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Biomedical subjects

M Matsuda

Publications and source records attributed to M Matsuda.

At least 379 records · Page 21Linked to original sources

Does endothelin-1 participate in the exercise-induced changes of blood flow distribution of muscles in humans?

Endothelin-1 (ET-1) is an endothelium-derived potent vasoconstrictor peptide that potentiates contractions to norepinephrine in human vessels. We previously reported that the circulating plasma concentration of ET-1 is significantly increased after exercise (S. Maeda, T. Miyauchi, K. Goto, and M. Matsuda. J. Appl. Physiol. 77: 1399-1402, 1994). To study the roles of ET-1 during and after exercise, we investigated whether endurance exercise affects the production of ET-1 in the circulation of working muscles and nonworking muscles. Male athletes performed one-leg cycle ergometer exercise of 30-min duration at intensity of 110% of their individual ventilatory threshold. Plasma concentrations of ET-1 in both sides of femoral veins (veins in the working leg and nonworking leg) and in the femoral artery (artery in the nonworking leg) were measured before and after exercise. The plasma ET-1 concentration in the femoral vein in the nonworking leg was significantly increased after exercise, whereas that in femoral vein in the working leg was not changed. The arteriovenous difference in ET-1 concentration was significantly increased after exercise in the circulation of the nonworking leg but not of the working leg, which suggests that the production of ET-1 was increased in the circulation of the nonworking leg by exercise. The present study also demonstrated that the plasma norepinephrine concentrations were elevated by exercise in the femoral veins of both the working and nonworking legs, suggesting that the sympathetic nerve activity was augmented in both legs during exercise. Therefore, the present study demonstrates the possibility that the increase in production of ET-1 in nonworking muscles may cause vasoconstriction and hence decrease blood flow in nonworking muscles through its direct vasoconstrictive action or through an indirect effect of ET-1 to enhance vasoconstrictions to norepinephrine and that these responses may be helpful in increasing blood flow in working muscles. We propose that endogenous ET-1 contributes to the exercise-induced redistribution of blood flow in muscles.

Adolescent↗

Gene expression of PDGF and PDGF receptor in various forms of glomerulonephritis.

Platelet-derived growth factor (PDGF) is an important mitogenic factor for various cells. In order to elucidate the role of PDGF in the development of human glomerulonephritis, we examined the gene and protein expression of the PDGF-B chain (PDGF-B) and PDGF-beta receptor (PDGFR-beta) in renal biopsy specimens from patients with various forms of glomerulonephritis using a nonradioactive in situ hybridization and an immunohistochemical technique. The mRNA expression of PDGF-B and PDGFR-beta was significantly increased in the glomeruli of patients with mesangial proliferative glomerulonephritis (IgA nephropathy, Henoch-Schönlein purpura nephritis, and lupus nephritis) compared with those in normal glomeruli. In cases with increased protein expression of PDGF-B and PDGFR-beta, each mRNA expression was also increased. The degree of glomerular injury was positively correlated with the number of mRNA-positive cells for both PDGF and PDGF receptor. There was also a positive correlation between the number of mRNA-positive cells for PDGF-B and PDGFR-beta. PDGF-B and PDGFR-beta were also expressed on cells of the capillary wall, cellular crescents and infiltrated cells in the interstitium. The results suggest that PDGF acts as an important and common mediator for the development of various forms of human mesangial proliferative glomerulonephritis. Furthermore, PDGF may participate in crescent formation and tubulo-interstitial injury.

Adolescent↗

Role of Crk oncogene product in physiologic signaling.

v-Crk is a member of the family of adaptor-type signaling molecules that consist mostly of SH2 and SH3 domains. The cellular homologs of v-Crk includes CrkI, CrkII, and CrkL; these have been isolated from species ranging from lower vertebrates to man. Crk-family proteins are involved in a variety of signaling cascades such as those of growth factor receptor, integrin, T-cell receptor, B-cell antigen receptor, and cytokines. It has been postulated that the primary function of Crk is to recruit cytoplasmic proteins in the vicinity of tyrosine kinases through SH2-phosphotyrosine interaction. Thus, the output from Crk depends on the SH3-binding proteins, which include the C3G guanine nucleotide exchange protein for Rap1, Abl tyrosine kinase, DOCK180, and the Sos guanine nucleotide exchange protein for Ras. The variety of the Crk-binding proteins indicate the pleiotropic function of Crk.

Animals↗

Demonstration and organization of duct-associated lymphoid tissue (DALT) of the main excretory duct in the monkey parotid gland.

Duct-associated lymphoid tissue (DALT) of the main excretory duct in the monkey parotid gland was first demonstrated by light microscopy and by transmission and scanning electron microscopy. The DALT included a follicular area, a parafollicular area and a specialized overlying epithelium with distinct fine-structural elements. There was usually a solitary lymphoid follicle located in the subepithelial area near the orifice of the parotid duct. The lymphoid follicles typically had a distinct germinal center. Numerous immune cells often infiltrated into the epithelium overlying the lymphoid follicle. The superficial epithelial cells of the DALT were larger and flatter than the ordinary duct epithelial cells, and had short irregular microvilli on their luminal surface. They were also in close contact with immune cells such as dendritic cells and lymphocytes. Goblet cells were rare in this area. In addition, bacteria, seen at the duct orifice, were sometimes taken up by the flattened epithelial cells near the orifice. Latex microspheres administrated as particulate antigens at the duct orifice were selectively taken up by the flattened epithelial cells and also by the intraepithelial dendritic cells of the DALT. These morphological findings suggest that the epithelial cells of the DALT in parotid glands take up antigens from the duct lumen and transport them to adjacent immune cells, and that the DALT in parotid glands may serve as one of the inductive sites in the common mucosal immune system.

Animals↗

Effect of hormones on expression of prolactin receptor messenger ribonucleic acids in pancreatic islets of adult female mice in vitro.

We studied the effects of hormones on expression of prolactin receptor (PRL-R) mRNA in pancreatic islets of adult female mice in vitro. We quantified mRNA expression in small amounts of the islet tissue by competitive PCR and one-sided competitive PCR. Fifty pancreatic islets from adult female mice were cultured in a wall for 4 days with or without ovine prolactin (PRL), bovine growth hormone or estradiol-17 beta. PRL (1 microgram/ml) significantly increased the insulin secretion and the amount of PRL-R mRNA relative to that of beta-actin mRNA. Growth hormone (1 microgram/ml) also increased the relative amount of PRL-R mRNA, although it did not significantly increase the insulin secretion. Neither insulin secretion nor the relative amount of PRL-R mRNA was affected by estradiol (100 ng/ml). The ratio of the short form to the long form of PRL-R mRNA was not altered by these hormones. The present observation that PRL increased PRL-R mRNA expression in pancreatic islets thus suggests the possibility that PRL up-regulates the tissue sensitivity to PRL itself during lactation.

Animals↗

Increased expression of intercellular adhesion molecule-1 (ICAM-1) in diabetic rat glomeruli: glomerular hyperfiltration is a potential mechanism of ICAM-1 upregulation.

Mononuclear cells, including monocytes/macrophages and T-cells, are considered to be involved in the progression of diabetic nephropathy, although the mechanism of their recruitment into diabetic glomeruli is unclear. The intercellular adhesion molecule-1 (ICAM-1) promotes the infiltration of leukocytes into atherosclerotic lesions as well as inflammatory tissues. In the present study, we investigated the expression of ICAM-1 in the glomeruli of streptozotocin-induced diabetic rats. The expression of ICAM-1 was increased significantly during the early stage of diabetes. The number of mononuclear cells, primarily monocytes/macrophages and lymphocytes, was significantly increased in diabetic glomeruli. Mononuclear cell infiltration into diabetic glomeruli was prevented by anti-ICAM-1 monoclonal antibody. Insulin treatment decreased ICAM-1 expression and mononuclear cell infiltration. The ICAM-1 expression on cultured human umbilical vein endothelial cells was not induced under high glucose culture conditions. Glomerular hyperfiltration is a characteristic change in the early stage of diabetic nephropathy. Treatment with aldose reductase inhibitor, which prevented glomerular hyperfiltration without changes in blood glucose levels, decreased ICAM-1 expression and mononuclear cell infiltration. Moreover, we examined the ICAM-1 expression in the glomeruli of the 5/6 nephrectomized rat, which is a model for glomerular hyperfiltration without hyperglycemia. The ICAM-1 expression and infiltration of mononuclear cells was significantly increased in the glomeruli of 5/6 nephrectomized rats. We conclude that ICAM-1 is upregulated and promotes the recruitment of mononuclear cells in diabetic glomeruli. Moreover, glomerular hyperfiltration that occurs in the early stage of diabetic glomeruli may be one of the potential mechanisms of ICAM-1 upregulation in diabetic nephropathy.

Aldehyde Reductase↗

Endogenous nitric oxide production in Kawasaki disease.

To evaluate in vivo nitric oxide production in Kawasaki disease (KD), urinary nitrite/nitrate (NOx) excretion was measured in 8 children with KD (age 1.1-2.7 years). Urinary NOx excretion was 0.66 +/- 0.22 mmol mmol-1 creatinine (mean +/- SD) in the 8 children with KD in the initial stages. The levels were significantly increased compared with those of 12 age-matched healthy control subjects (0.35 +/- 0.08 mmol mmol-1 creatinine). Urinary Nox excretion was serially determined in four patients. For each patient, there was a further rise in urinary NOx excretion from baseline levels coincident with the administration of intact-type gammaglobulin and aspirin. With clinical and laboratory improvement, however, urinary NOx excretion declined to the normal range. These findings suggest that endogenous nitric oxide production is enhanced in children with acute KD. Further studies are needed to clarify the role of nitric oxide in the pathogenesis and clinical course of KD.

Child, Preschool↗

A new trocar approach insertion site for laparoscopic surgery: the xiphoidal approach.

Laparoscopic cholecystectomy (LC) has become the standard treatment for removing a diseased gallbladder. Endoscopic surgical techniques are used to perform appendectomies, bowel resections, and gastrectomies. This minimally invasive surgery is favored because it decreases the patients' postoperative pain and length of hospitalization. However the incidence of complications with this technique is not negligible. As a new technique is evolving, the potential for complications is high. This increase in complication rate is undoubtedly due to inexperience during the initial phase of the surgeon's learning curve. Demand for the procedure has required rapid training and credentialing of many surgeons with limited experience in endoscopy and the use of instruments that allow only limited viewing of abdominal structures.

Journal Article↗

[Evaluation of combination chemotherapy with 5-FU and CDDP for human gastric carcinoma transplanted into nude mice].

Combined chemotherapy of 5-FU and CDDP is useful for advanced or recurrent gastric cancer. To evaluate the efficacy of this chemotherapy, using human gastric carcinoma (NSC-30) maintained in the subcutaneous (sc) space in nude mice, we designed the following four experimental groups: 1) control group, 2) 5-FU group, 3) CDDP group, and 4) combined therapy group of 5-FU and CDDP (FP group). 5-FU (150 mg/kg) was injected into the intraperitoneal space for seven days using AlZet osmotic pumps. CDDP (9 mg/kg) was injected into the intraperitoneal space at one time. The tumor growth of drug administered groups was inhibited compared with the control group, especially in the FP group. Body weight and general condition of nude mice did not differ between groups. We also measured tumor concentrations of 5-FU and thymidylate synthetase (TS) total, free, inhibition rate between 5-FU group and FP group. The tumor 5-FU concentration of FP group was slightly higher than in 5-FU group, but the TS inhibition rate was almost the same. In conclusion, this combined therapy using Alzet osmotic pump is a useful drug sensitivity test as a conventional system.

Animals↗

Changes in serum concentrations of matrix metalloproteinases, tissue inhibitors of metalloproteinases and type IV collagen in patients with various types of glomerulonephritis.

One of the major causes of glomerular sclerosis which precedes renal failure is an increase in glomerular extracellular matrices (ECMs). Glomerular ECMs which are composed of mesangial matrix and basement membrane play an important role in physical, mechanical and structural functions of the glomerulus. Matrix metalloproteinases (MMPs) are the enzymes which degrade both the collagenous and noncollagenous components of the ECMs. Tissue inhibitors of metalloproteinases (TIMPs) are inhibitors of MMPs. The regulations by MMPs and TIMPs are considered to contribute to maintain homeostasis in the production and degradation of ECMs in the glomeruli. In the glomeruli of patients with glomerulonephritis, the imbalance between production and degradation of ECMs is supposed to cause the increase in ECMs and glomerular sclerosis. In this study, serum concentrations of MMP-1, -2, and -3, TIMP-1 and 2 and type IV collagen were measured in patients with IgA nephropathy, lupus nephritis and membranous nephropathy. In patients with IgA nephropathy and lupus nephritis which are mesangial proliferative glomerulonephritis, the levels of MMP-3 and TIMP-2 were increased. On the other hand, the levels of type IV collagen, MMP-2 and TIMP-1 were increased in patients with membranous nephropathy in which the thickening of basement membrane is characteristic. These differences may be caused by the difference of the pathogenesis of these diseases. The present results suggest that the imbalance between the metabolism of ECMs occurs in patients with glomerulonephritis and contributes to the progression of glomerulonephritis.

Adult↗

[Tuberculous pleuro-peritonitis showing increased levels of CA125].

A 53-year-old woman was admitted because of dyspnea and coughing of about 8 months duration. On examination she had left pleural effusion and ascites. The serum CA125 level was high (1150 U/ml) but gynecological examinations were negative. Radiological and ultrasonic studies revealed bilateral pleural effusions and ascites. Cytological and bacteriological studies of the pleural effusions and ascites were all negative. The pleural fluid was exudate with high lymphocyte counts and elevated ADA (87.4 IU/l) and CA125 (1800 U/ml). Tuberculous pleuritis was diagnosed based on the findings of sputum culture and of pleural biopsy. The latter revealed epithelioid cell granulomas and giant cells. Cells in both pleural effusion and ascites were stained with antibodies to CA125. Antituberculous chemotherapy was started and the patient responded well. Both pleural effusions and ascites decreased; the level of CA125 also decreased to the normal range in about two months.

CA-125 Antigen↗

The role of topoisomerase I in HIV-1 replication.

The mechanisms involved in the restriction of the cellular tropism of HIV-1 to cells of primate origin remain to be clearly defined. However, a number of studies have shown that this is determined not only at the level of the cellular receptor(s) or virus entry, but at a number of additional and later stages in virus replication. We have recently reported that the reverse transcription of HIV-1 RNA is markedly enhanced by the association of the gag encoded nucleocapsid p15 protein and cellular topoisomerase 1. In the present study we have now investigated if the recruitment of cellular topoisomerase I during virus replication is important in determining the cellular tropism of HIV-1. Employing a stable murine cell line, L929, expressing both human CD4 and topoisomerase I, it could be demonstrated that effective proviral DNA synthesis occurred following infection. In contrast in cells expressing only human CD4 proviral DNA synthesis was not detected. In addition we have co-expressed fusin, a protein known to act as an accessory factor as the virus entry stage in infection of T cell tropic HIV-1, to support viral entry completely. However no progeny virus could be detected after HIV-1 infection. These results suggest that reverse transcription in vivo is critically dependent on the presence of cellular topoisomerase I, and support the view that involvement of this enzyme is in HIV-1 replication. Moreover the findings suggest that other factors which remained to be identified, are involved in restricting HIV-1 replication in non-primate cells.

Animals↗

The role of topoisomerase I in HIV-1 replication.

The mechanisms involved in the restriction of the cellular tropism of HIV-1 to cells of primate origin remain to be clearly defined. However, a number of studies have shown that this is determined not only at the level of the cellular receptor(s) or virus entry, but at a number of additional and later stages in virus replication. We have recently reported that the reverse transcription of HIV-1 RNA is markedly enhanced by the association of the gag encoded nucleocapsid p15 protein and cellular topoisomerase I. In the present study we have investigated if the recruitment of cellular topoisomerase I during virus replication is important in determining the cellular tropism of HIV-1. Employing a stable murine cell line, L929, expressing both human CD4 and topoisomerase I, it could be demonstrated that effective proviral DNA synthesis occurred following infection. In contrast in cells expressing only human CD4, proviral DNA synthesis was not detected. In addition we have co-expressed fusin, a protein known to act as an accessory factor as the virus entry stage in infection of T cell tropic HIV-1, to support viral entry completely. However no progeny virus could be detected after HIV-1 infection. These results suggest that reverse transcription in vivo is critically dependent on the presence of cellular topoisomerase I, and support the view that involvement of this enzyme is important in HIV-1 replication. Moreover the findings suggest that other factors which remained to be identified, are involved in restricting HIV-1 replication in non-primate cells.

Animals↗

The p53-deficient hemopoietic stem cells: their resistance to radiation-apoptosis, but lasted transiently.

Hemopoietic stem cells lacking with p53 are known to be resistant to radiation apoptosis: p53-product induces, on one hand, the cells that have been injured by radiation to stop cell-cycle at G, phase, and on the other hand the cells that have not been repaired to go into apoptosis. Thus, in the p53-deficient mice, the hemopoietic stem cells after graded dose of radiation show a flatter survival curve for radiation, i.e., like a curve for radio-resistant phenotype. However, we found the radio-resistance in the stem cell was only transient, and an apoptosis in p53-deficient hemopoietic stem cells, we made concentrated analysis including the end-labeling technique to detect double strand breaks of DNA. Results clearly showed that, according to the end-labeling for spleen colonies, the p53-deficiency showed rather higher incidence of apoptosis (30-50%) as compared with the wild-control (17%). Irradiation with 200cGy for the recipient mice two months after transplantation, showed an induction of higher incidence of hemopoietic malignancies, when the heterozygous marrow was repopulated, however, none of increase was observed in the recipient mice repopulated with the homozygous bone marrow. Clear difference between the hetero- and the homozygous in inducing hemopoietic malignancies with the 200cGy-radiation may be reflected by the different degree of delayed appearance of apoptosis during the development of the spleen colonies.

Animals↗