[Clinico-epidemiological study on obesity in relation to mortality figures. Twenty years follow-up results in Hisayama study].
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Biomedical subjects
Publications and source records attributed to T Shikata.
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The activities of serum acid ribonuclease (RNase) were determined in patients with malignant neoplasm or with renal failure. The levels were markedly increased in myelogenous leukemia and renal failure, and only slightly increased in solid cancers, lymphoid malignancies and multiple myeloma. These increases correlated significantly with serum LDH activity in myelogenous leukemia and with creatinine levels in other malignancies or renal failure. The acid RNase content of granulocytes was 22.7-fold higher than that of lymphocytes. The increase of serum acid RNase may suggest an increased granulocyte destruction in myelogenous leukemia and a reduced glomerular filtration in other malignant neoplasms and renal failure.
The following is a clinicopathologic analysis of 57 hepatectomy cases of hepatocellular carcinoma (HCC). The rates of complication from precirrhosis and cirrhosis were 33.3% each. Cirrhosis seemed to have preceded HCC in 13 cases (39.4%) and both diseases appeared to have developed simultaneously in 18 cases (54.5%). Growth patterns of HCC were related to histologic features of livers bearing HCC: HCCs occurring in normal livers were significantly larger in average tumor size than those occurring in cirrhotic livers (9.2 as compared to 4.7 cm) and tended to exhibit a microtrabecular growth pattern (83% of the cases), while HCCs occurring in cirrhotic livers were most commonly macrotrabecular (67%). The factors most significantly influencing survival were the smallness of removed liver and tumor, histologic grades, the presence of bile production, and the absence of satellite tumors and giant cells. The positivity rates of serum hepatitis B virus (HBV) surface antigen averaged 47.2% and the relation of HCC to the role of HBV in the pathogenesis of HCC was discussed.
The protective efficacy of a hepatitis B vaccine against infections from transfusions of large volumes of highly infective blood in five immunized chimpanzees was assessed. Hepatitis B surface antigen (HBsAg) became positive and antibody to HBsAg (anti-HBs) disappeared soon after transfusion in the five chimpanzees. Two chimpanzees that had HBsAg only on the day of transfusion did not develop infection. However, the remaining three chimpanzees with persistent HBsAg antigenemia for three to four days developed serologic evidence of infection. Two chimpanzees did not have hepatitis and the third had a mild, transient case of acute hepatitis. The hepatitis B vaccine prevented the four immunized chimpanzees from developing illness. The remaining chimpanzee developed hepatitis, but a rapid booster response of anti-HBs owing to the previous vaccination appeared to lighten the severity of the disease and prevent chronicity.
Detection of T4 and T3 in paraffin sections of the rat thyroid gland in various functional states was attempted by an immunoenzyme technique. Both hormones showed a similar localization, being detected mainly in the colloid in the follicular lumen, and sometimes in certain regions of the cytoplasm of the follicular epithelium. Following administration of TSH, their stainability was increased, and the localization within the cytoplasm became more remarkable. Decrease or disappearance of stainability was observed after hypophysectomy or administration of PTU. These findings support the view that the immunostainability of T4 and T3 is closely correlated with the functional state of the thyroid gland.
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A case of a chimpanzee with fulminant hepatitis caused by spontaneous hepatitis A virus (HAV) infection was reported. The liver at autopsy revealed massive liver cell necrosis with mononuclear and polymorphonuclear cell infiltration. Aggregation of HAV-like particles (22-25 nm in diameter) were found within the vesicles of hepatocytes under the electron microscope. Immunofluorescent examination of the liver showed positive staining for HAV antigen, C1q, C3, C4, immunoglobulin M (IgM), and immunoglobulin G (IgG) in the hepatocytes and/or Kupffer cells in a granular fashion. The anti-HAV antibody (IgM type) and circulating immune complexes were detected in the postmortem serum. The present study suggests the possibility that the deposition of immune complexes of HAV and anti-HAV antibody in the liver cell plays an important role in the pathogenesis of massive liver cell necrosis in fulminant type A viral hepatitis.
Cryostat sections of the liver representing fulminant B-viral hepatitis were investigated with antisera against human immunoglobulin G(IgG), immunoglobulin M(IgM), C3, C4, C1q, hepatitis B surface antigen (HBsAg), and T-lymphocytes using the immunofluorescence and immunoperoxidase techniques. The liver showed positive staining for IgG, IgM, C3, C4, C1q, and HBsAg in the viable and necrotic hepatocytes and Kupffer cells in a granular fashion. Furthermore, the cell membrane of lymphocytes present in the liver were positively stained with anti T-lymphocyte sera. The numbers of T-lymphocytes recognized were predominant both in portal tracts and within hepatic lobules over those of non-T-lymphocytes. It suggests that perhaps some of the end results of fulminant hepatitis inflammatory reactions may be mediated in part by T-lymphocytes.
For the first time, hepatitis A viral antigen (HAAg) was shown in liver biopsy tissue from a patient in the acute phase of hepatitis type A by light and electron microscopy, using the peroxidase-antibody technique. Under light microscopy, the staining for HAAg appeared as a fine, granular reaction product, scattered throughout the cytoplasm of hepatocytes and sinusoidal lining cells. Standard thin-section electron microscopy revealed virus-like particles, 24 to 27 nm in diameter, in cytoplasmic vesicles of hepatocytes and Kupffer cells. By immunoperoxidase electron microscopy, HAAg was detected on particles aggregated within cytoplasmic vesicles of hepatocytes, thus demonstrating that the virus-like particles (24 to 27 nm) are hepatitis A virus. The surrounding membrane of the vesicles was also positive for HAAg. The distribution patterns of HAAg in human liver were virtually identical to those described for experimentally infected marmosets. It is notable that most HAAg was detected within vesicles of liver cell cytoplasm, suggesting the possibility of vesicle-oriented morphogenesis of hepatitis A virus.
The occurrence of alpha-fetoprotein (AFP)-containing hepatocytes in 12 human embryos and fetuses ranging from 30-32 days of estimated ovulation age (Streeter's horizon XIV) to 16-17 weeks of estimated menstrual age was investigated using the direct (horseradish peroxidase (HRP)-labeled anti-human AFP horse IgG(Fab')2) and/or indirect immunoperoxidase methods. Under light microscopy, the AFP-containing hepatocytes were successfully demonstrated in paraffin-embedded liver tissues fixed with 4% paraformaldehyde(PFA)-picric acid solution containing 0.5% glutaraldehyde (GA). As a result of the studies of the human fetal livers at different developmental stages, only a small number of AFP-containing hepatocytes were initially identified immunohistochemically at the stage of Streeter's horizon XIX. Ultrastructural immunohistochemistry (the block-staining method using anti-human AFP horse IgG(Fab')2) revealed that the immunoreactive products against AFP were demonstrated on the ribosomal granules of the rough endoplasmic reticulum (rER), outer nuclear envelopes, free ribosomes, and Golgi's apparatus, and also in the cisternal lumina of the ER. No reactive products were noted in the nuclei or mitochondria. Our observations confirmed the presence of AFP-producing ability of the hepatocytes and the ultrastructural localization of the sites of protein synthesis in the early stage of development of human livers. Furthermore, we describe the extreme usefulness of the block-staining method for demonstrating the subcellular localization of AFP using HRP-labeled reduced anti-AFP antisera on liver tissues fixed with 4% PFA-picric acid solution containing 0.5% GA.
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The NIH strains F and H of non-A, non-B hepatitis were studied by transmission to chimpanzees. They developed biochemical and ultrastructural evidences of non-A, non-B hepatitis. Chimpanzee's plasma containing the strain F was passaged further three times in the present study, and the results were identical to the original report made by SHIMIZU et al. In contrast to the original report, however, the prototype strain H inoculum or human plasma supposedly containing only the strain H, induced both SHIMIZU's cytoplasmic and nuclear changes in one chimpanzee. This result may pour further oil on the flame of recent controversy regarding the sequestration of the strains H and F, but we believe at present that the strains H and F are separate infectious agents. This is based on the fact that the strain F never induced SHIMIZU's nuclear changes, and our detection of an additional infectious agent of non-A, non-B hepatitis identical to the NIH strain H. We suspect the NIH strain H inoculum provided to us was contaminated by the strain F. The conclusion of controversy regarding the strain H should await for further studies including a further cross challenge study between the strain H and the strain F. Ultrastructural changes of the chimpanzee's liver associated with non-A, non-B hepatitis are described.
In 97 nontoxic thyroid tumors, detection of thyroxine(T4) and triiodothyronine(T3) was attempted by the immunoperoxidase method. T4 was demonstrated in 58 tumors (59.8%) and T3 in 76 (78.4%). The feasibility of biosynthesis of T4 and T3 by such tumors was thus established. In 65 of the tumors, we applied the immunostaining method to serial or semiserial sections to study the correlation among the localizations of thyroglobulin(Tg), T4, and T3. The localization of T4 agreed relatively well with that of Tg, and part of the Tg-positive structure frequently revealed simultaneous positive staining for T4. The localization of T3, however, did not always correspond with that of T4 or Tg. T4 and T3 with localizations identical to that of Tg may be considered to be bound to Tg, but the mode of existence of T3 without correspondence in localization to Tg remains unknown.
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