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Biomedical subjects

M Noda

Publications and source records attributed to M Noda.

At least 163 records · Page 9Linked to original sources
PubMed2000

[Construction of a subjective fatigue scale for adolescent students].

OBJECTIVE: There is no appropriate scale to evaluate subjective symptoms of fatigue (SSF) in everyday life in adolescent students. An existing scale long before constructed for laborers has been used. It is essential to establish a practical, rational scale. The purpose of this study was to construct a practical scale to measure subjective symptoms of fatigue for high school and college students. METHODS: A questionnaire on SSF was administered to 5,435 students aged 15-20 yr. Factor analysis based on the oblique Promax rotation method was applied to a correlation matrix consisting of 44 items. RESULTS: Six factors were interpreted as follows: difficulty with concentrated thinking, languor, reduced activation, reduced motivation, drowsiness and feeling of physical disintegration. A subjective fatigue scale (SFS-Y: 24 items) was constructed using these factors. The eigen-value of principal component analysis, alpha reliability coefficients, and test-retest reliability coefficients for each subscale were very high. CONCLUSION: The SFS-Y generated in the present study is a very practical scale with high validity and reliability.

Adolescent↗
PubMed1999

HPLC analysis of dental resin composites components.

Five uncured commercial dental resin composites (two bis-glycidyl methacrylate based products and three non-bis-glycidyl methacrylate based products) were examined for contamination with bisphenol A, which is a known xenobiotic. After the samples were processed with acetonitrile for extraction of their components, high performance liquid chromatography analysis was performed and the eluted peaks were fractionated for comparison using UV spectra. The results suggested that all the resin composites tested were contaminated with bisphenol A or its derivatives. Theoretically, bisphenol A is not a component of dental resin composite, but it could remain as an impurity of the composite during the synthesis of Bis-GMA. The results suggest that it is necessary to investigate the ability of this impurity and its derivatives in dental resin composites to cause estrogenic effects, as well as to evaluate the release of the impurity from cured resin composites.

Benzhydryl Compounds↗
PubMed1999

Calbindin-D(28k) controls [Ca(2+)](i) and insulin release. Evidence obtained from calbindin-d(28k) knockout mice and beta cell lines.

The role of the calcium-binding protein, calbindin-D(28k) in potassium/depolarization-stimulated increases in the cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and insulin release was investigated in pancreatic islets from calbindin-D(28k) nullmutant mice (knockouts; KO) or wild type mice and beta cell lines stably transfected and overexpressing calbindin. Using single islets from KO mice and stimulation with 45 mM KCl, the peak of [Ca(2+)](i) was 3.5-fold greater in islets from KO mice compared with wild type islets (p < 0.01) and [Ca(2+)](i) remained higher during the plateau phase. In addition to the increase in [Ca(2+)](i) in response to KCl there was also a significant increase in insulin release in islets isolated from KO mice. Evidence for modulation by calbindin of [Ca(2+)](i) and insulin release was also noted using beta cell lines. Rat calbindin was stably expressed in betaTC-3 and betaHC-13 cells. In response to depolarizing concentrations of K(+), insulin release was decreased by 45-47% in calbindin expressing betaTC cells and was decreased by 70-80% in calbindin expressing betaHC cells compared with insulin release from vector transfected betaTC or betaHC cells (p < 0.01). In addition, the K(+)-stimulated intracellular calcium peak was markedly inhibited in calbindin expressing betaHC cells compared with vector transfected cells (225 nM versus 1,100 nM, respectively). Buffering of the depolarization-induced rise in [Ca(2+)](i) was also observed in calbindin expressing betaTC cells. In summary, our findings, using both isolated islets from calbindin-D(28k) KO mice and beta cell lines, establish a role for calbindin in the modulation of depolarization-stimulated insulin release and suggest that calbindin can control the rate of insulin release via regulation of [Ca(2+)](i).

1-Methyl-3-isobutylxanthine↗
PubMed1999

Sympathetic potentiation of cyclic ADP-ribose formation in rat cardiac myocytes.

We examined the role of cyclic ADP-ribose (cADP-ribose) as a second messenger downstream of adrenergic receptors in the heart after excitation of sympathetic neurons. To address this question, ADP-ribosyl cyclase activity was measured as the rate of [(3)H]cADP-ribose formation from [(3)H]NAD(+) in a crude membrane fraction of rat ventricular myocytes. Isoproterenol at 1 microM increased ADP-ribosyl cyclase activity by 1.7-fold in ventricular muscle; this increase was inhibited by propranolol. The stimulatory effect on the cyclase was mimicked by 10 nM GTP and 10 microM guanosine 5'-3-O-(thio)triphosphate, whereas 10 microM GTP inhibited the cyclase. Cholera toxin blocked the activation of the cyclase by isoproterenol and GTP. The above effects of isoproterenol and GTP in ventricular membranes were confirmed by cyclic GDP-ribose formation fluorometrically. These results demonstrate the existence of a signal pathway from beta-adrenergic receptors to membrane-bound ADP-ribosyl cyclase via G protein in the ventricular muscle cells and suggest that increased cADP-ribose synthesis is involved in up-regulation of cardiac function by sympathetic stimulation.

ADP-ribosyl Cyclase↗
PubMed1999

Molecular cloning and biological activity of a novel Ha-Ras suppressor gene predominantly expressed in skeletal muscle, heart, brain, and bone marrow by differential display using clonal mouse EC cells, ATDC5.

We cloned a cDNA encoding a novel mouse protein, named A-C1, by differential display between two mouse cell lines: embryonic fibroblast C3H10T1/2 and chondrogenic ATDC5. The deduced amino acid sequence of A-C1 consists of 167 amino acids and shows 46% identity with that of a ras-responsive gene, rat Ha-rev107. Northern blot analysis showed a distinct hybridization band of 3.2 kilobases. Expression of A-C1 mRNA was detected in undifferentiated ATDC5 cells and myoblastic C2C12 cells, while none of C3H10T1/2 cells, NIH3T3 fibroblasts, Balb/c 3T3 fibroblasts, osteoblastic MC3T3-E1 cells, and ST2 bone marrow stromal cells expressed A-C1 mRNA in vitro. Moreover, A-C1 mRNA was expressed in skeletal muscle, heart, brain, and bone marrow in adult mice. By in situ hybridization, A-C1 gene expression was localized in hippocampus as well as bone marrow cells. By immunocytochemistry, A-C1 protein was detected in the cytoplasm as well as perinuclear region of the cells. Transfection of A-C1 cDNA into Ha-ras-transformed NIH3T3 cell line caused increase in the number of flat colonies and inhibition of cell growth. Our data indicate that A-C1 is expressed in some specific tissues in vivo and modulates Ha-ras-mediated signaling pathway.

3T3 Cells↗
PubMed1999

Involvement of the Sp1 site in ras-mediated downregulation of the RECK metastasis suppressor gene.

We have isolated and characterized the 5'-flanking region of the mouse RECK gene aiming to understand the mechanism of oncogene-mediated suppression of RECK gene expression. The upstream 52-base region was found to contain a promoter activity which is, to some extent, suppressed by the ras oncogene. This region contains two Sp1-binding motifs, one cEBPb-binding motif, and one CAAT box. Although both of the Sp1 sites were found to associate with Sp1 as well as Sp3 proteins, ras responsiveness seems to be mediated only by the downstream Sp1 site. Our data indicate that the Sp1 motif in certain contexts can serve as a negative target for the Ras signal.

3T3 Cells↗
PubMed1999

Articular cartilage cells immortalized by a temperature sensitive mutant of SV40 large T antigen survive and form cartilage tissue in articular cartilage environment.

A chondrogenic cell line, TC6, was established by using cells derived from articular cartilage of transgenic mice harboring a temperature-sensitive mutant simian virus (SV) 40 large T-antigen gene. TC6 cells express genes encoding proteins related to cartilage phenotypes such as type II collagen. To examine the in vivo behavior of the TC6 cells, these cells were implanted into cavity-shaped full-thickness defects made in the articular cartilage of the central part of the patellar grooves of mouse femora. One week after implantation, the morphology of the cells was still fibroblastic but these cells were just about to start to form a cartilage-like matrix. By 6 weeks after implantation, the cells had produced abundant cartilaginous matrix and their morphology became closer to that of authentic chondrocytes. This was in sharp contrast to the fibroblastic morphology of these cells in an in vitro environment even after long-term culture. These observations indicate that a cartilage-matrix environment provides a scaffold for the TC6 cells to form cartilage tissues. Our data show that the genetically engineered chondrocytic cell line, TC6, can form a cartilage-like matrix in vivo.

Animals↗
PubMed1999

Protein tyrosine phosphatase zeta/RPTPbeta interacts with PSD-95/SAP90 family.

PTPzeta/RPTPbeta is a proteoglycan-type receptor-like protein tyrosine phosphatase specifically expressed in the brain. Although several ligands of PTPzeta have been identified, proteins interacting with the intracellular region of PTPzeta are still unknown. We performed yeast two-hybrid screening using the intracellular region of PTPzeta as a bait, and found that the C-terminal sequence of PTPzeta binds to the PSD-95/SAP90 family through the second PDZ domain. Immunohistochemical analysis revealed that PTPzeta and PSD-95/SAP90 are similarly distributed in the dendrites of pyramidal neurons of the hippocampus and neocortex. Furthermore, subcellular fractionation experiments indicated that PTPzeta is concentrated in the postsynaptic density fraction. These results suggested that PTPzeta is involved in the regulation of synaptic function as postsynaptic macromolecular complexes with PSD-95/SAP90.

Animals↗
PubMed1999

Induction of apoptosis of monocyte-macrophage lineage cells by 5-S-GAD.

We found that 5-S-GAD, an insect-derived antibacterial peptide, inhibited murine osteoclast formation in vitro. We examined the specific time point of the inhibitory action of 5-S-GAD on osteoclast formation and found that it mainly suppressed differentiation of osteoclasts in the middle of the culture period. Using HL60 cells that are able to differentiate into multinucleated macrophage-like cells, we found that 5-S-GAD induced apoptosis of HL60 cells by producing H(2)O(2). Thus, the inhibition of osteoclast formation by 5-S-GAD could be, in part, due to apoptosis of the cells of an osteoclast lineage.

Acid Phosphatase↗
PubMed1999

NADH shuttle system regulates K(ATP) channel-dependent pathway and steps distal to cytosolic Ca(2+) concentration elevation in glucose-induced insulin secretion.

The NADH shuttle system is composed of the glycerol phosphate and malate-aspartate shuttles. We generated mice that lack mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH), a rate-limiting enzyme of the glycerol phosphate shuttle. Application of aminooxyacetate, an inhibitor of the malate-aspartate shuttle, to mGPDH-deficient islets demonstrated that the NADH shuttle system was essential for coupling glycolysis with activation of mitochondrial ATP generation to trigger glucose-induced insulin secretion. The present study revealed that blocking the NADH shuttle system severely suppressed closure of the ATP-sensitive potassium (K(ATP)) channel and depolarization of the plasma membrane in response to glucose in beta cells, although properties of the K(ATP) channel on the excised beta cell membrane were unaffected. In mGPDH-deficient islets treated with aminooxyacetate, Ca(2+) influx through the plasma membrane induced by a depolarizing concentration of KCl in the presence of the K(ATP) channel opener diazoxide restored insulin secretion. However, the level of the secretion was only approximately 40% of wild-type controls. Thus, glucose metabolism through the NADH shuttle system leading to efficient ATP generation is pivotal to activation of both the K(ATP) channel-dependent pathway and steps distal to an elevation of cytosolic Ca(2+) concentration in glucose-induced insulin secretion.

Animals↗
PubMed1999

Suppression of the poly(ADP-ribose) polymerase activity by DNA-dependent protein kinase in vitro.

It has been suggested that DNA-dependent protein kinase (DNA-PK) is a central component of DNA double-strand-break repair. The mechanism of DNA-PK action, however, has not been fully understood. Poly(ADP-ribose) polymerase (PARP) is another nuclear enzyme which has high affinity to DNA ends. In this study, we analysed the interaction between these two enzymes. First, DNA-PK was found to suppress the PARP activity and alters the pattern of poly(ADP-ribosyl)ation. Although DNA-PK phosphorylates PARP in a DNA-dependent manner, this modification is unlikely to be responsible for the suppression of PARP activity, since this suppression occurs even in the absence of ATP. Conversely, PARP was found to ADP-ribosylate DNA-PK in vitro. However, the auto-phosphorylation activity of DNA-PK was not influenced by this modification. In a competitive electrophoretic mobility shift assay, Ku 70/80 complex, the DNA binding component of DNA-PK, was found to have higher affinity to a short fragment of DNA than does PARP. Furthermore, co-immunoprecipitation analysis suggested direct or close association between Ku and PARP. Thus, DNA-PK suppresses PARP activity, probably through direct binding and/or sequestration of DNA-ends which serve as an important stimulator for both enzymes.

Antigens, Nuclear↗
PubMed1999

Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption.

Osteopontin is one of the major noncollagenous bone matrix proteins produced by osteoblasts and osteoclasts, bone cells that are uniquely responsible for the remodeling of mineralized tissues. Osteoclasts express the alphavbeta3 integrin, which is one of the receptors for osteopontin. Recent knockout studies revealed that noncollagenous bone matrix proteins are functionally important in regulation of bone metabolism. However, the significance of the presence of osteopontin in in vivo has not been known. We report here that osteopontin knockout mice are resistant to ovariectomy-induced bone resorption compared with wild-type mice. Microcomputed tomography analysis indicated about 60% reduction in bone volume by ovariectomy in wild-type mice, whereas the osteopontin-deficient mice exhibited only about 10% reduction in trabecular bone volume after ovariectomy. Reduction in uterine weight was observed similarly in both wild-type and osteopontin-deficient mice, indicating the specificity of the effect of osteopontin deficiency on bone metabolism. We propose that osteopontin is essential for postmenopausal osteoporosis in women. Strategies to counteract osteopontin's action may prove effective in suppressing osteoporosis.

Animals↗
PubMed1999

Noggin expression in a mesodermal pluripotent cell line C1 and its regulation by BMP.

Osteoblasts and chondrocytes are derived from mesodermal stem cells and their differentiation is under the control of coordinated interaction among signaling molecules. Noggin is one of the signaling molecules which bind to and inactivate BMPs to induce neural tissues and dorsal mesoderm in Xenopus. However, its expression and regulation in mammalian cells has not been known. In this study, we investigated expression of noggin in murine pluripotent mesodermal cell line, C1. Noggin expression was very low in these C1 cells before they were induced to differentiate. When C1 cells were induced to differentiate into chondrocytes in aggregate cultures in the presence of dexamethasone(dex), noggin expression was significantly increased. In a sharp contrast, when the C1 cells were induced to differentiate into osteoblastic cells by the treatment with beta glycerophosphate (betaGP) and ascorbic acid (AA), noggin mRNA expression remained to be barely detectable. Noggin expression was also observed in the developing cartilage of vertebrae in 15.5 dpc mouse embryos. The noggin mRNA level in C1 cells in monolayer cultures was enhanced significantly by the treatment with BMP4/7 in a dose-dependent manner with a maximal effect at 100 ng/ml. The BMP4/7 effect on noggin expression was time dependent starting within 12 h and peaked at 24 h. These results indicate that noggin is expressed in the pluripotent mesodermal cell line C1 and that its expression is regulated by BMP.

Animals↗
PubMed1999

Effects of intraalveolar oxygen concentration on alveolar fluid absorption and metabolism in isolated rat lungs.

We evaluated the effects of intraalveolar oxygen concentration on alveolar fluid absorption and metabolism in isolated rat lungs. Alveolar fluid absorption was determined by measuring increase in albumin concentration in the instillate solution during 2 h of incubation. Oxidative phosphorylation was assessed by gas analysis of the solution. Glycolysis was assessed by determining glucose escape and lactate release in the solution. We found that alveolar fluid absorption did not change under hyperoxic and hypoxic experimental environments (range 100-10% oxygen). Glycolysis was reduced under hyperoxia and stimulated under hypoxia, however, lung ATP content did not change. When oxidative phosphorylation was inhibited by NaCN, both alveolar fluid absorption and lung ATP content were reduced. Our data indicate that isolated rat lungs maintain optimal energy production for alveolar fluid absorption by stimulating glycolysis, even though glycolysis alone is not enough. We conclude that alveolar fluid absorption determined in isolated rat lungs is not influenced by intraalveolar oxygen concentration in the range above 10% oxygen.

Adenosine Triphosphate↗
PubMed1999

A receptor-like protein-tyrosine phosphatase PTPzeta/RPTPbeta binds a heparin-binding growth factor midkine. Involvement of arginine 78 of midkine in the high affinity binding to PTPzeta.

Midkine is a 13-kDa heparin-binding growth factor with 45% sequence identity to pleiotrophin. Pleiotrophin has been demonstrated to bind to protein-tyrosine phosphatase zeta (PTPzeta) with high affinity. In this study, we examined the binding of midkine to PTPzeta by solid-phase binding assay. Midkine and pleiotrophin binding to PTPzeta were equally inhibited by soluble pleiotrophin and also by some specific glycosaminoglycans. For both bindings, Scatchard analysis revealed low (3.0 nM) and high (0.58 nM) affinity binding sites. These results suggested that PTPzeta is a common receptor for midkine and pleiotrophin. Midkine is structurally divided into the N- and C-terminal halves, and the latter exhibited full activity for PTPzeta binding and neuronal migration induction. The C-terminal half contains two heparin-binding sites consisting of clusters of basic amino acids, Clusters I and II. A mutation at Arg78 in Cluster I resulted in loss of the high affinity binding and reduced neuronal migration-inducing activity, while mutations at Lys83 and Lys84 in Cluster II showed almost no effect on either activity. Chondroitinase ABC-treated PTPzeta exhibited similar low affinity binding both to the native midkine and midkine mutants at Arg78. These results suggested that Arg78 in midkine plays an essential role in high affinity binding to PTPzeta by interacting with the chondroitin sulfate portion of this receptor.

Animals↗