Kiyotaka Kamegaya

Hepatic fibrosis produced in guinea pigs by chronic ethanol administration and immunization with acetaldehyde adducts

Experimental hepatic fibrosis was produced in the guinea pig. We produced hepatic necrosis associated with inflammatory cell infiltration in guinea pigs immunized with acetaldehyde adducts and fed ethanol for 40 days. Extending the period of these treatments to 90 days resulted in producing hepatic fibrosis developing around individual hepatocytes in the terminal hepatic venule areas and portal areas, accompanied by an increase in hepatic hydroxyproline content. In contrast, no fibrosis was observed in the livers of the control groups that had been exposed to nothing, ethanol alone, or a combination of ethanol and immunization with unmodified human hemoglobin. Minimal fibrotic changes were observed in animals immunized with human hemoglobin acetaldehyde adducts but not fed ethanol. These results indicate that the formation of acetaldehyde adducts and the acquisition of immunity against them can produce hepatic fibrosis. Immune mechanisms against acetaldehyde adducts may, in part, be involved in the pathogenesis of hepatic fibrosis seen in alcoholics.

Relationship between hepatitis C virus subtypes and clinical features of liver disease seen in alcoholics

The influence of hepatitis C virus and its subtypes on the clinical course of liver disease in alcoholics was assessed. Hepatitis C virus infection was confirmed by a reverse transcription and polymerase chain reaction method for the hepatitis C virus NS-5 region in the sera of alcoholics with various stages of histologically proven liver disease. The frequency of hepatitis C virus was significantly higher in alcoholics with chronic hepatitis (73%) than in those with liver fibrosis (18%), alcoholic hepatitis (17%), and fatty liver (0%). Hepatitis C virus subtypes, namely K1 and K2, were determined by dot-blot hybridization analysis of the polymerase chain reaction products with specific probes, and their frequencies were 68% and 32%, respectively. The proportion of patients whose serum transaminase levels returned to normal following 4 weeks of abstinence in hospital was significantly lower in alcoholics with hepatitis C virus viremia (glutamic oxaloacetic transaminase: 53.8%; glutamic pyruvic transaminase: 42.3%) than in those without viremia (glutamic oxaloacetic transaminase: 86.2%, p < 0.01; glutamic pyruvic transaminase: 89.7%, p < 0.01). When alcoholics with the K1 and K2 subtypes of hepatitis C virus were compared, normalization of transaminase levels was less frequent in alcoholics with K1 (glutamic oxaloacetic transaminase: 42.8%; glutamic pyruvic transaminase: 28.6%) than in those with K2 (glutamic oxaloacetic transaminase: 88.9%, p < 0.05; glutamic pyruvic transaminase: 77.8%, P < 0.05). These data indicate that hepatitis C virus infection is associated with a reduced rate of recovery of serum transminase levels following abstinence in subjects with alcoholic liver disease, more so in the K1 subtype than in the K2 subtype.

Histiocytic Medullary Reticulosis (Reticuloendotheuosis with Striking Erythrophagocytosis)

Under the generic term of ‘keticuloses” or “reticuloendothelioses”, over 60 cases have been reported in Japan for the last 20 years. No cases, however, can be found in which special emphasis is placed upon the stiiking erythrophagocytosis throughout the reticuloendothelial system. Recently a case was examined at autopsy characterized by pyrexia, general malaise, hepatosplenomegaly, generalized lymphadenopathy, anemia, jaundice and a systematized prolifeartion of histiocytic cells with active erythrophagocytosis, which seems to be identical with “histiocytic medullary reticulosis” claimed as a distinct clinicopathologic entity by SCOTT and ROBBSMITH^) in 1959; the findings form the basis of this report.

Ectopic Formation of Elastic Cartilage in Exsc Animals

The paper presents the experimental ectopic formation of elastic cartilage, which has not previously been reported, in five guinea pigs observed in our department.

Statistical follow-up studies on146 cases of liver cirrhosis

SummaryThe present study reported 5 year survival curves in 146 cases of liver cirrhosis diagnosed between 1965 and 1972. The 146 subjects included 15 cases who were complicated with hepatoma at the first time of consultation. Five year survival curves were constructed by the life table method of Cutler and Ederer. Five-year survival rate was 53.1 ± 5.6% in 146 cases (liver cirrhosis with and without hepatoma), and 59.2 ± 6.2% in 131 cases (liver cirrhosis without hepatoma). Five-year survival rates of 75 cases of compensated and 56 cases of decompensated liver cirrhosis were 74.5% and 39.5% respectively. Five-year survival rate in the patients with jaundice was 41.9%, in the patients with ascites 11.7%, and three-year survival rate in the patients with rupture of esophageal varices was 50.8%. These results suggest improved survival rates compared with those of previous reports, most probably reflecting the improved treatment of decompensated liver cirrhosis. The therapeutic effects of adrenocortical steroids and diuretics were also investigated. No significant effects of steroid therapy on the survival rates of cirrhotic patients were observed. Diuretics were seemed to be slightly effective.

An autopsy case of liver cirrhosis due to schistosoma japonicum, combined with hepatoma and gastric cancer

SummaryNot many cases have been reported of liver cirrhosis due to schistosomiasis complicated by hepatoma except for those recently reported by Iuchi and his co-workers. Furthermore, a simultaneous occurrence of hepatoma and gastric carcinoma appears to be extremely rare.The authors report a case of a 48-year-old Japanese male with liver cirrhosis probably due to schistosomiasis as well as hepatoma and a superficial spreading type of carcinoma of the stomach.

The experimental study on restraint-induced gastric ulcer—alteration of the microcirculatory system in the gastric wall

Immobil izat ion has been employed as an useful method for the exper imenta l product ion of gas t r ic lesion in the rat . However, the endeavor of the present s tudy was aimed a t some methodological development to produce chronic ulcer, and some considerat ion was given in i ts mechanism. Subjects: Albino ra ts of Wistar-King A s t ra in were used. These an imals were 120~180 days old at the beginning of the experiment . Procedure: Immobil izat ion was applied in following schedule; 24 hrs a day (one t r ia l group), 20 hrs a day for 7 days (long te rm immobil izat ion group), 20 hrs a day for 4 days wi th subcutaneous inject ion of h is tamine (his tamine combined group). Results: Incidence of gas t r ic lesion in the his tamine combined group was h igher than t h a t of control group. In the long t e rm immobil izat ion group, h igher incidence and much more sever i ty of ulceration, up ti l l per fora t ion in some cases, was found in the lumen than those of one t r ia l group. However, a lmost s imi lar findings was shown in the glandular s tomach, in bo th groups. Microscopic findings. (1) Lumen; Circumscr ibed necrosis in both the mucosa and the submucosa are observed. In the bed of ulcer, exist active chronic inf lammatory cell infi l tration and regenera t ion of capillary. These findings suggest the feauture of chronic ulceration. Most cha rac te r i s t i c findings in the lumen of this group are format ion of th rombus or angi t is in the submucosa. These histological changes suggest tha t p r imary vascular changes produce subsequent degenerat ion or necrosis in the submucosa, and thereby it may develop into ulceration. (2) Glandular s tomach ; The muscular i s mucosae is destroyed already, and necrosis extended up to the submucosa. Active chronic inf lammatory cell infi l tration is also seen in the bed of ulcer, however these chronic inf lammatory changes are localized at the affected region of the stomach. In the submucosa, th rombus or angit is can not be observed. These findings of chronic ulcerat ion can be obtained only in the h is tamine combined group. These resu l t s suggest t h a t gas t r ic acid may play a impor tan t role to extend the damage of the injured gas t r ic mucosa. Acknowledgements, We thank Prof. Dr. S. Ueki and Prof. Dr. K. Tanaka and Dr. A. Sumiyoshi for helpful suggest ion and discussion.

Histologic findings of the liver in “autoimmune diseases” with special reference to thymic abnormalities

94 cases of acute hepat i t is were observed in our clinic dur ing past 3 years. They included 48 cases of infect ious hepat i t is and 46 cases of serum hepati t is . F luminan t hepat i t is were 7 cases (7.5%), cholangioli t ic type were 11 ones (11.7%), included 6 who were older than 60 years. 3 cases (3.2%) of them were fatal, 6 (6.4%) progressed to l iver cirrhosis . 6 (12.5%) of infect ious hepat i t is progressed to prolonged or chronic hepati t is , while 14 (21.2%) of serum hepat i t i s did to them. Case report Case 1 was 61 years old female wi th dominant jaundice (total b i l i r u b i n > 2 0 m g / d l , total cho le s t e ro l>380mg/d l and a lka l inephospha tase>5 Bessey unites), under the diagnosis of extrahepat ic obs t ruct ion or in t rahepat ic cholestasis operat ion was done, but ext rahepat ic obstruct ion was not found. Her illness progressed to chronic cholangioli t is . Case 2 was 32 years old female. Dominant elevations of t r ansaminase act ivi ty were observed at six t imes dur ing 3 years, and she was diagnosed to acute hepat i t is by liver biopsy. In interval, her l iver funct ion tes ts showed normal value and biopsy specimens did normal feature. She was dignosed to chronic reccurent hepat i t is .

The role of lymphatic truct on intestinal absorption (II) protein absorption in mackee’s dogs

ConclusionIt was emphasized that lymphatic truct played important role on intestinal absorption and transportation of protein as well as portal vein.

Hypotonic duodenography: Its diagnostic value on pancreatic diseases

Hypotonic duodenography, deviced by D. Liotta, is a method for the diagnosis of the pancrea t ic diseases. The duodenum is placed hypotonic s tate with the in t ravenous inject ion of parasympathetic blocking agents followed by the int roduct ion of surface anes thet ics th rough the duodenal tube into the duodenum. The duodenal port ion is filled ba r ium meal th rough duodenal tube, thereaf te r examined roentgenologically. Th i s is to evaluate the or iginal method. 7 cases of acute pancreat i t is , 6 chronic pancreat i ts , 3 carc inoma of the pancreas and 10 wi th the diseases of the bi l iary t racts , were examined wi th this procedure. All the pat ients wi th the pancreatic diseases were found to have some abnormal i t ies in the duodenum on th is procedure. The following abnormal configurat ions were the common findings: the dislocation of the first and second portion, pro t rus ion of a few folds due to the adhesion to the head of the pancreas and defects due to compress ion wi th the enlarged pancreas, and so forth. Slight disconfipuration of duodenal folds was noted in cases of acute pancreat i t i s , while moderate compression of duodenal wall was found in cases of chronic pancreat i t i s . Localized definite defect was observed in cases of the carc inoma of the pancreas . Var ious degrees of abnormalities were found in 9 out of 10 cases of b i l iary t r ac t diseases, which s t rongly suggests the involvement of the pancreas in these cases.