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Biomedical subjects

T Itoshima

Publications and source records attributed to T Itoshima.

At least 19 recordsLinked to original sources

Proliferation of collagen fibrils and Ito cells in the liver after Japanese sake administration in undernourished rats as demonstrated by scanning electron microscopy.

Intralobular fibrosis of the liver was induced in undernourished rats by administering Japanese sake for 12 days. Control rats administered the equivalent calories with glucose solutions did not show any fibrosis. In the sake group, Ito cells were increased and often clustered under the scanning electron microscope (SEM). Many collagen fibrils 0.1 microns in diameter twisted around Ito cells which had numerous microvillous projections. On the contrary, fibrils were not increased and Ito cells had rather smooth surfaces in the control group. The number of Ito cells counted under the SEM at 500 magnifications was increased in the sake group (mean +/- standard deviation; 70 +/- 23/mm2) as compared to the control group (44 +/- 9; P less than 0.01). The fact that Ito cells had proliferated and were tangled with collagen fibrils in the sake group was demonstrated three-dimensionally by SEM.

Animals

Observation of microvascular casts of human hepatocellular carcinoma by scanning electron microscopy.

The microcirculation of hepatocellular carcinomas (HCCs) and surrounding tissue was observed three-dimensionally by scanning electron microscopy of vascular casts made from 10 livers at autopsy. The livers were perfusion-washed and cast with resin through both the hepatic artery and portal vein branches. The HCCs observed ranged from several millimeters to 3 cm in size. A vascular plexus proliferated around the HCC nodules in all cases. Both portal vein and hepatic artery branches proliferated markedly to form the plexus in 5 patients. These vessels communicated directly with the blood sinuses of the HCCs as feeder vessels. HCC cells replaced normal cells while maintaining the liver's trabecular structure in 2 cases. At the borders of these HCCs, there was direct communication between the hepatic sinusoids and the tumor blood sinuses. Efferent vessels of the tumors were generally difficult to identify but vessels resembling hepatic vein branches were detected in one 4-mm HCC nodule after microdissection. Thus, HCC was demonstrated to be supplied not only by the hepatic artery but also by the portal vein and hepatic sinusoids. This may be one of the reasons why cancer cells survive in the tumor margins and daughter nodules after transcatheter arterial embolization of HCC.

Adult

Experimental liver cysts induced by 2-acetylaminofluorene.

Liver cyst formation was studied serially in an experimental model in which rats were fed a diet containing 0.02% 2-acetylaminofluorene, a carcinogen, for 6 weeks, followed by a normal diet for 42 weeks. Cysts appeared in the portal tracts at the 12th week, by which time the intrahepatic bile ducts had also proliferated and dilated. Some of the dilated bile ducts were cavernous or multicystic and appeared to represent a transitional form between the bile duct dilation and cystic formation. After 20 weeks cysts were observed in the majority of rats. The number and the size of cysts in the liver increased with time; after 40 weeks, there were up to 20 cysts as large as 15 mm in diameter. Carcinoma or cirrhosis did not develop in this model. Indocyanine green dye injected intravenously did not accumulate in the cysts, which denies the possibility of communication between cysts and the bile duct. Scanning electron microscopy demonstrated that the cysts were composed of a few intercommunicating cavities and were lined with epithelial cells similar to those of the intrahepatic bile duct, which had numerous microvilli and a central cilium. These observations suggest that liver cysts originate in the bile duct.

2-Acetylaminofluorene

Three-dimensional fine structure of the biliary tract: scanning electron microscopy of biliary casts.

The three-dimensional structure of the biliary tract was studied by scanning electron microscopy (SEM) of biliary casts. The replica of the biliary tract was successfully prepared by retrograde injection of low viscosity resin into the common bile duct. Bile canaliculi are intricate networks in which hexagonal and pentagonal meshworks are interconnected. Each hexagonal or pentagonal meshwork is on a plane, but adjoining meshworks are on different planes. Bile canalicular networks connect with bile ductules at the periphery of the portal tract. The intrahepatic bile duct showed considerable interspecies variation. The human bile duct has plexiform side branches and periductal sacculi, which are most numerous near the liver hilum and fewest in the smaller portal tracts. The hilar plexus and sacculi are present on opposite sides of the bile duct. The plexus formed at the bifurcation of the bile ducts exhibits a plane. Periductal sacculi were also observed in the monkey and pig bile ducts, particularly the latter, while rat bile ducts possess a peculiar portal bile ductular plexus situated between the portal tract and the surrounding liver parenchyma. No such structures were observed in either the dog or rabbit bile ducts. SEM of the biliary casts showed that the biliary tract was not a simple draining tube but had additional structures, such as periductal sacculi and plexiform side branches. These structures, together with the peribiliary vascular plexus, may be implicated in the modification of bile.

Biliary Tract

Hepatitis B virus markers in patients with schistosomiasis, liver cirrhosis and hepatocellular carcinoma in Khartoum, Sudan.

Markers of hepatitis A and B virus were tested in 88 adult Sudanese subjects in Khartoum, Sudan. The subjects consisted of 25 control hospitalized patients, 21 volunteer blood donors, 23 patients with hepatosplenic schistosomiasis, 13 patients with liver cirrhosis and 6 patients with hepatocellular carcinoma (HCC). Antibody to hepatitis A virus was detected in 96% of the total. Hepatitis B surface antigen (HBsAg) was positive in 4, 24, 22, 31, and 67% of the subject groups, respectively. Antibody against hepatitis B core antigen (HBcAb) of undiluted serum was positive in 60, 57, 65, 77 and 83%, and there was no difference in incidence among the groups. It was positive in 200X diluted serum in 4, 24, 17, 23 and 60%. HBsAg and HBcAb (200X) were detected more often in HCC patients than in the control subjects (p less than 0.01). Hepatitis B virus is an important factor in the etiology of HCC in the Sudan.

Adult

Phalloidin-induced alterations of bile canaliculi.

Phalloidin, a toxin from the plant Amanita phalloides, irreversibly polymerizes actin filaments and causes cholestasis. Three-dimensional structural changes induced by phalloidin in the bile canaliculi and the intra-acinar localization of these changes were studied in the rat liver by scanning and transmission electron microscopy. After 3 days of treatment, canalicular changes appeared mainly in zones 2 and 3 of Rappaport's acinus, but after 7 days of treatment changes occurred in bile canaliculi of the whole acinus. The changes in the bile canaliculi included tortuosity, saccular dilatation, loss of microvilli, bleb formation and elongation of canalicular side branches. Some side branches extended near to Disse's space, leaving only a thin cytoplasmic rim between the canalicular lumen and Disse's space. Kupffer cells were occasionally situated near such extended bile canaliculi and protruded their processes into the hepatic cord. These results suggest that bile canaliculi in zone 3 are more susceptible to phalloidin toxicity than those in zone 1 and that biliary constituents may leak from such altered bile canaliculi.

Animals

Photodynamic therapy of rat liver cancer: protection of the normal liver by indocyanine green.

The application of photodynamic therapy (PDT) to hepatocellular carcinoma (HCC) has been difficult because hematoporphyrin derivatives (HpD) accumulate not only in cancer cells but also in normal hepatocytes and, hence, laser irradiation causes injuries in both tissues. Protection of the normal liver tissue from laser phototoxicity was demonstrated using indocyanine green (ICG) as a protective agent. In vitro, argon laser irradiation decolored the green tint of ICG much faster in solutions containing HpD than those without, suggesting that ICG captured singlet oxygen from HpD. Degeneration of Change hepatocytes induced by HpD and laser irradiation was prevented by an addition of ICG into the medium. In vivo, laser irradiation of the rat liver surface caused hyperemia when HpD was injected two days before, while the hyperemia was much milder in rats additionally receiving ICG injection 10 minutes before the irradiation. ICG injected into rat HCC accumulated only in the normal liver tissue. Laser irradiation of rat HCC preinjected with both HpD and ICG destroyed only the cancer tissue, while the surrounding liver tissue was preserved. Both in vitro and in vivo results suggest that ICG has a scavenger effect against excited oxygen and it might be used as a protective agent in PDT of HCC.

Animals

Follow-up study of 582 liver cirrhosis patients for 26 years in Japan.

A long-term follow-up study of liver cirrhosis (LC) was performed in 582 patients diagnosed by peritoneoscopy and liver biopsy in the 26 years from 1958 to 1984. The etiology of LC consisted of hepatitis B virus (HBV) in 21%, alcoholic in 39% and cryptogenic in 39%. Fifty-nine percent of patients had died. Causes of death were hepatocellular carcinoma (HCC 44%), liver failure (30%), rupture of esophageal varices (14%), gastrointestinal bleeding (4%) and non-liver-related causes (8%). HCC accounted for increasing percentages (68%) since 1980. In all groups classified by the etiology, the causes of death had the same order in incidence. The age of onset of LC increased by 10 years from 42 to 52 years old and the age of death by 15 years from 43 to 58 in the 26-year period. The cumulative survival rate improved over the period. The 50% survival year was 7.9 in total patients, and 7.0, 8.5 and 10.0 in the three periods 1958-64, 1965-74 and 1975-84, respectively. It was 9.5, 6.3 and 9.8 in HBV, alcoholic and cryptogenic, respectively. LC patients survived 40-44% of the life expectancy of the general population in Japan in all age groups. Cox's multiregression life-table method selected three important prognostic factors from 7 parameters: a poor prognosis with a history of heavy alcohol consumption and old age at onset, and a better prognosis with recent onset.

Actuarial Analysis

Treatment of hairy cell leukemia with alpha-interferon and splenectomy.

A typical case of hairy cell leukemia, very rare in Japan, is described. The biological characteristics of the disease and histological features of liver and spleen are also reported. Treatment with alpha-interferon and splenectomy was successfully performed, and the patient is now in good health.

Follow-Up Studies

Injurious effects of ethanol on rat Kupffer cells.

The effects of ethanol on rat Kupffer cells were studied functionally and morphologically. Eight g ethanol per kg body weight per day was intragastrically administered to rats for 7 days. An isocaloric glucose solution was administered to control rats. The phagocytic activity of the reticuloendothelial system was measured by the carbon clearance method (57 mg carbon particles per kg body weight) on the 7th day. Kupffer cells having phagocytized carbon particles were counted under the light microscope. Kupffer cells were also observed by scanning electron microscopy. Both the carbon clearance and Kupffer cell number were lower in ethanol-administered rats (32 +/- 8 X 10(-4) mg/ml; 0.6 +/- 0.3/0.01 mm2 liver lobule) as compared to control rats (63 +/- 15; 3.1 +/- 1.0). Microvilli and filopodia of Kupffer cells were fewer in ethanol-administered rats than in control rats. Carbon clearance correlated with Kupffer cell number per 0.01 mm2 liver lobule and liver weight. These results suggest that the decrease in carbon clearance induced by ethanol is due mainly to the decrease in Kupffer cell number and partly to the decrease in Kupffer cell activity as demonstrated by the disappearance of microvilli and filopodia.

Animals

Peritoneoscopy of alcoholic liver cirrhosis in comparison with non-alcoholic liver cirrhosis.

Peritoneoscopic findings of 39 patients with alcoholic liver cirrhosis (ALC) were compared with those of 95 patients with non-alcoholic liver cirrhosis (NALC). They were selected from 245 patients with liver cirrhosis subjected to peritoneoscopy in the 7 year period from 1975 to 1981. Out of the 95 NALC patients, 24 had hepatitis B surface antigen. The ALC patients had nodules which varied in size (61%), large depressions (69%), and a markedly rounded edge of the liver (33%) more often than NALC patients (18, 43 and 3%, respectively). Nodularity differed between the right and left lobes in ALC (41%) more often than in NALC (16%). Interstitial reddish markings and patchy nodules were, however, more frequent in NALC (51 and 28%, respectively) than in ALC (8 and 5%, respectively). Lymphatic vesicles were observed both in ALC (85%) and NALC (78%). In conclusion, the peritoneoscopic features which suggested ALC were the coexistence of nodules of various sizes, large depressions and a markedly dull edge of the liver. Interstitial reddish markings and patchy nodules were more indicative of NALC than ALC.

Adult

Comparison of estimation methods of liver maximum removal rate of indocyanine green.

Three linear plots by which the liver's maximum removal rate (Rmax) of indocyanine green (ICG) and the Michaelis constant (Km) can be calculated were compared in a microcomputer simulation study. The widely-used Lineweaver-Burk plot (1/V vs. 1/S; V, ICG initial removal rate (mg/kg/min); S, ICG loading dose (mg/kg] presented the greatest bias and variance. There was no remarkable difference in bias between the S/V vs. S plot and the V vs. V/S plot, but the latter possessed a smaller variance. Therefore, the V vs. V/S plot was considered the best for estimating Rmax. The best combination of three ICG loading doses was 0.5, 2, and 5 mg/kg. This combination was selected by comparison of the Rmax estimated from three points with that estimated from six points (0.5, 1, 2, 3, 4 and 5 mg/kg).

Humans

Evaluation of Talbot's safety zone of infusion volume and osmolality in infusion therapy for decompensated liver cirrhosis.

Problems with infusion therapy for correcting fluid and sodium imbalance in decompensated liver cirrhosis (DLC) were investigated by establishing the safety zone of Talbot et al. for parenteral fluid therapy in 4 DLC patients infused with over 900 ml of fluid each day for at least 9 days. The safety zone was different in each case. The safe infusion volume decreased and the safe electrolyte concentration shifted to a lower osmolality when there was ascites with renal failure than ascites without renal failure. Infusion therapy was performed without deterioration of the water and sodium balance in those patients whose infusion volume and fluid osmolality were in the safety zone. In contrast, ascites retention increased and peripheral edema appeared in patients whose infusion volume and osmolality were out of the safety zone. Therefore, the safety zone should be determined repeatedly during infusion therapy.

Aged

Comparative diagnosis of alcoholic liver diseases by multivariate and histological analysis.

Sixty-seven cases of alcoholic liver disease were histologically classified into 4 groups: alcoholic liver cirrhosis (ALC), alcoholic hepatitis (AH), alcoholic liver fibrosis (ALF) and alcoholic fatty liver (AFL). They were statistically reclassified by the likelihood method using age, total alcohol intake, hepatomegaly and 12 liver function tests. A score table for likely diagnosis was constructed from the incidences of each range. The cases were re-evaluated using the score table, with an overall correct diagnosis rate of 73%. The best combination of 5 parameters included the indocyanine green plasma disappearance rate, total alcohol intake, cholesterol, choline esterase and glutamic oxaloacetic transaminase/glutamic pyruvic transaminase ratio. A correct diagnosis rate of 75% was attained using these 5 parameters, and 94% of patients were correctly diagnosed by the first or the second likelihood diagnosis. Differential diagnosis of alcoholic liver diseases was easily and confidently obtained with the likelihood score table.

Adult