Detection of serum RNA specific for blood-borne non-A, non-B hepatitis.
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Biomedical subjects
Publications and source records attributed to T Tsuji.
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To evaluate the significance of pre-S(2) in the liver, the authors studied the relationship between serum and intrahepatic pre-S(2) in 27 patients with chronic hepatitis B. Intrahepatic expression of pre-S(2) was observed under light and electron microscopy and compared with that of HBsAg and HBcAg. All patients were positive for hepatic pre-S(2), and 25 for serum pre-S(2). Intrahepatic pre-S(2) expression was membranous or both membranous and cytoplasmic in 18 cases and was cytoplasmic in 9. The serum levels of pre-S(2) were significantly higher in cases whose intrahepatic pre-S(2) was membranous than in the cytoplasmic cases. These findings indicate that membranous expression of pre-S(2) reflects its secretion into the circulation. Intrahepatic pre-S(2) expression was found almost completely to resemble that of HBsAg on both light and electron microscopy. Membranous pre-S(2) was seen in the liver of 16 of 25 cases who were positive for intrahepatic HBcAg. In detailed studies of membranous pre-S(2) and HBcAg, both membranous pre-S(2) and HBcAg appeared in the liver of all 7 cases before or at the peak of acute exacerbation, but after it, membranous pre-S(2) was not found in 4 of 8 cases. These results suggest that disappearance of membranous pre-S(2) and HBsAg may be related to hepatic cell necrosis in some cases with acute exacerbation.
A random primed lambda gt11-cDNA library was constructed from donors plasma presumably infected by blood-borne non-A, non-B hepatitis (hepatitis C:HC) agent and immunoscreened with serum pooled from patients with acute or chronic HC. Twelve lambda gt11-cDNA clones were isolated that was shown to encode antigens associated specifically with HC infection in Japan as well as in USA. Of these two, as well as another clone which is specific only to Japanese HC infection, have unique nucleotide sequences and were extensively studied. They are not derived from host DNA and have no homology to the sequences of known human viruses including hepatitis A, B and D viruses, Ebstein-Barr virus, coxsackievirus, immunodeficiency virus type 1 or Japanese encephalitis virus. These results suggest that they are derived from the genome of HC agent(s). In addition, of these, one clone seems to encode epitopes derived from both the core and the surface polypeptides of the agent.
The activity of serum type IV collagen-degrading enzyme was measured in 21 patients with hepatocellular carcinoma, and the changes in the enzyme activity were investigated with respect to metastasis. The activity of serum type IV collagen-degrading enzyme did not increase until tumor invasion to the portal vein and intrahepatic metastasis were clearly detected ultrasonographically. Activities did not increase during the observation period in patients whose tumor grew slowly and did not invade the portal vein. Thus, the enzyme activity increases in relation to the metastasis of hepatocellular carcinoma and may be useful to detect ongoing metastases.
Adult rat hepatocytes formed floating multicellular spheroids in primary culture in an uncoated plastic dish with a positively charged surface. Cells in the spheroids formed in such a simple way were similar to those formed in dishes coated with proteoglycan fraction isolated from rat liver reticulin fibers; in both cases, cells maintained high ability to produce albumin and poor ability to proliferate in response to epidermal growth factor. Coating dishes with albumin was also helpful in spheroid formation; coating with 2-hydroxymethyl methacrylate resulted in formation of incomplete spheroids. Elimination of serum factors was essential for the formation of spheroids; when cells were washed with serum-containing medium before seeding or if the medium was replaced with a serum-containing medium, spheroid formation was completely inhibited. Collagens, fibronectin, and laminin, all of which promote the adhesion and spreading of hepatocytes on substrates, inhibited spheroid formation. Furthermore, collagens disintegrated spheroids, and cells in the monolayer initiated proliferation. Thus, two distinct, mutually exclusive features of primary culture of adult hepatocytes apparently exist; monolayer culture with proliferative activity in an adherent environment and spheroid culture with poor proliferative activity and high albumin-producing ability in a nonadherent environment.
The hepatocellular expression of the carbohydrate antigen sialyl monomeric Lewis X (SMLex) and sialyl oligomeric Lewis X(SOLex) in chronic hepatitis was examined using specific monoclonal antibodies. Both of these sialyl Lewis X (SLex) antigens were membranously expressed in chronic hepatitis in spite of their absence in normal liver. Although SMLex was detected in mild hepatic inflammation, the expression of SOLex was associated only with moderate to severe necroinflammation. Hepatocellular expression of these antigens increased significantly as histological diagnosis advanced. Chronological observation also showed the change of SLex expression according to the histological change. The present observations suggest that hepatocellular SLex is a novel histological marker with a close correlation to the severity of necroinflammation in chronic hepatitis.
We have previously reported that the heat-labile enterotoxin (LTc) isolated from a chicken enterotoxigenic Escherichia coli (ETEC) was identical to LTh produced by human ETEC (Tsuji et al. (1988) FEMS Microbiol Lett. 52, 79-84). In this study, we purified an LTc-like toxin (LTc') from another strain isolated from a chicken that developed diarrhea at a different place and time to the previously reported chicken. Its molecular weight and antigenicity were compared with those of purified LTs from porcine and human ETEC (LTp and LTh). The A subunit of LTc' was identical to those of the purified LTs in mobility on SDS-polyacrylamide gel electrophoresis. The Ouchterlony test demonstrated that LTc' was antigenically identical to LTp. The isoelectric point and amino acid composition of LTc' were also identical to those of LTp. These data suggest that chicken ETEC can be grouped with both the porcine and human types on the basis of the LTs produced.
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Masking protein (MP), which neutralizes the activity of transforming growth factor type beta 1 (TGF-beta 1), is composed of a dimeric N-terminal part of a TGF-beta 1 precursor of Mr 39,000 and an unknown large subunit of Mr 105,000-120,000. The deduced primary structure of the MP large subunit was elucidated by determining the nucleotide sequence of its cDNA. The cDNA encodes a prepro-precursor of 1712 amino acid residues with a calculated Mr of 186,596. The mature large subunit seems to be derived proteolytically from a prepro-precursor and the calculated Mr is 91,606. The precursor has seven N-linked glycosylation sites and an unusual structure containing 18 epidermal growth factor-like domains and four cysteine-rich internal repeats. The large subunit mRNA is synthesized in parallel with the expression of TGF-beta 1 mRNA in various rat tissues.
A patient with diabetes mellitus who developed the typical classic lesions of Kaposi's sarcoma is described. Our patient presented with a reddish-purple papulonodular lesion on the right foot of five months' duration. A skin biopsy specimen showed a proliferation of spindle cells forming numerous vascular slits and a diffuse extravasation of erythrocytes. The patient's sera was negative for human immunodeficiency virus (HIV) antibodies and cytomegalovirus (CMV) antibodies. Ultrastructural examination demonstrated fibroblast-like spindle cells phagocytosing and digesting red blood cells to form vascular spaces. The patient died, due to gastrointestinal hemorrhage, and the autopsy revealed an extensive visceral involvement of Kaposi's sarcoma.
Twenty patients with severe psoriasis were treated with the oral administration of 5 mg/kg/day of cyclosporin A (CyA) for 12 weeks. These patients had either failed to respond to or had become unresponsive to conventional treatments including PUVA, UVB, or combinations of etretinate and PUVA or UVB. Complete clearance and marked improvement were observed in 12 (60%) and 4 patients (20%), respectively. The average score of the Psoriasis Area and Severity Index (PASI) was 26.2 before treatment, decreasing to 18.3 in 2 weeks, 8.2 in 6 weeks, and 5.1 in 12 weeks of CyA treatment. There was a tendency for patients with lower blood levels of CyA to show smaller decreases in their PASI scores. In four patients who received skin biopsies, histological improvement was noted within 10 days of treatment; epidermal thickness had decreased by 32%, intraepidermal mitoses by 66%, and parakeratosis had disappeared almost completely. No clinical side effects or alterations in laboratory values were observed that required cessation of CyA. Exacerbations of psoriasis occurred in 11 of 16 patients within 6 weeks after stopping treatment. These results suggest that CyA could be the first choice of treatment for resistant severe psoriasis.
Three patients with subungual exostoses, two involving the great toe and one the fourth toe, are presented. Local excision was performed, and the specimens were processed for light and electron microscopy. Light-microscopic study revealed that the tumours consisted of a proliferative fibrocartilaginous cap that merged into mature trabecular bone at its base. Electron-microscopic examination revealed that the tumour was composed of two types of cells: one was rich in cell organelles including rough endoplasmic reticulum, well-developed Golgi apparatus, and glycogen granules; the other cell had few such cell organelles. The former cells seemed to be osteoblasts actively engaged in bone formation, and the latter to be osteocytes related to those situated deeper in bone matrix in normal bone. However, ossification or calcification in subungual exostosis is rather casual, and osteocytes in this disorder may lack the capacity to elaborate compact bone.
Eighty-two patients with sporadic acute viral hepatitis were detected at Okayama University Hospital between January 1982 and March 1989. Thirty of them had non-A, non-B hepatitis (NANBH); 20 had hepatitis A (HA); and 32 had hepatitis B (HB). Ten (33%) of NANBH, five (25%) of HA, and nine (28%) cases of HB were hospital employees. Two (20%) of 10 hospital employees with NANBH developed chronic hepatitis. Antibody to hepatitis C virus (anti-HCV, ELISA) was tested in 10 patients with NANBH (five hospital and five non-hospital employees). Forty percent of both hospital and non-hospital employees had anti-HCV. The percentage of hospital employees among patients with NANBH was similar to that of those among patients with HB. Therefore, it appears that NANBH as a disease entity may be a source of a significant occupational hazard in personnel who either examine or care for patients with hepatitis.
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Preventional and reversal effects of a new aldose reductase inhibitor FR74366 on the rat galactose cataract were examined biochemically and light microscopically. A high concentration (0.075%) FR74366 showed sufficient effects both to prevent and reverse cataract, but low concentrations (0.025%) FR74366 was not effective as 0.075% FR74366. These results indicate that FR74366 can be useful drug for cataract.
In cases of herpes simplex encephalitis, a low density lesion in the temporal lobe is a common CT finding, whereas hemorrhagic lesion is rarely observed on CT in this disorder despite the frequent occurrence on pathologic studies. Two cases of hemorrhagic lesion observed on CT in herpes simplex encephalitis are reported, and atypical CT findings of herpes simplex encephalitis is discussed.
A case of renal pelvic transitional cell carcinoma accompanied by an adeno-squamous carcinoma component in a horseshoe kidney is reported. This case is the first case reported in Japan to the best of our knowledge.