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Biomedical subjects

M Tsukamoto

Publications and source records attributed to M Tsukamoto.

At least 91 records · Page 5Linked to original sources
PubMed1995

GSH-independent denitration of organic nitrate esters in rabbit hepatic and vascular cytosol.

The denitration of organic nitrate esters in rabbit hepatic cytosol was characterized. Sephadex G-200 chromatography of ammonium sulfate precipitate (40-80%) from hepatic cytosol demonstrated the presence of two distinct activities (peak I and peak II) responsible for the denitration of nitroglycerin (NTG) and isosorbide dinitrate (ISDN). The denitration of peak I required dithiothreitol (DTT), but not glutathione (GSH), and was not inhibited by S-alkyl GSH, an inhibitor of glutathione S-transferase (GST). Whereas, the denitration activity of peak II was potentiated by GSH, and was inhibited by S-alkyl GSH. These results strongly suggest that the denitration of organic nitrate esters, such as NTG and ISDN, can be catalyzed by at least two enzymes, GSH-independent denitration (peak I) and the GSH-dependent denitration (peak II, GST), in rabbit hepatic cytosol. The denitration activity of peak I was inhibited by SH-modified reagent, indicating that free thiol(s) is (are) critical for expression of the denitration activity. Also, in rabbit vascular cytosol, the cofactor requirement for denitration and response to S-hexyl GSH suggest the participation of GSH-independent enzyme which is responsible for the denitration of organic nitrate esters.

Animals↗
PubMed1994

Adenovirus-mediated transfer of the HST-1 (FGF4) gene induces increased levels of platelet count in vivo.

The HST-1 (fibroblast growth factor 4, FGF4) protein is a potent mitogen for a variety of cell types of mesodermal and neuroectodermal origin, including fibroblasts, endothelial cells, and melanocytes in vitro. To identify the cells and tissue targets of HST-1 in vivo, adenovirus-mediated HST-1 gene transfer was performed. In nude mice, intraperitoneal injection of 3 x 10(9) plaque-forming units of adenoviruses carrying the HST-1 gene (Adex1HST-1L) caused an increase in the number of platelets in the peripheral blood. The number of platelets reached twice the pretreated level by 12 days after the virus injection and the increased level continued up to 20-30 days thereafter. Administration of recombinant HST-1 protein resulted in a transient increase in the platelet count. The number of megakaryocytes in the bone marrow and spleen of the animals with Adex1HST-1L was increased compared with the control animals. Other hematological changes attributed to HST-1 were not observed. Although the mechanisms involved in increased levels of platelet count by HST-1 protein remain to be elucidated, these findings also suggest that adenovirus with the HST-1 gene may be efficiently used for the treatment of thrombocytopenia in various diseases.

Adenoviridae↗
PubMed1994

Anti-annexin V antibody in systemic lupus erythematosus patients with lupus anticoagulant and/or anticardiolipin antibody.

We investigated anti-annexin V antibody (aANX) in patients with systemic lupus erythematosus (SLE), and correlated to positivity with lupus anticoagulant (LA)/anticardiolipin antibody (aCL). aANX was positive in 12/47 SLE patients (26%), including 7 with beta 2-glycoprotein 1 (GPI)-dependent aANX. The positivity of aANX was higher in patients with aCL (19%) and LA/aCL (50%) than in those without LA/aCL (10%). From these results, it is concluded that aANX is an autoantibody closely related to LA/aCL, and can be a possible new risk marker for thrombosis.

Annexin A5↗
PubMed1994

Plasma concentrations of total/free and functional protein S are not decreased in systemic lupus erythematosus patients with lupus anticoagulant and/or antiphospholipid antibodies.

We conducted an investigation to clarify whether or not the levels of total, free, and functional protein S and C4-binding protein (C4bp) in plasma are decreased in systemic lupus erythematosus (SLE) patients, especially those with antiphospholipid antibody (aPL), which is known to be a causative factor of such complications as habitual abortion and arteriovenous thrombosis. Fifty patients with SLE were recruited as subjects of the study. Serum aPL (anticardiolipin, antiphosphatidyl serine, antiphosphatidyl inositol, and antiphosphatidic acid antibodies) were measured by ELISA. Lupus anticoagulant was determined by a PTT, KCT, and diluted RVVT. Furthermore, plasma concentrations of total, free, and functional protein S and C4bp were measured. There were no significant differences in the mean levels of total, free, or functional protein S and C4bp between aPL-positive, aPL-negative SLE patients, and the healthy controls. From these results, we concluded that the protein S level is not the sole factor causing complications, and that other factor(s) may be involved in the induction of such complications in this clinical setting.

Antibodies, Antiphospholipid↗
PubMed1994

A high concentration of glucose alters the production of tPA, uPA and PAI-1 antigens from human mesangial cells.

To elucidate a role of tPA, uPA and PAI-1 for the development of diabetic glomerulosclerosis, the effect of high glucose concentration on the production of both basal and thrombin-mediated tPA, uPA and PAI-1 antigens from human mesangial cells was investigated. The culture of mesangial cells in the presence of high glucose (33 mM) for 11 days resulted in an increase in the synthesis of tPA and uPA when compared with that in normal glucose concentration (5 mM). In contrast, the cells grown in high glucose produced less PAI-1 than those in normal glucose. Thrombin stimulated dose-dependently the production of tPA, uPA and PAI-1 from the cells grown in either 5 or 33 mM glucose. However, the magnitude of the increase in tPA, uPA and PAI-1 from the cells grown in high glucose was less than that in normal glucose. These results suggest that the plasmin activity in mesangial cells may increase under a high glucose condition, leading to increased proteolysis of mesangial matrix. In addition, either fibrinolysis or proteolysis mediated by thrombin may be altered by high glucose concentration. Therefore, it is postulated that the turnover of mesangial matrix may be increased in diabetic nephropathy.

Cells, Cultured↗
PubMed1994

Preliminary report on an automated screening test for detection of antibody to human immunodeficiency virus type 1 in whole blood.

We developed and evaluated an automated screening test for antibody to human immunodeficiency virus type 1 (HIV-1) using EDTA-2Na-treated whole blood and an extract of paper disk-absorbed dried whole blood from 60 hemophiliacs infected with HIV-1 and 210 diseased and healthy controls. The specificity and the sensitivity of this system were judged to be 100% with both the whole blood and the extract. This test allows measurement of HIV-1 antibody in whole blood and dried whole blood on a small paper disk and gives a result within 13 minutes; the system can process 150 samples per hour. Therefore, it may be useful at many testing sites, such as emergency departments, intensive care units, blood banks, and commercial laboratories, as well as for mail-order testing from remote areas and developing countries.

AIDS Serodiagnosis↗
PubMed1994

A cooperative randomized controlled study of adjuvant chemoendocrine therapy for breast cancer in Japan.

A randomized trial was carried out in 55 Japanese institutions to examine the significance of postoperative adjuvant chemoendocrine therapy in Stages II and IIIA breast cancer patients after radical mastectomy. A total of 619 patients were entered from November 1982 to November 1984, of whom 554 were eligible. Patients were administered MMC (13 mg/m2) after surgery, and were randomized by the envelope method into either group A (ftorafur, 400 mg/m2/day; 275 patients), or group B (ftorafur, 400 mg/m2/day, and tamoxifen, 20 mg/day; 279 patients). Treatment was continued for 1 year from postoperative day 7. There were no significant differences between the two groups with regard to age, menopausal status, ER status, method of operation, stage, or number of positive lymph nodes. There was also no significant difference between the two groups in the 5-year survival and disease-free survival (DFS) rates (Kaplan-Meier method). Stratification by ER status, nodal status, or menopausal status produced no significant differences between the groups. However, postmenopausal patients and lymph node-positive patients who were also ER-positive showed a significantly higher DFS in group B. Furthermore, group B in ER-positive patients with four or more positive lymph nodes also had a higher survival rate.

Adult↗
PubMed1994

Clinical significance of serum 2,5-oligoadenylate synthetase and soluble interleukin-2 receptor in hemophiliacs positive and negative for human immunodeficiency virus type 1.

We measured serum 2,5-oligoadenylate synthetase (2,5-AS) levels and soluble interleukin-2 receptor (sIL-2R) levels in human immune deficiency virus type 1 (HIV-1)-positive and HIV-1-negative hemophiliacs in order to clarify the clinical significance of these parameters in hemophiliacs. Serum 2,5-AS levels were measured by a radioimmunosorbent assay, and sIL-2R levels were measured by an enzyme-linked immunosorbent assay. The mean serum 2,5-AS levels were higher in AIDS-related-complex and AIDS patients, asymptomatic carriers, and HIV-1-negative hemophiliacs than in hepatitis C virus-positive patients and healthy controls. Serial determinations showed that the 2,5-AS levels tended to increase in HIV-1-positive patients, especially those with AIDS-related complex or AIDS, although it showed a substantial decrease in the terminal stage. The serum sIL-2R levels were higher in HIV-1-positive patients, HIV-1-negative patients, and hepatitis C virus-positive patients than in controls. Serial studies showed little change in the HIV-1-positive and HIV-1-negative groups, although sIL-2R levels showed a tendency to decrease with zidovudine treatment. On the basis of the present results, we may well conclude that 2,5-AS and sIL-2R are not specific markers for hemophiliacs with HIV-1 infection. However, serial measurement of these markers can still be useful for assessing the progression of AIDS and the prognosis for patients with AIDS, as well as for monitoring the response to zidovudine.

2',5'-Oligoadenylate Synthetase↗