Motomu Kashiwadani

Cholestatic jaundice in two patients with primary amyloidosis : Ultrastructural findings of the liver

Two patients with primary amyloidosis (amyloid light chain case) and severe cholestatic jaundice are described. Liver biopsy in the preterminal stage demonstrated amyloid deposits in the perisinusoidal space and in portal tracts, and hepatocytes were atrophic because of compression by amyloid fibrils. Ultrastructural findings showed amyloid fibrils not only in Disses space but also in the sinusoids, and the hepatocyte microvilli facing the amyloid fibrils were spicular. There were aggregates of lysosomal granules in the vicinity of bile canaliculi and some bile canaliculi were dilated with loss of microvilli. Amyloid fibrils in the portal tract compressed bile ductules, causing wide intercellular space and separated basement membranes from their epitheliums. These findings suggested disturbance in transporting not only of essential materials from sinusoids to hepatocytes but also of secretory vesicles into bile canaliculi and leakage of bile juice from small bile ductules in preterminal stage of primary amyloidosis.

Iatrogenic superior mesenteric arteriovenous fistula: ultrasonographic, CT and angiographic features and histological findings of the liver biopsy.

Iatrogenic superior mesenteric arteriovenous fistula is rare. We treated a patient with this problem 6 years after small bowel resection for intestinal obstruction. The symptoms and signs were those of intestinal ischaemia and portal hypertension with an abdominal bruit. Ultrasonography and enhanced computerized tomography of the abdomen suggested the presence of superior mesenteric arteriovenous fistula, with a dilated portal vein and a communication between the dilated superior mesenteric vein and its artery. The exact location of the fistula was then determined by selective superior mesenteric arteriography. The fistula was ligated in an emergency operation to prevent cardiac or renal failure and to relieve portal hypertension. Liver biopsy showed no cirrhotic changes, but fibrosis was seen around the portal veins. We describe here not only the diagnostic arteriographic findings of superior mesenteric arteriovenous fistula, but also the interesting and suggestive ultrasonographic and computed tomographic findings. Early correction of such fistulas is recommended to prevent cardiac or liver failure.

Effects of colchicine on the synthesis and transport of albumin: A combined electron cytochemical and autoradiographic study

We investigated the intracellular transport of albumin in the livers of rats treated with colchicine using immunoperoxidase study as well as combined immunoelectron microscopy and autoradiography with [3H]‐leucine. Immunoreaction of albumin was observed in all hepatocytes. Its subcellular location was in the rough endoplasmic reticulum, Golgi apparatus and lysosomes. After the injection of [3H]‐leucine through the portal vein, a combined technique revealed accumulated grains on the albumin‐positive Golgi apparatus or the albumin‐positive vesicles in the vicinity of the Golgi apparatus. These findings suggest that albumin transport from the Golgi apparatus to sinusoids is disturbed by colchicine. Enzyme histochemistry showed many acid phosphatase‐positive lysosomes in hepatocytes of the liver treated with colchicine. Albumin retained in the vicinity of the Golgi apparatus may be digested by lysosomes.

Demonstration by light and ultrastructural immunoperoxidase study of α-fetoprotein-positive non-hepatoma cells and hepatoma cells during 3−methyl-4-dimethylaminoazobenzene hepatocarcinogenesis

SummaryImmunoreaction of α-fetoprotein (AFP) has been described in cholangiolar “oval” cells in the early stage of 3′-methyl-4-dimethylaminoazobenzene hepatocarcinogenesis. The subcellular location of AFP in the oval cells was in the perinuclear space, rough endoplasmic reticulum and Golgi apparatus. In livers with hyperplastic nodules there were two different types of foci containing AFP-positive cells. One type had a normal nucleocytoplasmic ratio and was seen in well-preserved hepatic trabecular structures, and the other had less cytoplasm and occurred in trabecular structures in disarray. AFP-immunoreactivity in the former type was visible in the perinuclear space and rough endoplasmic reticulum but scarce in the Golgi apparatus, and in the latter type it was present in the proliferative smooth endoplasmic reticulum and in several parts of Golgi apparatus in the submembranous or pericanalicular areas. In livers with hepatocarcinoma, AFP immunoreaction was detected in well-differentiated hepatocellular carcinomas, and the subcellular location of AFP was in the perinuclear space, rough endoplasmic reticulum and many developed Golgi complexes. Therefore, AFP-positive cells in livers with hyperplastic nodules are a new cell population in hepatocarcinogenesis, and each type is morphologically different from the oval cell.

Immunocytochemical investigation of hepatitis B virus-associated antigens in cases of liver cirrhosis and HBsAg antigenemia and their relationship to development of hepatocellular carcinoma

SummaryUsing light and ultrastructural immunoperoxidase techniques, we examined the distribution of hepatitis B virus (HBV)-associated antigens and the subcellular localization of hepatitis B surface antigen (HBsAg) in liver biopsies of HBsAg—positive patients with cirrhosis. The localization patterns of HBsAg in hepatocytes were membranous, cytoplasmic, festoon and inclusion body types. Cytoplasmic and festoon types were seen more often than the membranous type in pseudolobules, and hepatitis B core antigen (HBcAg)—positive cells with cytoplasmic type were distributed in the periphery of pseudolobules with active inflammation. Immunoelectron microscopy in the cytoplasmic or festoon type of HBsAg showed immunoreaction in the cisternae and on virus-like particles in the cisternae in patients with hepatitis B e antigen (HBeAg) antigenemia. Simultaneous staining of HBsAg and HBcAg revealed that hepatocytes with cytoplasmic or festoon type of HBsAg contained HBcAg—immunoreactivity. The inclusion body type of HBsAg was characteristic of liver cirrhosis with hepatocellular carcinoma (HCC); the subcellular localization of HBsAg was seen in clusters of the endoplasmic reticulum around the nucleus, and HBsAg—immunoreactivity was observed on many virus-like particles in most of the cisternae in those with HBeAg antigenemia. These findings suggest that the synthesis of HBsAg is active in patients with liver cirrhosis and that the formation of HBV is also active in those with HBeAg antigenemia and that HBV may be retained more in cirrhotic livers with hepatocellular carcinoma after proliferation than in those without it.

Synthesis of secretory protein in regenerating liver of rat after partial hepatectomy.

Abstractu2002 Albumin immunoreactivity in the liver was examined on days 2, 5 and 10 after two‐thirds partial hepatectomy by light and ultrastructural immunoperoxidase methods and the ultrastructural area of the rough endoplasmic reticulum (ER) in hepatocytes was measured. Albumin immunoreactivity was seen in the rough ER and Golgi apparatus of all hepatocytes in the hepatectomized liver and ultrastructural analysis showed a significantly greater area of rough ER on day 5 than on days 2 or 10. Albumin mRNA was studied by the in situ hybridization technique using radioisotopes and their numbers were determined visually. Albumin mRNA was present as grains in all hepatocytes and the grains varied in number during regeneration of the liver, being more abundant on day 5 than on days 2 or 10. The activity of [3H]‐leucine incorporated into albumin synthesis, an indicator of translational activity, was higher on days 5 and 10 than on day 2 and was highest on day 5. In conclusion, albumin synthesis varied during liver regeneration after partial hepatectomy, being reduced at the peak of cell proliferation on day 2 and being most active on day 5.

Mechanisms of α-fetoprotein synthesis in hepatoma cells

SummaryImmunoreaction of α-fetoprotein (AFP) was detected not only in well-differentiated hepatocellular carcinoma but also in hepatocytes forming foci in livers with hyperplastic nodules during 3′-methyl-4-dimethylaminoazobenzene hepatocarcinogenesis. The subcellular location of AFP in hepatoma cells was in the rough endoplasmic reticulum, perinuclear space and well-developed Golgi apparatus around the nucleus. In livers with hyperplastic nodules it was also in some parts of the smooth endoplasmic reticulum and Golgi regions in hepatocytes in the vicinity of submembranous areas or bile canaliculi. These findings suggest that the Golgi apparatus in hepatoma cells acts mainly as an organelle for glycosylation of AFP and that the Golgi complexes in the hepatocytes in livers with hyperplastic nodules are organelles for secretion of AFP.Combined light microscopic immunoperoxidase study and autoradiography with 3H-thymidine revealed a higher cumulative labeling index in AFP-positive hepatoma cells than in non-tumorous areas. Combined electron microscopic immunoperoxidase study and autoradiography showed that hepatoma cells with AFP immunoreactivity only in the rough endoplasmic reticulum had a significantly higher labeling index than did cells with AFP immunoreactivity in both rough endoplasmic reticulum and Golgi apparatus. These findings suggest that AFP is synthesized in hepatoma cells before or during the stage of their DNA synthesis and is then transported to the Golgi apparatus.

Investigation of albumin synthesis in rat livers during the perinatal period using immunocytochemistry andin situ hybridization

The immunoreactivity of albumin (ALB) was observed in the hepatocytes of fetal rats on day 18 of gestation, and was especially observable in immature rough endoplasmic reticulum (rER) and Golgi apparatus (GA); by then, a small amount of silver grains of ALB mRNA could already be detected. Just after birth, immunoreactivity of ALB could be observed in fine granules or diffusely in all hepatocytes, and was present in rER and GA. One week after birth immunoreactivity of ALB was observed in all hepatocytes and was visible in developed rER and GA; the grains of ALB mRNA were present in all hepatocytes.

Histiocytosis X with marked jaundice.

症例は20歳,女性.18歳時に尿崩症と診断され,2年間vasopressin治療をうけていた.食思不振,全身倦怠,黄疸および高熱が出現したため入院した.現症では,皮膚・結膜の黄染と肝腫大とを認め,検査成績では,貧血と著明な肝胆道系酵素の上昇を認めた.腹腔鏡では,白斑が禰漫性にみられ,肝生検組織では,門脈域に組織球様細胞の増生所見が観察された.組織球様細胞の免疫組織化学的検索では,S蛋白染色が陽性であり,リゾチーム染色は陰性であった.超微形態的には,組織球様細胞内にBirbeck顆粒を認め,Histiocytosis Xと考えられた.Vinblastine投与により,尿崩症の改善,黄疸の軽減,肝機能検査の著明な改善が得られ,臨床経過,治療効果ならびに形態学的特徴より,本例を肝臓を主病変としたHistiocytosis Xと診断した.