Biomedical subjects
Publications and source records attributed to S Hashimoto.
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In a 73-year-old man with acute myelomonocytic leukemia (M4 on FAB classification) Auer rods were demonstrated in mature granulocytes and monocytes in the blood as well as the bone marrow. Cytochemically, a significant number of leukemic blasts were positive for both alpha-naphthyl-acetate esterase and naphthol-AS-D-chloroacetate esterase. Auer rods in mature granulocytes were associated with immature cytoplasm and not infrequently with pseudo-Pelger anomaly. The significance of these observations is discussed.
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The purpose of this study was to determine the immunoreactivity of myocardial actin filaments with actin antiserum and to examine the significance of its application to diseased human cardiac muscle. The actin was extracted and purified from chicken gizzards. Anti-actin rabbit serum was prepared and purified by affinity chromatography and defined by an immunoblotting test. Using the avidin-biotin-peroxidase complex (ABC) method, the actin antiserum was applied to paraffin sections prepared from hearts taken from routine autopsies of patients who had died of myocardial infarction. Reactivity was shown to be completely lost, not only in necrotized fibers, but also in non-specific degenerative fibers which could be identified by their eosinophilic cytoplasm with pyknotic nuclei, and clearly remaining and/or diminished cross-striations stained with hematoxylin-eosin. In contrast, hypertrophic myocardial fibers adjacent to granulation or scar tissue and those adjacent to infarcted foci exhibited a more intense reaction. These results indicated that the immunohistochemical reaction of actin filaments can be used for the easy detection of very mild degrees of degeneration of cardial muscle fibers, and for hypertrophic fibers adjacent to diseased foci. Studies of the immunoreactivity of actin protein suggestive of alteration at the molecular level might yield morphological clues regarding the nature of functional activity in the contraction of cardiac fibers.
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We found a new thrombophilic tendency in a family with protein S deficiency. The propositus, a 38-year-old Japanese man, is an offspring of consanguineous marriage and suffered from recurrent episodes of thromboembolism. Hemostatic studies, including platelet counts, platelet aggregation, assays of coagulation factors, and plasminogen activity were all within normal limits. The levels of antithrombin III, alpha 2-macroglobulin, protein C, and protein C inhibitor were also normal. However, functional protein S activity in plasma was markedly decreased (9%) in the propositus. The family study revealed that the reduced levels of functional protein S, less than 5% to 29% of normal (normal range: mean +/- 2 SD of 15 normal adults were 44 to 180%), were found in 11 members of this family over three generations. Six of 11 members had severe protein S deficiency (less than 5%), whereas five had partial deficiency. Four of eight adults with protein S deficiency had recurrent episodes of thrombosis. Immunologic levels of protein S antigen were variable in this family and did not correlate closely with the functional levels. These results suggest that the recurrent thrombotic disease in this family appears to be associated with an inherited deficiency of functional protein S.
The relationship between the saccharide chain on the endothelial cell surface and the permeability of intracerebral blood vessels has been studied. In the present study, wheat germ agglutinin (WGA) was perfused into capillaries in the area postrema of the normal Mongolian gerbil, where the blood brain barrier (BBB) is known to lack, and into intracerebral blood vessels, the BBB of which had been destroyed by experimentally induced brain ischemia. The light microscopic features of the sections from WGA-perfused brain tissues of the normal gerbil revealed that most of the blood vessels, including capillaries in the brain parenchyma, showed positive findings (the reaction induced a very distinct staining of the vascular wall) from which the course and structure of the fine vessels could be determined. The reaction to WGA on the diaphragma fenestra (DF) in capillaries in the area postrema was relatively weak, and DF without the reaction were occasionally revealed by electron microscopy. The gerbil, in which cerebral ischemia had been induced, also showed partial defect of the reaction with WGA on the luminal side of the endothelial cells. The results of the present experiment suggest some degree of correlation between the saccharide chains, including the specific monosaccharide of WGA, on the endothelial cell surface and permeability. It was considered that lectin can be used as an index for morphological observations, suggesting an alteration in function of the endothelial cell membrane. In addition, the perfusion method in this experiment suggested the possibility of distinguishing pinocytotic vesicles from pits of cell membranes.
The relationship between endothelial reactivity to Ulex europaeus agglutinin-1 (UEA-1) and the permeability of the vascular wall in human autopsied cases of cerebral infarction was studied. Sections from the cerebral cortex were reacted with horseradish peroxidase UEA-1 to demonstrate the surface membrane of endothelial cells. Albumin in the neuropil of sections was demonstrated for the estimation of increased vascular permeability. The results showed that endothelial reactivity to UEA-1 was reduced in cases where death had occurred 3 to 5 days after onset of cerebral infarction. Reactivity was also diminished in cases where death had occurred after 13 and 25 days; these cases showed fresh ischemic lesions caused by re-attacks of infarction. Albumin extravasation into the neuropil was demonstrated in these intermediate cases. Chronic cases, dying after more than 52 days, showed no reduction of endothelial reactivity to UEA-1 and no albumin extravasation was proved. It was concluded that UEA-1 can be employed as a useful morphological marker for evaluation of endothelial function and vascular permeability.
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For the treatment of patients with early breast cancer, breast conservation surgery with irradiation is gaining world wide acceptance as opposed to more mutilating operations. In Japan, however, most surgeons and radiation oncologists are still unfamiliar with this technique. To achieve optimum functional and cosmetic results, understanding the philosophy and details of the technique is of primary importance. We propose a method of executing the procedures. Tumor excision with a tumor-free margin and breast irradiation with tangential fields are the essential part of the treatment. The entire breast should not receive more than 50 Gy. Limited axillary dissection is used for deciding the indications for chemotherapy, and it is necessary to obtain more than five nodes. Irradiation to the lymph nodes is optional.
The combined effects of X-ray irradiation and 5-FU derivatives (5-FU, tegafur, HCFU) treatment were investigated in mouse adenocarcinoma-755. Mice were given a single irradiation 5 Gy or 10 Gy of 6-MV X-rays and orally administered 5-FU derivatives at the time of pre- or post-irradiation. Under these conditions, antitumor activity and survival time were compared between pre- and post-irradiation. Under these conditions, antitumor activity and survival time were compared between pre- and post-irradiation, in combination with 5-FU, tegafur or HCFU. The antitumor effects and survival time were greater for pre-irradiation treatment than for post-irradiation. Among 5-FU derivatives, the highest combination effect was shown by HCFU, followed by 5-FU and tegafur. The concentration of 5-FU in the tumor was correlated with the antitumor effect of each drug.
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The antihypertensive effect of a new calcium channel blocker (FK 235) were evaluated in 10 patients with mild-to-moderate essential hypertension. The study consisted of 4 weeks of placebo and 12 weeks of the drug, 2 to 4 mg twice a day. Overall systolic and diastolic blood pressures (mean +/- SE) were reduced from 173 +/- 4 to 158 +/- 2 mm Hg (p less than 0.001) and from 97 +/- 2 to 89 +/- 1 mm Hg (p less than 0.001), respectively, with a dose of 5.6 +/- 0.7 mg/day. No relevant changes in heart rate, body weight, and plasma levels of renin activity and aldosterone concentration were observed. No side effects were encountered during the therapy. Our data indicate that the novel active calcium channel blocker can be used as a safe, effective and well tolerated antihypertensive for the treatment of essential hypertension.