Biomedical subjects

M Ozawa

Publications and source records attributed to M Ozawa.

At least 55 records · Page 3Linked to original sources

PubMed1999

Central effects of pituitary adenylate cyclase activating polypeptide (PACAP) on gastric motility and emptying in rats.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a new member of the secretin-glucagon-vasoactive intestinal peptide (VIP) peptide family. PACAP is widely distributed not only in the mammalian brain but also in the gastrointestinal tract. Here, we investigated the effects of central and peripheral administrations of PACAP on gastric motility and gastric emptying in rats. We found that the intracerebroventricular or intracisternal injection of PACAP increased gastric motility in a dose-dependent manner. The intracisternal injection of PACAP delayed gastric emptying. These central effects of PACAP on gastric motility and emptying were blocked by bilateral vagotomy. In contrast, intravenous administration of PACAP decreased gastric motility and delayed gastric emptying. The peripheral inhibitory effect was unaffected by bilateral vagotomy, adrenalectomy, phentolamine, and propranolol. We investigated the effect of PACAP38 on blood glucose levels (BGL) at the same doses as those used in the gastric motility and emptying studies in urethane-anesthetized rats. The intravenous but not intracerebroventricular injection of PACAP38 (1-8 nmol/rat) produced a significant increase in the BGL. We conclude that PACAP has opposite central and peripheral effects on gastric motility, ie, central PACAP activates the vagal pathway in the central nervous system to increase gastric motility, whereas peripheral PACAP inhibits gastric motility via an unknown pathway. The delay in gastric emptying after the central administration of PACAP might be due to the lack of coordinated gastropyloroduodenal contraction, whereas that after the peripheral administration might be due to the inhibition of gastric contraction, and this effect may be related to the hyperglycemic action of PACAP.

Adrenalectomy↗

PubMed1999

Corticotropin-releasing factor but not urocortin is involved in adrenalectomy-induced adrenocorticotropin release.

Urocortin, a new corticotropin-releasing factor (CRF)-related peptide, has been reported to have the ability to bind to CRF receptors and to stimulate adrenocorticotropin (ACTH) secretion from the rat anterior pituitary in vivo and in vitro. In this study, we examined the effect of intravenous administration of urocortin-antiserum to investigate the role of endogenous urocortin on ACTH secretion from rat anterior pituitary after adrenalectomy. Male Sprague-Dawley rats, which were maintained in a conscious and undisturbed condition, were administered non-immunized rabbit serum (NRS), CRF-antiserum or urocortin-antiserum at a volume of 1 ml/kg b.w. 15 min before the injection of secretagogues. Synthetic rat urocortin (2 microg/kg B.W.) increased plasma ACTH concentrations by about sixfold the basal concentration. The pretreatment with urocortin-antiserum but not CRF-antiserum abolished the urocortin-induced increase in plasma ACTH concentrations. In adrenalectomized rats, plasma ACTH concentrations were markedly increased at basal conditions, and rapidly reduced after the administration of CRF-antiserum. By contrast, administration of urocortin-antiserum did not alter ACTH secretion induced by adrenalectomy. Our results suggest that endogenous urocortin is unlikely to be involved in ACTH release in adrenalectomized rats.

Adrenalectomy↗

PubMed1999

N-cadherin expressed on malignant T cell lymphoma cells is functional, and promotes heterotypic adhesion between the lymphoma cells and mesenchymal cells expressing N-cadherin.

Cadherins are Ca2+-dependent cell-cell adhesion molecules, and are involved in the formation and maintenance of the organocellular architecture. Using a combination of molecular biologic and biochemical methods, we analyzed cadherins expressed on cultured human malignant lymphoma cell lines (adult T cell lymphomas, human T cell leukemia virus type 1-negative T cell lines, and thymus-derived lymphoma cell lines), and obtained evidence that N-cadherin is the major cadherin expressed on these cells. These cells were found to form cell aggregates in a Ca2+-dependent manner, and more importantly to coaggregate and adhere with cells expressing N-cadherin, suggesting that N-cadherin on lymphoma cells is functionally active. Therefore, N-cadherin expressed on lymphoma cells could underlie the frequent invasion of these cells into the mesenchymal tissue in the skin and the central nervous system.

Cadherins↗

PubMed1999

The majority of epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines, interferon-gamma, interleukin-2, and tumor necrosis factor-alpha, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients.

Psoriasis vulgaris is a skin disease potentially mediated by pro-inflammatory cytokines produced by type 1 lesional T cells. The capability of individual T cells to produce these cytokines in lesional skin is not known. In this study we measured the ability of lesional and peripheral blood T cells to produce intracellular interferon-gamma, tumor necrosis factor-alpha, interleukin-2, interleukin-4, and interleukin-10 proteins as detected by flow cytometric analysis. Cytokine synthesis was induced by activation with ionomycin/phorbol myristate acetate (in the presence of Brefeldin A, which inhibits the exocytosis of these cytokines). After stimulation, we found relatively high percentages of epidermal CD8 and CD4 T cells capable of producing interferon-gamma, tumor necrosis factor-alpha, and interleukin-2, whereas few T cells, < 11%, expressed interleukin-4 or interleukin-10. Hence both CD8+ and CD4+ T cells are capable of type 1 effector functions (TC1 and TH1, respectively). This activation scheme was repeated on peripheral blood T cells from psoriatic patients versus healthy controls, where we also found a type 1 bias. In order to evaluate quantitatively the type 1 cytokine bias, we compared the frequency of type 2 interleukin-4 producing versus type 1 interferon-gamma producing T cells in our assay and found a shift towards type 1 producing cells. This shift reveals a type 1 differentiation bias in both lesional areas and in the peripheral blood, which may indicate an imbalance within the T cell population, which is contributing to the chronic or sustained immunologic activation of T cells found in this disease.

Adult↗

PubMed1999

Secretion of ovarian inhibin and its physiologic roles in the regulation of follicle-stimulating hormone secretion during the estrous cycle of the female guinea pig.

To characterize inhibin secretion during the estrous cycle in guinea pigs, the concentrations of plasma inhibin, estradiol, progesterone, and FSH were determined. A significant positive correlation was observed between inhibin and estradiol throughout the estrous cycle. Plasma inhibin and estradiol started to increase a few days before ovulation (Day 0 = day of estimated ovulation), and decreased after ovulation. These two hormones remained low during the luteal phase. The immunoreactivity of inhibin alpha, betaA, and betaB subunits was colocalized in the granulosa cells of one or two healthy large follicles in the ovary before ovulation. There was no positive reaction of inhibin alpha and beta subunits in the corpora lutea or other follicles. Ovariectomy resulted in an abrupt decrease in plasma inhibin and a significant increase in plasma FSH. Injection of anti-inhibin serum into adult female guinea pigs induced an elevation in plasma FSH in a dose-dependent manner. This report presents the first description of sequential changes in plasma inhibin and estradiol during the estrous cycle of guinea pigs. Results suggest that inhibin is secreted mainly by granulosa cells of a few healthy large follicles in the ovary and that it plays an important role in the regulation of FSH secretion during the estrous cycle in guinea pigs.

Animals↗

PubMed1999

Interleukin-11 therapy selectively downregulates type I cytokine proinflammatory pathways in psoriasis lesions.

Psoriasis is a chronic inflammatory skin disease in which epidermal hyperplasia results from skin infiltration by type I T lymphocytes and release of associated cytokines. A multifunctional cytokine, rhIL-11, modulates macrophage and type I T-lymphocyte function in cell culture and shows anti-inflammatory activity in animal models. We are testing subcutaneous delivery of rhIL-11 to patients with psoriasis in a phase 1 open-label dose-escalation clinical trial. Tissue was obtained from lesional and uninvolved skin before and during treatment with rhIL-11 and was examined by histology/immunohistochemistry and quantitative RT-PCR. Expression of over 35 genes was examined in all patients, and multiple genetic markers of psoriasis were identified. Expression of numerous proinflammatory genes was elevated in psoriatic tissue compared with nonlesional skin. Seven of 12 patients responded well to rhIL-11 treatment. Amelioration of disease by rhIL-11, as shown by reduced keratinocyte proliferation and cutaneous inflammation, was associated with decreased expression of products of disease-related genes, including K16, iNOS, IFN-gamma, IL-8, IL-12, TNF-alpha, IL-1beta, and CD8, and with increased expression of endogenous IL-11. We believe that this is the first study in humans to indicate that type I cytokines can be selectively suppressed by an exogenous immune-modifying therapy. The study highlights the utility of pharmacogenomic monitoring to track patient responsiveness and to elucidate anti-inflammatory mechanisms.

Antigens, Surface↗

PubMed1999

Comparisons between hemodynamics, during and after bathing, and prognosis in patients with myocardial infarction.

The purpose of this study was to establish the safest way to bathe patients with myocardial infarction (MI) through measuring the hemodynamics during and after bathing. Seventy patients with MI were bathed supine in a Hubbard tank filled with 42 degrees C tap water for 5 min. The subjects were divided into 2 groups depending on their hemodynamic values 10 min after bathing: pulmonary capillary wedge pressure unchanged even after bathing (group A), and decreased pressure after bathing (group B). The left ventricular ejection fraction of group B was significantly higher than that of group A: 53.6% vs. 39.7%, respectively (p<0.01). The physical work capacity of group B was significantly higher at 5.6 METs, than that of group A with 4.5 METs (p<0.05). During the average of their 37-month follow-up period, there were 3 cardiac events in group B and 6 in group A. There were 2 cardiac events during bathing, both of which occurred in group A. When patients with MI take a bath, it is essential to closely monitor them, especially to those patients with lower cardiac function, because they have a higher possibility of a cardiac event.

Aged↗

PubMed1999

Structural conversion from non-native to native form of recombinant human epidermal growth factor by Brevibacillus choshinensis.

Brevibacillus choshinensis (Bacillus brevis) HPD31 is a very efficient producer of recombinant human epidermal growth factor (EGF). The produced EGF is secreted into the medium with high efficiency. However part of the EGF that accumulates in the medium, exists as multimeric forms which are biologically inactive. We found the bacterium has the activity to structurally convert multimeric forms to the monomeric, native ones. Optimal temperature and pH for the conversion were 40 degrees C and pH 9, respectively. The reaction was promoted in the presence of reduced glutathione or cysteine. But the cells which had been sonicated or exposed to moderate heat treatment completely lost the activity. Thus, it was presumed that the activity might be due to the enzyme(s) that catalyze the protein disulfide exchanging reaction, and that they resides on the surface of viable cells.

Bacillus↗

PubMed1999

[A study on the concentration of eosinophil cationic protein in chronic sinusitis].

The relationship between eosinophil and chronic sinusitis was investigated by measuring the concentration of eosinophil cationic protein (ECP). In addition to the blood, a cytological brush was inserted into middle meatus to scrape the nasal membrane, and the concentration of ECP in the collected specimen was measured. There was a moderate degree of correlation between the blood eosinophil count and the ECP concentration in the blood (r = 0.543, p < 0.01). On the other hand, there was high degree of correlation between the number of EG2-positive cells and ECP of the nasal membrane in the middle meatus (r = 0.805, p < 0.001), reflecting the amount of ECP in the nasal mucous membrane. The ECP in 10 control group subjects and 14 patients with severe chronic sinusitis and nasal polyps was significantly lower than that in 14 patients with severe chronic sinusitis and asthma (p < 0.01). The ECP concentration of the nasal membrane in the middle meatus was significantly lower in patients showing a good postoperative course compared with patients showing a poor postoperative course following Endoscopic Sinus Surgery (p < 0.01). These findings suggest that eosinophils are closely related to the pathology and clinical course of chronic sinusitis, and that the ECP concentration of the nasal membrane in the middle meatus reflects the pathology of chronic sinusitis. The ECP concentration thus has potential as a prognostic indicator for chronic sinusitis.

Adult↗

PubMed1999

Experimental impression tray fabricated with a NiTi shape memory alloy plate.

A small experimental impression tray was fabricated with a NiTi shape memory alloy plate. After recovery of the shape memory effect, the upper rims of the tray holding the impression were opened to some extent, the resistance during removal of the model from the impression was significantly decreased compared to a commercially available tray and the tray before recovery of the shape memory effect. The pull-out force of the model from the impression was 23.5(0.2)N for the commercially available tray, 23.5(3.9)N for the experimental tray before recovery of the shape memory effect and 14.7(4.0)N after recovery of the shape memory effect (heated for 15 min at 70 degrees C). Therefore the tray should be useful in teeth fracture free modeling.

Dental Alloys↗

PubMed1998

Identification of the region of alpha-catenin that plays an essential role in cadherin-mediated cell adhesion.

alpha-Catenin is an intrinsic component of the cadherin adhesion complex and is a 102-kDa protein with multiple interaction sites, including homodimerization sites, and binding sites for beta- and gamma-catenin (plakoglobin), alpha-actinin, and actin. Besides the binding to beta- or gamma-catenin, it is unknown, however, which interaction is critical for the function of cadherins. By expressing a series of E-cadherin-alpha-catenin chimeric molecules on leukemia cells (K562), we have identified the region of alpha-catenin that confers aggregation inducing activity to nonfunctional tail-less E-cadherin. The region has been mapped to the carboxyl-terminal 295 amino acids of alpha-catenin. Consistent with this result, expression in alpha-catenin-deficient cells (DLD-1/Delta alpha) of a mutant alpha-catenin molecule consisting of the amino-terminal beta-/gamma-catenin-binding site and the carboxyl-terminal cell adhesion region identified in the above experiments induced E-cadherin-mediated cell aggregation and compaction. Cells expressing E-cadherin chimeric molecules with the homologous carboxyl-terminal region of vinculin, which contains the actin-binding site of vinculin, did not, however, aggregate as strongly as ones expressing E-cadherin-alpha-catenin chimeric molecules.

Base Sequence↗

PubMed1998

The membrane-proximal region of the E-cadherin cytoplasmic domain prevents dimerization and negatively regulates adhesion activity.

Cadherins are transmembrane glycoproteins involved in Ca2+-dependent cell-cell adhesion. Deletion of the COOH-terminal residues of the E-cadherin cytoplasmic domain has been shown to abolish its cell adhesive activity, which has been ascribed to the failure of the deletion mutants to associate with catenins. Based on our present results, this concept needs revision. As was reported previously, leukemia cells (K562) expressing E-cadherin with COOH-terminal deletion of 37 or 71 amino acid residues showed almost no aggregation. Cells expressing E-cadherin with further deletion of 144 or 151 amino acid residues, which eliminates the membrane-proximal region of the cytoplasmic domain, showed E-cadherin-dependent aggregation. Thus, deletion of the membrane-proximal region results in activation of the nonfunctional E-cadherin polypeptides. However, these cells did not show compaction. Chemical cross-linking revealed that the activated E-cadherin polypeptides can be cross-linked to a dimer on the surface of cells, whereas the inactive polypeptides, as well as the wild-type E-cadherin polypeptide containing the membrane-proximal region, can not. Therefore, the membrane-proximal region participates in regulation of the adhesive activity by preventing lateral dimerization of the extracellular domain.

Binding Sites↗

PubMed1998

Single muscle fiber analysis in patients with 3243 mutation in mitochondrial DNA: comparison with the phenotype and the proportion of mutant genome.

An A-to-G point mutation at nucleotide pair (np) 3243 (3243 mutation) in mitochondrial DNA (mtDNA) is a well-known pathogenic mutation, which has been found in approximately 80% of patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). It has been reported that the 3243 mutation also occurs in individuals with non-MELAS phenotypes. The reasons for the phenotypic heterogeneity of the 3243 mutation have not been clarified, although it may be closely related with mtDNA heteroplasmy and their differing proportions in different tissues. We examined the proportion of mutant DNA in muscle specimens at the cellular level using single fiber analysis in five patients with the 3243 mutation: three were diagnosed clinically as having MELAS and two had mitochondrial diabetes mellitus (MDM). In both phenotypes, ragged-red fibers (RRF) contained a higher percentage of mutant DNA (average 89.8%) than non-RRF (average 42.4%). On the other hand, the proportion of mutant DNA in non-RRF revealed a wider range than in RRF and the average was higher in MELAS patients (58.5+/-27.3%) than that in MDM patients (26.3+/-27.9%), which correlated with biochemical and morphological mitochondrial abnormalities in muscle. These findings may reflect the underlying mechanisms of tissue specificity in each phenotype.

Adolescent↗

PubMed1998

Altered cell adhesion activity by pervanadate due to the dissociation of alpha-catenin from the E-cadherin.catenin complex.

Leukemia cells (K562) that grow as non-adhesive single cells and have no endogenous cadherin were transfected with an E-cadherin expression vector, and cell clones stably expressing E-cadherin on their surface were established. The expression of E-cadherin induced the up-regulation of catenins, and E-cadherin became associated with catenins. The transfected cells grew as floating aggregates. Cell aggregation was Ca2+-dependent and was inhibited by E-cadherin antibodies. The aggregates dissociated into single cells on the addition of pervanadate. Pervanadate caused a dramatic augmentation of the phosphorylation of E-cadherin, beta-catenin, and gamma-catenin (plakoglobin), but alpha-catenin was not detectably phosphorylated. After pervanadate treatment, beta-catenin and gamma-catenin migrated more slowly on gel electrophoresis, suggesting changes in their conformations due to eventual changes in their phosphorylation levels. In the treated cells, a significant amount of alpha-catenin was dissociated from the E-cadherin.catenin complex. Aggregates of cells expressing an E-cadherin chimeric molecule covalently linked with alpha-catenin were not dissociated on pervanadate treatment, supporting the idea that the dissociation of alpha-catenin from the complex underlies the observed E-cadherin dysfunction.

Cadherins↗

PubMed1998

Effects of changes in the criteria for nationally shared kidney transplants for HLA-matched patients.

BACKGROUND: Nine years ago, a prospective trial began in all U.S. transplant centers to determine whether the results of renal transplantation would improve with the nationwide shipment of kidneys from cadaveric donors to HLA-matched patients. Since then, the stringency of criteria for HLA matching have been liberalized twice, from sharing only those kidneys that matched at all six HLA-A, -B, -DR antigens, to sharing phenotypically HLA-matched kidneys, and most recently to sharing zero HLA-mismatched kidneys. METHODS: Data reported to the United Network for Organ Sharing Scientific Renal Transplant Registry from October 1987 to December 1996 were analyzed to examine the transplant results of nationally shared HLA-matched kidneys and the effects of changes to the HLA matching criteria on graft survival and the distribution of HLA-matched kidneys. RESULTS: The overall 1-year graft survival rate of 5102 HLA-matched transplants was 88% compared with 81% for 58,207 recipients of kidneys with at least one HLA mismatch (P < 0.001). HLA-matched kidneys had a projected 12-year graft half-life, 50% higher than the 8-year half-life of mismatched grafts (P < 0.01). After the first change in the match criteria in August 1990, 1365 phenotypically matched kidneys with fewer than six HLA antigens identified had an 89% 1-year graft survival rate compared with 84% for 466 six antigen-matched kidneys transplanted before the change. After March 1995, 1067 zero HLA-mismatched kidneys that were not phenotypically identical nor six antigen matched, had a 1-year graft survival rate of 88%. Graft survival has not decreased as a result of these changes in the criteria for national sharing, despite an increase in the percentage of matched transplants from 2.5% during the six antigen-match era to 15.5% during the zero antigen-mismatch era. CONCLUSIONS: Changes to the United Network for Organ Sharing policy for national sharing of HLA-matched kidneys have increased the number of patients, and especially minority patients, who can benefit by receiving a well-matched graft without compromising the high graft survival rates provided by an HLA-matched kidney.

Cadaver↗

PubMed1998

Distribution and concentration of urocortin, and effect of adrenalectomy on its content in rat hypothalamus.

We developed a specific and sensitive radioimmunoassay (RIA) for rat urocortin (rUcn) and investigated the tissue distribution and concentration of immunoreactive (IR-)Ucn in rats. Antiserum was obtained by immunizing rabbits with synthetic rUcn21-35 coupled with bovine thyroglobulin. 125I-[Tyr]18-rUcn19-37 was used as the tracer. The RIA detected synthetic rUcn1-40 as low as 0.4 fmol/tube, and did not cross-react with other corticotropin-releasing factor-related peptides. IR-Ucn was widely distributed in central nervous system, endocrine organs, and digestive system. Its concentration was highest in pituitary (11.0 +/- 1.36 pmol/g.w.w., mean +/- SEM, n=4). Reverse-phase HPLC revealed that hypothalamic IR-Ucn had similar chromatographic mobility to synthetic rUcn1-40. However, bilateral adrenalectomy did not influence the hypothalamic IR-Ucn content. Our results suggest that Ucn may play important roles in various tissues in normal rats, but not behave as a hypothalamic hypophysiotropic factor in mediating adrenocorticotropin secretion in adrenalectomized rats.

Adrenal Glands↗

PubMed1998

Effect of urocortin and its interaction with adrenocorticotropin (ACTH) secretagogues on ACTH release.

We examined the effect of urocortin (Ucn) on the adrenocorticotropin (ACTH) release from cultured rat anterior pituitary cells and AtT 20 cells. Synthetic rat (r)Ucn was not soluble in 0.1 N HCl but soluble in alkaline solvents with diminished corticotropin-releasing activity. rUcn dissolved in 0.1 M sodium phosphate buffer as a stock solution maintained its bioactivity and had the equal corticotropin-releasing activity with rat/human corticotropin-releasing factor (r/hCRF). rUcn stimulated the adrenocorticotropin release via CRF-receptors accompanied by the additive effect with r/hCRF, the synergistic effect with arginine vasopressin and the dose-dependent inhibition of a potent CRF-receptor antagonist.

Adrenocorticotropic Hormone↗

PubMed1998

Impingement after total knee arthroplasty caused by cement extrusion and proximal tibiofibular instability.

A 57-year-old patient with rheumatoid arthritis showed posterolateral impingement after total knee arthroplasty. The radiographs showed bone cement extrusion posterolateral to the tibial tray. Arthrotomy through a posterolateral approach revealed that the impingement was caused not only by cement extrusion against the fibular head but also by proximal tibiofibular joint instability. It was speculated that rheumatoid arthritis had caused proximal tibiofibular instability, active knee motion had caused fibular head shift by tension of biceps femoris and the fibular head had been impinged on the extruded cement. In cementing the tibial tray, especially in a rheumatoid patient, it is of paramount importance to take caution against posterolateral cement extrusion in order to minimize the risk of fibular head impingement during total knee arthroplasty.

Arthritis, Rheumatoid↗