S. Nakazawa, N. Koide, K. Imai, N. Matsuo, Y. Yamamoto

and M. Shiobara 2nd Dept. of Int. Med., Nagoya Univ.,

Sch. of Med. The effect of calcium on gastric secretion

was studied in 10 duodenal ulcer patients, 6 gastric ulcer patients and 1 case of Z-E syndrome. After the overnight fasting, the patients' gastric contents were evacuated by gastric tube and the saline was administered intravenously at the rate of 5.5 ml/min. The gastric juice was collected through the tube every one hour. After the 2 basal collections, calcium-gluconate containing 15mg/kg of calcium ion was added to the saline solution and it was infused over following 4 hours.

During calcium infusion the gastric juice was collected every hour, and venous blood was also drawn at the same time.

For the samples of gastric juice, the acid and peptic activity were estimated, and for blood samples, serum gastrin level was assayed by the radioimmunological method.

The followings were the results of this investigation :

Before calcium infusion, serum calcium level was 4.484-.06mEq/l and it rised to 4.41 4-.56, 5.234-.08, 5.534-. 11 and 5.734-.37 mEq/1, respectively at 1st, 2nd, 3rd and 4th hour of calcium infusion.

Gastric secretory volume per hour was 63.004-8.64, 40.924-8.51 ml respectively for 1st and 2nd basal collection and it was 45.284-5.64, 78.714- 12.56, 72.644- 10.02 and 86.64• 11.49 ml respectively for calcium induced collection. The acid output per hour was 3.494-.01 and 1.874-.47 at the time of 1st and 2nd basal collection and it was 2.174-.53, 5.504-1.39, 5.294-1.10 and 7.01 4-1.31 Emq respectively at the time of 1st, 2ncl, 3rd a.nd 4th calcium-induced collection.

Peptic activity assayed for 1st and 2nd basal collection and for lsti 2nd, 3rd and 4th calcium induced sample were respectively 5.774-1.20,

5.73• 7.67-4-.02, 9.81• 11.67• and 12.844-4.34 tyr. mg/ml. Serum gastrin level was assayed for the smples before calcium infusion and 1,2,3 and 4 hours after calcium infusion. Ist level was respectively 43.56 4-7.92, 31.524-6.85, 61.934- 12.43, 65.854-9.94 and 74.25• pg/ml.

The mean value of calcium stimulated acid output was 4.834-.93 mEq/h. This was equal tO 374-8% of tetragastrin-induced acid output. To the contrary its rate in Z-E syndrome was 73%.

Summary: calcium infusion test could be carried out without any side effect. Through this test we knew that calcium retains the ability of gastric acid secretion, peptic secretion and gastrin release.

(102) STUDIES ON THE PH VALUES IN THE REMNANT STOMACH

- - W I T H SPECIAL REFERENCE TO THE STOMAL ULCER CASES--

H. Shimada, K. Kawai, K. Machida, N. Okabe, Y. Hoshi, Y. Koizumi

and T. Watanuki. 1st Dept. of Surg., Jikei Univ.

Sch. of Med., Tokyo

Easy and dependable accessment of the gastric acidity using telemetering capsule has developed new field of gastric junction tests.

The gastric acidity was measured by the pH capsule, gastric secretion was stimulated by subcutaneous use of tetragastrin 4r/kg and potassium bicarbonate was loaded for neutralization.

The results obtained were as follows: 1) During immediate postoperative peri-

ods, pH of the remnant stomach fell into two groups, pH below 3.0 and pH over 5.0.

But it gradually shifted into individual proper pH and stabilized 6 months after the surgery.

2) In the good gastrin responsive groups, most of the patients with post-operative complaints had basal pH value lower than 3.0.

3) The acid content of the gastric remnant is approximated by measuring amount of potassium bicarbonate required to raise pH over 4.0, 45 minutes after gastrin load. Free

186 Proceedings of the 59th Annual Meeting, 1973-Kagoshima

acid in the remnant stomach was below 0.25

mEq in the non-stomal ulcer group, while it was high between 0.5 and 4.0 mEq in the

stomal group.

4) All 24 cases of stomal ulcer but one

had basal pH below 2.0 and symptomatic. The ulcer was solitary and U1 I I I to IV in

nature.

Majority of the ulcers were located in the

efferent loops. Only one patient had the ulcer in the remnant stomach.

Operation was performed on 11 cases with good results.

(103) I N T R A - G A S T R I C P R E S S U R E

BY A R A D I O - T E L E M E T E R I N G C A P S U L E (II) :

I N T R A - G A S T R I C P R E S S U R E C H A N G E

U N D E R D I F F E R E N T C O N D I T I O N S BY A R A D I O - T E L E M E T E R I N G

C A P S U L E A N D C O R R E L A T I O N

O F I N T R A G A S T R I C P R E S S U R E AND PH

Y. Hiroshima, Y. M. atsusaka,

K. Katase, Y. Sakuma

and N. Matoba Osaka ~l/Iun. Kita Citizen's Hosp.

N. Murata Matsushita Electric Industrial Co.

a) Intra-gastric pressure change was noted in various conditions as follows:

1) Stand up and sit down 2) Speaking 3) Cough 4) Deep Breathing 5) Laugh-

ing 6) Belching 7) Hiation 8) Bor-

borygmus

b) The acceleration of intra-gastric pressure change was obtained after taking

whisky and tea, but not appeared after taking milk.

c) After injection of Prifinium promide, the decline ofintragastric pressure was observed

in a subject whose pressure fluctuation was accelerated, on the other hand the acceleration

of the pressure fluctuation observed in cases of declined intra-gastric pressure.

d) The acceleration of intra-gastric pres-

sure was obtained following the administration of Bethanechol Chloride and Meto-

clopra.~..ide.

c) Any correlation was not recognized between intra-gastric pressure and pH by

2 channel method after the administration

of Tetragastrine and Sodium Bicarbonate.

(104) ON T H E A R T E R I O - V E N O U S A N A S T O M O S E S IN E X P E R I -

M E N T A L S T O M A C H U L C E R

Y. Toyama, S. Murai, A. Nukaga, N. Ishimatsu, Y. Watanabe

and M. Abe

4th Dept. of Int. 3lied. (Prof. M. Abe, M.D.) Tokyo Jikeikai Univ. of Med.

In experimental stomach ulcers in rats,

their vascular changes have been investigated by means of a plastic model of the blood

vessels. Because of the pressure in injecting

acryl ester, the diameter of the plastic model of the vessels underwent some artificial changes.

We think the artificial changes can be pre-

vented if a fixing solution is injected into the vessels with constant pressure for a period.

At present, we consider that it is preferable

to inject 10~ formalin solution for two minutes,

with a pressure of 120 mm Hg. We produced reserpine ulcer, gastrin ulcer and curling's

ulcer in rats. Their plastic models were produced. In case of reserpin ulcer, around

the ulcers anastomoses between arterioles

and venules were seen on the muscularis mucosa. On the other hand, in cases of

gastrin ulcer and curling's ulcer, the arterio- venous anastomoses were seen in the submucosa

but not on the muscularis mucosa.

(105) S T U D Y ON T H E D I S T R I B U -

T I O N O F M U C O S A L CAPIL- L A R I E S OF C A N I N E

S T O M A C H Y. Ono, K. Hirai, S. lwabuchi, K. Suzuki,

T. Aoki, K. Masamura, K. Yoshida,

,J. Ikeuchi and F. Nagao

2rid Dept. of Surg., Jikei Univ. Sch. of Med. (Director: Prof. F. Nagao)

We studied on the distribution of mucosal capillaries of canine stomach by photolucency

method using Olympus E.M.M. type II photoelectric cell.

The less the number of mucosal capillaries

is, the greater is the photolucency, because


the capillaries are filled wi th Ind ian Ink.

Four teen dogs were used in our experiment.

Left thoracotomy was performed under

general anesthesia to expose the thoracic

aor ta into which a polyethylene catheter

was introduced, and I n d i a n Ink, warmed

a r o u n d 37~ was injected via this catheter

at constant pressure. Microscopical paraffin

sections were obta ined from each specimen.

R e s u l t s : The average value of de termined

each photolucencies in fundic gland area

was 19.4%, and tha t of pyloric gland area

was 35.7%. Then, this difference was highly

significant. (P<0 .01 ) O n each of various

par ts of the stomach, namely anter ior wall,

posterior wall, lesser curvature , and greater

curvature , this difference in photolucency

similarly existed between fundic and pyloric

g land area. At the level of 1 cm oral to

mucosal boundary , no significant difference

in photolucency was observed among these

four regions. (P<0 .05 ) Similarly, at the

level of 1 cm anal to mucosal boundary , no

significant difference was observed among

these four regions. ( P < 0 . 0 5 )

O n the line of the greater curvature, the

value of 4 cm oral to mucosal bounda ry and

tha t of 1 cm oral to mucosal boundary are

statiscally different in spite of the same fundic

g land area. (P<0 .05 )

S u m m a r y : As the photolucency is inverse-

ly propor t ional to the n u m b e r of capillaries

(vascularity), the vascu la r i ty of fundic g land

area is greater by twofold than tha t of pyloric

g land area. And, on the line of greater

curva ture two different vascularities were

observed in the same fundic gland area.

After all, it seems likely tha t the local difference

in mucosal vasculari ty exists in differeng

par ts of canine stomach.

(106) M U C O S A L V A S C U L A R I T Y

O F F U N D I C A R E A A N D

P Y L O R I C A R E A

A. Kobayashi , S. Toriie, M. Nakajima,

M. Kcthli, K. Ida, K. Kawai

and M. M a s u d a

3rd Dept. of Int. Med. Kyoto Pref. Univ. of Med.

T. Hat tor i a n d S. Fuji ta

2nd Dept. of Pathol., Kyoto Pref. Univ. of Med.

Although Dr. Oi repor ted the location of

gastric ulcer has relations to in termediate

zone of gastric mucosae, we suppose tha t it

has relat ion not only to in termedia te zone

bu t also to difference of mucosal vascularity.

In this paper, we demons t ra ted the difference

of vasculari ty between fundic area and pyloric

area.

O u r present study was done with two

technical methods to visualize vascular pat tern .

O n e of them was to observe the specimens

unde r light microscope, which were obta ined

from resected s tomach after inject ing black

ink through main gastric artery. Another

me thod was to observe the corrosion casts

unde r scanning electron microscope. This

s tudy revealed that there are capil lary anasto-

motic nets in the middle par t of the glands,

which we name "Capi l la ry meshes of g landular

por t ion" , and that they are fine and dense in

fundic area, whereas gross and rough in pyloric

area. The mucosal vascular dis tr ibut ion

in fundic area is two and hal f times as dense

as in pyloric area.

(107) E X P E R I M E N T A L S T U D I E S

O F G A S T R I C B L O O D F L O W

- - P A R T I C U L A R L Y O N T H E

R E S P O N S E T O S T I M U L A -

T I O N BY H O R M O N A L

S U B S T A N C E S - - -

T. Tamada , K. Inoue, T. Usui,

S. Yamaya, K. Ohtsuka,

Y. Shiraki, S. Fujishima,

O. Toch ikubo and

S. Miyamoto

2nd Dept. of lnt. Med., Yokohama City Univ. Sch. of Med.

A. U e d a

Dept. of Int. Med., Kanagawa Pref. Hosp., Center for Adult Dis.

W e have reported our serial studies on

the correlat ion of the secretory function

and the blood flow of the s tomach in the

rabbi ts with the use of 133Xe-clearance method.

This report includes our fur ther investiga-


tions in which the response of the gastric

blood flow following the administration of

various hormonal substances such as gastric hormones in the rabbits.

After the rabbits were laparotomized under

the intraperitoneal anesthesia, x~aXe-physio-

logic saline (Neiser) was injected into the subserosa of the stomach, and measurement

of the gastric blood flow which was achieved

by the analysis of the 183Xe-clearance curve and was expressed as the mean transit t ime

(t), was carried out. And the changes of

the gastric blood flow at the time of developement of "serotonin-ulcer" in the rats were also studied.

The results of these studies are summarized

as follows: (1). There was no significant differences of the gastric blood flow between

at the corpus (t-=2.49~z0.58 rain.) and at the

pylorus (}-~2.69• min.). (2). Increases

of the gastric blood flow in the rabbits were observed with a peak at 15 to 30 minutes

following the i.v. injection of tetragastrin

(5 ug/kg) and histalog (1 ktg/kg), respectively. (3). I.v. injection of secretin (10 u) yielded

a significant decrease of the gastric blood flow in the rabbits particularly 60 minutes

after the injection both at the corpus and

at the pylorus. (4). No blood pressure changes were observed following the i.v. injection of these substances. (5). Signi-

ficant increases of the gastric blood flow were also observed following i.v. injection of sero-

tonin (20 pg/kg) at the time of developement of "serotonin-ulcer" in the rats. The mean

transit time (t-) before and 15, 30, and 60 minutes after the injection were 2.20~0.48,

3.96-4-0.98, 4.37• and 4.16:~0.93 minutes respectively, showing a significant

increase. On the other hand, the blood pressure fell transiently for about 30 minutes following the injection. These results seem

to reveal that developement of gastric ulcer could be induced by decrease of the gastric

blood flow and the blood pressure following the serotonin-injection, as a result of constric-

tive effect on the vessels and the smooth

muscles. These phenomena were assumed to be a state of reduction of protective abilities

of the living.

(108) S T U D I E S O N T H E E T I O L O G Y

A N D T R E A T M E N T OF P E P T I C U L C E R

K. Asano, M. Kunisada, H. Miyake,

Y. Fujii, S. Yoshimoto and K. Hiramatsu

Dept. of Int. Med., Okayama City Hosp.

The etiology of peptic ulcer and the effect of prostaglandin on stomach were investigated

by measurement of gastric and duodenal blood flows.

It has been found that there are differences

of blood flow between the regional border of corpus and antrum, and between anterior

wal l and posterior wall of corpus. The gastric blood flow was maximum in anterior

wall of corpus, and minimum in antrum.

The significant increase of blood flow by histamine occurred in fundic gland area, and

remarkable increase of blood flow occurred

in corpus, especially at the muscular layer of lesser curvature by the administration of

acetylchofine. These results mean that there are the warps of blood flow among each

gastric regions.

The significant increase of blood flow of stomach with ulcer was observed at the

surrounding area of ulcer in experimental

ulcer of rabbit stomach and human gastric ulcer.

The blood flow of duodenum was also

studied by the same method. The blood flow of anterior wall of duodenum was much

than posterior wall, and the blood flow of anterior wall of bulbus was the most variable by the stimulation with some agents.

These results suggest that there are relation-

ship among the gastroduodenal blood flow, gastroduodenal functions and peptic ulcer.

The variations of blood flow induced by

acetylcholin and histamine were inhibited by

the administrations of atropine or some anti- ulcer agents. Prostaglandin has recently been

reported to inhibit the gastric motility and secretion. Therefore, the effect of prostag-

landin on the gastric blood flow was studied.


Prostaglandin E 1 and a potent synthetic prostaglandin (PG226) also inhibited the

variations of blood flow induced by acetylcho- line and histamine.

(109) CLINICAL SIGNIFICANCE

OF PERIVATERIAN DUODE-

NAL D I V E R T I C U L A S. Nakano, T. Takeda, K. Kitamura,

Y. Horiguchi and K. Okada

2nd Dept. of Int. Med. (Dept. of Gas- troenterl) Ohgaki Mun. Hosp.

Large (above 20 mm in diameter) and

double duodenal diverticula in the perivaterian portion were seen at the rate of 36% of all

(210 cases).

As associated diseases, choledocho-, chole-

lithiasis and pancreatic lesions were seen very often. (33% and 11% respectively.)

Incidence of hyperamylasuria and diabetic

pattern in G.T.T. were observed frequently. (30% and 700/0 respectively.) As for pan-

creozymin secretin test, abnormal function of the exocrein pancreas was seen frequently

with retarded bile secretion. (37%) Symptomatology and functions of the

pancreas and biliary tract were studied in

36 cases without associated diseases in order to elucidate the clinical significance of the

perivaterian large diverticula. Most frequent sign was upper abdominal pain (30~70%).

Fever and jaundice were observed in 22% of them. Abnormal junction of the exocrine

pancreas and retarded bile secretion were observed in 30% and 60% of them respectively.

5 in 210 cases were picked up for analysis

because each entry of the common bile duct and the pancreatic duct was seen in the

duodenal diverticula. Chief complaint was jaundice in 2 of them. Pancreozymin secretin

test was carried out in 4 cases and abnormal function of the exocrine pancreas was obtained

in half of them. Elevated blood amylase after the stimulation of the hormones was

also observed in the same incidence. As

for bile secretion, the bile concentration was low in the half of them.

Conclusively, large diverticula of perivaterian portion evokes bad influence on the

pancreas and biliary tract frequently and it

may play an important role in etiology of biliary and pancreatic inflammation.

(110) COMPARATIVE STUDY

BETWEEN X-RAY & ENDO-

SOPIC FINDING OF DUODENAL ULCER

M. Okada, T. Kuwabara, M. Tanaka,

K. Konno, T. Hattori, K. Isobe, A. Iwasaki T. Unoura,

M. Matsumoto, T. Yoshida, I. Takahashi, M. Abe,

H. Maeda, T. Hayashi,

H. Koizumi, M. Iwasaki, K. Takahashi, T. Honda

and K. Ariga

3rd Dept. of Int. Med., Nihon Univ. Sch. of Med.

61 cases of single duodenal ulcer (located

39 cases in the anterior wall and 22 cases in the ante-posterior wall) was investigeted.

The subjects were picked up adequate roentgenographic examinations with method of

fullness, compulsion and double contrast. Also the duodenal ulcers were demonstrated

as scaring .duodenal ulcer by duodenoscopy and biopsy. It is easier to make a diagnosis as scaring duodenal ulcer with no niche, just

shows radiating folds to the scaring point on

the roentgenographic examination. But there are some problems on the distribution

of the scaring duodenal ulcer with niche.

(111) H I S T O C H E M I C A L AND CHEMICAL STUDIES

OF D U O D E N I T I S S. Mohri, Y. Suga, T. Ono

and K. Kobayashi

3rd Dept. of Int. Med., Osaka City Univ. Med. Sch.

Previously we had reported that endoscopic, histological, microscopic (dissecting type), and histochemical studies of acute or chronic

inflammatory change in the duodenum were very important as essential approach for

diagnosis of the so-called duodenitis. The aim of this paper is to discuss chemical

investigation by reference to histochemical


approach in biopsy specimens which obtained by duodenofiberscope and in materials which obtained experimental studies in dogs by stimulation using ethyl alcohol (20--30%) and HC1 (2%).

The results are as follows: 1. In the human duodenum, the activity

of the alkaline phosphatase was measured by the Kind and King's method.

1 u n i t = l T phenol/rag, prot. Normal group (endoscopically): 750--

2000 The group with inflammatory change

(endoscopically): 200-- 1000/~. The activity of the alkaline phosphatase

in the group with inflammatory change was lower than normal.

2. The activity of the alkaline phosphatase in dogs A. Normal group : 10• 102/~ B. The group of the dogs which were

obtained acute inflammatory change by stimulation of HCI (2%): 10• ~ - 50x 102/t

C. The group using ethyl alcohol (20-- 30%): 5xl l3~--10• ~/t

D. The group of the dogs which were obtained chronic inflammatory change by repeated stimulation: 30• 102- 120• 10~/t The alkaline phosphatase activities in the groups with acute inflammatory change (B and C) were lower than in normal groups. On the other hand, in the group with

chronic inflammatory change, its activity became same level compared with normal group.

(1 t2) HYPERTHYROIDISMS AND STOMACH ULCER

T. Mizuno, Y. Sameshima, Y. Shiozaki, M. Sasakawa A. Hiramatsu,

K. Ikehara, T. Nagata and K. Tatsumi

2nd Dept. of lnt. Med., Kansai Med. Sch.

The present work introduced the results of clinical investigation in patient with hyper-

thyroidisms accompanying stomach ulcer and animal experiment with respect to the same subject as well. A. Clinical Results

a) There have been five patients with hyperthyroidisms accompanying stomach ulcer for the past five years, which was 1.7% of the total patients with stomach ulcer treated in the IInd department of internal medicine, Kansai Medical School. There were four cases with hyperacidity of gastric juice whereas the other with hypoacidity among the patients. B. Animal Experiment

The animals used were normal white rats, divided into three groups which orally received Thiouracil, 0.05 g/rat L-Thyroxine 10 rag/rat L-Thyroxine 20 rag/rat, and respectively for the thirty days, while the each group of animals served as control was fed in the same nutri- tional conditons for the same period. Gastric analysis for the determination of Triosob resin sponge uptake in sera, and volume, acidity, acid output and peptic activity of gastric juice were performed sacrificing the animals twenty hours after pyloric ligation or occurrence of stress ulcer.

a) The incidence of ulceration was lower in Thiouracil group with paralleled notable decrease in volume, acidity, and peptic activity of gastric juice, while in Throxine group diminished incidence of ulceration was exhibited with increased dosing of the drug accompanying the similar findings of gastric juice obtained in Thiouracil group.

b) The incidence of stress gastric ulcer was lower in Thiouracil group in contrast with higher incidence in Thyroxine group.

(113) STUDIES ON RELATIONSHIP BETWEEN PEPTIC ULCER

AND CHRONIC PAN- CREATITIS (II)

M. Abe (Director), M. Aoki, S. Iwasaki T. Aizawa,

K. Kajiwara and K. Sata

Hiratsuka Civic Hosp., Int. Med. S. Omata, K. Imamura, K. Kondo

and H. Sajima

Proceedings of the 59th Annual Meeting, 1973-Kagoshima t 91

Yokohama Civic Hosp., Int. Med. Y. Sato, H. Kiryu, S. Mimoto

and T. Masuoka

Nihon Kokan Hosp., Int. Med.

Gastrin is a potent stimulant of acid secretion

and serum gastrin levels can now be measured

using sensitive radioimmunoassay. Fasting serum gastrin levels and acid secretion

during 6 months to one year has been measured by radioimmunoassay in 14 patients with

duodenal ulcer, 12 patients with duodenal

ulcer and chronic pancreatitis and compared with that in normal controls. Fasting serum

gastrin levels in duodenal Ulcer is Sometimes

in the low part of the normal range. I t is known that in dogs, gastrin secretion is in-

hibited at a pH of between 1 and 3 (feed back

mechanism), in patients with duodenal ulcer and chronic pancreatitis the fasting levels of

gastrin and gastric acid secretion were generally

lower compared to some of patients with

duodenal ulcer. Also diurnal (8:00-18:00) serum gastrin

levels produced similar patterns. The effect of protein meal was also assessed

in a group of these patients. There is a peak at 45-60 minutes with a gradual fall to normal.

In patients with duodenal ulcer and chronic

pancreatitis gastrin levels at 45, 60, 75 minutes were significantly lower than those of some

groups of patients with duodenal ulcer.

(114) P A T H O G E N E S I S OF A C U T E U L C E R A N D C H A N G E S OF

DEFENSE M E C H A N I S M OF T H E G A S T R I C A N D

D U O D E N A L M U C O S A IN O B S T R U C T I V E

J A U N D I C E K. Kira, R. Mizumoto, H. Kuratsuka,

and I. Honjo

1st Dept. of Surg., Kyoto Univ. Med. Sch.

In obstructive jaundice, gastrointestinal bleeding occurs occasionally and makes one

of the important causes of death postopera-

tively. We have reported that a difference in

between pathogenesis of gastric ulcer and

duodenal ulcer is from a difference in between

mucosal structure, especially mucopolysaccha- rides, of the stomach and the duodenum, and

also that the mucous barrier covers the mucosa and acts as defense mechanism against peptic

juice and it consists of two kinds of layer, one

is a superficial glycoprotein layer and another

is a profound mucoprotein layer. In this study, changes of mucosal structure

of the stomach and pathogenesis of acute ulcer were observed in the rat with obstructive

jaundice after ligation of the common bile

duct and confinement in the stress cage for

18 hours. 1) One of four rats, treated only by ligation

of the common bile duct, showed superficial mucosal defect with decrease of mucoprotein

in the mucous barrier. 2) Three of four

rats, treated only by confinement in the

stress cage, showed multiple erosions with decrease of glycoprotein of the mucous barrier,

3) When rats were treated by ligation of the common bile duct .with confinement

in the stress cage, all four rats sho.wed multiple and deep ulcers up to the muscularis mucosae

with destruction of the two mucous layers of

the barrier. As mucoprotein layer of the mucous

barrier is destructed in the obstructive jaundice and glycoprotein layer in+ the stress, it seems

that the mucosa is digested by self-secreted

peptic juice and acute ulcer develops in the jaundice after ooerative stress.

(115) G A S T R I C C H A N G E S ON T H E P A T I E N T S T R E A T E D

W I T H L O N G - T E R M DIALYSES

Y. Hojo, H. Nakajima, T. Tosaka, O. Arai, N. Kobayashi

and N. Obata

Dept. of lnt. Med., Nagaoka Red-Cross Hosp.

It is often known that uremic patients treated with long-term dialyses, have digestive

complaints. Then we try to make clear the

reason in this paper. Materia l and Method;

56 patients managed with peritoneal dialyses


or hemodialysis from July, 1969 in our hospital were comprised in the substance of this study.

24 patients were examined by the gastric

X-ray. 26 patients were gastroendoscopied. 16 patients were revealed in the gastric juice

after injection of the Tetragastrin and 34

patients were measured the serum gastrin by radio-immunoassay. Results:

Hematoemesis and melena were found in

14.3%, gastric carcinoma in 1.8%, peptic ulcer in 12.5%, Antrum-gastritis in 5.4%,

mucosal bleeding in 38.5%. Linear redness, as it were Kammr6tung, were shown in 23.1%.

Hyperplasia of the mucosal folds were also seen in 44.8%.

Gastric juice analysis revealed 87.2 mEq/1

on the average of the peak acid output and 8.88 mEq/h on one hour acid output.

The mean level of serum gastrin were 397.3 pg/ml.

Comment; The discussion has been centering on sex,

age, method, duration of dialysing uremic

patients and their digestive disorders. I t

was thought that there were no relationship between mechanism of peptic ulceration on dialysed patients and gastric acid output.

Linear redness and mucosal bleeding were

frequent in treating over one year. 4 cases were accompanied by bleeding, 2 cases were bled along the linear redness.

The level of serum gastrin was clearly high,

comparing with normal control group who was 163.1pg/ml on the average.

The serum gastrin level on dialysed patients

was inversely proportional to the gastric acid output.

It was reasonable to presume that hyper- gastrinemia was dependent on suppression of disintegration and renal excretion of the

gastrin according to low sensitivity to the target organ.

(116) N E W M E T H O D S F O R

D E T E R M I N A T I O N OF S E R U M L E U C I N E A M I N O P E P T I -

DASE (LAP) A N D

M O N O A M I N E O X -

IDASE (MAO) S. Ito, T. Takaoka, Y. Uragami

Y. Ki t amura and S. Kishi

2nd Dept. of Int. Ailed., Sch. of Med., Tokushima Univ.

S. Fujii and H. Okuda

Dept. of Enzyme-Physiol. Inst. for Enzyme Res., Sch. of Med. Tokushima Univ.

A new methods was presented for estimation of leucine aminopeptidase (LAP) and monoa-

mine oxidase (MAO). The principle of the

method consists in measurement of ammonia liberated by the action of deaminases with

a direct colorimetric determination of ammonia reported by Fujii and Okuda.

Leucine naphthylamide has been widely

used as the substrate for the estimation of

LAP in the present clinical examination, but leucine amide was used in our new method.

In the early stage of hepatitis and obstructive

jaundice, serum LAP activity was much higher by our new method than by the method in

which leucine naphthylamide was used as the substrate. I t was demonstrated that the

plasma of normal rats and CC14-treated rats

contained several isozymes which showed different substrate specificities toward leucine amide and leucine naphthylamide.

These results suggest that leucine amide is

preferable substrate for estimation of plasma LAP in clinical examinations.

(117) C L I N I C A L S I G N I F I C A N C E OF T H E ANALYSIS OF

S E R U M A L K A L I N E P H O S P H A T A S E I S O Z Y M E S : (II)

ANALYSIS O F A L K A L I N E PHOS- P H A T A S E I S O Z Y M E S BY

C E L L U L O S E A C E T A T E

E L E C T R O P H O R E S I S O N T H E P A T I E N T S

O F H E P A T O - B I L I A R Y DISEASES

K. Hirano, H. Kano, M. Ogino, Y. Ueda, K. Nishiwaki

and N. Iwamura Dept. of Gastroenterl.

T. Aoki Dept. of Clin, Pathol., Chukyo Hosp.

Using the method presented before the


meeting of the Japanese Society of Gastro- enterology in 1972, the sera of 77 patients with

hepato-biliary diseases were subjected to cellulose acetate electrophoresis and analyzed

for the alkaline phosphatase isozymes. The

results were classified into 4 types according to the electrophoretic pattern of the isozymes:

type Ia (al peak=>a2 peak), type Ib (otl<a2), type II (a2 only was observed), and type

V (a2 and post-/~ were observed). Since a close relation was observed between the

types of enzymogram and the diseases, it

is likely that the electrophoretic analysis of alkaline phosphatase isozymes is useful

for the differential diagnosis of hepatobiliary

diseases and for detecting the metastasis of malignant tumors to the liver.

(I 18) CHANGES OF THE ACTIVI- TIVES OF THE LIVER ENZYMES

FOLLOWING THE FOCAL HEPATIC DAMAGE

K. Hiramatsu, T. Kamada, T. Suematsu,

H. Fusamoto, H. Okuda and H. Abe

1st Dept. of Med., Osaka Univ. Med. Sch.

The present study deals with the changes

of activities of enzymes in the liver lobe with localized damage and in residual liver lobe.

Male albino rats of Sprague-Dawley strain

weighing approximately 300 g were injected a 50 mg of silica suspended in 20% glucose,

I to 5/t in diameter, beneath the liver capsule of the left lateral lobe under laparotomy.

The rats were sacrificed at 1,3, 7 and 14 days after the silica injection. The liver homoge-

nate and subcellular fractions of the silica- injected lobe and of the median lobe were

prepared, and the activities of glutamic pyruvic transaminase (GPT), acid phosphatase

and N-acetyl-/~-glucosaminidase (/~-GL.) were

measured. Control groups were injected 20% glucose alone.

The specific activity of GPT in the serum

was elevated in a few hours after injection, and in the liver the activity was decreased

in a day after injection. The decrease of the activity was most prominent in supernatant

fraction. The activities of acid phosphatase

and B-GL. in the liver, especially in particle

fraction, decreased maximally 3 days after

injection. The changes of the activities of these enzymes in subcellular fractions were

almost similar in the silica-injected lobe and also in the residual lobes.

From these results, it may be suggested

that focal liver damage would cause the same change in the residual lobes as was seen in the damaged lobe.

(119) ON THE ANALYSIS OF LACTATE DEHYDROGENASE

BY E L E C T R O F O C U S I N G

(IV) THE CHANGES IN LDH pI ISOZYME

PATTERNS IN T U M O R BEARING RATS

S. Katayama, K. Yamaguchi and M. Fukuda

Dept. of Med. Cancer Res. Inst., Sapporo Med. Col.

In the previous reports, applicability of isoelectric focusing on the analysis of lactate

dehydrogenase isoenzyme in a variety of diseases including malignancy was reported.

An characteristic pI isoenzyme of pI 6.5, of which appearance was observed in a signi-

ficant number of advanced carcinoma cases,

was also identified in a large number of cord sera obtained at normal delivery.

To substantiate pI isozyme change in malignancy, experimental tumors produced

in rats including Yoshida sarcoma, 3'Me

DAB hepatoma, were analysed for their pI isozyme composition with regenerating rat

liver and acute hepatic injury produced by CC14.

Resu l t s : Serial gel electrofocusing of SLDH of Yoshida sarcoma inoculated rats revealed

the appearance of peculiar pI isozymes after 7th day of inoculation. This change could

not be ascertained by ordinary disc electrophoresis carried out in parallel. A similar

fractionation pattern was noted in the extract of ascites tumor cells. Isozyme analysis

of hepatoma tissues developed in 3' Me DAB fed rats also closely resembled to those of

Yoshida sarcoma tissues. Interestingly, pI's of the fetal rat liver corresponded to those of


malignant tumors. Furthermore, regenerating rat liver at 24 hrs. after the operation,

at which time mitotic index was the highest,

disclosed the close similarity in pI isozyme pattern to those of malignant tumors. At 38

hrs, however, the fractionation pattern showed

a rapid return to those of normal liver. On the other hand, acute hepatic injury produced

by CC14 administraton resulted in a significant

decrease of acidic components. Implication of the present results were discussed.

(120) C L I N I C A L S I G N I F I C A N C E OF S E R U M M A L I C D E H Y D R O -

GENASE A C T I V I T Y AND ITS

I S O E N Z Y M E , ESPECIALLY IN L I V E R DISEASES

T. Ishii, I. Kaito, S. Sato,

H. Sasaki and H. Onodera

1st Dept. of Int. Med. Iwate Med. Univ., Morioka, Japan

Serum Malic dehydro genase (MDH) activity and its isoenzyme pattern were

determined in 44 cases with acute hepatitis, 30 with chronic hepatitis, 29 with liver

cirrhosis, 18 with malignant obstructive jaundice, 5 with myocardial infarction, 5

with acute leukemia and with 39 normal

subjects. Serum M D H activity was determined by

Mehler 's method, its isoenzyme was isolated by agar gel electrophoresis and stained by

the method of Yakulis et a l . .

The following results were obtained. 1 ) Serum M D H activity increased in

liver diseases, especially in a) the acute stage of acute hepatitis, b) hepatoma and c) malig-

nant obstructvie jaundice. In myocardial infarct ion-and acute leukemia serum M D H

activity also increased. 2) Serum M D H was electrophoretically

separated into five fractions which were found

to be MDHx_ 5 from the anodal side. MDH~

corresponded with a l b u m i n ~ a i-globulin, M D H 2 with a l~a2-g lobu l in , M D H 8 with a2-globulin, M D H 4 with f l~r -g lobul in ,

M D H 5 with Z-globulin. 3) In hepatitis and liver cirrhosis M D H 4

increased, and MDHx. 2 decreased. In metastatic hepatic cancer and malignant obstruc-

tive jaundice, M D H 4 increased and MDH4, was found. In myocardial infarction, M D H 3

decreased and M D H 4 increased. In acute

leukemia M D H 4 was unchanged, but M D H 5

was found. 4) There was a significant correlation

between serum M D H activities in acute

hepatitis, but the period for a return to a normal value was longer with M D H than

with LDH. The same results were obtained

in myocardial infarction. 5) Therefore, it is believed that the

determination of the activity and the isoenzyme of serum M D H is useful in differential diagnosis

and observation of the progress of liver diseases

and myocardial infarction.

(121) S E R U M DNASE AND DNASE

I N H I B I T O R LEVELS IN H E P A T I C DISEASES

M. Yamanaka, K. Akagi, S. Miyazaki,

M. Okumura and T. Omae

2nd Dept. of Int. Med., Kyushu Univ. Sch. of Med. Fukuoka

City, Japan

A simple and reliable method was devised for determining the activities of serum DNase

and DNase inhibitor, and the clinical significance of those was investigated with special

reference to hepatic diseases. DNase activity was measured in a reaction

mixture (0.33ml) containing 10/tmoles of

Tris-HC1 buffer, p H 8.0, 1.25/tmoles of MgCI2, 5 m/tmoles of 82P-DNA and 0.05,ml

of serum. DNase inhibitor was assayed in a reaction mixture (0.32 ml) containing

3 ktmoles of Tris-HC1 buffer, pH 7.5, 1.5

pmoles of MgCI 2, 5 m,umoles of 82P-DNA, 20 ng of bovine pancreatic DNase and 0.02 ml of serum. The reac t ion was conducted at

37 ~ for 50 min for DNase and 5 min for DNase inhibitor, respectively. One unit of DNase

was the amount which catalyzes the degrada- tion of 1.0% of the substrate into the acid-

soluble form and one unit of inhibitor was that which causes 1% inhibition of pancreatic

DNase activity.

Proceedings of the 59th Annual Meeting, 1973-Kagoshmai 195

DNase activities determined were: normal adults 106:~23/2; chronic hepatitis 122zk29 p; cirrhosis 197Jz32/2; hepatoma 133=k50/2; other malignancies including metastatic liver tumor 6 8 i 30 ft. Activities of DNase inhibitor were: normal 33• p; chronic hepatitis 38:k24/2; cirrhosis 16• 14/2; hepatoma 66=k17/2 and other malignancies 57• Significant correlation between serum DNase and transaminase levels was not observed.

The results indicate: 1) Determination of serum DNase is useful for the differential diagnosis of chronic hepatitis and cirrhosis; 2) Increased DNase and decreased DNase inhibitor levels were observed in cirrhosis, and the reverse relationship was noticed in malignancies. Thus the determination of DNase and DNase inhibitor was helpful for differentiation of cirrhosis from hepatic tumor; 3) A possible role of DNase inhibitor on serum DNase levels was postulated.

(122) CLINICAL SIGNIFICANCE OF ?'-GLUTAMYL TRANSPE- PTIDASE ACTIVITY (T-GTP)

IN CHRONIC LIVER DISEASES

Y. Nakamura, M. Wada and Y. Nakai Dept. of Int. Med., Nagoya City Johoku

Hosp., Kita-Ku, Nagoya

The determination of r -GTP activity is known to be of diagnostic value in obstructive jaundice, alcoholic cirrhosis, hepatoma, and active stage of chronic liver disease. Our present study deals with the correlation between the /'-GTP activity and histological picture of active chronic hepatitis.

The F-GTP level was determined by modified Oslowski method. The materials included 100 normal controls (23.3~13.7) in which male obtained higher activity than female.

Among 83 patients, 51 had chronic hepatitis, the remainder of patients were classified into fulminant hepatitis, terminal stage of acute hepatitis, chronic active hepatitis, partial obstructive jaundice .and alcoholic liver diseases. Liver biopsy was performed in 18 cases of active chronic hepatitis. The degree of cellular infiltration of Glisson's capsule,

fibrotic changes, mobilization of Kupper ceils, destruction of limiting membrane, etc. were graded from (--) to (~r~)-

Those cases who had higher ?'-GTP activity (~I00) showed more advanced histological findings and vice versa.

Liver biopsy was repeated in 9 patients in whom 5 cases except one who showed exacerbation of histological findings had increased ~'-GTP activity (> 100). However, 4 cases who showed improvement of histological findings had decreased V-GTP activity (less than I00). There was close correlation between 7-GTP activity and BSP (r=0.89).

It is suggested that the determination of r-GTP activity is beneficial in the prognosis of active chronic hepatitis.

(123) STUDIES OF GAMMA GLUTAMYL TRANS-

PEPTIDASE S. Inoue, T. Arima and S. Yamasaki Dept. of Int. Med. and Clin. Lab., Sch.

of Med., Kurume Univ., Kurume

The mechanism of elevation of serum gamma glutamyl transpeptidase (/'-GTP) activity was studied clinically and experimen-

tally. High r-GTP levels were demonstrated in

patients with intrahepatic cholestasis, primary and secondary liver cancer and extrahepatic biliary obstruction.

Significant increases in r -GTP activity were observed in sera of dogs following common bile duct ligation, but no increase in the sera of rabbits with hepatic in injuries by CC14 administration.

There was found high histochemical activity of the enzyme surrounding the bile canaliculi and in the walls of hepatic veins of rats liver with ligation of common bile duct.

High histochemical enzyme activity was found in the human hepatoma cells, while high activity was seen in liver tissue surrounding the hepatoma mass in autopsy materials.

Two or three isozymes of the enzyme were demonstrated by agar electrophoresi of sera in the hepatobiliary disease.

In sera of patients with hepatoma, higth


activity of ?'-GTP was shown at electrophoretic

mobility of a2 globulin.

(124) STUDIES ON ASPIRIN

ESTERASE ACTIVITY (VII)

T. Takano, Y. Katsuta, T. Yano, K. Isoda, T. Aramaki, N. Fukuda,

T. Ichikawa and H. Okumura

1st Dept. of Int. Med., Nihon Med. Sch., Tokyo

As previously reported, anoxemia and liver fibrotic of chronic liver diseases are observed

to reflect sensitively on aspirin esterase activity (AE). The present studies are to clarify

whether or not it becomes a good indication for the prognosis of chronic liver diseases

and to know the relationships to hepatic

area, total scanning score by Johnson's method and histological findings.

The mortality of 31 cirrhotic patients who were observed for 2 years was 32%. The

mortality of 16 patients showing low level of serum AE ( < 162/tg) was 44%, in contrast,

15 patients whose AE level were within normal limit was 20%.

In 28 patients with chronic hepatitis,

serum AE, r-globulin, ZTT and T T T were tested twice at 2 year intervals and were

compared to each other. The mean value of r-globulin significantly incresed in 17

patients whose serum AE decreased and that of ZTT decreased in 11 patients with increased

AE. The relation of serum AE to such histologi-

cal findings of the liver as inflammation, necrosis, degeneration, cholestatic and fibritic

changes were examined. Serum AE had a significant negative correlation to inflammation

and necrosis in 7 cirrhotic patients, but was not correlated to histological findings in 18

patients of chronic hepatitis. The hepatic and splenic areas and total

scanning score by Jonson's method were estimated by hepatic scannogram using 198Au

in chronic hepatitis and liver cirrhosis. Serum

AE had a significant correlation to hepatic

area only in chronic hepatitis, but no correlation to total scanning score in both diseases.

(125) EFFECTS OF BUCOLOME

AND O T H E R DRUGS ON LIVER M I C R O S O M A L ENZYMES

AND CYTOPLASMIC

O RG A N IC ANION- BINDING PRO-

TEINS Y. Adachi, R. Inoue, Y. Iwasaki,

S. Tanaka, T. Yamamoto

and G. Wakisaka Kyoto Univ., Fac. Meal., Div.

First Int. Med.

Jaundice of Gilbert's disease is known to be successfully treated with phenobarbital (PB)

and phetharbital (PT). As it was reported previously, bucolome (BC) was found by us

to have the same effect on jaundice of Gilbert's

disease, and these three drugs showed the induction of UDP-glucuronyl-transferase (GT)

activity in rat liver. In the present report the effects of these three drugs on microsomal

enzymes and cytoehromes as well as brom-

sulphalein(BSP)-binding capacity of cytoplasmic proteins were observed in rat liver

to study the mechanism of action of these drugs on the bilirubin metabolism respectively.

(Melhod) Four groups of male Wistar rats (around 100 g) were given (1) water (2) BC

50 mg/100 g/day (3) PB 10 mg/100 g/day

(4) PT 25 mg/100 g/day orally. After 7 days of administration, liver microsomal

and 105,000• supernatant fractions were prepared. Activities of GT and aniline

hydroxylase(AH), contents of cytochromes

P-450 and b5 were determined in microsomal fraction. BSP-binding capacities of cyto-

plasmic protein fractions of Y and Z were measured by the Sephadex G-75 upward

column chromatography. (Results) BC administration produced slight increase in

liver weight and GT activity. But it showed no effect on AH, cytochromes P-450 and b5,

and BSP-binding capacities of Y and Z fractions. Administration of PB and PT,

on the other hand, produced marked increase in liver weight, induced GT and AH activities

as well as cytochromes P-450 and b5. BSP-

binding capacity of Y fraction showed marked increase, but that of Z fraction showed di-

minished capacity after PB and PT administra-


tion. From these results, it is concluded that BC induces GT relatively and selectively and it gives only slight effects on BSP-binding capacities of cytoplasmic proteins. It is suggested, therefore, that the action of BC on liver cell bilirubin metabolism differs considerably from those of PB and PT.

(126) CLINICAL EVALUATION OF SERUM PROTEIN SUB-

FRACTION LEVELS IN VARIOUS LIVER

DISEASES H. Nakaya, S. Takase, F. Ikegami

and A. Takada Dept. of Int. Med., Kanazawa

Med. Univ. K. Kobayashi and J. Takeuchi

1st Dept. of Int. Med., Sch. of Med., Kanazawa Univ.

Serum protein sub-fraction level was estimated in several liver diseases and the meaning of its changes was analyzed from several respects. Mate r ia l and Method: Sixty three patients with liver diseases, including 15 of acute hepatitis(A.H), 8 of sub-acute hepatitis(S.A.H), 20 of chronic hepatitis active form(C.A.H), 9 of chronic hepatitis inactive form(C.I.H), 7 of compensated liver cirrhosis(C.L.C) and 6 cases of decompensated liver cirrhosis(D.L.C) were studied. The diagnosis of all cases were confirmed by liver biopsy specimens except for 2 cases of A.H. Serum protein sub- fraction levels were estimated by the universal immunodiffusion method according to Terano et al. Resu l t s : Serum prealbumin(prealb.) level was decreased remarkably in A.H and S.A.H and moderately in C.A.H and D.L.C. ot2-HS glycoprotein(ot2-HS gh), /3x-CA globin (fix-CA gl.) hemopexin and /~2-I glycoprotein (~2-I gl.) levels were significantly decreased only in S.A.H and D.L.C. Significant decre- creases in haptoglobin and transferrin were seen only in D.L.C. Ceruloplasmin was increased in A.H and decreased in S.A.H. Significant increases of macroglobulin and ax-antitrypsin were observed in A.H, C.A.H and L.C. In S.A.H, a2-HS gh level was

significantly lower than that of A.H, while prealb, level was decreased in both diseases without any significant difference. However, prealb, level was returned to normal level accompanying with its clinical improvement in A.H, but the level remained constantly low during all its clinical course in S.A.H. In C.H, significant differences between active and inactive form were only observed in prealb, and /~2-I gl. levels. Several protein sub-fractions showed remarkably low levels in D.L.C but scarcely lowered in C.L.C. /~I-CA gl. level was not significantly different between A.H and C.A.H, and not related to the presence of Australia antigenemia in chronic liver diseases. However, in the highly active C.A.H without Au-antigenemia, Ill-CA gl. level and the ratio of/~I-CA gl. to a2-HS gl. was decreased, indicating an increased com- sumption of the complement in highly active C.A.H.

These results suggested that the measurement of serum protein sub-fraction level is one of the good indices of the diagnosis and evaluation of the prognosis in various liver diseases.

(127) EFFECT OF BETAMETHA- SONE ON ALBUMIN SYNTHESIS

IN ISOLATED PERFUSED LIVER OF NORMAL

AND CCL 4 IN- TOXICATED

RATS Y. Kato, A. Funayama, S. Kakumu,

S. Ito and S. Okuyama 3rd Dept. of Int. Med., Nagoya

Univ. Sch. of Med.

The effect of betamethasone on plasma albumin synthesis was studied i!~ isolated perfused liver of normal and CCI 4 intoxicated rats using carbonate-14C. Livers of normal and CCI 4 intoxicated rats were perfused with heparinized rat blood diluted with Krebs- Henseleit bicarbonate buffer for 3 hours. At 90 minutes after the start of perfusion, 4 mg of betamethasone or 500/tg of actinomycin D was added respectively into the perfusate. On the other experiments, betamethasone and aetinomysin D was added


simultaneously. The rate of albumin synthesis was calculated from the specific activity of newly formed urea and the total 14C in guanido carbon of arginine in albumin.

Albumin synthesis rate of normal rats was 5.4mg/hour/100g body weight, and the rate increased to 8.7 mg by the addition of betamethasone. The difference was significant statistically. The synthesis rate of the intoxicated livers in acute stage was 4.3mg/hour/100g body weight. This was lower than the rate of normal rats. The rate increased to 7.3 mg by the addition of betamethasone. The difference was also significant statistically. The synthesis rate of cirrhotic livers was 3.1 mg/hour/100 g body weight, and the rate increased to 5.3 mg after the addition of betamethasone.

In order to elucidate the mechanism of the action of betamethasone on albumin synthesis, the additon of betamethasone and actinomycin D were held in normal liver perfusion. The synthesis rate after the addition of actinomycin D was 5.0 mg/hour/100 g body wight, and the rate after the simul- taneous infusion of betamethasone and actinomycin D was 5.2 mg. That is, actinomycin D did no t inhibit the albumin synthesis of normal livers, but inhibited the increase of synthesis rate by the addition of betamethasone.

From these results, it was clarified that the rate of albumin synthesis decreased significantly in proportion to the progress of the injury of the liver, the synthesis rate in normal and CC14 intoxicated livers was promoted by the addition of betamethasone and actinomycin D inhibited the increase of albumin synthesis rate by the addition of betamethasone.

(128) SERUM GLYCOPROTEIN ANALYSIS FOR THE AC-

CURATE DIAGNOSIS OF LIVER CAR- CINOMA AND RELATED DIS-

EASES Y. Taoka, T. Endo, R. Chizuka,

T. Yanagida, and S. Chizuka Tokyo Rosai Hosp. (Tokyo Univ., Sch. of

Med., Ohta-ku, Tokyo)

Analysis for electrophoretical patterns of serum glycoproteins (periodic acid-Schiff staining) on "Cellogel" in patients of liver carcinoma and related diseases is very useful for accurate diagnosis.

In primary liver carcinoma (mainly hepatoma) are recognized prominent and wide a l and a2-GP peaks ("malignant pattern"), and also ot 1 is usually higher than 0t2 whereas a2 is more prominent than otl in metastatic liver carcinoma.

Protein-bound sialic acid is significantly increased in metastatic liver carcinoma and protein-bound hexosamine is enhanced in other carcinoma without liver metastasis.

No remarkable change is noticed for protein- bound amino-sugars between primary liver carcinoma and liver cirrhosis without malignancy.

On serum glycoprotein subcomponents are markedly increased ot 1-acid glycoprotein (a 1-AG) and a 1-antitrypsin (a 1-AT), haptoglobin (Hp) and ceruloplasmin (Cp) in liver carcinoma and other carcinoma without liver metastasis whereas 0~2-macroglobulin (a2-M) and ot2-heat stable glycoprotein are rather decreased in these conditions.

No definite correlation is illustrated in this paper between primary and metastatic liver carcinoma and related diseases for haptoglobin subtypes (1-1, 2-1, 2-2).

(129) SOME CHARACTERS AND CLINICAL SIGNIFICANCE

OF LP-X H. Usui, T. Ando, T. Takai,

T. Wakahara, M. Kojima, T. Fukazawa and

Y. Takahashi 1st Dept. of Int. Med. G~, Univ.

The presence of abnormal lipoprotein (Lp-X) in the blood of patients with obstructive jaundice was proved from the study with electron microscope, lipid analysis, gel filtration, electrophoresis and immunology.

The electron microscope revealed the presence of the abnormal disks with major axis 400-600A in the blood of patients with obstrutive jaundice. The special disks have


the tendency to form a rouleaux. The com-

position of the disks was characterized by high PL, low TG, abnormally low cholesterol

ester ratio and low level of protein content. The fraction containing the purified disks

did not react with anti a - or /9-Lp antibody.

Gel filtration of the serum of the patient

showed abnormal fractions between chylomicron and LDL. Anti Lp-X antibody

reacted with the abnormal fractions and the lipid compositon of the abnormal fractions

was similar to that of purified Lp-X. Clinically,

L p - X was observed in cholestatic hepatitis (6/13), extra-hepatic biliary obstruction

(16/20) primary biliary cirrhosis (2/2) and metastatic liver tumor (5/8), and the incidence

of Lp-X was increased as the level of serum

alkaline phosphatase increased. It was

concluded that the detection of Lp-X was useful for analyzing the presence of biliary

obstruction.

(130) T R A N S F E R R I N IN L I V E R DISEASE A N D ITS

P R O G N O S I S - - E F F E C T OF T R A N S F E R R I N

O N L I V E R R E G E N E R A -

T I O N - S. Miyamura, T. Urakawa, T. Shima,

K. Miyaji and T . Okazaki

3r&Dept. of Int. Med., Mie Univ. Sch'. of Med.

The liver is an organ active for regeneration and repair and Such function should be taken

into consideration in liver disease. However

there is no such indicator in the current liver function tests. We have reported the useful-

ness of serum T I B C to serve such purpose. Sixty five per cent of the cases of acute

hepatitis with a serum T I B C value below 330/.tg/dl on admission took a prolonged

course, all cases of fatal fulminant hepatitis were below 200/ tg/dl and cases of liver cirrho-

sis were of low values Acccording to Higgins method two-thirds

of liver were. resected and the variation of transferrin was investigated during the course

of regeneration. At the peak of regeneration there was an increase in hepatic TIBC. After

the peak there was an increase in serum TIBC

parallel to the hepatic TIBC. From this result the produced transferrin was assumed

to be related to liver regeneration. To

confirm this assumption various amounts of human apotransferrin were injected in-

traperitoneally into rats of 200 g and the

incorporation of 3H-thymidine into hepatic D N A was found maximal at the level of

10mg which is equivalent to 100/tg/dl of human TIBC. When was injected the animal

serum which was obtained at the peak of

liver regeneration, despite the low level of transferrin, the SH-thymidine incorporation

was increased. Thus though factors other than transferrin also play a roll in liver re-

generation, transferrin itself activates liver regeneration.

(131) M E T A B O L I S M O F V O L A T I L E F A T T Y A C I D IN R A T L I V E R

IN E X P E R I M A N T A L B I L I A R Y

O B S T R U C T I O N S. Kashimura, K. Koyama, H. Yamauchi,

Y. Matsuo, Y. Takagi, L Muto, Y. Owada, T. Otowa

and T. Sato

1st Dept. of Surg., Tohoku Univ. Sch. of Med., Sendai

I t is the clinical evidence that considerable number of patients with severe obstructive

jaundice in our clinic died of hepatic coma. However, the etiological factors of the condition

are still obscure. The purpose of this paper is to examine

the metabolism of volatile fatty acid (VFA)

which has been considered to be one of the important factors inducing hepatic coma.

In one group, 20 of Wistar rats were subject-

ed to ligation and section of the common bile duct. In another group of 7 rats, 20%

carbon tetrachloride (CCL4) solution was injected into the peritoneal cavity. The

rats of the former group were killed every week during four weeks and those of t h e

latter group were done 48 hours after the injection. The thin liver slices were prepared

for the examination of the metabolism of VFA. The consumption of VFA was diminished


of graded degree correspondiing to the duration of the bile duct obstruction, especially remarkable at three weeks after the biliary obstruction and the most conspicuous decrease was found in the liver of CCL 4 injection rats. Diminution in the consumption of VFA was preceded by that of ketogenesis, which was most apparent at two weeks after the biliary obstruction and the magnitude of the decrease in ketogenesis was higher than that of the decrease in the consumption of VFA. How- ever, both of them became almost the same at three weeks after the ligation. The volume of diminution in VFA exceeded that of ketogenesis at four weeks after that, and similar tendency was demonstrated in the liver of CCL 4 injection rats.

It was clarified that the consumption of VFA decreased in volume in proportion to the duration of the biliary obstruction and its diminution was caused mainly by that in ketogenesis. It was also presumed that the disturbance in ketogenesis was presented in the earlier stage than that in the TCA- cycle in the liver in biliary obstruction, but both TCA-cyele and ketogenesis were disturbed at the period of three weeks after the hiliary obstruction. The studies on metabolism of VFA and ketogenesis possibly enable us to determine the grade of the hepatic dysfunction in patients with bitiary obstruction and to forecast the occurrence of hepatic coma.

(132) METABOLISM OF CHYLOMI- CRON-TRIGLYCERIDES (TG)

AND FREE FATTY ACIDS (FFA) BY ISOLATED

HEPATOCYTES C. Naito and K. Okada

1st Dept. of Int. Med., Facul. of Med., Tokyo Univ., Tokyo

Isolated hepatocytes were prepared gently using collagenase and hyaluronidase.

Trypan blue stainable cells were less than 5%. When 14C-chylomicron was incubated with isolated hepatoeytes at a low temperature (4~ total 1~C uptake by the cells was equal to that incubated at 37~ However, the incorporation of a*C into metaholites of fatty

acids (Co 2 and ketone bodies) was much less at the low temperature. When x~C-oleic acid was used instead of 14C-chylomicron, the similar results were observed. These results, taking together with the fact that 14C-chylomicron contained 14C-FFA (3 to 4%), suggested that 14C-chylomicron was taken up by hepatocytes in the form of not 14C-TG but 14C-FFA. When postheparin serum containing high activity of lipoprotein lipase was added to the incubation medium, not only total x4C uptake by hepatocytes but also the incorporation of 1~C into metabolites of fatty acids increased significantly.

However, no effects of post-heparin serum addition were observed on the uptake and incorporation of 14C from 14C-oleic acid. Moreover, when Krebs-Ringer phosphate buffer was used as the incubation medium instead of dialyzed serum, total 14C uptake by hepatocytes from t4C-chylomicron and the ~4C activity of TG fraction of hepatocyte lipids increased significantly. Nevertheless, the incorporation of 14C into metabolites of fatty acids did not increase at all.

In the medium of Krebs-Ringer buffer solution, adhesion of chylomicron to the surface of hepatocytes has been suggested. Therefore, the increase in radioactivity of total and TG fraction appeared to be due to the adhesion, but not to the real uptake by the cells. Conclus ion: Chylomicron-TG can be taken up by hepatocytes only after hydrolysed to FFA but not as such.

(133) A STUDY ON CHANGES OF BLOOD GLUTHATIONE

(GSH AND GSSG) AND G-6-PD ACTIVITY

IN JAUNDICE K. Sugawara, T. Nokiba, Y. Fujii,

H. Kido. M. Sasaki, Y. Su~ai and G. Nishimura

1st Dept. of Surg., Nihon Univ., Sch. of Med.

In the 55th meeting of this society, we reported tendencies of a decrease of blood GSH and an increase of blood GSSG in obstructive jaundice. This time, we performed, in jaun-


diced cases, experimental and clinical studies on changes of G - 6 - P D activity which has an

intimate relationship with the oxidation and

reduction of gluthatione and the comparison was made with those of gluthatione.

Experimentally, using dogs, bile ducts were ligated and severed. By the time went on,

icterus index increased. But blood GSH and

G S H / H t index showed tendencies to decrease. On the contrary, blood GSSG showed an

increase. The activity of blood G - 6 - P D showed a definite tendency to decrease. The

activity was almost completely found in the

blood corpuscles. In liver tissue of bile duct ligated dogs, we

noted a decrease of G S H and an increase of GSSG. But G - 6 - P D activity in liver showed

an increase, contrary to the change in blood.

In 28 patients with jaundice of various origins, the relationships between the degree

of jaundice and GSH, GSSG and G - 6 - P D

activity in b lood were studied. Blood GSH showed a decrease but no direct relationship

was observed between GSH level and icterus index. No difference was noted in GSSG

level from the control. As for G - 6 - P D ac-

tivity in blood, most of the cases showed an increase if jaundice was slight or moderate,

and a decrease if jaundice was marked. In a study of a hepatitis patient and a case of

post-operative carcinoma of the head of the

pancreas, we found that the activity of G - 6 - P D was more closely related with icterus index

than blood GSH, when jaundice was improv- ing. In these cases, blood G - 6 - P D activity

was increasing as icterus index was decreasing.

(134) H E P A T I C F U N C T I O N A L

R E S E R V E IN O B S T R U C T I V E

J A U N D I C E F R O M A STAND- P O I N T OF M I T O C H O N D R I A L

M E T A B O L I S M

H. Nanbu, Y. Kamiyama, T. Yamada, Y. Yamaoka, H. Takeda, T. Ohsawa,

.

T. Kamano, T. Mizukami,

O. Kitamura, K. Ozawa, H. Takasan and

I. Honjo 1st Dept. of Surg., Kyoto Univ.

Sch. of Med.

The hepatic mitochondrial metabolism in

regard to the cytochrome a(+a3)- turnover number of phoshporylative capacity and the

contents of respiratory enzymes were investigated in 11 patients of obstructive jaundice

and 109 rabbits subjected to ligation of the

common bile duct. These could be classified into three groups; mitochondria having

normal or enhanced A T P synthesis capacity

with normal contents of cytochrome a(+a3) (group I), lowered A T P synthesis capacity

with normal level of cytochrome a (+aa) (group II) , and severely inhibited A T P

synthesis capacity with marked decrease of cytochrome a (+as ) content (group I I I ) .

The hepatic functional reserve, estimated

from the postoperative hepatic dysfunctions and mortality, was maintained enough in group I, fairly in group I I and poor in group

I I I .

(135) H I S T O L O G I C A L CHANGES OF R A T L I V E R BY A D M I N I S T R A -

T I O N OF H E M O L Y S A T E R. Miyasaki, T. Katayama,

T. Amakawa, K. Hirose, Y. Furukawa, M. Noguchi,

M. 'Okamoto and

H. Maezawa 1st Dept. of Int. Med., Tokyo Med.

and Dent. Univ.

This report describes the hepatic changes

of rats after injection of hemolysate. Two ml of the hemolysate, produced by the

method reported previously, was administered

into rats intraperitoneally once a week for 6

months. Then the liver was examined morphologically by light and electron microscope. And the serum G O T , Al-p and 131I-BSP

retention rate were measured. In the light microscopy, the degeneration

and the decrease content of glycogen of hepatocyte were recognized, but the cell

necrosis was scarcely found. Kupffer cells


became proliferated a n d enlarged moderately.

And the addi t ional features were the format ion

of vacuole and the proliferation of fiber along

the sinusoidal marg in of hepatocyte. In

electron microscopy, the vacuole was del imited

by a single m e m b r a n e and the nucleus,

mitochondrion, and endoplasmic re t iculum of

the hepatocyte h a d a normal appearance .

The cytoplasmic process of endothelial l ining

of sinusoids became so thick that no fenestra-

tion was observed. Collagen fibers were

ploriferated in space of Dissse which was not

uniform in width.

I t was es t imated tha t these sinusoidal

changes is identical wi th socalled "capi l -

lar izat ion" of sinusoid.

In the funct ional studies, serum G O T , G P T

and Al-p were in normal range, bu t x3XI-BSP

retent ion rate in the rats adminis tered the

hemolysate were increased than that in the

control.

From these histological and funct ional

studies, it was concluded tha t some substance

in the hemolysate led to damages of the liver,

especially sinusoidal walls and sinusoidal

surface of hepatocytes.

(136) M E T A B O L I S M O F V I T A M I N

B-12 IN L I V E R D I SE A SE W I T H

S P E C I A L R E F E R E N C E T O

T R A N S C O B A L A M I N S A N D

N A T U R A L O C C U R R E N C E

O F C O B A L A M I N S

N. Tanaka , S. Yamada , T. Hisata,

C. Ha ta , J . Sawa, Y. Kato, Y. M i t u d a and S. Oohi ra

2nd Dept. of Int. Med., Jikei Univ., Sch. of Med.

The de te rmina t ion of serum B-12 concentra-

t ion and unsa tu ra ted B-12 binding capacity,

separation of T ranscoba lamin 11 and Trans-

cobalamin 1, measurement of endogenous

B-12 in Transcobalamins , and investigation

of na tura l occurrence of cobalamin in serum

and Transcoba lamins were done on sera

f rom heal thy individuals and patients wi th

acute hepatitis.

In acute hepat i t is the elevation of serum

vi tamin ]3-12 was marked and the unsa tu ra ted

vi tamin B-12 b ind ing capacity was slightly

decreased as compared wi th heal thy individ-

uals. Me thy lcoba lamin in serum and Trans -

cobalamin 1 f rom heal thy individuals and

acute hepatit is pat ients were found as the major

form of occurrence, bu t DBCC and Hydroxoco-

ba lamin were slightly increased in serum and

Transcoba lamin 1 f rom acute hepatitis pat ients

as compared wi th hea l thy individuals.

In Transcoba lamin 11 from heal thy individ-

uals the propor t ion of occurrence of O H - B - 12,

CH-B-12 , and DBCC was considerably

similar, bu t DBCC was relatively increased

in Transcoba lamin 11 from acute hepati t is

patients, suggesting tha t it is due to a release

of DBCC from the damaged liver.

(137) P O S T O P E R A T I V E N U T R I -

T I O N C O N T R O L SPECIAL

R E F E R E N C E T O A M I N O -

A C I D M E T A B O L I S M

- - - - E S P E C I A L L Y O N A M I N O -

A C I D M E T A B O L I S M IN

D I A B E T E S M E L L I T U S - -

A. Hayasaka, T. Okuyama,

S. Fukui, T. Takeda,

T. Furuichi , S. Yamamitsu ,

K. Yamauchi , and

Y. Konishi

1st Dept. ofSurg., Sapporo Med. Col.

Our recent s tudy on this par t i cu la r

condit ion was repor ted and summar ized as

follow:

I) Branched chain amino-acid becomes

higher in its concent ra t ion than normal

range even in a mi ld case and the level tends

to increase more in a modera te or severe

c a s e .

2) Arg. reveals h igher level even in a mi ld

case.

3) All other amino-acids show same tendency

in their levels as above.

Proceedings oft he 59th Annual Meeting, 1973-Kagoshima 203

(138) STUDIES ON THE PROFILE

ANALYSIS OF ORGANIC ACIDS

(I) DEVELOPMENT OF A NEW T E C H N I Q U E FOR ANALYSING

ORGANIC ACIDS RELATED

TO TCA CYCLE S. Maeda, S. Setoyama and

S. Otsuji Central Clin. Lab., Kagoshima Univ.

Hosp., Kagoshima

Purpose: A new chromatographic tech-

nique was devised to analyse simultaneously

organic acids related to TCA cycle. The chromatogram was designated as TCA-

Acidogram. The purpose of this study was to apply TCA-Acidogram to the clinical and

biochemical researches and to the diagnosis

or follow-up of various pathological conditions. Mater ia l s and Methods Partition chro-

matography with silicic acid column and

gradient elution with tert. amyl-alcohol/ chloroform were found to be suitable for the analysis. Automatic indicator titration be O-Nitrophenol Na was applied to column

eluate in order to continuously measure

absorbancy at 350nm of each separated organic acids.

Resu l t s : Acids were well separated in TCA-Acidogram of 11 authentic acids mixture.

TCA-Acidograms of some biological materials

were as follows: Acetate, fumarate, lactate, succinate, trans-aconitate, malate and citrate

were clearly identified in rat liver. The chromatographic difference between normal

and CCI 4 treated rats was discussed. Acetate,

lactate, succinate and trans-aconitate were demonstrated in gastric juice. Additional

peak of citrate was appeared in ulcer and the difference was revealed between normal and

ulcer profiles. Pyruvate, fumarate, lactate, succinate, alpha-ketoglutarate, trans-aconitate,

cis-aconitate, malate and citrate were detected in serum. In liver cirrhosis, those acids were

decreased and increased acetate peak was additionally identified. The difference of

profiles was discmsed between normal and liver cirrhosis.

It could be conceivable that TCA-Aci-

dogram of biological materials would promote

understanding and clarification of biochemical

mechanism in various pathological processes.

(139) METABOLIC A L T E RA T IO N

OF ERYTHROCYTE F R O M THE

PATIENT W I T H CH RO N IC LIVER LESIONS

T. Ibata, H. Niu, A. Ogawa, E. Tujioka, T. Maeda,

M. Takewa, T. Matumoto, K. Tamada, A. Maeda,

H. Sumita, Y. Iseki,

S. Yukawa, Y. Nitta,

K. Isida and H. Nomoto

Dept. of Metabolism, Int. Med., Wakayama Med. Col.

Several metabolic changes of matured

erythrocyte from liver damaged patients were

studied.

Methods and Mater ia l s :

Several enzyme activities, added glucose or

xylitol utilization and lipids of human erythrocyte having chronic hepatitis or liver cirrhosis

were observed. Lactate was measured by Barker-Summer-

sons method and pyruvata was by Marbachs.

Glucose-6-phosphate dehydrogenase, 6- phosphogluconate dehydrogenase, glyceralde-

hyde-3-phosphate dehydrogenase, glutathione

reductase, pyruvate kinase and lactic dehydrogenase were by Miwa's method.

Reduced glutathione of erythrocyte was measured with the method described by

Beutler.

Resul t s and d i s c u s s i o n :

1. Low levels of glutathion reductase

activity and reduced glutathione of erythrocytes from chronic hepatitis and from liver

cirrhosis were obtained, on the contrary with the elevated glucose-6-plmsphate de-

hydrogenase from that of erythrocytes. 2. Suspension of erythrocytes in xylitol

added Krebs-Ringer solution was incubated

for 3 hours at 37~ and production ofpyruvate and production of pyruvate and lactate were

measured. The ratio of lactate/pyruvate from chronic

hepatitis, esp. from liver cirrhosis was very


high value, that was suggested increased

N A D H 2 to N A D or increased permeabili ty of xylitol into erythroeyte from patient having liver cirrhosis.

3. Lactate producing activity of erythrocytes from diabetics was disturbed, but when advanc-

ed liver damage was combinated, the activity recovered to or exceeded normal value.

On the other hand, the lipid constitutions of

erythrocyte from chronic hepatitis or liver cirrhosis were resemble to that of spherocytosis,

namely the quantities of phosphatidyl serine to total lipids was decreased. These ex-

perimental results suggested the possibility

of characteristic change of erythrocyte membrane from patient with chronic liver lesions.

(140) S T U D I E S ON T H E

L E U K O C Y T E G L Y C O L Y T I C R A T E - L I M I T I N G

E N Z Y M E IN D I A B E T I C S (I)

S. Setoyama, S. Maeda

and S. Otsuji

Central Clin. Lab. Kagoshima Univ. Hosp., Kagoshima

The purpose of this study was to reveal some aspects of pathological mechanism and to

promote the clinical understanding of diabetes mellitus.

M a t e r i a l s a n d M e t h o d : Leukocyte pre-

paration was isolated from human venous blood by the modified polyvinylpyrrolidone separa-

tion procedure devised by authors. Both in 30 normal subjects and in 50

diabetics (composed of 13 severe, I0 moderate and 27 mild types), the activities ofhexokinase

(HK), phosphofructokinase (PFK) and pyruvate kinase (PK) were determined.

R e s u l t s : 1. Average PK activity of diabetics was significantly lower than that of normal subjects. 2. Both average PK activ-

ties of 27 mild and of 13 severe diabetics were significantly lower than that of normal subjects,

but the differences of average PFK and H K activities between diabetics and normal subjects

were not significant. 3. Correlation between the degree of obesity of diabetics and the

activities of enzymes: In mild diabetics, it

was significantly correlative to H K activity; and in thin type, it had significantly negative

correlation with the activities of HK, P F K and PK. 4. Correlation between the activities of

enzymes and serum lipids: Significant cor-

relation was found in between phospholipid and the activities of P F K and PK, and also

found in both between non-esterified fatty acid and the activity of P F K and between

triglyceride and that of PK.

(141) H E P A T I C C H A N G E S IN A C U T E C I R C U L A T O R Y

F A I L U R E

R. Sato, G. Sato, S. Toyokawa, G. Yamamoto, S. Ohtomi,

M. Haga and Y. Ueno

Dept. of Int. Med., Mishuku Hosp.

M. Fukuda

Dept. of Clin. Pathol. R. Endo

Laboratory

We reviewed 580 autopsied cases which had

done in the past several years in our hospital and evaluated them in both morphological

and functional aspects. 58 out of 580 cases, with exception of 18 cases of acute or subacute

hepatitis showed hepatic necrosis caused by acute circulatory failure, in which 11 cases

were of focal and zonal necrosis, 30 cases of submassive central necrosis and 17 cases of

massive necrosis. Their primary diseases were

made of liver cirrhosis with massive hemor- rhage from ruptured varices, hemorrhagic gas-

tro-duodenal ulcer, acute heart failure in myocardial infarction or valvular diseases, mesenteric insufficienty, malignant tumor

and other disorders. Hepatic degeneration and necrosis were

considered to be caused by acute circulatory

failure in liver followed by low cardiac output which resulted into ischemia or hypoxia in liver cells.

Findings of liver function tests were very

similar to them of acute hepatic parenchymal damage, especially of subacute hepatic necro-

sis. Levels of serum G O T and GPT showed significant elevation and G O T to GPT ratio


was over 1.0 in many cases. Elevated levels of L D H and I C D H were more remarkable

than those of G O T and GPT. Elevation of serum bilirubin level was lower in spite of

abnormally high levels of liver enzymes.

There were often presented leukocytosis, increased BUN and serum creatinine.

(142) C H A N G E S O F H E P A T I C

A R T E R I A L F L O W A N D L I V E R F U N C T I O N

T. Yokota, J . Ohsawa, A. Kohno, E. Ohtoshi, H. Yasugi,

H. Ichikawa, R. Mizumoto

and I. Honjo.

1st Dept. of Surg., Kyoto Univ. Med. Sch.

It is very important to study on the effect of

the hepatic artery in various conditions upon liver function, because the liver in portal hyper-

tention is mainly supplied by the hepatic artery with vascular disturbance of the portal flow

and because complication of cirrhotic liver

restricts operability of primary carcinoma of the liver.

1. The portal branches of the right half of the liver and the hepatic vein of the left

half were ligated after the performance of large side to side portacaval anastomosis in

dog. Under these circumstances, right half of the liver was supplied merely by the hepatic

artery with normal outflow tract into the

hepatic vein and left half merely by the hepatic artery with retrograde outflow tract via the

portal vein above the shunt. The function of the liver with postsinusoidal block in the left half was compared with that of the liver

with presinusoidal block in the right half of the same dog, using 131I-BSP excretion rate

in the bile, bile volume and oxygen consumption rate immediate and 8 weeks,

after the operation. Immedia te after the operation, bile volume,

'31I-BSP excretion rate and oxygen consumption rate in the right half with presinusoidal

block were the .same as that in the left half with postsinusoidal block, showing no damage

to the liver cell in each side. 8 weeks after the operation, 181I-BSP excretion rate in the right

half was about two times higher than in the left half and oxygen consumption rate

in the right half was significantly higher than

in the left half. On the histological section, the liver in the left half showed more promi-

nent degenerative changes than in the right half. These results indicate that retrograde

flow of the hepatic artery into the portal vein is less effective than normograde flow into the hepatic vein.

2. Resectability of the liver in various

conditions of the hepatic artery was investi-

gated. When the hepatic vein was ligated with portacaval anastomosis and liver showed

postsinusoidal block, many dogs survived more than 2 weeks after 30~ hepatectomy, but all

died after 50% hepatectomy. When the portal vein was ligated with portacaval

anastomosis and when the liver showed presinusoidal block, many dogs survived more

than 2 weeks after 50% hepatectomy, but few

dogs survived after 70% hepatectomy. It is concluded that the liver function with

retrograde outflow of hepatic artery in

postsinusoidal block was only 50~176 of that with normograde flow of hepatic artery in presinusoidal block.

(143) S T U D I E S O N H E P A T I C

C I R C U L A T I O N : A L T E R A T I O N S

OF H E P A T I C B L O O D F L O W IN D O G S W I T H

H E P A T I C I N T O X I C A T I O N BY D I M E T H Y L N I T R O -

S A M I N E ( D M N A ) K. Ando, H. Suzuki, T. Nishiwaki,

T. Kishimoto, T. Miki, K. Takeshige, M. Sawada, R. Hidemura

Dept. of Surg., Nagoya Univ. S. Yamamoto and S. I toh

Dept. of Surg., Aichi Med. Col.

Values of hepatic blood flow (HFB) estimated by different methods are not necessarily

consistent. Comparat ive studies were carried out between clearance methods with results

obtained by electromagnetic flowmeter (EMF) as the standards in dogs with hepatic intoxica-

tion induced by Dimethylnitrosamine (DM-


NA). Hepatic arterial flow (HAF) and portal

venous flow (PVF) were directly measured

using EMF, HBF being calculated as the sum

of these two components. Clearance studies were performed using Indocyanine green

(ICG, 0.25mg/kg) and colloidal radiogold (Au 198, 50/ tCi) . Peripheral disappearance

rate (K) and hepatic extraction rat io(ER)

were calculated for each indicator. To test the effects of superimposed mechanical re-

duction of HBF, the same clearance studies were repeated on the same animals after 40

and 70% hepatectomies(HX), hepatic arterial l igation(HAL) and end-to-side portacaval

anastomosis(PCA).

In animals with DMNA-induced hepatic intoxication, both H A F and HBF as measured

by EMF were increased by 42 and 14% respectively compared with normal controls.

This observation corresponds to the observation

in hepatic intoxication by carbon tetrachloride (CC14). While values of HBF obtained by Au lg8 clearance method and E M F were in

fair approximation, dissociation was noted

between results obtained by I C G method and EMF. Although the effect of D M N A on the

liver was morphologically less severe than that of CC14, the effect on the functional aspect of the liver was fairly severe.

I t might be concluded that alterations of

HBF induced by D M N A intoxication is reflected more closely on Au xgs clearance than

on ICG clearance, since impairment of the liver induced by D M N A is more functional than morphological.

(144) S T U D I E S O N H E P A T I C

H E M O D Y N A M I C S BY S C I N T I P H O T O S P L E N O

P O R T O G R A P H Y

T. Kashiwagi, M. Kishida and O. Imamura

Dept. of Med., Kansai Rosai Hosp. T. Suematus and T. Kamada

1st Dept. of Med., Osaka Univ. Med. Sch.

A new method of visualization of portal venous system was developed.

After injecting 99mTcO4- (5-8 mCi/ml)

into the spleen, scintiphoto was taken by Picker Dyna Camera. This method was

named scintiphotosplenopor tography. Twenty-eight patients were studied. Pat-

terns of portal circulation were classified into

four groups. Ia : no collaterals, no tortuous vein

Ib: no collaterals with tortuous vein I I : collaterals with liver image

I I I : collaterals without liver image Patterns with collaterals were thought to

suggest the existence of por ta l hypertension.

In the present study, scintiphoto seemed to be more reliable for the detection of eso-

phageal varices than the conventional X-ray

and endoscopic examinations.

(145) C O R R E L A T I O N OF B I L I A R Y T R A C T DISEASES A N D

P O R T A L H Y P E R T E N S I O N . K. Sakoda, T. Kawada, Y. Arima,

T. Kamimura , M. Takesue,

T. Katsuki and H. Akita

2nd Dept. of Surg., Kagoshima Univ. Sch. of Med.

Recently, it has been demonstrated that biliary tract infection is one of the most

frequent antecedent cause of portal vein

obstruction and cholelithiasis occurs with unusual frequency in hypersplenism and liver cirrhosis.

In this paper, four cases of portal vein

obstruction, three cases of hypersplenism, and nine cases of liver cirrhosis and fibrosis ac-

companied by biliary tract diseases with gallstone are reported.

The cases of portal vein obstruction were accompanied by cholelithiasis in one, cholelithiasis, choledocholithiasis, and intrahepatic

caliculi in two, and intrahepatic caliculi with biliary fistula in another one. In all cases

hepato-petal and fugal collaterals developed. Splenic pulp pressure elevated remarkably.

Serum bilirubin, especially direct bilirubin increased. Histologically liver revealed in- f lammatory infiltration and proliferation of

connective tissue mainly in portal areas.


The cases of hypersplenism had cholesterol stone in one and bilirubin stone in two associat-

ed with the high values of indirect serum bilirubin. Portal hypertension was recognized

in one case. The cases of liver cirrhosis and fibrosis had

bilirubin stone in eight and cholesterol stone

in one. Histologically liver revealed portal cirrhosis in four, postnecrotic cirrhosis in

three, and fibrosis in two. Portal pressure

was elevated remarkably. Of the 48 patients with liver cirrhosis recognized by laparotomy

7 (14.6%) had gallstone in biliary tract. A higher incidence of gallstone have been

reported in cirrhotic patients by several

investigators. The association and relationships of biliary

tract diseases and portal hypertension should

be further investigated.

(146) H I G H I N F L O W P O R T A L H Y P E R T E N S I O N A N D ITS

S U R G I C A L T R E A T M E N T Y. Yakeishi

Dept. of Surg., Hiroshima Red-Cross Hosp.

I. Takehisa, K. Miyasato and H. Yoshida

2nd Dept. of Surg., Sch. of Med., Tokushima Univ.

Hemodynamic studies and follow-up examination after splenectomy, microangiogram

and electron-microscopic studies of the removed spleen, direct measurement of splenic

artery blood flow, and histometrical studies in the splenic arterial system were undertaken

between so-called Bant's disease, hepatic cirrhosis and normal control cases.

A marked decrease in portal vein pressure

after splenectomy was seen in cases which had shown the most severe arterial congestion

without severe sinus hyperplasia. The number of branches of splenic penicilliary was greater

in so-called Banti's disease (37.5 branches/cm 2) than in the congested spleen (24 branches/cm2).

In the spleen of ' so-ca l led Banti's disease, capillaries and penicilliary arteries are ex-

tremely tortuous and form many close capillary plexus. The splenic blood flow was on the

average 123.3ml/min and the blood flow

per unit weight of spleen was 0.86 m/gm/min

in the control cases. In the cases of so-called Banti's disease, the splenic blood flow showed

a marked increase, that is 2-5 times above the value of the control cases and in the cases

of hepatic cirrhosis, the splenic blood flow was only a little larger than that of the control

c a s e s .

The elevation of the portal vein pressure seemed to be related mainly to an increased

blood flow which entered into the portal

vein through the spleen in the earlier stages of so-called Banti's disease. From this point

of view, it can be called a high inflow portal

hypertension. For this kind of portal hypertension, we

recommend the distal spleno-renal shunt

as a rational surgical treatment.

(147) L A C T U L O S E F O R T H E

T R E A T M E N T O F P O R T O - S Y S T E M I C E N C E P H A L -

O P A T H Y : A D O U B L E - B L I N D T E S T

BY C R O S S - O V E R M E T H O D R. Hidemura, K. Kubota, S. Aoki,

S. Suzuki, T. Kishimoto,

T. Miyahara, K. Ando, T. Nishiwaki, T. Miki,

K. Takeshige, and

M. Sawada

Dept. of Surg., Nagoya Univ. S. Itoh and S. Yamamoto

Dept. of Surg., Aichi Med. Col.

Effectiveness of lactulose in the treatment of portosystemic encephalopathy has already

been demonstrated and was reported previously. A series of double-blind tests were carried out in clinical materials to reevaluate the

effectiveness of lactulose. Included in this study were 8 patients

(4 males and 4 females, age ranging from 44 to 60) who had undergone end-to-side porta-

eaval anastomoses 5 to 17 years previously. Preliminarily, an optimal dosis of 50~ la-

ctulose solution was determined in each individual with clinical signs and symptoms

as indices. A double-blind test was then carried out using 20 and 50~ solution for


a total period of 4 weeks each solution for 2 weeks. Subjective symptoms, bowel

habit, results of liver function tests, blood ammonia level, psychoneurological signs were

closely observed. To be noted was that completion of tests

with 20% solution was impossible without supplementing with 50% solution in the

middle of the course because of appearance of signs and symptoms pertinent to porto-

systemic encephalopathy. Blood ammonia

level was affected by a maximum of 20% by the difference of concentration of lactulose

solution. Fecal p H was consistently lower while the patient was on 50% solution than

while he was on 20% solution. In 7 cases out of 8 were noticeable differences between

psychoneurological signs in two test periods,

while no remarkable difference was observed in neurological reflexes as well as liver func-

tion indicated by blood chemical studies.

In a strictly controlled double-blind test, effectiveness of laetulose o n protosystemic

encephalopathy was reconfirmed.

(148) E S T I M A T I O N OF C O L L A G E -

NASE IN E X P E R I M E N T A L F I B R O S I S O F R A T L I V E R

K. Fujiwara, T. Sakai, T. Oda and S. Igarashi

1st Dept. of Int. Med., Tokyo Univ.

Collagenase activity, active or masked,

was determined in rat liver and its relationship to the fibrosis of the liver was studied. In-

active form of the enzyme was activated by

treating with trypsin or NaSCN. (Materials and Methods) Fibrotic l iver: Male Wistar rats were administered with

0.1 ml CCL 4 subcutaneously twice a week

for 4 to 18 weeks. Preparat ion o f the e n z y m e : The enzyme samples for assay were prepared as follows,

1) the liver homogenate with 0.1% Tri ton X-100 (crude), 2) the crude sample after

incubation with 5 mg/ml trypsin (trypsin

treated), 3) the homogenate following dialysis against 3M NaSCN (SCN treated).

Substrate and m e t h o d for assay: The

enzyme activity was measured by liberating

soluble peptides from native reconstituted fibrils of guinea pig skin neutral soluble

collagen labelled with 14C-glycine as a sub-

strate. Identif ication o f c o l l a g e n a s e : The enzyme samples were purified by affinity chromato-

graphy, then were incubated with acid soluble rat skin collagen. The reaction products

were examined by disc electrophoresis.

(Results) Collagenase activities in the control and slight fibrotic group were negligible

i n the crude samples, but significantly increased after treating with SCN, especially

more evident in the latter. Besides, a good

correlation between the activity and the hydroxyproline content in the fibrotic liver

tissue was observed, while in the marked fibrotic group it was much higher even in the

crude samples. The activity was also increased by treating

with trypsin in the control group. Disc electrophoresis showed several frag-

ments smaller than aA and /~A after incubat-

ing collagen with all the purified samples obtained by the affinity chromatography.

(Conclus ion) Collagenase in liver tissue was detected as an active enzyme form,

as well a s an inactive form. The activity of the two forms was found to increase in the

fibrotic liver tissue of rats.

(149) T H E E F F E C T OF ELASTASE

ON E X P E R I M E N T A L L I V E R

F I B R O S I S (III) M. Fukuhara, T. Tsujii, T. Tamura,

Y. Matsuoka, H. Takahashi, T. Sakamoto, S. Fukuda,

M. Oku, T. Matsui, T. Morita,

Y. Oyazato, K. Kimura, W. Moriya, and S. Fukui.

1st Dept. of lnt. Med., Nara Med. Univ.

Previously we reported that elastase in-

hibits the development of experimental liver

fibrosis caused by CCI 4. The effect of elastase on established liver cirrhosis and the mechanism of inhibition of liver cirrhosis by

Proceedings of the 59th Annual Meetings, 1973-Kagoshima 209

elastase were studied in this report.

E x p e r i m e n t a l m e t h o d Sprague-Dawley male rats were divided into 6 groups (Group

A, B, C, D, E, F). A subcutaneous injection of CC1, was given to A twice a week for 20

weeks. To B was subcutaneously injected

elastase everyday in addition to CC1,. C was given elastase for 10 weeks in addition

to CCI 4 after 10 weeks' t reatment with CC14. E was given elastase only for 4 weeks after

20 weeks' treatment with CCI 4. F was given

elastase only for 6 weeks. Each group was examined in liver HOP, AMPS, and lysosomal

enzymes (cathepsin, /~-glucuronidase, col-

lagenolytic activity) at definite intervals. Digestive activity ofelastase for soluble collagen

extracted from guinea pig skin was observed

by disc electrophoresis. R e s u l t s Gradual increase in H O P of

B was obviously small as compared with that of A, but there was no difference between

those of C and A. H O P of E was distinctly

less than that of D. Change in AMPS of B showed a pattern similar to that of A, but

A M P S quanti ty of B was obviously small as compared with that of A. A M P S quantity

of C, D, and E did not differ from that of A.

There was no difference in lysosomal activity among A, B, and C. Lysosomal level of D and E was higher than that of A. There

was no difference in /5-glucuronidase activity

between D and E. Cathepsin activity was higher in E than in D, while collagenolytic

activity higher in D than in E. There was

observed no remarkable change in lysosomal activity of F through the experimental period.

Digestive effect of elastase on soluble collagen was shown as disappearance of fl-fraction on

disc electrophoresis. Moreover, there was histochemically observed no increase in elastic

fiber during development of liver fibrosis by

CC14. The above results suggest that the inhibitory effect of elastase on liver fibrosis may be attributed to its collagenolytic action,

which may be non-specific proteolytic action

of elastase.

(150) C L I N I C A L S T U D Y OF

S U P E R F I C I A L V A S C U L A R

P A T T E R N O F T H E L I V E R BY PER-

I T O N E O S C O P Y K. Suzuki, S. Morimoto, S. Tsuiki,

K. Shoji, Y. Nakai, M. Hata,

J . Kubo, K. Yoshizawa, K. Nagayama, Y. Ozawa,

M. Yoshida and M. Horiguchi

Dept. of Gastroenterl. 3rd Hosp., Jikei Univ. Sch. of Med.

We emphasize the hepatic pre-cirrhosis is very important state of the liver disease

because it is irreversible and may progress to cirrhosis. So, we give diagnosis carefully

by many examinations, such as biochemical,

structural, hemodynamical and endoscopical. For the peritoneoscopical examination, it

is very important to accept the stage of the

surface, edge and color of the liver, etc. Ne- vertheless, correct diagnosis is now very

difficult by peritoneoscopy. Many authors reported about intrahepatic

vascular derangements of hepatic cirrhosis. But, there are few reports concerning superficial

vascular pattern of the liver, so we tried to observe the superficial vascular pattern of the

liver by peritoneoscopy. We could see many vessels beneath the surface of the pre-

cirrhotic and cirrhotic liver, but so many vessels beneath the surface of the normal,

fatty liver and the liver of hepatitis. Fur- thermore, individual vessel beneath the

surface of the normal liver showed branching

in a Y-shape and extending smoothly. But that of the pre-cirrhotic and cirrhotic liver

showed various morphological changes ; distortion, flexion, dilatation, constriction,

interruption and augmentation and tortuosity of small branches. These changes could not

be shown in the other hepatic diseases, so we consider these vascular changes is due to proliferation of connective tissue, regenera-

tion of parenchyma and disturbance of intrahepatic circulation.

We consider if we observe the number and morphological pattern of the superficial

vessels of the liver by peritoneoscopy, we can more easily and correctly give diagnosis

210 Proceedings of the 59th Annual Meetings, 1973-Kagoshima

of the l iver disease, especially hepat ic pre-

cirrhosis and cirrhosis.

(151) C I L I N C A L A N D P A T H O L O G I -

CAL S T U D I E S O N C I R R H O S I S

O F T H E L I V E R (II I )

G A S T R O I N T E S T I N A L BLEED-

I N G O N C I R R H O S I S

O F T H E L I V E R

A. Machi i , Y. Nitta, Y. Also,

N. Ki t aha ra , E. Ki tazawa,

K. Fukuda, N. Saiti,

Y. Murakami , Y. Nao

Dept. of Int. Med., Sch. of Med., Keio Univ.

T h e 29 fatal cases of cirrhosis of the liver

seen at our clinic between 1969 and 1972

were studied. T h e 15 cases of the study

group were recognized gastrointest inal bleed-

ing (group A) and the r emain ing 14 cases

were not recognized gastrointestinal bleeding

(group B).

In g roup A there were 14 males and 1

t~male a n d in group B there were 6 males

and 8 females. In terval from clinical onset

of cirrhosis of the liver to dea th was 2.7 years

on the average in group A and 2.6 years in

group B. J a u n d i c e was found in 7 cases of

group A a n d in 13 cases of group B. Ascites

was found in 11 cases of group A a n d in 14

cases of g roup B. The period from appe rance

of ascites was 2.5 months on the average in

group A a n d 11 months in group B. In the

past history acute hepatit is was seen in 5

cases of g roup B and heavy drinkers were

seen in 8 cases of group A and in 3 cases of

group B. Se rum G O T and L D H level were

increased in group A than in group B. De-

crease of serum a lbumin and increase of

serum T-globulin were seen in group B than in

group A. Oesophageal varices were found

in 4 cases of group A and in 7 cases of group

B. The dura t ion of bleeding was 1-4 days

in 8 cases and was over 30 days in 2 cases.

Autopsy findings; There were 10 cases of

autopsy in each groups. In group A, At- type

of cirrhosis of the liver was found in 1 case

and B-type was found in 8 cases. In group

B, At- type was found in 4 cases and B-type was

in 6 cases. H e p a t o m a was found in 5 cases

of group A and in 6 cases of group B. Peptic

ulcer was found in one case in each groups.

T he weight of liver was 1612 g. on the average

in group A and 819g. in group B. T h e

volume of ascites was 2815 ml on the average

in group A and 3811 ml in group B. Oeso-

phageal varices was found in 8 cases of g roup

A and in 4 cases of these cases in the total

length of the oesophagus and in 5 cases of

group B in the lower port ion of the oesophagus.

In the fatal cases of cirrhosis of the liver

clinical features and pathological findings of

gastrointest inal bleeding were studied.

(152) F O L L O W - U P S T U D I E S O N

146 CASES O F L I V E R C I R R H O S I S

- - W I T H S P E C I A L R E F E R E N C E

T O S U R V I V A L A F T E R T H E

A P P E A R A N C E O F P H Y S I C -

A L S I G N S - -

I. Okazaki , K. Funatsu, K. M a r u y a m a ,

B. Takagi , S. Yasuraoka, K. Ishii,

S. Matsuzaki , H. Takahashi ,

H. Ishii, K. Kamegaya ,

and K. Sambe

Dept. of Int. Med., Sch. of Med., Keio Univ.

The present s tudy reported 5 year survival

curves in 146 cases of liver cirrhosis diagnosed

between 1965 a n d 1972. 82 pat ients (56%)

were diagnosed by laparoscopy and /o r l iver

biopsy, 50 cases (34%) by definite diagnostic

physical signs such as massive ascites, esophage-

al varices and so forth, 14 cases (10%) based

upon liver scint igram and selective celiac

ang iography in addi t ion to physical a n d labora-

tory findings. T h e 146 subjects inc luded

15 cases who were complicated with h e p a t o m a

at the first t ime of consultation. 5 year

survival curves were contructed by the life-

table m e t h o d of Cutler and Ederer . 0.5,

1, 2, 3, 4 and 5 year survival rates of 146

cases were 83.9, 75.8, 72.2, 66.9, 62.6 and

53.1%, respectively. Those of 131 cases

(only liver cirrhosis at the first t ime of diagno-

sis) were 92.2, 84.7, 80.6, 74.6, 69.8 and

59.2%, respectively. 5 year survival rates

of 75 cases of compensated and 56 cases of

Proceedings of the 59th Annual Meetings, 1973-Kagoshima 211

decompensated liver cirrhosis were 74.5% and 39.5%. The present data suggest improved survival rates compared with those of previous reports, most probably reflecting the improved treatment of decompensated liver cirrhosis. 5 year survival rates after the appearance of jaundice, ascites and the physical signs of portal hypertension were 41.9, 11.7 and 58.9%, respectively. The therapeutic effects of steroids and diuretics were also investigated. No significant effects of steroid therapy on the survival rates of cirrhotic patients were observed. Diuretics were supposed to be slightly effective as far as the first 2 years' survival rates were con- cerned.

(153) REGULATION OF GALL- BLADDER PRESSURE WITH

SPECIAL REFERENCE TO AUTONOMIC NERVES

H. Ishikawa, Y. Tajima, A. Kuroda, Y. Ishihara, N. Sato, I. Ishikawa

and T. Noro 1st Dept. of Surg., Tokyo Univ.

Sch. of Med., Tokyo

The nervous regulation of the gallbladder pressure was investigated on 35 dogs. Gall- bladder pressure was measured through polyethylene catheter which was inserted into the gallbladder and connected to electro- manometer.

1) Gallbladder pressure was elevated by electrical stimulation of the peripheral ends of vagal nerves and infusion of cholinergic drugs.

2) Gallbladder pressure was decreased by electrical stimulation of the peripheral ends of the splanchnic nerves and beta-stimulation by isoproterenol infusion.

3) Gallbladder pressure did not change by division of both vagal and splanchnic nerves.

4) When autonomic denervation and adrenalectomy were performed, gallbladder pressure seeroed to increase gradually to its initial pressure after evacuation of gallbladder bile and fall gradually to its initial pressure after injection of saline solution into the

gallbladder. From this experiment, it is supposed that gallbladder pressure is regulated by the autonomic action of the gallbladder.

5) The common bile duct was divided and a polyethylene catheter was introduced into the proximal end of the common bile duct and outflow of the bile from the catheter was recorded. Thereafter, any effect of the sphincter of Oddi on bile flow was left out in this experiment. Following injection of Pancreozymin, gallbladder pressure elevated markedly, and outflow of bile from the catheter increased simultaneously, and ceased 30 minutes after injection of Pancreozymin. On the contrary, in dogs with ligated cystic duct, outflow of bile from the catheter increased transiently, but did not decrease to zero, 30 to 60 minutes after injection of Pancreozy- rain.

6) From these experiments, it is supposed that: Before contraction of the gallbladder, gallbladder pressure and flow of gallbladder bile are regulated by the dual sympathetic and parasympathetic innervation, and autonomic action of the gallbladder. During contraction, gallbladder pressure is elevated, and outflow of gallbladder bile is increased by stimuli of Pancreozymin and vagal nerves. After contraction, gallbladder pressure is decreased below the initial pressure by stimuli of the splanchnic nerves, and inflow of bile into the gallbladder is induced.

(154) ABSORPTION AND BILIARY EXCRETION OF DIGITOXIN

IN JEJUNAL PERFUSION OF RATS

Y. Kakumoto, H.S. Mekjian and N.R. Thomford

The Ohio State Univ., Col. of Med., U.S.A.

Digitalis glycosides are commonly used as important cardiotonic agents. But relatively little is known about their metabolism under normal physiologic conditions. The purpose of this study is to determine jej~unal absorption, liver extraction and biliary excretion of digitoxin using ~H-digitoxin as a tracer.

212 Proceedings of the 59th Annual Meeting--1973--(H)--

Also the effect of bile acids on them was studied.

Using 42 Wistar rats, ten centimeters of jejunal loop was prepared for perfusion.

Biliary fistula was made at the same time for

collection of bile. The perfusate was Krebs Ringer solution with PEG. 5 Gm./L. , digitoxin

5 ug./ml., 3H-digitoxin 2.5 uc./dl., pH. 8

and temperature 37~ Three hours after

surgery, w h e n the rat was awakened from anesthesia, the je junum is perfused at a

constant rate (0.47 ml./min.) with an infusion pump. After 20 minutes equilibration perfu-

sion, test perfusion was performed 75 minutes. Radioactivity was counted with Tricarbo

3375 counter (Packard).

When sodium taurocholate was infused into the i leum during jejunal perfusion, bile

acid output increased markedly (p<0.005) without significant increase of biliary digitoxin

excretion. Sodium cholate added to the perfusate f a i l ed to alter the absorption rate

significantly. But 10mM./L . sodium tau-

rocholate in the perfusate showed inhibition of digi toxin absorption (p<0.05) . Con-

centration dependency was :examined by 5/ tg . , 10 pg. and 20/ tg. /ml. of digitoxin

and showed lineal absorption rate suggesting

passive diffusion. One third to one fifth of absorbed digitoxin was extracted from the liver and approximately 3% of absorbed

digitoxin was excreted in the bile during 75 minutes perfusion. Correlation between

biliary excretion and bile acid output was minimal ( r=0.2) .

(155) E F F E C T OF A N T I B I O T I C S O N

BILE A C I D C O M P O S I T I O N O F BILE (2)

T. Yokomura, S. Adachi

and A. Yamamoto

2nd Dept. of Int. Med. Osaka Univ. Med. Sch., Osaka

The bile acid composition of rat and hamster

bile was determined before and after administration of antibiotics. A mixture of tetracycline and oleand.omycin, streptomycin

or chloramphenicol was administered orally, intraperitoneally or intramuscularly, at a

level of 10 mg per day for 5 days. Bile was

collected from the common bile duct or gall

bladder. Bile acids were extracted with chloroform/ methanol 1:1 and estimated by

combination of TLC-spectrophotometric and

T L C - G L C procedures. The ratio of glycine conjugated bile acids

to taurine conjugated ones (G/T ratio) in

rat bile was 0.19 in average for cholate, and 0.22 for d i - O H bile acids. After administra-

tion of antibiotics, glycine conjugates were almost completely disappeared. In hamster

bile G / T ratio was 2.56 for cholate and 2.96 for d i -OH bile acids, and the ratio of de-

oxycholate to chenodeoxycholate (DC/CDC ratio) was 0.54. After the antibiotic treat-

ment, G / T ratio was decreased to the level

of 0.13-1.88 for cholate, 0.10-2.08 for d i -OH bile acids. The decrease of G / T ratio was

shown by the oral administration of the

nonabsorbable antibiotics almost to the same extent as absorbable ones. But the decrease

was much more marked in animals in which antibiotics were given by the injection.

D C / C D C ratio was also decreased by oral

administration of antibiotics, but not decreased when the antibiotics were given by injection.

The oral administration of a mixture of tetracycline and oleandomycin caused a

marked increase in ursodeoxycholate in humans, and an increase in an unidentified

bile acid component in rats. The use of antibiotics seems to give an in-

fluence on the balance of glycine and taurine

conjugates through their effects on bacteria flora in the intestinal lumen as well as through

the direct effect on the conjugation system in the liver.

(156) C L I N I C A L AND E X P E R -

I M E N T A L S T U D I E S O N B L O O D C O A G U L A T I O N

A N D F I B R I N O L Y S I S IN O B S T R U C T I V E

J A U N D I C E

I. Saito, A. Kawamura, M. Miyata,

S. Kasai, N. Kawanishi, A. Tamaki ,

M. Mito and Y. Kasai

Proceedings of the 59th Annual Meeting--1973--(H)-- 213

1st Dept. of Surg. Hokkaido Univ. Sch. of Med.

Object ive; The authors have experienced often increased fibrinolytic activity in obstructive jaundice clinically. Thus, we studied blood coagulation, lysis, liver function and hystology in experimental obstructive jaundice.

Material and Methods; Adult mongrel dogs weighing 10 to 15 kilograms were anes- thetized with isozol. A celiotomy was performed. The common bile duct was exposed and ligated and was divided. After three weeks, a cholecystoduodenostomy was performed as a reconstruction. Specimens of blood was drawn from femoral vein and hepatic vein every one week for coagulation studies and liver function. Fibrinolytic activity was estimated with eugloburin lysis time (ELT), available plasmin test and active plasmin test. Other tests performed included analysis of plasma fibrinogen and one stage (Quick) determination of the prothrombin complex. Liver function was evaluated by serum biliruhin, S-GOT and T-GTP.

Results; Serum bilirubin level elevated remarkably after one week and reduced after reconstruction. Units of S-GOT was elevated 181.6 after one week, T-GTP was reached maximum after three weeks. Pro- thrombin time was prolonged after dividing of common bile duct. Plasma fibrinogen level was increased after ligation and was reduced after reconstruction. In fibrinolytic activity, ELT, available plasmin test and active plasmin test were activated after ligation and they were decreased in three weeks after reconstruction. In observation of blood which was obtained by femoral vein and hepatic vein, prothrombin time was remarkably shorter in blood of hepatic vein than in blood of femoral vein.

Conclus ion; It might be that blood coagulation and fibrinolysis were activated together in obstructive jaundice. Moreover, fibrinolytic activity might be accelerated by reduced antiplasmin and increased activator in hepatic disorder after ligation of common bile duct.

(157) IDIOPATHIC CHOLEDOCH- AL DILATATION

IN ADULTS

A. Hasumi, T. Uchiyama, Y. Tachikawa, T. Takanashi, T. Kanke, K. Matsuda,

T. Takanashi, T. Kanke, K. Matsuda,

G. Hamana, M. Sakuma, T. Sugita, K. Tomita, S. Yamasaki,

T. Tsuzuki and M. Uekusa

Dept. of Surg., Keio Univ. Sch. of Med. M. Matsuzaki, B. Takagi

and M. Tsuchiya Dept. of Int. Med., Keio Univ.

Sch. of Med.

The experience of 16 cases of the idiopathic choledochal dilatation in adults disclosed the difference from that of pediatric patients. We classified it into 3 types; a) cystic type, b) cylindric type without chdedochal stones, and c) cylindric type with choledochal stones. The cystic type has a slightly stenotic opening into the duodenum, whereas the cylindric types have no stenosis at the end of the choledochus, presenting the similar appearance of the dilated eholedochus due to choledochal stones. These 3 types are presumed to be incomplete type of that of the pediatric patients and are characterized by the frequent complications of cholangitis with choledochal stones.

It is assumed that bile stasis in the dilatation is a precipitating factor in the pathogenesis of the complications.

(158) PATHOGENESIS ON PERFORATION OF

THE BILIARY TRACT

M. Uchimura, T. Murohisa, Y. Muto, J. Ishigaki

and S. Waki Dept. ofSurg., Hamamalsu

Iryo Center

R. Tsuchiya, M. Sho and M. Furukawa


Dept. of Surg., Nagasaki Univ. Sch. of Med.

Since September in 1969, we have experienced 10 cases of perforation of the biliary tract of 242 cases with cholelithiasis and choledocholithiasis in Nagasaki University Hospital and Hamamatsu Iryo Center.

There were 7 women and 3 men. Per- foration of the gallbladder was seen in 8 cases and that of the choledochus, in 2 cases. All patients were admitted with complaints of high fever from 38~ to 39~ and colic pain of the right upper quadrant. Seven patients had surgery within 4 days after onset and three, 7 days.

Laboratory study showed leukocytosis, increased B.U.N. and abnormal value of serum bilirubin. Plain X-ray of the abdomen disclosed distended loops in the upper quadrant.

Cultures of bile showed gram-negative bacteria, namely Escheric.hia coli and Kleb- siella. All cases with perforation of the gallbladder surgically revealed incarcerated stones within the cystic duct. Histologically the gallbladder of these cases showed deep Rokitansky-Aschoff's sinuses with acute severe inflammation. One of these markedly in- flammed sinuses revealed perforation.

On pathological examination, 78 of 91 surgically resected gallbladders revealed Rokitansky-Aschoff's sinuses. The gallbladder with severe inflammation showed more and deeper sinuses, and that with mild inflammation revealed marked thickening of the bladder wall.

Considering these pathological findings, the case with many deep sinuses and silent stone may develop perforation of the biliary tract following increasing intracystic pressure due to incarcerated stone and acute inflammation.

(159) ROLE OF SULFATED GLYCOPROTEINS IN

THE GALLSTONE FORMATION

N. Suzuki, H. Nagashima,

T. Matsushiro, T. Saitoh, N. Nakamura,

T. Hatanaka, N. Kobayashi, Y. Nakamura and

T. Sato Dept. of Surg., Tohoku Univ.

Sch. of Med.

As reported previously, sulfated glycoproteins were thought an important factor as linear polymer for the formation of gallstones in pathological bile. In this paper, the coagulating effect of some glycoproteins obtained from the human bile will be discussed.

Control bile was collected by gallbladder puncture from the patients without any hepatic and biliary tract disturbance. Pa- thological bile, infected with E. coli, was obtained through T-tube from the patient with intrahepatic gallstones.

Bile samples were acidified with HC1 and fractionated centrifugally to give four fractions (Frs. 2, 2R, 3 and 3R). Of these fractions, Fr. 3 obtained from pathological bile showed strong coagulating effect for calcium carbonate suspension in water, whereas any coagulating effect was not found in the fraction obtained from the control bile.

Moreover, 0.2 MFr. and 0.3 MFr. obtained by Gel-filtration on DEAE-Sephadex A-25 of Ft. 3 had the similar coagulating effect to Fr. 3.

Especially, 0.2 MFr., contained hexose (21.8%), hexosamine (18.5%), L-fucose (5.9%) and sulfate (1.3%), had the strongest coagulating effect in all fractions. H 2 0 F r . and control bile contained only glycoproteins and had weak coagulating effect.

These results indicated that 0.2 MFr. and 0.3 MFr. obtained from Fr. 3 were sulfated glycoprotein and suggested to be an abnormal component in the bile. Therefore, sulfated glyc0proteins in pathological bile are possible polymers which play an important role in the formation of gallstones.


(160) ON THE EFFECT OF THE MUCOPOLYSACCHARIDE PRODUCTION IN INDUC-

ING PROLIFERATING CHANGES OF THE

GALL BLADDER MUCOSA IN

CHOLELITHIASIS

K. Tooi, Y. Tanaka, N. Kadokura, Y. Okada, I. Yanakgi, N. Tanaka,v

M. Sekiya, K. Adachi, M. Miyashita, Y. Moriyama, M. Onda, M. Yoshioka, T. Teraoka, Y. Shimizu, G. Fujishima,

K. Ookawa, M. Miki, A. Shirota and K. Aihara*

1st Dept. of Surg. and Pathol.* Nippon Med. Sch.,

Tokyo, Japan

It has been generally accepted that the cholelithiasis and carcinoma of the gall bladder has intimate relationship statistically and in our surgical clinic, twenty three cases (74.2%) out of thirty one cases of the gall bladder carcinoma associated with cholelithiases. To elucidate the interrelationship between these disease conditions, the present correlative histochemical, biochemical studies of the mucopolysaccharide alteration in the gall bladder mucosa of cholellthiasis as well as the ultrastructural study have been undertaken and the following results are obtained.

1) In approximately 20% of the patients suffering from chronic cholecystitis with gall stone shows marked proliferated mucosal pattern in which linear or zonal increase of sialomucin which is substantiated with PAM, PAS, and Alcian Blue stainings histochemical ly. As the matter of fact, proliferating pattern of the mucosal epithelium, particularly of mucin producing cells are confirmed electron microscopically and intense stainability of the microvilli and cytofolds are also confirmed in virtue of the Ruthenium red and Colloidal iron staining procedures respectively.

2) The authors, furthermore, have made observations of the extracted mucopolysaccharide of the gall bladder mucosal epithelium

biochemically, using cellulose acetate and pevicon powder electrophoresis.

In the sight to moderate cases of the chronic cholecystitis, the main biochemical constitu- ents are consisted of hyaluronic acid, heparitin monosulfate and chondroitin sulfate, while in cases of the repeated attacks, striking quantitative increase of the sialomucopolysaccharide has been encountered.

Thus it is concluded that the mucopolysaccharide, particularly of sialomucopolysaccharide may act as one of the inducing factors in proliferation of the gall bladder in persisted chronic cholecystitis and functional importance of the substance in inducing carcinogenesis based in the cholelithiasis has been emphasized.

(161) INTRAMURAL GALL- STONES (70 cases report)

Y. Tachikawa Dept. of Surg., Keio Univ.

Sch. of Med. (Director: Ass. Prof. M. Uekusa)

Pathological study was performed on seventy cases of the intramural gallstones experienced during past 51/2 yeas.

Intramural gallstones were formed, in some of the cases, in the lymphatic duct of the gallbladder wall and pressed in it by the intragallbladder stones, though in most of the cases formed in the Rokitansky-Aschoff Sinus and inflammatory packed to the wall which have been observed.

A possible process of the gallstone formation, the intramural gallstones would be extruded into the cavity of the gallbladder and grow to the gallstones, was discussed.

(162) POSTOPERATIVE COM- PLAINTS IN PATIENTS WITH

GALL STONE DISEASE

T. Shiga, H. Sano and S. Hayashi Dept. of Surg., Sch. of Med.,

Shinshu Univ.

At the present time, it has been found that the operative treatment for gall bladder stone

216 Proceedings of the 59th Annual Meeting--19 7 3--( H )--

or choledochal stone is one of the incompletely

satisfied procedures, especially from the view- point of the long-term follow-up study of

postoperative clinical course. Authors have

studied on the lomg-term results in 84 cases treated with several kinds of operations for

the gall stone disease during the past 13 years.

R e s u l t s : 1. 96% of all cases have accepted that these patients had gained some beneficial

effects by receiving the operation of the bile duct system. 2. On the other hand, 59%

of patients had some kinds of postoperative complatins. Higher incidence of postopera-

tive complaints were found in female cases,

compared with male cases. 3. Over 90% of cases have been able to show the satisfied

social activity postoperatively. 4. Number

of cases with the incomplete returning to the preoperative status of social activity during

the postoperative course, have been increased among patients with several kinds of preopera-

tive complications, with choledochal stones, or the the dilatation of the common bile duct,

measured on the postoperative drip infusion cholangiogram. 5. Long-term follow-up

study showed that the diameter of the common

bile duct was not increased postoperativily, compared with the diameter of the common bile duct at the time of discharging the hospital,

in cases without any evidence of the recurrence

of gall stone. 6. Among eases with the dilatation of the common bile duct, much more

cases have been affected from the impaired

liver function, postoperative complaints, or being unable to do the previous social

activity completely. These evidences showed that it might be

very important to check the diameter of the

bile duct by the drip infusion cholangiogram even in cases with no evident choledochal stone.

(163) STUDY ON THE ROENT-

GENOLOGICAL DIAGNOSIS OF P R O T R U D E D LESIONS

IN T H E COLON W I T H EMPHASIS ON THOSE

IN THE SIGMOID AND R E C T U M

M. Hori, H. Sato, Y. Chuman,

S. Tsukase, N. Nakahara, S. Ehira,

S. Setoyama, H. Nishimata, T. Irisa, K. Tokutome, Y. Nakashima,

H. Koga and H. Yokoyama

2nd Dept. of Int. Med., Facul. of Med., Kagoshima Univ.

T. Otsuji

Dept. of Surg., Nampu Hosp.

During five years from May 1969 to February 1973 110 lesions in 76 colon polyp

cases were observed by means of both barium

meal and barium enema methods. By studying the films of 91 lesions in 65

sigmoid and rectum polyp cases, we have obtained the following results:

1) Polyps found in the haustras or in and near the flexures of sigmoid and rectum were

frequently overlooked.

2) It was difficult to establish the gener- alized roentgenological examination method to

reveal polyps in the sigmoid due to patient's individuality. In examining the flexure or

overlapped part of colon, therefore, the

part should be compressed carefully and X- rays on different postures should be taken.

3) Left or right anterior oblique position was required to demonstrate the polyps in

the flexures of rectum. 4) High concentration barium enema

method was supposed to be better for demonstrating more clearly the protruded lesions.

(164) CONSIDERATION OF

EARLY DIAGNOSIS OF

THE CARCINOMA OF THE COLON

Y. Chujo et al. Matsuyama Red-Cross Hosp., Japan

This report is an attempt to evaluate

retrospectively the clinical signs in the early

diagnosis of the carcinoma of the colon. 46 patients, who have been operated on with

a diagnosis of the carcinoma of the colon over a decade from 1963 through 1972, were

studied. Rectal cancer was excluded. Thir- ty-three of 46 patients were malignant and

others were benign. The average age was

Proceedings of the 59th Annual Meeting--1973--(II)-- 217

57 years in patients of both groups.

In cancer patients, the location of the lesion was the sigmoid in 11 patients, the ileocaecal

region in 8, the ascending colon in 5, transverse colon in 4 and the remains in 3. In 13 patients

with benign diseases, the location of the lesion

was the ileocaecal region in 10 patients and

the remains in 3. In about 40%, over 4 month was needed to diagnose that they were

malignant disease of the colon. They were

misdiagnosed appendicitis, cholecystitis, colitis .... etc.

The most common initial symptom was slight

abdominal pain. In 63.6% of patients, the

abdominal mass was palpated and the location of the lesion in 60% of patients, in whom ab-

dominal mass was not palpable, was the sig- mold. The tumor was mostly ulcerative and

localized and it was histologically papillar

or tubular adenocarcinoma with well dif-

ferentiation. Laboratory data showed the

tendency of hypochromic anemia, leucocytosis and acceleration of blood segmentation rate

and occult blood was present in 47.4% of cancer patients.

There was not a special sign to diagnosis of the carcinoma of the colon, and we must

pay regard to popular symptom for early

diagnosis of the colon carcinoma.

(165) R A D I O I M M U N O A S S A Y

OF C A R C I N O E M B Y O N I C A N T I G E N

T. Yamamoto, S. Gotoda, S. Uchiyama G. Kosaki

The Center for Adult Dis., Osaka

Carcinoembryonic antigen (CEA, Gold) was extracted from the serum of a patient with

the metastatic liver tumor from gastric cancer. The extraction of CEA was performed es-

sentially according to the method of Gold (1965). From 200ml serum 3.2rag CEA was

purified. The monospecific antiserum against CEA was obtained from goat immunized with

the CEA. This antiserum contained the

same antibody as that given by Dr. Gold. CEA was labeled using chloramine T and

N a P 2s. The specific activity of labeled CEA

was 1.2/tCi//tg. Radioimmunoassay of C F A was carried out by a modified method of

Thomson et al. (1969). Radioactivity of the precipitate obtained by adding saturated

ammonium sulfate after the immunoreaction

was counted and calculated using a calibrated inhibition curve.

Eight normal healthy adults showed less than 10ng/ml CEA in their sera. Sera

from 12 preoperative patients of cancer of

colon and rectum showed more than 300ng/ml CEA and 5 out of these postoperative sera,

CEA levels declined to the normal after 7 or 10 days after the removal of cancers. One

of 23 gastric cancer showed over 300/tg/ml CEA, but the remaining 22 was in the normal level.

The technique for the detection and quan- titation of CEA is thought not established

yet. Our results strongly suggests usefulness for follow up of operated patients with malignant tumor.

(166) R A D I O I M M U N O A S S A Y OF C A R C I N O E M B R Y O N I C

A N T I G E N

H. Ohkura, T. Mukoj ima

and N. Hattori

Dept. of Clin. Lab. and Int. Med., Nat. Cancer Center Hosp.

To make the clinical evaluation of the carcinoembryonic antigen (Gold's C.E.A.)

in cancer clinic, a radioimmunoassay system was developed with double antibody technique.

From a metastatic liver tumor of rectum origin, single fraction was prepared through perchloric acid extraction, Sepharose-4B and

Sephadex-G150 gel columns, DEAE Sephadex A50 gel and adsorption with antisera against

NHS and normal tissue homogenates. Final purification was made by Disc-electrophoresis. Specific antisera were obtained from rabbits

after immunizations of crude DCEA and adsorption with NHS-polymer. One clear

precipitation line was found on the slow beta

area by agar-gel immunoelectrophoresis using

218 Proceedings of the 59th Annual Meeting--1973--( H)--

these antigen and antibody. The antigen was labelled with 125I through Chloramine-T technique, and a radioimmunoassay was made as follows; 0.5ml of sample serum extract, 0.I ml of antiserum, and 0.1 ml of labelled antigen were incubated for 24 hrs. at 4~ 0.1 ml of second antibody was added and incubated again. The bound antigen was separated through a centrifugation 3,000 rpm, for 30 minutes at 4~ A linear standard curve was drawn between 30 nanogramms and 1 microgramm of purified antigen.

Positive values over 30 ng. were found in 6 of 10 cases of rectal carcinoma, 2/2 ofsigmoid and 5/11 of colon cancer, 4/9 of colon polyposis, 1/4 of colitis, 12/40 of gastric carcinoma and 1/11 of normal control. C.E.A.-radioimmunoassay is not so specific for G.I-tract malignancies, although it has still a value as a screening test in cancer clinic. The importance should be laid on the quantitative follow up by positive cases.

(167) HISTOPATHOLOGICAL STUDY OF POLYPOSIS OF

THE LARGE BOWEL, ESPECIALLY ON THE

RELATIONSHIP BETWEEN POLYPS AND CARCINOMAS

O. Sasaki, K. Soejima and K. Inokuchi

2ncl Dept. of Surg., Facul. of Med., Kyushu Univ.

In the present study concerning the relationship between colonic polyps and carcinomas, a series of six cases of colonic polyposis were analyzed histopathologically.

Atypical glands appearing in polyps were classified into the following six descriptive types: (1) Atypical glands composed of goblet cells, the nuclei being regularly in the basal position. (2) Those characterized by the single-layered cells with narrow or no supranuclear space and elongated and hyperchromatic nuclei occupying nearly whole length of cells. (3) Those characterized by the cells with eosinophilic supranuclear

space and elongated and hyperchromatic nuclei in the basal position. (4) Those lined by the cells showing irregular arrangement and hypertrophy of stratified elongated and hyperchromatic nuclei. (5) Those of high degree of structural atypicality but mild degree of cellular atypicality of vice versa. (6) Those of high degree of both structural and cellular atypicality without manifest invasion, but being strongly suggestive of carcinoma.

The frequency of polyps containing type 4, 5, 6 atypical glands increased proportionally to the size of polyps. Focal carcinomatous foci often appeared in the larger lesion. Moreover, close similarity with respect to anatomical distribution of carcinomas and adenomatous polyps in different cases, frequent small foci of invasive carcinoma in the polyps, remnants of adenomatous lesion in invasive carcinoma, carcinomatous replacement of atypical glands and a morphological re- semblance between malignant glands of abvanced caricnomas and atypical glands of adenomatous polyps nearby in the same case were seen.

These circumstantial evidences support the concept of the intimate relationship of adenomatous polyp to carcinoma in polyposis of the large intestine.

(168) GASTRIC LESIONS OF FAMILIAL POLYPOSIS OF

THE COLON

J. Utsunomiya, T. Maki, T. Iwama, Y. Matsunaga, T. Shimomura,

T. Nakajima, S. Ichikawa, T. Miyanaga, K. Sengoku

and E. Hamaguchi 2nd Dept. of Surg., Tokyo Med. and

Dent. Univ. Sch. of Med. N. Aoki

Dept. of Pathol. T. Nomura

Kanamachi Daiichi Hosp. A. Matsuoka Matsuoka Clin.

N. Suzuki Musashino Red-Cross Hosp.

Dept. of Surg.

Proceedings of the 59th Annual Meeting--1973--(II)-- 219

The reliable informations on the stomach of the fifteen cases of familial polyposis of the

colon including the thirteen eases intensively

examined by X-ray and/or endoscopy and two autopsy cases have been collected and in

the ten of them (66.7%), the polypoid lesions

have been detected. The fact that these cases

are distributed in the independent six polyposis families indicates that the cases submitted

for this study are not confined in special type of polyposis.

Reviewing world literatures, very few have

been known on the gastric lesion of this disease. The nation-wide inquiry on familial polyposis

conducted by us revealed rather low incidence

of gastric polyps (9/88, 10%). These facts are now considered as for an incomplete

examination on the stomach of this disease probably because of so attractive manifestation

and high risk of malignancy of the colonic lesions.

The gastric polyps we detected are multi-

ple and uniformly rather small in size and semispheric in shape. They are distributed

diffusely in the entire stomach in six cases and in other four cases they are scattered in the

fornex or in the antrum. Histological examination carried out in

six cases revealed that rather sharply demarcat-

ed accumulation of atypical epitherium of intestinal origin indicating neoplastic nature

of this lesion. Based on the above mentioned observation,

it is assumed that an association of gastric polyps are one of the essential characteristics

of familial polyposis of the colon and the same

mechanism which affects on the colon may affect on the other tissue including the stomach, and it is claimed that careful examination

on the stomach is essential in preoperative

diagnosis as well as in postoperative surveil- lance of familial polyposis of the colon.

(169) O U T C O M E OF COLONIC POLYP IN THE UNITED

STATE

A. Nagahama

Dept. of Surg., Juntendo Univ. Sch. of Med.

255 polyps of 177 cases of colonic polyp are removed via the colonoscope by the snare-

cantery device at the Beth Israel Hospital

in New York during the period July, 1971

through June, 1972. On the other hand, colonic polyps are very few in Japan. For example, it is only 13 cases in the department

of surgery of Juntendo University during the same period.

In these 255 polyps, 54 are sessile type and

201 are pedunculated. Location of the 255 polyps are 8 in rectum (3.1%), 139 in sigmoid

colon (54.5%), 88 in descending colon (34.5%), 4 in splenic flexure (1.6%), 12 in transverse

o / colon (4.7%), two in hepatic flexure (0.8/o),

one in ascending colon (0.4%) and one in cecum (0.4%) respectively.

Pathological diagnosis in these polyps,

adenomatous polyp are 140, mixed villous

and adenomatous polyp are 35 and villous adenoma are 33.

17 cases of 255 polyps were carcinoma, 7 are adenocarcinoma, 6 are adenomatous

polyp with ca in situ and 4 are villous adenoma with ca in situ.

(170) A CASE OF C R O N K H I T E - CANADA'S SYN/)ROME

T. Kazumi and H. Miyawaki

Kanebo Hosp.

T. Sakamoto

Kyoto Univ. Sch. of Med.

K. Miyasaki

Kobe Univ. of Med.

A case of Cronkhite-Canada's syndrome characterized by the gastrointestinal polyposis,

alopecia, nail atrophy and pigmentation, is reported.

A 62-year-old Japanese male with the Cronkhite-Canada's syndrome died from ileus

22 months after the onset of symptoms. The family history was negative. He was admitted with the complain of diarrhea and poor ap-

petite, developing nail atrophy, alopecia and skin pigmentation in the hand, face and

forearm. The predominent features were hypoproteinemia and polyposis in the stomach,

colon and rectum, which were examined


endoscopically.

The microscopic examination reveals the adenomatous polyps with highly proliferation

of mucoepithelium which may have hyper-

function of secretion. This phenomenon is

assessed electronmicroscopically from presence

of granular substance with low electron density.

In the laboratory examination, there were marked hypoproteinemia (2.1 to 3.6 gm. per

100 ml. in the total serum protein), hypocal-

cemia, low level of serum iron and copper, hypoacidity in the gastric juice. All the liver

function test, kidney function test and endo~ crinological test showed within normal limits.

The patient was autopsied, and the clinical and pathological features are reported in the

paper.

(171) A CASE O F M A L I G N A N T

M E L A N O M A OF T H E

A N O R E C T A L

R E G I O N

K. Kato, Y. Miyazaki, N. Harada,

and K. Yamada

Dept. of Surg., Isesaki Hosp., Gunma

A 67 year old woman who complained of

constipation and anal bleeding of three month's duration, was admit ted to our clinic on Sept.

I6, 1972. Physical examination revealed tumors at the anorectal region. Biopsy

specimen of the tumor showed a picture of

malignant melanoma, which was considered to have its origin in anorectal junction.

Abdominoperineal resection of the rectum and inguinal lymphadnectomy was performed

with success.

(172) E N D O S C O P I C F I N D I N G S O N T H E U L C E R A T I V E

L E S I O N A N D U N S P E C I F I C I N F L A M M A T I O N OF

T H E C O L O N

S. Tashiro, K. Sakai, N. Ho,

H. Murayama and

M. Yada

3rd Dept. of Int. Med., Facul. of Med., Niigata Univ.

It is compared with endoscopic findings in the 10 cases of the acUve and remission

stages ulcerative colitis, the 12 cases of clinical

diagnosis of chronic colitis, and the 4 cases of acute colitis. In the active stages, endo-

scopic diagnoses are not so difficult, but in the remisssion stages are most difficult to dif-

ferentiate from chronic colitis. I t was seen

muddy and rough mucosa, and easily of bleeding more than chronic colitis. Biopsy findings

were more seen degenerated epithelial ground, infiltrated leucocyte and dilatation of small

vessels than the later, too. But most impor-

tant things are continuous or repeated observation are necessary to diagnosis of the

unspecific inflammatory colonic lesion. We have had a case, like Solitary ulcer of the

rectum that of reported M.R.Madigan and

B.C.Morson in 1969. He is 23 year old young man, his complaints began about 4 years ago.

Complaint was bleeding on defaecation and lower abdominal pain. A shallow ulcer was

observed in 8~-~10cm from anal margin

endoscopically, and was not responded any

medical therapy for a long time. So it was surgically resected on Feb. 1972.

The ulcer size was 3.8 X 4.2 era. Histologi- cally it showed heavy fibrosis in the submucosal

tissue and very little inflammatory of cell infiltration. In the clinical and histological

aspects, this ease is different from ulcerative

colitis and Crohn's disease.

(173) A C L I N I C O - P A T H O L O G I - CAL S T U D Y OF N O N S P E C I F I C

C H R O N I C R E G I O N A L

C O L I T I T S .

T. Sakabe, H. Shimizu, M. Kuroki, S. Nishida, K. Kato

and S. Ishiyama

3rd Dept. of Surg., Nihon Univ.

Most frequent clinical symptoms of twelve cases experienced in our clinic were abdominal

pain and palpable mass with tenderness, slight

elevation of temperature and leukocytosis were also observed in five cases respectively,

however, diarrhea and bloody stool were not frequently seen.


Four cases had appendec tomy in their past

history, and ano ther one was considered to

be intestinal Behcet.

O f eleven cases, c i rcumscr ibed lesions were

d is t r ibuted in the r ight colon and of one case

in the rectum.

Pathological study were successfuly reviewed

on eleven casess, and microscopically, granu-

lomas were found in five cases and giant cells

were in seven cases, marked lymphoid hyper-

plasia were noted in two.

In two cases, pathological changes were

r a the r marked in serosal side of the intestinal

wall, and etiological factors of those cases were

considered to be strict relat ionship to the

previous appendectomy.

As a conclusion, there are m a n y similarities

in clinical symptoms, while there are some

pathological differences, and some quetions

such as those differences are due to the etiologi-

cal factor, to the stage of the disease or to the

secondary infection, are left.

(174) O N U L C E R A T I V E

C O L I T I S

K. Yukawa, M. Hayashi , K. Soh,

K. Doi, M. Fukuda, A. Nakagawa.

and E. Yukawa

Yukawa Gastroenterl. Hosp.

Eighty-nine cases of u lcera t ive colitis we

experienced were discussed, in which rectosig-

moid type were fifty-five cases.

The male-female rat io was 1:1.9, and no

difference was observed in rectosigmoid

type and another types (total or left-sided

colitis). Only four cases out of eighty-nine

were more than sixty years old at the onset.

Symptoms of the rectosigmoid type were

mi ld in generally. T h e severity related to

the width of involved area. T he severity

of the first a t tack had no relat ion to the

prognosis in cases of left-side or total involve-

ment . There were two cases in which re-

ctosigmoid type underwen t left-sided or totally

involved type.s, so tha t rectosigmoid type at

the first a t tack seems good in thei r prognosis.

The classification of the clinical types such

as relapsing and remit t ing, chronic continuous

and so on seems to be meaningless based on

fourty-three cases of at least three year follow-

up (mean dura t ion; eight years).

(175) C L I N I C A L A N D R A D I O -

L O G I C A L F E A T U R E S OF

D I V E R T I C U L A R O F

T H E C O L O N :

Y. Uematsu, K. Nara , H. Hattori ,

M. Watanabe , H. Yoshida,

and K. Sato

Dept. of Surg., The Ashikaga Red-Cross Hosp.

Divert icular disease of the colon was demon-

s t ra ted on 75 patients for the past few 3 years.

T h e incidence of this diseases was 10 per cent

of 744 consecutive b a r i u m enema examina-

tion. The cases r anged in age from 17 to

73 years with a m e a n of 44 years and more

frequent ly of forth and sixth decades; 36 were

male and 39 females. T h e cases were divided

into acute and chronic relapsing group depend-

ing on the clinical manifestat ions, 16 were acute

and 59 were chronic relapsing. Divert iculums

of 44 cases located in the r ight colon, 25 cases

along the ' entire Colon a n d 13 cases in the left

colon. The mean n u m b e r of divert iculums

is 8.5 in acute and 7.0 in chronic showing no

difference in the behavior of diver t iculum in

regard to clinical course, whilst of the 3.8 in

the r ight colon and 12.4 along the entire colon,

wi th a very considerable relat ion between the

n u m b e r and the location of divert iculum. In

the group of entire colon diverticulosis the

relat ion of numbers to dis t r ibut ion of sites

was more markedly disclosed, cases with less

than 5 located in the r ight colon and with

between 10 to 19 in no characterist ic par t of

the colon while cases wi th more than 20 ap-

peared in the left colon.

T h o u g h the age of the affected patients

was not related to the n u m b e r of diver t iculum

in bo th acute and chronic type, the tendency

to develop numbers was considered to increase

progressively with advanc ing age above 40

years especially in the group with entire

colon diverticulosis. I r r i tabi l i ty of colon was

revealed in the r ight sided diverticulosis


in 59.1 per cent and in the entire colon diver-

ticulosis in 90.3 per cent. The area showing

irri tabil i ty occurred more frequently and wider

in segment of colon in the entire colon

diverticulosis t han the r ight sided diverticulosis.

As for the most interest ing complications,

there were 6 cases wi th rectal bleeding a n d

they were de te rmined by sigmoidscopy present-

ing as a similar gross appearence to tha t of

the ulcerative colitis. 5 cases were t rea ted

by the surgical operaioin, the r ight hemicolec-

tomy was carr ied out in 4 cases for the inf lam-

matory mass format ion and 1 was ileocolecto-

mized for in t rac table abdomina l pain.

(176) C L I N I C A L S T U D I E S

O N P E P T I C U L C E R : C L I N I -

CAL S T U D Y O N F A C T O R S

A F F E C T I N G T H E C O U R S E

O F N A T U R A L H E A L I N G

O F G A S T R I C U L C E R

S. Okuse

Dept. of Gastroenterl., Kotoni Luke Hosp., Sapporo

K. Sato and T. Muro t an i

Dept. of Gastroenterl., Sapporo Dokokai Hosp.

S. Takasu, M. K o n t a and T. Uchiya

1st Dept. of Int. Med., Sapporo Med. Col.

A series of 60 hospital ized patients wi th

incipient single s tomach ulcer under a placebo

regimen were subjected to a study in which

factors affecting the heal ing of the ulcer loci

were surveyed. The cure ra te within 8 weeks

was 71%, and tha t wi th in 12 weeks was 89%.

T h e cure rate wi th in 8 weeks in pat ients

under 45 years of age was 81.5%, whereas

the value in older pat ients was 60.7%. T h e

cure rate wi th in 8 weeks in patients wi th

ulcers measur ing less t han 15 m m in the

maximal diameters was 80%, whereas the

value in patients wi th larger ulcers was 58.3%.

A similar difference was also observed between

cases with and wi thou t a t rophic changes of

the s tomach mucosa, the cure rate in pat ients

with atrophic changes being 89.9% and the

value in patients wi th a t rophic changes be ing

42%. O n the o ther hand , no significant

difference of cure ra te between hyper -

secretory and normo- and hypo-secretory

groups was observed, the value in the former

group being 70.1% and tha t in the later g roup

being 69.1%. The cure ra te of ulcers localiz-

ed in the mid- and upper corporeal regions was

20%, and the value for ulcers localized in

lower corporeal, angula r and ant ra l regions

was 30%.

I t is therefore concluded tha t age of pat ients

and size of ulcer are the pr imary factors

affecting the heal ing of ulcer, while presence

or absence of a t rophic gastritis and the

secretory funct ion are no more than the

secondary factors in this respect. I t is sug-

gested that the heal ing is under no influence

of the secondary factors as far as the size of

ulcer is sufficiently small, a l though the effects

mus t also be considered in larger ulcers.

(177) A S T U D Y O N L O C A T I O N

O F G A S T R I C U L C E R

N. Fujimaki , K. Yoshida,

K. Yoshikawa, M. Uchida,

N. N a k a m u r a and

F. Nagao

2nd Dept. of Surg. Jikei Univ. Sch. of Med.

I t has been known tha t chronic gastric

ulcer is likely to occur on the lesser curva tu re

or on the posterior wall. As the ulcer locat ion

of preponderance Oi and his colleagues say

it occurs within a cer ta in area over the lesser

curva ture designated by mucosal and muscle

ana tomy (dual control mechanism). In the

present study ulcers of 251 stomachs were

examined and were de te rmined as to which

wall of the s tomach they were on as well as to

dual control mechanism, and the following

result was obtained. Ulcers were found in the

aforement ioned small area of dual control

mechanism and, wi th in this area, fu r the rmore

they were mostly on the lesser curvature or

on the posterior wall.

Proceedings of the 59th Annual Meeting--1973--( II)-- 223

(178) A S T U D Y O N D I R E C T I O N

O F R E C U R R E N C E OF G A S T R I C

U L C E R

S. Kawana, K. Tamura ,

T. Hashimoto, K. Kobayashi,

T. Hara, J . Nosaka and O. Fukui

Dept. of Gastroenterl., Nat. Osaka Hosp.

285 cases of recurrent gastric ulcer which

were found by repeated gastrofiberscopic examinations after healing of antecedent

ulcers, were studied on their gastroscopic

films in order to find the direction of recurrence of ulcers.

Out of 285 cases 225 had single recurrence

and 60 had recurrence more than twice.

About 225 cases of single recurrence group, 97%, of ulcers of antrum recurred in the direc-

tion toward oral area. Ulcers of gastric angle and lower gastric body more likely

recurred to the same direction, and this

tendency was more and more remarkable with aging. But ulcers of middle and upper gastric

body more often recurred toward anal than

oral. To the contrary ulcers of 60 cases of multi-

recurrence group more likely recurred at the

same place (52%). To elucidate those tendencies of recurrent

ulcers histologically, study was made on

surgical materials at the same time. As a result of the study, it was revealed that

fibrosis in submucosal layer around ulcer was intense at the oral side than at the anal side

in the cases under 50 years of age. Concerning about arteriosclerosis in the

cases of first occurred ulcers thickness of arteria wall was greater at the oral side of

ulcers of antrum and angle in the submucosal layer and near serosa, but in the area around

ulcers of middle and upper gastric body of this group thickness of arterial wall near

serosa was greater at the anal side than at the

oral side. These histological findings suggest that

decrease of blood flow around antecedent ulcers might influence on the direction of

recurrence of gastric ulcers.

(179) S T O M A C H DISEASES:

D E T E R I O R A T I N G F A C T O R S AND P R E S C R I P T I O N

E. Inaba, S. Otsukasa, K. Sanada, H. Hiraide

and G. Senyo

1st Dept. of Surg., Tokyo ivied. and Dent. Univ.

Stomach diseases are built up by accumulation of deteriorating factors to constitutional

tendencies. Considering the proportion of

both, stomach diseases could be classified to four groups: 1. By deteriorating factors,

2. Slightly constitutional, 3. Mainly constitutional, and 4. Constitutional, the later

two types often need surgical treatment.

Constitution means sensitivity to contract stomach diseases and composed of multiple

factors comprising weakness in defense and strength of offense. Character of patient

will act as catalyzer at disease forming reaction of deteriorating factors.

Workers in this country, both white- and

blue-collar, suffer from the strain of life with high prices, house famine, or educational

problems, and are driven by work with extra hours averaging two hours per day and four

days in a week. Considering the relation of medicine against

the deteriorating factors of stomach diseases, the principle exists that the stronger wins.

To expect efficacy of medicine, it is necessary

to remove or decrease the deteriorating factors that are piled up as bricks. The deteriorating

factors can be divided into direct and indirect factors, and when indirect factors are plentiful, stomach diseases will come out with trifling

direct moments.

(180) C L I N I C A L I N V E S T I G A T I O N O F F A C T O R S I N F L U E N C I N G

T H E H E A L I N G R A T E OF G A S T R I C

U L C E R

A. Ootani, T. Nakayama, S. Takei,

H. Miki, M. Tanaka, S. Minota

224 Proceedings qf the 59th Annual Meeting--1973--(H)--

and K. Nakayama*

3rd Dept. of Int. Med., Facul. of Med. Kyushu Univ. * Fukuoka Icho-

Shinzo Clin.

The purpose of this study is to exhibit the effect of treatment with 154 patients of gastric

ulcer (Inpatients 102 cases, Outpatients 52

cases.) and to investigate the factors influencing the healing rate of gastric ulcer.

1. Effect of t reatment with 154 patients of gastric ulcer as follows.

(1) Most effective healed 68 cases ulcer group. (Fully healed (44.2%)

at 2 months.)

(2) Moderately effective 54 cases healed ulcer group. (More (35.1%)

50 percentage decrease in diameter of the Niche at 2 months.)

(3) Less effective healed 32 cases

ulcer group. (Less 50 per- (20.7%) centage decrease in diameter of the Niche at 2 months.)

2. Factors influencing the healing rate of gastric ulcer.

(1) Influence of Age and Sex.

It is found that less effective healing

rate are similar, Ca. 20%, between the different age group. Most effective healed

ulcer group was found the highest incidence in younger age group. (Below 40 years.)

Moderately healed ulcer group was found the higher incidence in higher age group.

The healing rate was identical for males and females.

(2) Character of less effective healed ulcer.

1. Triangle shaped or irregular shaped Niche on the X-ray film.

2. Small ulcer size. (Below 10 m m

diameter measured on the X-ray film.) 3. Endoscopically, redness, edema, bleed-

ing surrounding ulcer edge was found in higher incidence.

(181) S T U D I E S O F T H E L O C A L T R E A T M E N T O F G A S T R I C

A N D D U O D E N A L

U L C E R S

- F U R T H E R S T U D I E S AND

R E C E N T F I N D I N G S -

K. Nakagawa, T. Shiraishi,

H. Kawauchi, H. Nagaya, K. Mizushima, Y. Tachimi

and M. Namiki

3rd Dept. of Med., Hokkaido Univ. Sch. of Med., Sapporo

We have developed the local injection

treatment of the gastric ulcer since 1965

and the results obtained have been often reported. Thenceforth, the effects of various

drugs including a few newly prepared ones

have been investigated on this method. The cases treated so far were over 1,000. The

present report summarized 1,000 cases untill

February, 1973 and also mentioned the local treatment of the duodenal ulcer recently

attempted.

Ninety seven point three % of 1,000 cases of gastric ulcer exhibited apparently the

healing findings from the endoscopical view point by means of the local injection. Even

as to the relatively prolonged ulcer, 757 out of 1,000 cases, 96.4% out of them was healed.

Recurrence of the ulcer after the t reatment

was observed in 11.1%, 70 cases, out of 630 cases which were followed up for a long

period of 1 to 7 years. Yearly changes in

the recurrence were as follows: 4.2% 1971, 8,0% 1972 and 11.1% in 1973, indicating

the higher incidence in the recurrence, the

longer course in the ulcer. Nevertheless, these values were much lower as compared

with those in the gastric ulcer otherwise treated. I t was also noticed that the recurred

patients possessed more or less social or environ- mental causes such as an inappropriate

living as well as psychosomatic problems.

Therefore, a gastic ulcer should be regarded as a systemic disease for its successful treat-

ment. The local injection of allantoin by the

use of the direct vision type of gastrofiberscope

(GIF-D) has been tried for the duodenal ulcer. This ulcer has been proved to be

more readily healed by the local treatment as compared with the gastric ulcer.


(182) C H A N G E IN B L O O D F I B R I N O L Y S I S IN

G A S T R I C U L C E R

K. Masuda, N. Mitsutani, T. Mukuta

and T. Koizumi

Dept. of Med., Osaka Koseinenkin Hosp.

The change in blood fibrinolysis was studied

on 83 cases of patients with gastric ulcer, who

consist of 29 cases followed up to the complete healing decided by X-ray and endoscopic examinations and 54 cases followed for several

durations but no ~o the healing. Euglobulin

lysis t ime determined at the t ime of diagnosis was showed a higher level in 55.4% of the

patients, and 45.7% of the patients showed a higher level in the results by standard fibrin

plate method. Patients with ulcer at middle or under portion of the gastric body showed

a higher euglobulin lysis t ime compared with

that with ulcer at the an t rum of the stomach. Age difference among these patients showed

that the elevated euglobulin lysis time was

seen in fifty decade. There was no difference in the percentage of the elevated blood fibrinolysis both euglobulin lysis time and

standard fibrin plate method, between single

and multiple gastric ulcers. The patients with refractory ulcer kept a higher level in

euglobulin lysis time throughout the course

of the disease and, on the contrary, the patients with giant ulcer showed a lower level until

the healing of the disease.

(183) A S T U D Y O N M U L T I P L E

U L C E R S OF S T O M A C H OF S U R G I C A L M A T E R I A L S

T. Takeuchi, T . Nemoto. H. Takabayashi, M. Takagi,

Y. Hongo, H. Kojima, M. Nishimura, S. Hino

and J . Hi rayama lcho Hosp., Tokyo

Of the 142 cases with proven ulcers of

stomach operated at this hospital for the past 10 years, and extensive pathological examina-

tion ensued multiple ulcers were found in 41 cases (29%). The result of study on multiple

ulcers of stomach were summarized as the

followings: (1) The total numbers of lesions were 109 consisting of 51 open ulcers

and 58 scars. (2) Age distribution revealed

that it was most common at fourtieth and more frequent in males. (3) Two lesions

in individual case were most fi 'equent findings and those with more than five lesions were

extremely rare. (4) In view of histopatho-

logical classification it was found that the most common type were those with all the lesions

confined in the intermediate zone (Group A. 19 cases or 46.3%), followed by those with

one lesion in the intermediate zone and the others in pyloric gland area (Group B. 12

cases or 29.2%), those with one lesion in the

intermediate zone and the others in the

fundic gland area (Group C. 8 cases or 19.5~ in order. There were 2 cases (4.9%) in

whom lesions were scattered in above three areas (Group D.). (5) O f the multiple ulcers

studied at least one lesion was found in the intermediate zone. (6) As to the relation

of localization to the depth of ulcers it was

observed that deep open ulcers were frequently located in the lesser curvature of the inter-

mediate zone common to all Group A, B and C. In Group A. deep ulcer scars were also observed while in Group B. and C.

scars in this areas were relatively rare. In

Group B. lesions in anterior and posterior wall of the intermediate zone were rather

infrequent as compared with that of other groups. In group B. distribution of lesions

in the pyloric gland area were mostly in lesser curvature while in Group C. lesion in the

fundic gland areas were in the lesser curvature

and posterior wall. (7) There were 3 definite cases of multiple ulcers in which

chronological events of ulcer developement were able to be determined by both follow-up studies of X-ray films and endoscopic exami-

nations, but no particular trend of clinico-

pathological features were noted.


(184) GENETIC CHARACTER- ISTICS IN PRIMARY

HEPATOMA

M. Nakamura, T. Irisa, S. Koga

and C. Hirayama

3rd Dept. of Int. Med., Facul. of Med., Kyushu Univ. Fukuoka

One hundred and four patients with primary

hepatoma were compared with blood donors in ABO blood groups and serum haptoglobin

phenotypes. There was a significant in-

creased frequency of blood group AB and of Hp 1 gene in hepatoma patients. Despite

the serum haptoglobin concentration decreased in the patients with Hp 1-1 phenotype, no

subjects with Hp 2-2 phenotype were found in the pedigree of the patients, suggesting

that Hp 1 phenotype seemed not to be acqu-

ired by hepatoma process. Since an increased frequency of Hp 1 gene was associated with

non-alcoholic cirrhosis, the persons with blood group AB might be at risk of suffering

from hepatoma.

(185) PRIMARY CARCINOMA OF

THE LIVER: ANALYSIS OF

CLINICAL AND HISTO- LOGICAL FEATURES

OF 54 CASES

S. Kikuch, M. Ito, S. Hidano, T. Ooya, H. Banno,

A. Tomura, K. Kato, T. Koyama,

T. Takei, T. Tomimura and M. Yamauchi

2nd Dept. of Int. Med., Sch of Med. Nagoya Univ.

The patients studied came from 4 institu-

tions. The diagnosis was established at autopsy. 90% of the patients was hepatocellular carcinoma and hepatic cirrhosis was

present in 83% of the patients. 50% of the cases with hepatic cirrhosis were categoriz-

ed as Laennec's cirrhosis. A majority of the cases without hepatic cirrhosis were diagnosed

as 3 or 4 grade in Edmondson's classification. Of 46 autopsied patients, 27 cases had ex-

trahepatic metastases. In 24 patients these

involved the regional lymph nodes. In 20 patients there were pulmonary metastases.

The most frequent complaint at early stage was upper abdominal pain and abdominal

fullness, next was anorexia and weakness. It was accompanied by weight loss and upper

abdominal mass. In 34% of the patients

there was past history of jaundice or liver disease. In 19% of the patients there was

family history of the liver diseases, in 16% was malignant tumors. 40 cases of 46 patients

with jaundice died during 6 weeks after the onset of jaundice. In the 7 patients the

cause of death was not known. Of the

remaining 45 patients, 18 died as a direct result of hepatic coma. 13 of these had a

terminal episode of gastrointestinal bleeding.

In 6 cases death was the result of a hemo- peritoneum. Alkaline phosphatase was

elevated in 22 of 28 patients at the time of 4 weeks before the death. It was more severe

in patients without cirrhosis than that with

cirrhosis and was found tendency to severe in cases with grade 3 and 4 than that with grade

2 in Edmondsons classification. GOT/GPT ratio was significantly high in primary hepatic

carcinoma and extremely high value was found in patients with extrahepatic metastases.

a-Fetoprotein was positive in 9 cases of 20

patients and 80% of these cases was negative

in Au-antigen.

(186) A C L I N I C O P A T H O L O G I C A L

STUDY OF PRIMARY

HEPATIC CANCER

K. Kobayashi, Y. Nakaya, S. Takase,

Y. Kato and J. Takeuchi 1st Dept. of Int. Med., Sch of Med.,

Kanazawa Univ. F. Ikegami, Y. Matsuda and A. Takada

Dept. of Int. Med., Kanazawa Med. Col.

The clinicopathological features of primary

hepatic cancer (PC) were studied in comparison with those of other various liver diseases.

Fifty-three cases of PC were selected for the study. The diagnosis of PC and other liver

diseases was verified by periotoneoscopy,

Proceedings of the 59th Annual Meeting--1973--( H)-- 227

angiography, liver biopsy and/or autopsy. The incidence of PC was 60.9% in autopsy

cases with cirrhosis during the period from 1962 to 1972, which was higher than that (43.5%) during the preceding period from 1941 to 1961 observed at the Department of Pathology, Kanazawa University. However, this difference was not statistically significant. Alpha-fetoprotein (a-f) was positive in 70% of PC with the mean titer highest among the other liver diseases. In other various liver diseases, a-f was ovten positive in the active stage of hepatic injury such as acute phase of acute hepatitis and chronic active hepatitis. The titer of Australia-antigen (Au-Ag) measured by RIA method showed the highest value in healthy carriers. The titer of Au-Ag was found to decrease as hepatic injury advanced. PC with cirrhosis was the lowest in the titer of Au-Ag. Au-Ag on IEOP method was positive in only 13% while Au- Ag on RIA method was positive in all cases of PC with cirrhosis. It was noticed that, in PC with cirrhosis, there was an inversed correlation between the fiter of ot-f and of Au-Ag on RIA method.

(187) STUDIES ON ALPHA I- FETORPOTEIN AND HB

ANTIGEN AND ANTIBODY IN

HEPATOCELLULAR CARCINOMA

K. Udo, M. Kojima, N. Hukuda, M. Kametani, T. Miyagawa, T. Wakahara, Y. Takahashi,

T. Imaeda and K. Senda

1st Dept. of Int. Med., Gifu Univ. Sch. of Med.

Alpha I-fetoprotein (AFP) and hepatitis B (HB) antigen and antibody were examined in hepatocellular carcinoma. In the 26 cases of hepatocellular carcinoma, 23 cases (88.5%) were males with the peak in 50~59 age group. The positive rate of AFP was 92.3%. The HB antigen positive was 14 out of 26 cases (53.8%) by S-RIA and 12

cases (46.1%) by CIEP. Therecases (11.5%) were HB antibody positive by PHA and HB antigen in these cases was negative. The AFP value of hepatocellular carcinoma was low in the cases with HB antigen and positive HB antibody, and the value no relation to the pathological type (Edomondson classification) of hepatocellular carcinoma. Only 2 AFP negative cases were found. The one was a case of type IV without cirrhosis, and was negative both for HB antigen and antibody. The other was a case of type II without cirrhosis, and was HB antigen negative and antibody positive case. The results showed no relationship between the pathological type and the occurencs of HB antigen and antibody in hepatocellular carcinoma, but in the 11 out of 12 cases of the HB antigen positive hepatocellular carcinoma, cirrhosis was observed. The HB antigen titer by S- RIA was high in healthy carrier and low in the cases with cirrhosis or hepatocellular carcinoma. However, the HB antibody titer was low in the healthy carrier and hepatocellular carcinoma.

(188) CLINICOPATHOLOGICAL STUDY OF a-FE-

TOPROTEIN.

S. Fujita, H. Okubo, K. Kanoda, B. Miyashita, H. Ishizuka,

T. Goto, K. Oto, H. Kaneda and

M. Hase 3rd Dept. of Int. Med., Nihon Univ. Sch

of Med. (Director: Prof. K. Ariga) J. Matsuda and T. Kawai Dept. of Clin. Pathol., Nihon

Univ. Sch. of Med.

The clinical significance of a-fetoprotein was studied on 361 cases of various diseases, according to radioimmunoassay method.

As a result, it was found that c~-fetoprotein appeared not only in primary hepatic cell cancer but also in other various hepatic diseases: 95% in primary hepatic cell cancer, 40% in cholangioma, 25% in liver cirrhosis, 31% in chronic hepatitis, 31%


typical acute hepatitis, 90% in fluminant hepatitis.

a-fetoprotein in serum was found in 10000 m/2g/ml or more in 70% of primary hepatic cell cancer.

However ot-fetoprotein was found ranging from 20m/2g/ml to 3000m/2g/ml in the positive cases of the acute hepatitis or chronic hepatitis and liver cirrhosis.

We thought especially in this group that there were a-fetoprotein positive cases with severe hepatic necrosis in the perilobular area.

In the experiment a-fetoprotein was measured in the serum of rats injected with cc14 by radioimmunoassay method.

As a result, we detected that a-fetoprotein appeared after 12hrs. The calculated of a-fetoprotein concentration of these serums varied from 40 m/~g/ml to 200 m/2g/ml.

The a-fetoprotein synthesis may be rapidly regenerated by liver parenchymal cells.

(189) ISOLATION OF RAT a-FETOPROTEIN

H. Ikehara, S. Baba, M. Ishii, T. Tozawa, E. Inoue, N. Mizuno, S. Saeki,

T. Nakaji, T. Narabayashi and

T. Okuno 2nd Dept. of Int. Med., Sch. of Med.,

Kobe Univ., Kobe, Japan

MATERIALS AND METHODS:(I) Pre- paration of crude AFP from fetal tissues. Fetal tissues were obtained from the uteri of S.D. rats after 15 to 20 days gestation. A number of fetal rats were homogenated in 0.9% NaC1 solution. Crude AFP was taken from homogenated fetal tissues by rivanol- aminotic fractionation, preparative disc electrophoresis(PDE). (2) Partial purification of rat AFP was performed with PDE and the AFP content was checked by single radial immunodifusion method. The AFP fractions were collected and further concentrated. (3) Purification of AFP was carried out by the method of immunoadsorption using

anti-rat serum protein antibody in order to exclude the adulterant protein in partially purified AFP and the technique of refractio- nation of PDE. In order to obtain the highly purified AFP, to identify AFP and to determine its isoelectric point, isoelectric focusing(IEF) was performed in a shallow pH to maximize their separation. RESULTS: 1) The purity of partially purified AFP isolated by PDE was demonstrated by immunoelectrophoresis(IE). Four protein precipitin lines were seen. These were identified as albumin, AFP, two al- globulins. 2) Purified AFP by the technique of immunoadsorption using anti-rat serum protein antibody was only AFP and no other detectable proteins but were detected as two precipitin arcs with complete identity and two bands on analytical disc electrophoresis (ADE). 3) In view of this finding, IEF was performed by a wider p H range of 3.0 to 6.0. AFP was found in two peaks. Peak I, at pH 5.06, was higher in concentration and symmetrical, whereas Peak 2 was smaller, wider, and covering a larger pH range. Peak I, isolated by IFE, yielded one precipitin line by IE and a single band by ADE. DISCUSSION : Microheterogeneity was observed by IE, ADE, IEF. All three techniques indicated the presence of at least two immunologically identical molecular forms, differing only in net charge. The two forms showed a line of complete identity by micro-Ouchterlony double immunodiffusion.

(190) SERUM ALPHA-FETOPRO- T E I N DETERMINATION BY

NEW RADIOIMMUNO- DIFFUSION METHOD

W I T H LABELED AFP.

H. Yamada, M. Tanno, K. Chiba and M. Iio

Dept. of Nuclear Med. and Radiol. Sci., Tokyo Metro. Geriatrics Hosp.

K. Shibata Scientific Sect. of Radiopharmaceutical

Div., Hoeehst Japan Ltd.

Proceedings of the 59th Annual Meeting--19 7 3--( H )-- 229

Determination of serum AFP is now in-

dispensable for the early detection .and differen- tiatial diagnosis of hepatoma. Conventional

R I A of AFP using double antibody system is proven to be much superior in sensitivity

to conventional non-radioactive immuno-

diffusion method. However, double antibody

method has several disadvantages. For example one has to accumulate numbers of

samples before examination. This inhibits the R I A method to become day by day

laboratory test. Because refreezed antibody

could not be used. To overcome these disadvantages radio;mmunodiffusion method was

developed.

Line of small well with 2.5 mm in diameter was punched out on the Agarose immunoplate

containing appropriately diluted antibody

of AFP. In these wells 1 p of 1-125 AFP with high specific activity was applied. After

that 5 / t l of standard AFP or sample serum

containing unknown amount of AFP was applied. Then the plate is incubated at

room temperature for two days to form precipitation rings. Autoradiography was

performed to measure the diameter of these

rings. Two standard curves were obtained to

cover 50 to 10000 ng/ml of A F P or 40 to 2000 ng/mh Therefore dilution of AFP-high

serum samples is not required in this method, while it is needed in double antibody method.

Other advantages of this method are as

follows: 1) Antibody of AFP is kept stable in immunoplate for more than 4 months.

2) One can examine any single case when it becomes necessary. 3) Only 5 r of

serum samples and very small activity are needed. 4 ) No radioactive soluble waste.

5) The procedure is very simple and 6)

no special instrument is required.

(191) BASIC A N D C L I N I C A L

S T U D I E S O N M I C R O -

D E T E R M I N A T I O N OF a - F E T O P R O T E I N

F. Furuhashi, K. Mizuochi, S. Ohashi, K. Kato, M. Nakano, S. Otsuka

and M. Irie 1st Dept. of Int. Med., Toho Univ.

Sch. of Med. M. Akima

Dept. of Pathol. Y. Maruyama and F. Oyamada

RI Lab.

Experimentally, a hepatic cancer was created in male Donryu rats; in this procedure,

the progress of the formation of hepatic

cancer was investigated in time-course as to the serum-AFP level, while pursuing the

progress histologically and electron-microscopically. On the other hand, clinical

significance was reviewed on a total of 406

cases, namely 128 patients with malignant tumor including primary hepatic cancer and

metastatic hepatic cancer as well as 244

patients with non malignant hepatic diseases, in relation to serum AFP-level. Determi-

nation of serum AFP-level was made by Radioimmunoassay 2 Antibody method.

AFP-level of rats treated with DAB was

increased after the 2nd week reaching peak of 6.2 • 104ng/ml in from 5 to 6 weeks,

and then lowered to 800 ng/ml after 8 weeks, thereafter, it was again sharply elevated

after 9 weeks, reaching 1.1 • 113~ ng/ml in

the 12th week, keeping its high level thereafter. Histological changes were similar

to those of AFP-level, the hepatic tissue in the 10th week showed a clear cancerous

formation.

In electron microscopic observation, the characteristic changes of the hepatic cells

were as in the following. (1) Hepatic cells at the time of increased

AFP-level are filled with small tubular en-

doplasmic reticulum. (2) Hepatic cancerous cells after 10 weeks

showed abnormal structure of rough en-

doplasmic reticulum, and the picture shows the encircling of the mitochondria, while

the "exuvial" of ribosome were ovserved, demonstrating the AFP-producing picture.

In the next step, as for the detective sensi-

tivity of AFP-level in human blood, the standard deviation was obtained with the normal human serum of 32 cases, and the

230 Proceedings of the 59th Annual Meeting--197 3--( H)--

normal level was set at that of less than 12 ng/ml. As for the relationship between malignant tumor and AFP-level, a distinct difference was observed on the metastatic cancer and primary hepatic cancer.

The abnormality up to 12~241 ng/ml was observed in 31% of the patients with hepatitis. Also, the abnormality up to 12~162 ng/ml was observed in 28% of the patients with hepatic cirrhosis. The level, however, was lowered with the improvement of morbid conditions, being less than 12 ng/ml. Thus, interesting facts were obtained in the basic and clinical studies on the production of AFP in serum.

(192) RADIOIMMUNOASSAY DETERMINATION OF

ALPHA-FETOPRO- TEIN :

SIGNIFICANCE IN DIAGNOSIS, TREATMENT AND PROGNO-

SIS OF HEPATOMA

E. Nagata, Y. Kubo, T. Arishima, Y. Otsuyama, A. Kaneto,

Y. Shimogawa, K. Tanigawa and

N. Okabe 2nd Dept. of Med., Kurume Univ.

Sch. of Med.

Serum Alpha-Fetoprotein (AFP) level was determined by radioimmunoassay in 106 patients with hepatoma, 179 patients with other various liver diseases, and 28 normal subjects. Hepatoma was possible over 400 ng/ml and probable'over 1000 ng/ml of AFP.

Repeated determination was necessary for diagnosis of hepatoma in cases of low AFP level. AFP over 1000 ng/ml could exclude non neoplastic hepatic diseases.

Rapid elevation of AFP in patient with hepatoma suggested short survival, while low elevation indicated long survival. AFP level considerably reflected clinical improvement and deterioration after anti-cancerous drug and surgical treatment.

Observation of AFP level at intervals

indicated prognosis and therapeutic effects in patients with hepatoma.

(193) CLINICAL SIGNIFICANCE OF a-FETOPROTEIN DE-

TERMINATION IN BLOOD ON FOLLOW-UP

STUDIES USING RADIO-IM-

MUNOASSAY PROCEDURE

K. Nakajima, S. Onishi, A. Kasahara, T. Shimizu, Y.Ikehara, H. Tajima,

A. Okamoto, T. Komibuchi, T. Negoro and A. Nihonsugi

Dept. of Int. Med., Osaka Red-Cross Hosp.

M. Ishii and T. Tozawa 2nd Dept. of Int. Med., Kobe

Univ. Sch. of Med.

1. The percentage of ot-fetoprotein(AFP)- positive responses of hepatomas was improved up to 93.6% using the radio-immunoassay (R.I.) combined with the single radial immunoassay(S.R.I.) of AFP, while it was less than 59.6% only by S.R.I.

2. Hepatomas in which all the values of AFP were having progressively increased up, contrasted remarkedly with histologically confirmed cirrhosis of 14 cases whose values of all were less than 20 m/t/ml even just before their death.

3. Following-up studies of 5 cases including 4 gastric and a ovarial cancers of AFP- positive responses by S.R.I. and 3 cases of these by R.I. about cancers of other organs besides hepatoma, we could find that the values of AFP in 3 cases of them increased progressively up as those of hepatoma, but the rest showed only transient initial increases of AFP-values, and then negative responses of them.

4. In the group of subacute hepatitis the rate of AFP-positive responses was high (69.2%) by R.I., and for the high AFP- positive cases of it "Exchange Transfusion" of blood seemed to be preferable as a treatment.

Proceedings qf the 59th Annual Meeting--1973--(H)-- 231

(194) CHANGES IN SERUM o~- F E T O P R O T E I N LEVEL IN

HEPATIC DISEASES (DISEASES)

Y. Ogawa, H. Otani

and M. Ishida

Dept. of Int. Med. H. Yashima

Dept. of Clin. Lab., Hiroshima Pref. Hosp.

We have developed the counter immuno-

electrophoresis method which, though having a sensitivity almost comparable to the radio-

immunoassay method, can be conducted

with relative ease. By this method semi- quantitative determination can be made of

the serum 0t-fetoprotein (a-F) level greater than 150 ng/ml. It responds positive in not

only hepatoma but also hepatitis, hepato-

cirrhosis, pregnancy and neonate. Therefore,

this is considered to be the most appropriate method for observing the changes in a-F

level in these diseases. This method was employed as a screening

test in a total of 3,268 cases including liver

diseases, pregnancy, and neonates, and positive results were obtained in 28 cases of hepatoma,

22 cases of hepatitis and hepatocirrhosis, 14 cases of pregnancy, 23 neonates, and 3 others.

There were 10 cases of hepatoma among the 32 cases of liver diseases showing positive

reaction of less than approximately 1000 ng/ml.

Of these cases hepatoma was not clinically suspected in 5 cases and only by ot-F test was

hepatoma suspected. This suggests a possibility in the early diagnosis of hepatoma.

Furthermore, even in fulminant hepatitis and hepatocirrhosis there is sometimes an

elevation to approximately 1000ng/ml. During the last trimester of pregnancy

ot-F is demonstrable in the maternal blood,

but this tendency becomes remarkable when pregnancy is complicated with hepatitis or

toxicosis, indicating a possibility of 0t-F serving as an indicator of placental function.

IN C H R O N I C LIVER DISEASES

K. Shoji, S. Tsuiki, S. Morimoto, Y. Nakai, M. Ryo, Y. Ozawa,

T. Tanaka and

M. Horiguchi

Dept. of Gastroenterl. 3rd Hosp., Jikei Univ. Sch. of Med.

The application of radioimmunoassay for

determination of ot-fetoprotein (AFP) led characteristic protein in hepatoma to common

to other liver diseases. AFP contents of serum was under 20m/tg/ml in normal

subjects. Higher content than 20 mpg/ml

of AFP were detected in many patients with liver disease, 50% in acute hepatitis, 57%

in chronic hepatitis, 59% in liver cirrhosis

and 50% in fatty liver. The content of AFP reached up to about 100 m/tg/ml 2-3

weeks after acute event of liver damage and came down to normal range within 7 weeks.

After 7 weeks, it still remained in abnormal

range in some cases and these eases usually transfered to persistent or chronic.

There was no relationship between the content of AFP and histological findings

in chronic hepatitis. Even if in active form, half of cases did not show abnormal value

of AFP during follow-up period. In eases

with liver cirrhosis, it was interesting fact that cirrhotic patients with diabetes showed

higher value of AFP than without diabetes.

And ,50% of fatty liver cases were also elevated in AFP. Histological characteristics in these

cases which showed high AFP contents during the course, were presence of basophilic he-

patocytes and polynuclear cells, compared with non-elevated cases in AFP.

From these results, it seems that chronological observation of AFP is important and

convenient for determining their prognosis, and elevation of AFP in serum may suggest

regeneration of liver cells.

(195) DYNAMIC ASPECTS OF a - F E T O P R O T E I N : ESTIMATED

BY RADIOIMMUNOASSAY

232 Proceedings of the 59th Annual Meeting---1973--(H)--

(196) UNDIFFERENTIATED

LIVER ENZYME PATTERNS

AND INCREASED SERUM

a - F E T O P R O T E I N CON- CENTRATIONS IN

PATIENTS W I T H HEPATITIS,

C I R R H O S I S OF THE LIVER

AND HEPATOMA

K. Taketa, A. Watanabe, Y. Yumoto,

A. Tanaka, A. Takesue, H. Aoe,

M. Ueda, J. Shimamura and K. Kosaka.

1st Dept. of lnt. Med., Okayarna Univ. Med. Sch.

Increased activities of glucose 6-phosphate

dehydrogenase, hexokinase, pyruvate kinase- M~ and decreased activities of glucokinase

and pyruvate kinase-L in livers of patients with chronic hepatitis and cirrhosis of the

liver have been found by our previous studies. The similarity of the above enzyme pattern

to that of hepatoma cells together with the

fact that a-fetoprotein(~f) concentration in serum of patients with hepatitis and cirrhosis

of the liver increases prompted us to analyze direct correlations between these parameters. The results with directly comparable values

obtained from 91 cases of non-malignant

liver diseases revealed lesser correlations between serum or liver a f concentration and

liver enzyme activities than those among the enzymes having a common mechanism

of increase in their activities in injured livers. Similar results were obtained with 8 hepatoma

patients, although the extent of the deviation

in a f concentration and enzyme activities was generally greater than that in other liver diseases. These results suggested that the

increase in serum a f concentration in hepatitis and cirrhosis patients may possibly be related

to the pathogenesis causing the undifferentiated enzyme pattern and involves disordered mechanisms of protein synthesis as may exist

in hepatoma cells, althougn the alternative possibility can not be excluded entirely.

(197) DIAGNOSTIC SIGNIFICANCE OF a - F E T O P R O T E I N IN

ABDOMINAL VISCERAL

SURGERY

E. Kashiwara, K. Orita, E. Konaga, K. Suzuki, S. Tanaka, S. Kaneda

and K. Ogawa

Dept. of Surg., Okayama Univ. Med. Sch.

In the past several years along with the

increase in number of cases positive to ~- Fetoprotein(AFP) one of the embryonic

proteins and with advance in precise measurement of it, the presence of AFP seems to

be no longer considered specific to primary

hepatoma. We have been studying differences in the AFP incidence due to the difference

in its estimation methods with 337 patients

admitted mainly for visceral surgery. We generally employ Ouchterlony's method (M.

O.) and in some instances, single radial im-

munodiffusion method (S.R.I.D.) and radioimmunoassay method(R.I.) for qualitative

and quantitative assays. Of the 337 cases,

15 cases proved to be positive to M.O. method. These 15 positive cases were composed of 11

out of 14 primary hcpatoma cases, 2 cases Of gastric cancer with liver metastasis, one

of liver cirrhosis and one of embryonic carcinoma in children. In 60% of lobectomy

cases of metastatic hepatoma the disappearance

of AFP was observed by R.I. method on 53 postoperative days. In 3 cases of primary

hepatoma where hepatic artery was ligated because radical operation was impossible,

two showed a decrease of AFP. Of 337

cases M.O. method, S.R.I .D. method and R.I. method were applied to 72 cases including

6 primary hepatoma cases to compare their results, and 5 cases (6.9%) gave AFP positive

result to M.O.method, !7 (23.6%) positive to S.R.I.D. method, ai,d 46 (63.9%) positive

to R.I. method. In summarizing, when

considered AFP as the core, the diagnostic efficacy is highest with M.O. method in

primary hepatoma, and in the case negative to M.O. method or for the follow-up of

disease processes S.R.I.D. and R.I. methods seem to be more suitable.

Proceedings of the 59th Annual Meeting--1973--( II)-- 233

(198) THE METHOD FOR PREVENTING HEMATO-

GENOUS LIVER METASTASIS

IN THE EXPERIMAENTAL ANIMALS

H. Tamura, S.Okanishi, T. Ueda, H. Horie and M. Kamachi

Dept. of Surg., Fukuchiyama Nat. Hosp. T. Asihara

Dept. of Pathol. R. Daido

Dept. of Surg., Kyoto Pref Univ. Med. Sch.

The vascular analysis was studied in relation to various growth stages of the liver metastasis induced by VX 2 infusion via portal veins in rabbits, and a method was proposed for preventing hematogenous liver metastasis. Histologically neoplastic cells in the early stages were observed to migrate from the portal veins to the Glisson's sheath by proliferating, and then to form the growth ex- pansively. The microangiographic technique during the course revealed that, for the advanced stages, peripheral vascularization with a few penetrating vessels mainly from arterial flow were prominent, but for the early stages, the portal system rather than the arteries played an important role for the blood supply to the neoplasms. To find out the effective use of the chemotherapy (Mitomucine C) for the metastasis, the survival of the animals administered in the various stages through the portal vein, the hepatic artery and the auricular vein was analyzed. In addition, the proliferative activity of the neoplastic cells in these experiments was also studied using 3H-thymidine autoradiography.

From the present study it is confirmed that the very early treatment from the portal vein is the most efficient method for preventing the metastasis.

(199) t~OLLOW-UP STUDY OF INDUCTION OF GASTRIC CANCER IN DOGS BY N-

ETHYL-N'-NITRO-N-

NITROSOGUANIDINE WITH X-RAY

ENDOSCOPY AND BIOPSY (II)

T. Izumi M. Kurihara M. Sumida M. Haraikawa H. Hayakawa

H. Shirakabe and A. Yasui

Dept. of Gastroenterl., Juntendo Univ., Tokyo, Japan

It was established that oral administration of potent mutagen and carcinogen, N-Methyl- N'-nitro-N-nitrosoguanidine (MNNG) in drinking water produced adenocarcinomas in the stomach of dogs by Sugimura et al. However, it takes more than 2-3 years to produce prominent tumorous change of gastric mucosa, and moreover sarcomatous lesions of the gastrointestinal tract are developed which prevents further investigation.

By using less reactive carcinogen, N-Ethyl- N'-nitro-N-nitrosoguanidine (ENNG) solution and by device to contact drug long-lastingly to mucosa of the stomach in dogs with enforced taking of ENNG soaked diet, period of carcinoma production was strikingly shortened.

At last autumn meeting of the Japanese Society of Gastroenterology follow-up study of induction of gastric cancer in mongreal dogs by ENNG with X-ray, endoscopy and biopsy was reported. In this paper we report that the same study with beagles were succeeded. Namely, biopsied materials of 3 beagle-stomachs were revealed atypical structures and glands at 12-16 months after administration of ENNG.

(200) EARLY MUCOSAL CHANGES IN EXPERIMENTAL GASTRIC

CARCINOMA OF DOGS INDUCED BY NG* (II)

M. Noguchi, M. Okamoto, Y. Furukawa, R. Miyasaki, K. Hirose,

T. Katayama and H. Maezawa

1st Dept. of Int. Med., Tokyo Med. and Dent. Univ.

As reported previously, oral administration of NG induced gastric carcinomas in the

234 Proceedings of the 59th Annual Meeting--197~-(H)--

6-month group dog and in the short duration

groups, atypical changes were observed surrounding shallow erosions and ulcers.

They were considered to be resulted from

the direct damages of NG to gastric mucosa as well as from the effect of NG as mutagen.

This experiment was performed in order to

compare gastric mucosal changes with these

after NG was discontinued. M e t h o d : About 300ml/day of NG so-

lution (80/ tg/ml) was administered orally to dogs with average weight of 8kg for 1, 4

and 6 months. Thereafter, they were given

water for 4 weeks and then sacrificed. Microscopically, no depressed lesions could

be observed, although mucosal surface was

somewhat atrophic and granular especially near the angular portions and in the upper

portions of the stomachs. Microscopically,

mucocellular adenocarcinomas were proved at the margins of regenerated erosions near

the gastric angles in 4- and 6- months groups

dogs. Atypical changes, which were often encountered in the previous experiment,

were less evident in this series associated with

the healing of erosions and ulcers. In some lesions, however, marked atypical epithelium

remained associated with fibrosis and epitheliar hyperplasia. Grandular atrophy was the

same as in the previous results. Intestinal

metaplasia was not evidently observed. It was suggested that there were two types

of atypical changes, i.e., one disappearing

and the other remaining. And the latter might be considered to develop into malignant

change. 3 * N-methyl-N'-nitro-N-nitrosoguanidine

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