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Biomedical subjects

M Matsuda

Publications and source records attributed to M Matsuda.

At least 181 records · Page 10Linked to original sources
PubMed2000

Pharmacokinetics and pharmacodynamics of insulin aspart, a rapid-acting analog of human insulin, in healthy Japanese volunteers.

Pharmacokinetic and pharmacodynamic properties of a rapid-acting analog of human insulin, insulin aspart, were compared with those of soluble human insulin in Japanese healthy subjects. Subcutaneous single injections (0.025 and 0.05 U/kg body weight (BW)) of insulin aspart produced a significantly earlier peak of exogenous insulin level in comparison with human insulin (30.8+/-13.8 versus 61.3+/-14. 6 min, P<0.9001 for 0.025 U/kg; and 39.2+/-18.8 versus 99.2+/-53.8 min, P<0.005 for 0.05 U/kg). The peak serum level of insulin aspart was higher than that of human insulin (23.0+/-6.0 versus 9.9+/-3.1 microU/ml for 0.025 U/kg; and 30.9+/-9.2 versus 13.3+/-4.1 microU/ml for 0.05 U/kg, P<0.0001). The time to the minimal level of glucose after insulin aspart was significantly shorter compared with human insulin (P<0.05 for 0.025 U/kg BW and P<0.01 for 0.05 U/kg BW). The Delta change in blood glucose induced by insulin aspart was larger than that observed for human insulin at any dose (P<0.001). The repeated injection of insulin aspart before each meal also resulted in a rapid rise in exogenous insulin level with peak level obtained approximately 40 min after insulin aspart at any dose. When compared with results of other trials with insulin aspart, the present results showed that pharmacokinetic and pharmacodynamic profiles of the rapid-acting analog insulin aspart in Japanese subjects are no different from those in nonJapanese subjects.

Adult↗
PubMed2000

Long-term increase of GluR2 alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor subunit in the dispersed dentate gyrus after intrahippocampal kainate injection in the mouse.

Intrahippocampal injection of a subtoxic dose of kainate in mice has been shown to induce a dispersion of granule cells of the dentate gyrus, which is a characteristic morphological change often seen in human hippocampal sclerosis. In addition, it has been shown recently that such injections lead to recurrent hippocampal seizures and changes in glucose metabolism, which are reminiscent of temporal lobe epilepsy. Previous reports on human hippocampal sclerosis have shown an increase of the expression of the GluR2 alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate subunits in the dispersed granule cell somata. However, no such changes have been observed so far in animal models of epilepsy with hippocampal sclerosis. In this study, the expression of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor subunits was examined by immunohistochemistry following intrahippocampal injection of kainate in mice and rats. In mice, such injection induced a persistent increase of GluR2 immunoreactivity in the granule cells for up to 180 days. By contrast, GluR1 immunoreactivity was transiently increased during the first four days after the injection and progressively decreased thereafter. By contrast, intrahippocampal injection of kainate in rats did not result in granule cell dispersion and no changes in GluR1 immunoreactivity or GluR2 immunoreactivity were observed. These results show that, in addition to morphological, clinical and metabolical similarities, intrahippocampal injection of kainate results in a persistent increase of GluR2 associated with granule cell dispersion, as in human hippocampal sclerosis. These data suggest the existence of common mechanisms between granule cell dispersion and regulation of GluR2 subunits associated with hippocampal sclerosis.

Animals↗
PubMed2000

Dietary docosahexaenoic acid can alter the surface expression of CD4 and CD8 on T cells in peripheral blood.

The effect of dietary docosahexaenoic acid (DHA) on T cell states in peripheral blood was investigated. Weanling male C57Bl/6N mice were kept on one of three 10% fat diets containing various amounts of DHA and linoleic acid for 4 weeks. Changing the concentration of dietary DHA did not alter the proportion of T cells expressing CD4 or CD8. However, increasing the concentration of dietary DHA lowered the expression of CD4 and CD8 on the cell surface. The decreased expression of these surface molecules involved in T cell proliferation has serious implications in the role of DHA as an immunosuppressant.

Animals↗
PubMed2000

A novel strategy for the tumor angiogenesis-targeted gene therapy: generation of angiostatin from endogenous plasminogen by protease gene transfer.

When NIH 3T3 fibroblasts were transduced with a retroviral vector containing a cDNA for porcine pancreatic elastase 1 and cultured in the presence of affinity-purified human plasminogen, the exogenously added plasminogen was digested to generate the kringle 1-3 segment known as angiostatin, a potent angiogenesis inhibitor. This was evidenced by immunoblot analysis of the plasminogen digests using a monoclonal antibody specifically reacting with the kringle 1-3 segment, and by efficient inhibition of proliferation of human umbilical vein endothelial cells by the plasminogen digests isolated from the culture medium of 3T3 fibroblasts. However, when Lewis lung carcinoma cells were transduced with the same vector and injected subcutaneously into mice in their back or via the tail vein, their growth at the injection sites or in the lungs was markedly suppressed compared with the growth of similarly treated nontransduced Lewis lung carcinoma cells. Nevertheless, the transduced cells were able to grow as avidly as the control cells in vitro. Assuming that the elastase 1 secreted from the transduced cells is likely to be exempt from rapid inhibition by its physiological inhibitor, alpha1-protease inhibitor, as shown in the inflammatory tissues, the elastase 1 secreted from the tumor cells may effectively digest the plasminogen that is abundantly present in the extravascular spaces and generate the kringle 1-3 segment in the vicinity of implanted tumor cell clusters. Although the selection of more profitable virus vectors and cells to be transduced awaits further studies, such a protease gene transfer strategy may provide us with a new approach to anti-angiogenesis gene therapy for malignant tumors and their metastasis in vivo.

3T3 Cells↗
PubMed2000

Lineage-specific regulation of cell cycle control gene expression during haematopoietic cell differentiation.

To maintain the fidelity and integrity of blood formation, the cell cycle is under strict regulation during haematopoietic cell differentiation. To elucidate the molecular mechanisms of cell cycle regulation during haematopoiesis, we examined cell cycle control gene expression during lineage-specific differentiation from CD34+ progenitor cells. Expression of cyclin-dependent kinases (cdks) and cyclins, except cdk4, was generally suppressed in CD34+ cells freshly isolated from the bone marrow of healthy volunteers. Among four major cdk inhibitors, p16 was expressed more highly in CD34+ cells than in CD34-negative bone marrow mononuclear cells, whereas the amounts of p21 and p27 transcripts increased in the CD34- population. The behaviour of cell cycle control genes during haematopoietic differentiation was classified into four patterns: (i) universal upregulation (cdc2, cdk2, cyclin A, cyclin B and p21); (ii) upregulation in specific lineages (cyclin D1, cyclin D3 and p15); (iii) no induction or stable expression (cdk4, cyclin D2, cyclin E and p27); and (iv) universal downregulation (p16). Lineage-specific changes included the sustained elevation of cdc2 and cyclin A during erythroid differentiation, cyclin D1 and p15 induction in myeloid lineage and selective upregulation of cyclin D3 in megakaryocytes. Blocking induction of cyclin D3 resulted in the inhibition of megakaryocytic differentiation. These results suggest that the expression of cell cycle control genes is distinctively regulated in a lineage-dependent manner, reflecting the cell cycle characteristics of each lineage. Some of these genes play an essential role in the process of differentiation itself.

Antigens, CD34↗
PubMed2000

Positron emission tomographic imaging of acoustic neuromas.

Positron emission tomography (PET) examination with both [11C]methyl-l-methionine (Met) and [18F]fluoro-2-deoxyglucose (FDG) was performed in the same patients with acoustic neuroma wherever possible in order to compare the usefulness of the two methods. The study included six patients who visited the Osaka City University Hospitals, between April 1994 and October 1998, for complaints associated with acoustic neuroma. All patients were examined by magnetic resonance imaging (MRI) and Met-PET. Four patients were examined by FDG-PET. The tumor's region of highest accumulation was selected as the region of interest; the tumor/normal ratio (T/N ratio) was defined as the ratio of radioisotope counts for tumor and normal gray matter. All tumors in this series were detected by MRI. In the Met-PET images, four tumors were easily identified, with a high T/N ratio. However, two tumors could not be identified using Met-PET. On FDG-PET, no cases could be identified. The T/N ratio for the four patients with positive Met-PET findings averaged 1.694 +/- 0.266. PET, especially Met-PET, is a powerful means of examination providing functional information on tumors in acoustic neuroma. Met-PET may therefore be useful for acoustic neuroma, which is known to proliferate slowly, as for malignant tumors, in evaluating the proliferating potential of a tumor, in determining patients in whom to perform radiological treatment and in monitoring post-treatment progress.

Adult↗
PubMed2000

Rap2 as a slowly responding molecular switch in the Rap1 signaling cascade.

Rap2 is a member of the Ras family of GTPases and exhibits 60% identity to Rap1, but the function and regulation of Rap2 remain obscure. We found that, unlike the other Ras family proteins, the GTP-bound active form exceeded 50% of total Rap2 protein in adherent cells. Guanine nucleotide exchange factors (GEFs) for Rap1, C3G, Epac (or cyclic AMP [cAMP]-GEF), CalDAG-GEFI, PDZ-GEF1, and GFR efficiently increased the level of GTP-Rap2 both in 293T cells and in vitro. GTPase-activating proteins (GAPs) for Rap1, rap1GAPII and SPA-1, stimulated Rap2 GTPase, but with low efficiency. The half-life of GTP-Rap2 was significantly longer than that of GTP-Rap1 in 293T cells, indicating that low sensitivity to GAPs caused a high GTP/GDP ratio on Rap2. Rap2 bound to the Ras-binding domain of Raf and inhibited Ras-dependent activation of Elk1 transcription factor, as did Rap1. The level of GTP-Rap2 in rat 3Y1 fibroblasts was decreased by the expression of v-Src, and expression of a GTPase-deficient Rap2 mutant inhibited v-Src-dependent transformation of 3Y1 cells. Altogether, Rap2 is regulated by a similar set of GEFs and GAPs as Rap1 and functions as a slowly responding molecular switch in the Rap1 signaling cascade.

3T3 Cells↗
PubMed2000

Intense exercise causes decrease in expression of both endothelial NO synthase and tissue NOx level in hearts.

Cardiac myocytes produce nitric oxide (NO). We studied the effects of intense exercise on the expression of NO synthase (NOS) and the tissue level of nitrite (NO(2)(-))/nitrate (NO(3)(-)) (i.e., NOx), which are stable end products of NO in the heart. Rats ran on a treadmill for 45 min. Immediately after this exercise, the heart was quickly removed. Control rats remained at rest during the same 45-min period. The mRNA level of endothelial NOS (eNOS) in the heart was markedly lower in the exercised rats than in the control rats. Western blot analysis confirmed downregulation of eNOS protein in the heart after exercise. Tissue NOx level in the heart was significantly lower in the exercised rats than in the control rats. The present study revealed for the first time that production of NO in the heart is decreased by intense exercise. Because NO attenuates positive inotropic and chronotropic responses to beta(1)-adrenergic stimulation in the heart, the decrease in cardiac production of NO by intense exercise may contribute to the acceleration of increase in myocardial contractility and heart rate during intense exercise.

Animals↗
PubMed2000

An analysis of serum interleukin-6 levels to predict benefits of medroxyprogesterone acetate in advanced or recurrent breast cancer.

Treatment of advanced or recurrent breast cancer with medroxyprogesterone acetate (MPA) shows high response rates and the accessory effects of appetite stimulation, improvement in performance status (PS) and bone marrow protection. In recent years, interleukin-6 (IL-6) has been reported to cause cachexia. In this study, to clarify the significance of IL-6 in advanced or recurrent breast cancer, the relationship between the IL-6 level and clinical findings or effect of MPA was investigated. Sixty-five patients with recurrent or advanced breast cancer participated in a prospective study. The age of patients ranged from 28 to 79 years with an average age of 51.3 years. IL-6 level was investigated in these patients dosed with 800 mg/day of MPA and in 17 postoperative nonrecurrent patients. Serum MPA level was measured by high-performance liquid chromatography and IL-6 level was measured prior to MPA administration, 4 weeks (in 59 cases) and 12 weeks (in 32 patients) after MPA administration by ELISA. Serum IL-6 level was significantly higher in recurrent cases, especially in those with visceral metastasis. Further, in patients for whom MPA therapy was effective, the IL-6 level prior to the treatment was clearly low. The IL-6 level was significantly increased after 4 weeks. However, response to MPA was significantly higher and PS was improved in those cases demonstrating less increased IL-6 levels after 4 weeks. In addition, the effect of MPA was significantly related to a higher serum concentration of MPA-positive ER, and longer disease-free interval, although there was no significant predictive factor for the clinical effect of MPA therapy in multivariate analysis. In conclusion, MPA therapy was effective in cases demonstrating a low IL-6 level and less increased IL-6 levels after 4 weeks. PS was improved in those cases in which the degree of IL-6 increase was suppressed by MPA, and many such cases showed low IL-6 levels prior to MPA therapy. Furthermore, PS was improved even in nonresponders to MPA. Therefore, it is suggested that MPA therapy might be useful in treating recurrent breast cancer, and its benefits might be mediated by IL-6.

Adult↗
PubMed2000

Dietary n-3 polyunsaturated fatty acid and status of immunocompetent cells involved in innate immunity in female rats.

The aim of this study was to estimate the contributions of dietary n-3 polyunsaturated fatty acid (PUFA), a representative dietary immunosuppressant, to the activity of both alveolar macrophages (AM) and natural killer (NK) cells, and compare them to those of n-6 PUFA. Twelve 5-week-old female Sprague-Dawley rats were divided into two dietary groups, one fed a 10% fat diet for 9 weeks enriched with n-3 PUFA (n-3 diet) and the other an n-6 PUFA (n-6 diet). AM reduced the release of nitric oxide, monocyte chemoattractant protein 1 and tumor necrosis factor alpha in the rats fed the n-3 diet, compared with rats fed the n-6 diet. NK cell activity was reduced by consumption of the n-3 diet. This study suggests that consumption of n-3 PUFA can ameliorate pulmonary inflammatory disorders which are affected by the reduction of not only proinflammatory cytokines but also chemokine released from AM.

Animals↗
PubMed2000

Induction of ubiquitin-conjugating enzyme by aggregated low density lipoprotein in human macrophages and its implications for atherosclerosis.

Recently, we have found that aggregated low density lipoprotein (agLDL) inhibits apoptosis of lipid-bearing macrophages, thereby facilitating foam cell formation and atherosclerosis. To clarify the mechanisms by which agLDL inhibits apoptosis of macrophages, we isolated the genes specifically induced by agLDL by using a subtraction-based cloning strategy. One of the cloned genes, termed low density lipoprotein (LDL)-inducible gene (LIG), encodes a human homologue of bovine ubiquitin-conjugating enzyme E2-25K. Although LIG mRNA was ubiquitously expressed among human tissues, including hematopoietic cells, the abundance of transcripts was markedly increased by agLDL treatment in activated monocytes. LIG mRNA expression was not enhanced by nonatherogenic lipoproteins such as native LDL and high density lipoprotein, suggesting a role in atherosclerosis. Polyubiquitination of intracellular proteins was observed in monocytes cultured with agLDL, which coincided with upregulation of LIG. Furthermore, ubiquitin-dependent degradation of p53, an inducer of apoptosis, was accompanied by LIG induction in agLDL-treated monocytes. The antiapoptotic effect of agLDL was abrogated by a specific proteasome inhibitor, which also increased the half-life of p53 in monocytes. These results suggest that LIG contributes to foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequent degradation of p53.

Amino Acid Sequence↗
PubMed2000

Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients.

Adiponectin is a novel, adipose-specific protein abundantly present in the circulation, and it has antiatherogenic properties. We analyzed the plasma adiponectin concentrations in age- and body mass index (BMI)-matched nondiabetic and type 2 diabetic subjects with and without coronary artery disease (CAD). Plasma levels of adiponectin in the diabetic subjects without CAD were lower than those in nondiabetic subjects (6.6+/-0.4 versus 7.9+/-0.5 microg/mL in men, 7.6+/-0.7 versus 11.7+/-1.0 microg/mL in women; P<0.001). The plasma adiponectin concentrations of diabetic patients with CAD were lower than those of diabetic patients without CAD (4.0+/-0.4 versus 6.6+/-0.4 microg/mL, P<0.001 in men; 6.3+/-0.8 versus 7.6+/-0. 7 microg/mL in women). In contrast, plasma levels of leptin did not differ between diabetic patients with and without CAD. The presence of microangiopathy did not affect the plasma adiponectin levels in diabetic patients. Significant, univariate, inverse correlations were observed between adiponectin levels and fasting plasma insulin (r=-0.18, P<0.01) and glucose (r=-0.26, P<0.001) levels. In multivariate analysis, plasma insulin did not independently affect the plasma adiponectin levels. BMI, serum triglyceride concentration, and the presence of diabetes or CAD remained significantly related to plasma adiponectin concentrations. Weight reduction significantly elevated plasma adiponectin levels in the diabetic subjects as well as the nondiabetic subjects. These results suggest that the decreased plasma adiponectin concentrations in diabetes may be an indicator of macroangiopathy.

Adiponectin↗
PubMed2000

A case of adult-onset Still's disease complicated by non-Hodgkin's lymphoma.

Left cervical lymphadenopathy developed in a 50-year-old male who had a history of adult-onset Still's disease for the preceding 18 months. Still's disease is characterized by rash, fever, and leukocytosis. Lymphadenopathy has been reported in about 60% of the patients, and most histopathologic studies have shown non-specific reactive hyperplasia. However, in this case, an open biopsy of the cervical node revealed a histology of diffuse large B-cell lymphoma. The B-cell malignant lymphoma that developed may have resulted from a sequential progression of a previous stage of benign lymphoproliferative lesion. Our case suggests that the pathophysiology of adult-onset Still's disease involves the stimulation of lymphoid systems to the point of progression towards lymphoma. Malignant lymphoma should be added to the list of life-threatening complications which, although rare, are associated with this disease.

Humans↗
PubMed2000

Glycosylation-dependent cell adhesion molecule 1 (GlyCAM 1) is induced by prolactin and suppressed by progesterone in mammary epithelium.

Glycosylation-dependent cell adhesion molecule 1 (GlyCAM 1), a mucin-like endothelial glycoprotein, was induced by PRL and suppressed by progesterone in the mammary gland of mice, and in HC11 mouse mammary epithelial cells. Complementary DNA microarray analysis revealed that expression of GlyCAM 1 was reduced in the mammary gland of PRL-gene disrupted mice (PRL-/-) compared with control (PRL+/-) littermates. This result was confirmed by in situ hybridization and immunostaining. The messenger RNA (mRNA) encoding GlyCAM 1 was present in mammary epithelia of PRL-stimulated mice. Immunohistochemistry indicated that GlyCAM 1 protein was detectable both in mammary epithelia and in the ductal lumen in PRL+/- virgin mice, but not in PRL-/- mice. GlyCAM 1 mRNA was highly induced by grafting pituitary glands from normal littermates. Trace amounts of mRNA for GlyCAM 1 were detected by RT-PCR in mammary tissue of PRL-/- mice. Progesterone inhibited both basal and PRL-stimulated GlyCAM 1 transcription. In HC11 cells, GlyCAM 1 mRNA was induced in cells treated with insulin, dexamethasone, and PRL. Similar to the in vivo studies, progesterone inhibited the induction of GlyCAM 1 transcription. In CHO cells, PRL stimulated transcription of a luciferase reporter gene containing an 800-bp promoter fragment of GlyCAM 1, and progesterone partially suppressed the PRL effect. These data demonstrate that expression of GlyCAM 1 in mammary gland is under the control of both PRL and progesterone.

Animals↗
PubMed2000

A site specific increase in recombination in Drosophila ananassae.

The e65 pi; bri ru stock of Drosophila ananassae produced an extremely high rate of recombination in males when made heterozygous with any one of the wild type stocks. We analyzed and characterized the genetic factors which caused this phenomenon. We show that the second chromosome of the e65 pi; bri ru stock carries an enhancer of male recombination. The enhancer, En(2)-ep, is located between Om(2C) and Arc. The enhancement of meiotic recombination both in males and females was also observed at the specific region between Om(2C) and Arc on 2L. The magnitude of increased recombination was 30-40 fold in males and 13-30 fold in females. The relation between the hotspot of recombination in both sexes and the enhancer of male recombination is discussed.

Animals↗
PubMed2000

A simple semisolid subtraction method using carbodiimide-coated microplates.

In this article, we develop a novel subtraction method using carbodiimide-bound microplates. This method utilizes the high affinity of carbodiimides for both single- and double-stranded nucleic acids. Carbodiimide-mediated end-attachment of driver RNA to microplates allows semisolid phase hybridization between driver RNA and target cDNA, and ensures easy removal of RNA/cDNA hybrids composed of the genes commonly expressed in driver and target. As a result, the target-specific genes are left unhybridized and enriched in the hybridization supernatant. We define the optimal conditions for the method as a target/driver RNA ratio of 1:10 and a period of hybridization of 24 h. There are at least three major advantages with the present method: (1) The entire procedure, which consists of two steps, is very simple; (2) hybridization efficiency can be monitored before further processing of the samples; and (3) rare transcripts can be effectively enriched. This method may be a powerful tool to isolate the genes specifically expressed in particular cell or tissue types, and is easily applicable to many studies in molecular biology and genetics. Isolation of polyploid megakaryocyte-specific genes is shown as an example.

Blotting, Northern↗