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M Yoshimura

Publications and source records attributed to M Yoshimura.

981 records · Page 55Linked to original sources

Effects of enalapril maleate on heart rate variability: a pilot study.

The effects of enalapril maleate on heart rate variability, an indicator of cardiac autonomic function, were evaluated by nonspectral analysis in 12 patients with standard deviation in the R-R interval for each 5-minute period for 24 hours (SDANN) of 80 msec or less. A 24-hour electrocardiogram was recorded before treatment and after 2 weeks of treatment with enalapril. No significant difference was observed in the mean R-R interval on 24-hour electrocardiography between the pretreatment and the posttreatment periods (824 +/- 84 msec vs 834 +/- 83 msec). The SDANN increased significantly (P < 0.01) between the pretreatment period (62.8 +/- 13.7 msec) and the posttreatment period (87.1 +/- 31.2 msec), as did the standard deviation of the R-R interval during the two monitoring periods (P < 0.001). However, no significant difference was observed in the mean value of the standard deviations of the R-R interval for 5 minutes; the proportion of adjacent R-Rs with a difference of more than 50 msec; or the root-mean square of the difference in successive R-Rs in the pretreatment period as compared with the posttreatment period. Causal blood pressure at rest decreased significantly (P < 0.05) after treatment with enalapril (124 +/- 17/66 +/- 7 mmHg) as compared with the pretreatment period (140 +/- 24/75 +/- 13 mmHg). Enalapril may be useful for maintaining normal autonomic nerve activity, preventing sudden cardiac death, and enhancing quality of life in our stressful society.

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Characteristics of the effects of the angiotensin converting enzyme inhibitor cilazapril on diurnal blood pressure.

Patients with stage I or II essential hypertension were assigned to receive 1 mg of cilazapril once daily in the morning (n = 11; mean age, 63 years); 2 mg of cilazapril once daily in the morning (n = 8; mean age, 60 years); or 1 mg of cilazapril twice daily (n = 9; mean age, 68 years). Blood pressure was recorded for 24 hours before treatment began and after 2 weeks of treatment. After all three doses of cilazapril, both systolic and diastolic blood pressures were lower than before treatment. Greater reductions in blood pressure were found after 2 mg of cilazapril daily than 1 mg daily. The antihypertensive effect of cilazapril was greater during the daytime than during the night. When the blood pressure effect was analyzed by the cumulative percentage method, it was noted that, after the two once-daily regimens, the magnitude of the blood pressure reduction was greater at higher blood pressures and smaller at lower blood pressures. No such trend was apparent after the twice-daily dose of cilazapril.

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Marked induction of HSP47, a collagen-binding stress protein, during solid tumor formation of ascitic Sarcoma 180 in vivo.

HSP47, a heat shock-inducible glycoprotein of Mr = 47,000, is assumed to be a molecular chaperone specific for collagen. In addition to its stress inducibility, HSP47 has transformation-sensitivity; that is, the synthesis of HSP47 decreases after malignant transformation. We developed a rat monoclonal antibody against mouse HSP47, which we then used to examine the amounts of HSP47 in transplanted tumors. HSC70 (HSP73) was expressed constitutively in these ascites as well as solid tumors. While HSP47 was not expressed in ascitic form of Sarcoma 180, its expression was markedly induced during solid tumor formation of ascitic Sarcoma 180 cells after subcutaneous transplantation. The average survival period of ascites Sarcoma 180-bearing mice was 20.3 +/- 3.6 days (mean +/- SD), and was much shorter than that of solid Sarcoma 180-bearing mice. These findings suggest an important role of HSP47 in solid tumor formation as well as a possible marker for tumor malignancy.

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Inhibition of HSP47 during the transition from solid to ascitic form of Sarcoma 180 in vivo.

HSP47, a collagen-binding stress protein, has transformation-sensitivity; that is, the synthesis of HSP47 decreases after malignant transformation. We examined the expression of HSP47 in transplanted tumours by Western blotting. While HSP47 was not detected in ascites tumours including Ehrlich, P388 and Sarcoma 180, marked expression of HSP47 was observed in solid tumours such as B16, B16-BL6 and Sarcoma 180. The expression of HSP47 in Sarcoma 180 cells disappeared completely after these solid tumour cells were dispersed and inoculated intraperitoneally. These findings suggested an important role of HSP47 as a marker for tumour malignancy.

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Decreased expression of HSP47 in highly malignant mouse fibrosarcoma.

HSP47, a heat shock-inducible glycoprotein of M(r) = 47,000, is assumed to be a molecular chaperone specific for collagen. In addition to its stress inducibility, HSP47 has transformation-sensitivity; that is, the synthesis of HSP47 decreases after malignant transformation. The expression of several HSPs in mouse fibrosarcoma, QRsP-1 and QRsP-4 were examined. HSP47 expression was weaker in the highly malignant QRsP-4 than in the weakly malignant QRsP-1, whilst HSC70 expression was similar in both cell lines. These findings suggested an important role of HSP47 as a marker of tumour malignancy of QRsP cell lines.

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Specific expression of HSP47 in human tumor cell lines in vitro.

HSP47 is a stress-inducible glycoprotein of 47 kd molecular weight, and is assumed to be a collagen specific molecular chaperone. The expression of HSP47 is closely related to that of collagen, which is the main component of the extracellular matrix. We investigated the expression level of HSP47 in human tumor cell lines to elucidate collagen biosynthesis in tumor cells. Western blot analysis showed higher levels of HSP47 in solid tumor cell lines than in leukemia cell lines. Tumor cell lines which were derived from metastatic carcinomas and were still metastatic in animals, synthesized higher levels of HSP47. These results suggested that HSP47 may play an important role in tumor metastasis and can be a prognostic marker for the metastatic activity of human tumor cells.

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Specific expression of HSP27 in human tumor cell lines in vitro.

The cells of all organisms respond to environmental stress by synthesizing a specific group of proteins called heat shock proteins (HSPs). While the protective role of HSPs has been observed against cellular stress, recent reports have suggested a number of functions of HSPs in various cellular processes in normal and pathological conditions. HSP27 is an important low molecular weight HSP (Mr: 27,000) found in human cells. HSP27 appears to be involved in intracellular signaling and drug resistance in addition to thermotolerance. In human breast tumors, a striking association between HSP27 overexpression and a shorter disease-free survival period was reported. In this paper, we evaluated the expression levels of HSP27 in the cell lines of human breast and other tumors. Western blotting of HSP27 has shown the correlation of HSP27 expression and metastasis and tumorigenicity of mammary and prostate tumors. Thus the biological significance of HSP27 in aggressive mammary and prostate tumors was indicated. HSP27 is suggested to be a prognostic marker for the malignancy of mammary and prostate tumors.

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Specific regulation of HSPs in human tumor cell lines by PSK.

Substantial progress has been make in elucidating the biochemical properties of HSPs (Heat Shock Proteins) as molecular chaperones in protein biogenesis and their roles in thermoprotection and cytoprotection against cellular insults. Recently, besides advantageous cellular functions, the detrimental role of HSPs has been implicated in a variety of diseases. HSP47 is assumed to be a collagen specific molecular chaperone and its involvement in the progression of fibrosis was observed. There have been a number of reports that suggest the role of HSP60 as an autoantigen in a variety of autoimmune diseases. PSK, a protein-bound polysaccharide, is a biological response modifier that is clinically used for the treatment of cancer patients in Japan. PSK shows a broad range of biological effects in addition to the antitumor activity. In this study, we evaluated the effect of PSK on the expression of HSPs in human tumor strains at the protein and mRNA levels. PSK was observed to suppress the expression of HSP47 and HSP60 but not HSP72/73 in human tumor cell lines. Thus, the novel pharmacological potential of PSK was suggested in the diseases derived from the aberrant expression of HSPs.

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Specific regulation of HSPs in human tumor cell lines by flavonoids.

While the protective role HSPs (Heat Shock Proteins) has been recognized against physiological stress such as heat shock, heavy metals and glucose starvation, recent progress has revealed another aspect of HSPs in various diseases. HSP27 has been shown to be involved in the acquired resistance of tumor cells hyperthermic and chemotherapeutic treatment. In human breast tumors, overexpression of HSP27 is associated with a shorter disease-free survival period. HSP47 is thought to be a collagen specific molecular chaperone. The involvement of HSP47 in the progression of fibrosis has been reported. Aberrant expression of HSP could cause various autoimmune diseases. Manipulation of HSP expression, therefore, could be a therapeutic target to reduce HSP-derived detrimental cellular effects. Flavonoids are a widely distributed group of plant substances, universally present in vascular plants. Although the flavonoids have been known as natural plant products as long as the alkaloids, their pharmacological effects and potential medicinal uses have been little studied by comparison. Today, the picture has changed and the biological and pharmacological activities of plant flavonoids look promising. We investigated the effect of flavonoids on the expression of HSPs in human tumor cell lines. Flavonoids inhibited the expression of HSP27, HSP47, HSP60 and HSP72/73. The results suggested the pharmacological possibilities of flavonoids in diseases derived from abnormal expression of HSPs.

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