PubMed Health⌕ Search

Biomedical subjects

M Iwao

Publications and source records attributed to M Iwao.

At least 19 recordsLinked to original sources
PubMed2001

Decline of hepatitis C virus load in serum during the first 24 h after administration of interferon-beta as a predictor of the efficacy of therapy.

BACKGROUND/AIMS: Hepatitis C virus (HCV) kinetics during interferon (IFN)-alpha treatment have been evaluated recently, however, little is known about the resultant viral kinetics in IFN-beta treatment. In this study, we evaluated HCV kinetics during the first 24 h of IFN-beta treatment, and also assessed their relationship to therapeutic outcomes. METHODS: We measured HCV RNA levels at 0 and 24 h after the initiation of IFN-beta treatment, and we calculated the decay slope, viral half-life, and viral production and clearance. Then we analyzed these factors as they related to therapeutic responses with IFN-beta as well as to clinical variables, i.e. genotype, diversity of hyper variable region, and histological findings. RESULTS: Patients with sustained responses (SR) displayed steeper decay slopes of the viral load than those without SR (2.87 +/- 1.41 vs. 1.82 +/- 1.66, P = 0.031). On the other hand, the decay slope was not affected by the clinical variables. The values of viral half-life and viral production and clearance showed no significant correlation to the response and the clinical variables. CONCLUSION: This study demonstrated that the decay slope of the viral load during the first 24 h is related to the virological response to IFN-beta treatment.

Adolescent↗
PubMed2000

Interaction of merosin (laminin 2) with very late activation antigen-6 is necessary for the survival of CD4+ CD8+ immature thymocytes.

The laminin alpha2-chain is a component of merosin, a member of the laminin family molecules, which is mainly expressed in the basement membranes of striated muscle. It is known that laminin alpha2 gene (lama2) null mutant mice (dy3k/dy3k) exhibit congenital muscular dystrophy (CMD). Because the laminin alpha2-chain is also expressed in the thymus, the role of merosin in the thymus was examined. In association with the onset of muscular dystrophy, CD4+ CD8+ double-positive (DP) thymocytes disappear by apoptotic cell death, while CD4+ CD8- or CD4- CD8+ thymocytes remain. In order to study the mechanisms leading to the selective death of DP cells in the absence of merosin, the role of the interaction between very late activation antigen-6 (VLA-6), a candidate merosin ligand in the thymus, and merosin was examined. The in vitro survival of thymocytes from normal mice was maintained by the addition of either anti-VLA-6 monoclonal antibodies (mAbs) or merosin. Furthermore, when the normal thymocytes were cultured on thymic epithelial cell lines, viable DP cell recoveries on wild-type epithelial cells were better than on cells from null mutant mice. The results suggest that DP cells are more sensitive to an uncharacterized apoptotic death signal, and that survival is supported by the interaction between VLA-6 and merosin.

Animals↗
PubMed1999

Green fluorescent protein-transgenic mice: immune functions and their application to studies of lymphocyte development.

Green fluorescent protein (GFP) transgenic (GFP+) mice express GFP in most tissues except erythrocytes and hair. Immune responses of GFP+ mouse and their application to studies of lymphocyte development were investigated. Flow cytometric analyses revealed that differentiation patterns of lymphocytes from GFP+ mice are equivalent to those from parental C57BL/6 mice. There was no difference in mature T-cell proliferative ability in response to allogeneic stimulator cells or anti-CD3epsilon stimulation between GFP+ and C57BL/6 mice. Furthermore, the anti-OVA antibody response of GFP+ mice was also the same as that of C57BL/6 mice. Taken together, these results show no immunological differences between GFP+ and C57BL/6 mice. Bone marrow transplantation and in vitro thymus reconstitution experiments were performed in an attempt to apply the GFP+ mice to the analysis of lymphocyte development. When bone marrow cells from GFP+ mice were transplanted. T and B lymphocytes containing GFP developed normally in scid recipients. Next we examined intrathymic T-cell development by hanging drop culture methods. GFP+ and CD4+8+ immature T-cells developed normally from bone marrow cells in the reconstituted thymus. The experimental system using hematopoietic cells from GFP+ mice is a powerful tool for visualizing lymphocyte development.

Animals↗
PubMed1999

Roles of integrins and CD44 on the adhesion and migration of fetal liver cells to the fetal thymus.

Adhesion and migration of mouse fetal liver (FL) cells to the thymus were investigated using cells from green fluorescent protein transgenic (GFP+) mice. FL cells from GFP+ embryos at 12 gestational days (E12) of mice were incubated with 2'-deoxyguanosine-treated fetal thymus lobe (from E14) by thymic repopulation (hanging drop) culture methods. GFP+ cells were observed in the thymus lobe at the end of the repopulation culture period. A large part of the infiltrated cells expressed CD44 until day 2 of culture on a permeable membrane, then lost the expression. CD25 expression was observed from day 1 to day 4. Around day 8, GFP+ cells became both CD4+ and CD8+. The results support the early observation of the sequential expression of CD44, CD25, and CD4/8 during the early stages of thymocyte development. When anti-CD44 mAb was added at the beginning of the repopulation culture period, GFP+ FL cells adhered to the surface of the thymus lobe but did not migrate into the thymus. Pretreatment of the thymus with hyaluronidase or hyaluronate produced results similar to the results of anti-CD44 treatment. On the other hand, the addition of anti-integrin alpha4 mAb inhibited adhesion to the thymus, and almost no GFP+ cells were seen on the surface of the thymus lobe. The data suggest that integrin alpha4 and CD44 play different roles, i.e., integrin alpha4 is required for the adhesion of FL cells to the thymus lobe and CD44 is required for the migration of the cells into the thymus.

Animals↗
PubMed1999

Effects of qigong walking on diabetic patients: a pilot study.

OBJECTIVES: The present study was designed to evaluate the advantages of qigong walking, a mild and slow exercise that uses all the muscles of the body, in comparison with conventional walking in patients with diabetes. INTERVENTIONS: Ten inpatients with diabetes mellitus and associated complications were studied on 3 different days. Either qigong walking (30-40-minute duration) or conventional walking was performed by the patients 30 minutes after lunch on 1 of the 3 study days. Plasma glucose levels and pulse rates were measured 30 minutes after lunch and again 20 minutes after exercising; that is, 90 minutes after lunch. These data were compared to those obtained on a day with no exercise after lunch. RESULTS: Plasma glucose levels decreased during both exercises (from 228 mg/dL before to 205 mg/dL after conventional walking) and (from 223 mg/dL before to 216 mg/dL after qigong walking). In both situations the results after exercise decreased more than those in the group with no exercise (229 mg/dL; p < 0.025). The pulse rates increased after conventional walking (from 77 to 95 beats per minute; p < 0.025) and were higher than those in the group with no exercise (70 beats per minute; p < 0.01) and those after qigong walking (79 beats per minute; p < 0.05). CONCLUSIONS: Qigong walking reduced plasma glucose after lunch without inducing a large increase in the pulse rate in patients with diabetes.

Aged↗
PubMed1999

Protein chemotaxonomy of the solanaceae. VI. Amino acid sequence of ferredoxin from Nicotian tabacum.

The complete amino acid sequence of [2Fe-2S] ferredoxin from Nicotiana tabacum has been determined by automated Edman degradation of the entire Cm-protein and of the peptides obtained by trypsin and Asp-N endoproteinase digestions. This ferredoxin exhibited 9, 10, 8, and 10 differences respectively in its amino acid sequence, when compared with the ferredoxins of Datura stramonium, D. metel, D. arborea, and Physalis alkekengi var.francheti but 17-28 differences for other angiosperms, and 34-37 differences for fern and horsetails. These results are in agreement with the taxonomic position for these plants.

Amino Acid Sequence↗
PubMed1998

Isoxazolidine-3,5-dione and noncyclic 1,3-dicarbonyl compounds as hypoglycemic agents.

Isoxazolidine-3,5-dione 2 (JTT-501), one of the cyclic malonic acid derivatives, was found to decrease blood glucose at an oral dose of 38 mg/kg/day in KKAy mice and is currently undergoing evaluation in phase II clinical trials. Further studies on a series of malonic acids and related compounds showed that the 1,3-dicarbonyl structure was important for insulin-sensitizing activity. Dimethyl malonate 10, which was selected as a successor for 2, was the optimum compound in a series of 1,3-dicarbonyl compounds and was more potent than the corresponding thiazolidine-2,4-dione 1.

3T3 Cells↗
PubMed1998

Induction of apoptosis by hepatocyte growth factor/scatter factor and its augmentation by phorbol esters in Meth A cells.

Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional cytokine with mitogenic, motogenic, and morphogenic activities. In addition, HGF/SF inhibits the proliferation of some tumor cell lines, but its mechanism remains poorly understood. We determined in this study whether HGF/SF induces cell death of a Meth A mouse sarcoma cell line in vitro, whose proliferation is remarkably suppressed by HGF/SF. Inhibition of Meth A cell growth by HGF/SF was dose-dependent and maximal at a concentration of 30 ng/ml. The percentage of dead cells increased to 22% upon treatment with 30 ng/ml of HGF/SF for 96 h, whereas that in untreated cultures was less than 5%. Staining of these cells nuclei with Hoechst 33342 revealed condensation of the chromatin and nuclear fragmentation. Gel electrophoresis of DNA from HGF/SF-treated cells showed a typical ladder pattern. Cells with a fractional DNA content also increased five-fold in the HGF/SF-treated cultures as analyzed by flow cytometry after propidium iodide staining. These are features typical of apoptosis. Concurrent addition of 12-O-tetradecanoylphorbol 13-acetate (TPA) with HGF/SF augmented the apoptosis induced by the growth factor, while TPA alone caused little death. This enhancement was largely blocked by addition of the specific protein kinase C inhibitor GF 109203X. These results indicate that HGF/SF induced the apoptotic cell death of the Meth A sarcoma cell line and that protein kinase C activation augmented the growth factor-induced apoptosis.

Animals↗
PubMed1998

Involvement of cytosolic phospholipase A2 in the ovulatory process in gonadotropin-primed immature rats.

The preovulatory LH surge induces a remarkable increase in ovarian prostaglandins (PGs) which help to mediate the ovulatory process. We investigated whether cytosolic phospholipase A2 (cPLA2) has a role in this PG production in PMSG/hCG-primed immature rats. The immunoreactive signal for cPLA2 was localized in both thecal and granulosa layers of mature follicles and became evident in response to gonadotropins. The PLA2 activity in the whole ovarian cytosol rose slightly after PMSG stimulation, persisted relatively constant until 24 h after hCG injection and thereafter increased gradually. Intra-ovarian bursal injection of arachidonyl trifluoromethyl ketone, a specific inhibitor for cPLA2 ( 1.0-3.0 mg/ovary), significantly reduced ovarian PGE2 content and the ovulation rate. These results suggest that cPLA2 exists in periovulatory follicles and functions in PG production related to the ovulation process.

Animals↗
PubMed1998

Stimulation of hepatocyte growth factor production by ascorbic acid and its stable 2-glucoside.

Hepatocyte growth factor (HGF), a cytokine which is generally produced by mesenchymal cells, has mitogenic, motogenic and morphogenic activities in epithelial cells and it also has tumor-suppressing activities. Induction of HGF production may be involved in organ regeneration, wound healing and embryogenesis. We examined the effects of ascorbic acid (AsA), which stimulates the proliferation of fibroblasts, and its stable derivative, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G), on HGF production by human skin fibroblasts. Basal HGF secretion was significantly stimulated by more than 0.1 mM AsA or AA-2G. Both vitamins synergistically enhanced HGF secretion stimulated by growth factors such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), cholera toxin and other inducers. Induction by EGF or bFGF was most markedly potentiated by the vitamins. HGF production by the KG-1 human leukemia cell line was also augmented by AsA or AA-2G. Another stable AsA derivative, ascorbic acid 2-phosphate (AA-2P) effectively promoted basal and EGF-induced HGF secretion by the fibroblasts, but ascorbic acid 2-sulfate (AA-2S) was much less effective. Intracellular AsA levels increased after the addition of AA-2G and AA-2P as well as AsA, but not after AA-2S. The effect of AA-2G was completely abrogated by the simultaneous addition of castanospermine, an alpha-glucosidase inhibitor, suggesting that the active form of AA-2G is AsA. Constitutive and EGF-induced HGF gene expression was also up-regulated after adding AsA or AA-2G to the cells. These results indicated that AsA acts alone or in synergy with several inducers to stimulate the production and gene expression of HGF in human skin fibroblasts and that the stable AsA derivative AA-2G is as effective as AsA in promoting HGF production.

Acetylcysteine↗
PubMed1998

Demographic features of patients seeking cosmetic surgery.

The demographic features of 415 patients seeking cosmetic surgery were investigated from a psychiatric point of view. Of the 415 patients, 198 (47.7%) were found to have mental disorders according to ICD-10 including: 17 with schizophrenia, 20 with other persistent delusional disorders, 33 with depressive episode, 47 with neurotic disorders, 42 with hypochondriacal disorder, five with paranoid personality disorder and 14 with histrionic personality disorder. The rate of subjects with poor social adjustment was 56.0%. It was noteworthy that such a considerable number of patients with mental disorders or with poor social adjustment had sought cosmetic surgery. Distinct gender differences were found: male subjects were characterized to have a greater number of mental disorders, especially dysmorphophobia (other persistent delusional disorders plus hypochondriacal disorder) and showed the narrow age range between teenage and young adult age when they were preoccupied with their 'deformity', and poor social function. A history of frequent operations was not considered to be an indicator for mental abnormality. The diagnostic issue in dysmorphophobia is briefly described.

Adolescent↗
PubMed1994

Expression of hepatocyte growth factor is up-regulated through activation of a cAMP-mediated pathway.

Hepatocyte growth factor (HGF) is a multifunctional cytokine with mitogenic, motogenic, morphogenic, and tumor-suppressing activities. Despite the broad spectrum of its biological activities, HGF is most likely the physiological hepatotrophic factor that triggers or modulates liver regeneration. Regulatory mechanisms for HGF production are crucial for understanding the control of liver regeneration. We previously reported that HGF production by human skin fibroblasts is stimulated by a protein kinase C (PKC)-mediated pathway. We determined here whether gene expression and production of HGF in human skin fibroblasts can be induced via activation of a cAMP-mediated pathway. HGF secretion by the cells was markedly stimulated by the cAMP-elevating agents, forskolin, cholera toxin, prostaglandin E2 (PGE2), and 3-isobutyl-1-methylxanthine, as well as by the membrane-permeable cAMP analogues, 8-bromo-cAMP and dibutyryl cAMP. The dose-response curves of induction of HGF secretion by cholera toxin and forskolin were nearly parallel with those of the intracellular cAMP levels. HGF mRNA levels did not significantly increase at 5 and 10 h, but increased considerably 15 h or more after the addition of cholera toxin. Forskolin, 8-bromo-cAMP, and PGE2 also caused appreciable up-regulation of HGF gene expression with a similar time course. Although human skin fibroblasts of various origins secreted variable amounts of HGF, the cAMP-elevating agents and the cAMP analogues caused a very marked increase in HGF production in all of them. The agents also enhanced highly active HGF secretion by MRC-5 human embryonic lung fibroblasts. Dexamethasone and transforming growth factor-beta 1, which inhibit PKC-mediated HGF secretion, down-regulated HGF mRNA expression and HGF production in the cells treated with the cAMP-elevating agents and the cAMP analogues. These results indicate that HGF expression in human skin fibroblasts is stimulated by activation of a cAMP-mediated pathway.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Expression of GTP-binding protein gene drg during Xenopus laevis development.

To study the genes which may play a role in the development of the vertebrate central nervous system (CNS) using a subtraction cloning approach, we previously identified a set of novel genes which are predominantly expressed in the mouse embryonic CNS and down-regulated during development. One of these genes, drg, encodes a novel 41 kilodalton GTP-binding protein (DRG), which is highly expressed in the embryonic CNS and shows remarkable evolutionary conservation. To study the biological role of this protein during Xenopus embryonic development, we cloned the Xenopus drg cDNA (Xdrg). The predicted Xenopus DRG protein (XDRG) is more than 95% identical to the mouse DRG. Analysis of Xdrg expression by Northern blots, whole-mount in situ hybridization and RNA-PCR revealed the presence of varying levels of transcript for this gene in embryos and adult tissues. Among the three mRNA species detected by Northern hybridization, two smaller ones show temporally regulated expression patterns during embryonic development.

Amino Acid Sequence↗
PubMed1992

A carboxyl-terminal truncated version of the activin receptor mediates activin signals in early Xenopus embryos.

The function of a carboxyl-terminal truncated version of the Xenopus activin receptor, encoded by a previously isolated gene XSTK2, was investigated in early embryos. The transcript corresponding to the truncated receptor gene was detected throughout embryonic development although the temporal expression pattern was different from that of an intact receptor. Injection of XSTK2 mRNA into early embryos resulted in the formation of a duplicated body axis. Mesoderm induction as evaluated by the activation of the alpha-actin gene in presumptive ectoderm (animal cap) treated with exogenous activin was significantly enhanced by the injection of XSTK2 mRNA. These results suggest that the truncated receptor is capable of transmitting the activin signal to the same extent as the native receptor.

Actins↗