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Biomedical subjects

G Ohta

Publications and source records attributed to G Ohta.

At least 37 records · Page 2Linked to original sources

Histological changes of bile duct in experimental graft-versus-disease across minor histocompatibility barriers. III. Immunoelectron microscopic observations.

Graft-versus-host disease (GVHD) was produced by injecting lymphoid cells from B10.D2 mice into BALB/C mice. Both are H-2-identical but differ only at multiple minor H loci. The expression and localization of MHC class II antigens on the bile duct epithelium was examined using an immunoelectron microscopical method. All GVHD mice developed bile duct lesions of chronic nonsuppurative cholangitis and expressed MHC class II antigens on their bile duct epithelium, while none of the control mice, which injected with the same number of syngeneic lymphocytes, developed bile duct lesions or expressed the antigens. The antigenic expression was characteristically localized on the basolateral surface of the bile duct epithelium but not on the apical surface. Furthermore, the expression varied markedly in its intensity and distribution within the same liver and even within a single bile duct. The infiltration of Lyt-1-positive helper/inducer lymphocytes in the duct epithelial layer apparent by electron microscopy was predominant to a much degree than that of Lyt-2-positive cytotoxic/suppressor lymphocytes and non-lymphocytic cells. The immunological mechanisms involving helper/inducer T cells in association with MHC class II antigens on bile duct epithelium may be important in the induction and progression of the bile duct lesions apparent in the present GVHD model.

Animals↗

An autopsy case of idiopathic enlargement of the right atrium, and a review of the literature.

A 69-year-old man in whom idiopathic enlargement of the right atrium was revealed at autopsy is described. The patient had had cardiomegaly of at least 19 years' duration prior to his death, even though cardiac symptoms were absent. Cause of death was pancreatic carcinoma. Postmortem examination revealed marked and diffuse dilatation of the right atrium and moderate dilatation of the left atrium. Measurement of the cardiac chambers showed that the right and left atria were 7.6 and 4.7 times as large as those of normal hearts, respectively. The volume of either ventricle was about twice the normal value. Histologically, widespread cardiac muscular degeneration and necrosis, diffuse fibrosis, and focal lymphocytic infiltration were found in the right atrium and also, to a lesser degree, in the left atrium. Such pathologic changes were not found in either of the ventricles. The etiology of these muscular changes, which might have been related to atrial enlargement, was unclear. The present case was thought to be consistent with idiopathic enlargement of the right atrium, and a brief review of the literature is given.

Age Factors↗

Primary pulmonary artery sarcoma. Report of two autopsy cases studied by immunohistochemistry and electron microscopy, and review of 110 cases reported in the literature.

Two cases of primary pulmonary artery sarcoma are reported. The patient in the first case was a 61-year-old male with a two-year history of cough and exertional dyspnea, who died of intractable cardiac failure two months after admission without establishment of a diagnosis related to the etiology of cardiac failure. Autopsy revealed a sessile tumor within the pulmonary trunk and a solitary metastatic lesion in the lung. Histologic, immunohistochemical and electron microscopic studies were performed and a diagnosis of malignant mesenchymoma was made. The patient in the second case was a 32-year-old male complaining of exertional dyspnea and back pain. Radiologic studies indicated a mediastinal tumor involving the pulmonary artery. Exploratory thoracotomy revealed that the mediastinal mass arose from the left pulmonary artery. He died of respiratory failure 26 months after onset of his initial symptoms. Histologic, immunocytochemical and electron microscopic studies of both surgical and autopsy materials revealed a malignant fibrous histiocytoma. One hundred ten previously reported cases of this tumor are reviewed, and its clinicopathologic and morphologic features and probable histogenesis are discussed.

Adult↗

Nonsyndromatic paucity of intrahepatic bile ducts in congenital syphilis. A case report.

The first case of nonsyndromatic paucity of the intrahepatic bile ducts is reported in congenital syphilis. The patient, a 2-week-old female, was born at the 31st week of gestation, weighing 1,910 g. She had a high titer of IgM antibody to Treponema pallidum and sera from both parents also showed a positive reaction in the hemagglutination test for Treponema pallidum. The patient had hepatosplenomegaly and increasing jaundice, and died of respiratory failure on the 70th hospital day. Autopsy examination revealed paucity of the intrahepatic bile ducts, prominent giant cell transformation of hepatocytes, cholestasis and extramedullary hematopoiesis of the liver. The ratio of the number of intrahepatic bile ducts to that of the portal tracts was approximately 0.2:1. There was marked proliferation of atypical bile ductules at the margin of the portal tracts. The exact relation of this paucity to Treponema pallidum remains unknown.

Autopsy↗

Histological changes of bile duct in experimental graft-versus-host disease across minor histocompatibility barriers. II. Electron microscopic observations.

Electron microscopic features of intrahepatic bile ducts of experimental mouse graft-versus-host disease (GVHD) across minor histocompatibility barriers were studied for 14 months after transplantation. In GVHD mice, the bile duct epithelial layer was consistently infiltrated by lymphoid cells and often accompanied by polymorphonuclear leukocytes, monocytes and rarely by plasma cells. The epithelial cells in close contact with and in the vicinity of these infiltrated cells showed a variety of degenerative changes, including darkness of the cytoplasm and the nucleus with shrunken, irregular contours, increase in the amount of endoplasmic reticulum and number of mitochondria, and formation of intracytoplasmic vesicles and diverticula, cytoplasmic blebs, and apoptopic bodies. Lymphocytes were in close contact with epithelial cells through a number of point-contacts and located in the lateral intercellular spaces and/or between the basement membranes and the epithelial cells. The localization of infiltrating lymphocytes beneath the epithelial cells with conspicuous detachment from the basement membranes strongly suggested a link with subsequent epithelial cell injury and death. The lymphoid cells had irregular cytoplasmic projections which occasionally extended into spaces created by retractions of the epithelial cell membranes, reflecting an activation of the lymphocytes. These findings support the notion that the bile duct lesions in GVHD across minor histocompatibility barriers are mediated by specifically sensitized lymphocytes against epithelial cell membrane antigens. From our previous finding that a large majority of the infiltrating lymphocytes had a phenotype of helper/inducer T cells, a putative role of these lymphocytes in the induction of the bile duct lesions is discussed.

Animals↗

Simultaneous detection of epidermal growth factor receptor (EGF-R), epidermal growth factor (EGF) and ras p21 in cholangiocarcinoma by an immunocytochemical method.

Expression of the epidermal growth factor (EGF), EGF receptor (EGF-R) and ras oncogene product p21 was simultaneously examined in 37 cases with intrahepatic cholangiocarcinoma (CC) by means of an immunocytochemical method. While normal livers were all negative for any of the antigens at the concentration of the antibodies used, EGF-R was positive in 12 (32.4%) CCs, EGF in 22 (59.5%), and ras p21 in 33 (89.2%). The positive incidence of the three antigens was not different among the histologic subtypes of the tumor. However, the number of EGF-R- and ras p21-positive tumor cells decreased with progressing histologic tumor grade, but the expression of EGF was not associated with the tumor grade. Expression of the three antigens was not related to the degree of metastatic spread of the tumor. Simultaneous expression of the three antigens was seen only in 4 CCs, and that of EGF-R and EGF in 4, EGF-R and ras p21 in 12, and EGF and ras p21 in 20. These data suggest that the expression of EGF, EGF-R and ras p21 on CC cells is not related to the tumor aggressiveness, and the activation of each respective gene is independent. Furthermore, the data also indicate that an autocrine model for tumor growth, as suggested by a combination of EGF and EGF-R, may be applicable only to very limited cases of CCs.

Adenoma, Bile Duct↗

Pathology of hepatolithiasis associated with biliary malformation in Japan.

A national survey of the morphologic features of hepatolithiasis in Japan disclosed that 13 (4.8%) of the 273 cases examined were associated with obvious biliary malformations: Caroli's disease with congenital hepatic fibrosis (one case), adult polycystic disease of the liver and kidneys (one case), choledochal cyst (nine cases), and anomalous pancreaticobiliary ductal union (four cases). The latter two malformations overlapped in two cases. Intrahepatic calculi in all of these cases were of brown pigment stones, suggesting that focal bile stasis as well as bacterial infection might have played an important role in their formation and growth. It seems likely that such phenomena occur in the congenitally dilated segments of the intrahepatic biliary tree. These data imply that biliary malformation is one of the lithogenic factors in hepatolithiasis in Japan.

Adult↗

Production of lymphokines by HBsAg-reactive human T cell clones upon antigenic stimulation.

The production of lymphokines by human HBsAg-reactive T cell clones was examined. The five clones were successfully obtained from an HBV-vaccinated person and were composed exclusively of Leu 1+, Leu 2a, Leu 3a+, helper/inducer T cells. Three of the five showed significant levels of gamma interferon (IFN-gamma) production and all of the five produced B cell growth factor (BCGF) by stimulation with HBsAg but not with unrelated antigens, including influenza A virus antigens and PPD, whereas no detectable amount of interleukin-2 was found in all clone supernatants. The magnitude of HBsAg-induced cell proliferation did not parallel the levels of IFN-gamma production among the clones. These results indicate from the view of lymphokine production that the HBsAg-reactive helper/inducer T cell clones were heterogeneous even from a source of the peripheral blood sample, and further suggest that the clones play important roles in the immune reaction against HBV infection by producing lymphokines upon antigenic stimulation.

Clone Cells↗

Human T cell clones reactive with hepatitis B virus (HBV) surface antigen from a HBV vaccine recipient.

Five T-cell clones reactive with HBsAg were obtained from peripheral blood lymphocytes of a HBV vaccine recipient by means of in vitro stimulation of lymphocytes for 5 days by HBsAg and subsequent re-culture of lymphocytes with HBsAg, feeder cells and T cell growth factor (TCGF) for 6 days, followed by the limiting dilution method. Clones, and subclones derived from one original clone showed a specific proliferative response to HBsAg in the presence of autologous feeder cells but not to unrelated antigens, such as influenza virus antigens, herpes simplex antigens, toxoplasma antigens, and PPD. All clones were found to have a surface marker of helper/inducer phenotype, Leu 1+, Leu 2a-, and Leu 3a+, detected by an indirect immunofluorescence method. These clones, however, did not show a substantial helper effect for in vitro anti-HBs production by autologous B cells. This suggests that the mechanism of the helper effect by specific T-cell clones is implicated, and functions of such clones other than specific helper effect on antibody-producing B cells must be considered.

B-Lymphocytes↗

Histological changes of bile duct in experimental graft-versus-host disease across minor histocompatibility barriers. I. Light microscopic and immunocytochemical observations.

Graft-versus-host disease (GVHD) across minor histocompatibility antigens was developed in mice and the bile duct lesions were surveyed for up to 7.5 months after spleen and bone marrow cell transplantation. Lymphoid cell infiltration was evident by day 3, reached maximum at 2 weeks, then reduced gradually and persisted during the observation period. Fibrous expansion of the portal tracts paralleled with the time after transplantation, but none of the cases progressed into liver cirrhosis. The infiltrates abutted the interlobular and septal bile ducts and distorted their appearance with a frequent infiltration of mononuclear lymphoid cells into the duct epithelial layer. The duct epithelium showed a variety of degenerative and hyperplastic changes, including nuclear enlargement with anisonucleosis, nuclear pyknosis, cytoplasmic and nuclear darkness, cytoplasmic vacuolization, focal epithelial dropout, formation of apoptotic bodies, and micropapillary infolding. Disappearance of the bile ducts and formation of granuloma around the bile ducts were not seen. Immunocytochemical study revealed the exclusive preponderance of helper/inducer T cells in the portal infiltrates and marked expression of I-A antigen on the bile duct epithelium in GVHD mice. These results suggest that immunological mechanisms by helper/inducer T cells against minor histocompatibility antigen on bile duct epithelium in association with class II molecules of MHC are important in the pathogenesis of the bile duct lesions. A putative role of such lymphocytes is discussed.

Animals↗

Primary trabecular carcinoid of the ovary.

A case of primary trabecular carcinoid of the ovary apparently occurring from the foregut element of a mature cystic teratoma was reported. The tumor was found incidentally and resected surgically from a 56-year-old female. The cystic teratoma found in the tumor was composed of only respiratory epithelium except a colliculus which showed a picture of tonsil-like tissue. No thyroid tissue was found. The trabeculae of the tumor cells were longer and wavier near the cystic teratoma, while they were straight and short at the periphery. The tumor cells had argyrophil granules but negative in argentaffin granules. The electronmicroscopy revealed many round neurosecretory granules measuring from 170 to 290 nm in diameter. The histogenesis was also discussed.

Carcinoid Tumor↗

Liver injury with perivenular fibrosis and alcoholic hyalin after pancreatoduodenectomy for pancreatic carcinoma.

We describe a patient who developed progressive hepatic failure one year after pancreatoduodenectomy for pancreatic carcinoma and died of gastrointestinal bleeding. He suffered from progressive weight loss after surgery, even though obstruction or stenosis of the gastrointestinal tract was excluded. At autopsy, the liver showed extensive perivenular fibrosis associated with variable loss of hepatocytes, perisinusoidal fibrosis, alcoholic hyalin and a lack of parenchymal regenerative activity, all of which closely resembled severe alcoholic liver disease. Stricture of both the main pancreatic duct and the pancreaticojejunostomy with almost complete loss of exocrine acini was also found, and the recurrent tumor was seen to have caused portal venous obstruction and hepatic arterial stenosis. A combination of these nutritionally unfavorable circumstances and prolonged ischemia appeared to have been responsible for the liver injury in this non-alcoholic patient.

Autopsy↗

Glandular elements around the intrahepatic bile ducts in man; their morphology and distribution in normal livers.

The morphology and distribution of the glandular elements around the intrahepatic bile ducts, hitherto poorly described, were examined in autopsied human livers with the aid of postmortem cholangiographs. The glands could be divided into intramural and extramural. The former were small in number, scattered within the bile duct walls, and were simple tubular mucous glands. The latter were more abundant, located in the periductal connective tissue, and were branched tubuloalveolar seromucous glands. Serial section observations revealed that neither gland communicated with the hepatic parenchyma, and the extramural glands drained into the large bile duct lumina via the conduits. The mucous cells of both glands contained neutral, carboxylated and sulfated glycoproteins. The extramural glands were distributed from the hepatic to the segment ducts in almost all livers, and were also discerned around the area ducts in two-fifths of the livers. The glands seemed to decrease in number as the bile ducts became more branched.

Aged↗

Immunohistochemical localization of ras p21 and carcinoembryonic antigens (CEA) in cholangiocarcinoma.

An expression of ras p21 proteins on cholangiocarcinoma (CC) (intrahepatic bile duct carcinoma) cells was examined by an immunoperoxidase method using an appropriate dilution of mouse monoclonal antibody RAP-5, with which no positive staining was obtained in livers with normal histology. Of 44 CCs examined 39 were positive for the antigens; well-differentiated adenocarcinoma usually showed a diffuse weak, cytoplasmic staining in nearly all tumor cells with the same staining intensity, while in moderately and poorly differentiated adenocarcinoma the expression of p21 varied markedly in intensity from cell to cell in the same cell nest. The number of positive cells decreased with the grade of tumor, and no or little staining was observed in undifferentiated areas. These findings indicate that the expression of ras p21 antigens was lost with increasing dedifferentiation of tumor cells. Carcinoembryonic antigens (CEA) were positive in 42 of 44 CCS. Well-differentiated adenocarcinoma expressed CEA along the apical surfaces of the tumor glands. With the dedifferentiation of tumor cells, the expression of CEA became prominent not only at the apical surfaces but also on the basolateral surfaces and in the cytoplasms, and further in the surrounding stromal tissue. There was no clear-cut correlation between the expression of p21 antigens and the production of CEA in CCs.

Adenoma, Bile Duct↗

Immunohistochemical detection of ras oncogene p21 product in liver cirrhosis and hepatocellular carcinoma.

Expression of the ras oncogene p21 product by hepatocytes of cirrhotic liver with hepatocellular carcinoma (HCC) was examined immunohistochemically using mouse monoclonal antibody RAP-5. At the concentration of antibody used, histologically normal liver tissues were negative for p21 antigen, whereas hepatocytes of cirrhotic nodules from 80 of 92 HCC patients (87.4%), and 10 of 32 patients without HCC (59.4%) were positive. This difference was statistically significant (p less than 0.05). The incidence of p21 expression by hepatocytes was significantly higher in macronodular cirrhotic patients than in those with micronodular cirrhosis (p less than 0.05) and tended to be higher in those positive for hepatic hepatitis B virus markers than in those that were negative (p less than 0.1). All 16 patients with liver cell dysplasia, and 17 of 18 with adenomatous hyperplasias showed increased expression of p21 antigen. In HCC it was detected on tumor cells of 63 of 101 patients (62.4%). Characteristically, its expression in well-differentiated HCC was mild and uniformly diffuse, and in moderately differentiated tumors was markedly heterogeneous in both intensity and distribution, whereas no expression was observed in cells of poorly differentiated HCC. These observations suggest that elevated ras p21 antigen expression is important in the development of both cirrhotic nodules and HCC, but that after tumor development, its sustained elevation is no longer necessary for cell proliferation and progression through the grades of anaplasia.

Antibodies, Monoclonal↗