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M Noda

Publications and source records attributed to M Noda.

At least 433 records · Page 24Linked to original sources
PubMed1992

DRG: a novel developmentally regulated GTP-binding protein.

Using a subtraction cloning approach we had previously isolated a series of murine cDNA clones representing the genes predominantly expressed in the embryonic brain and down-regulated during development. We now report that one of these cDNA clones encodes a novel type of GTP-binding protein. The predicted protein of 40.5 kD, named DRG, contains five structural motifs characteristic of the GTP-binding proteins. Consistently, bacterially expressed and cellular DRG proteins are capable of binding GTP in vitro. Sequences closely related to the DRG protein are found in other species including Drosophila and Halobacterium. Based on these observations, we propose that DRG represents an evolutionarily conserved novel class of GTP-binding protein which may play an important role in cell physiology.

Aging↗
PubMed1992

Expression of DRG during murine embryonic development.

We had previously characterised a cDNA which encodes a novel GTP-binding protein DRG. The expression of drg gene is down-regulated during the embryonic development of murine central nervous system. Further analysis of drg mRNA and protein in adult mouse tissues and various cell lines of different origins indicated that it is expressed widely, albeit at low and variable levels. In situ hybridisation analysis of mRNA expression in sections of mouse embryos indicated that drg is expressed strongly in various embryonic tissues. The expression of drg mRNA is greatly reduced in newborn animals. At cellular level, DRG protein can be detected in the cytoplasm. These observations suggest that DRG may play multiple roles in development and normal cell metabolism.

3T3 Cells↗
PubMed1992

Left ventricular relaxation in dilated cardiomyopathy: relation to loading conditions and regional nonuniformity.

OBJECTIVES: The purpose of the present study was to investigate how loading conditions and regional nonuniformity affect left ventricular relaxation in dilated cardiomyopathy. BACKGROUND: Left ventricular relaxation is impaired in dilated cardiomyopathy. It has been suggested that relaxation abnormality is related to loading conditions and regional nonuniformity in the diseased heart. METHODS: Left ventriculography with simultaneous pressure manometry was performed in 10 patients with dilated cardiomyopathy before and during nitroprusside infusion. Ten normal subjects served as a control group. Left ventricular hemodynamics, regional wall motion (assessed by the area method) and regional wall stress (Janz method) were analyzed. RESULTS: When compared with control subjects, the patients with dilated cardiomyopathy had a reduced left ventricular ejection fraction (p < 0.01) and prolonged relaxation time constants (p < 0.01). Left ventricular wall motion was both hypokinetic and asynchronous in the patient group. In addition, systolic regional wall stress was significantly greater, the time to peak wall stress was longer and the regional myocardial relaxation time constant was greater for each ventricular area assessed in the patient group (each p < 0.01). Administration of nitroprusside reduced left ventricular pressure and increased ejection fraction in the 10 patients with dilated cardiomyopathy. For each region, systolic regional wall stress and the time to peak wall stress decreased, and both regional hypokinesia and asynchrony lessened. These changes in loading conditions and regional nonuniformity were accompanied by an improvement in both regional and global ventricular relaxation that was significant, particularly during the early to midrelaxation phase when regional asynchrony was greatest. CONCLUSIONS: These results suggest that myocardial relaxation is sensitive to loading conditions and regional nonuniformity in dilated cardiomyopathy and that load reduction can improve both relaxation and systolic performance of the left ventricle.

Analysis of Variance↗
PubMed1992

Identification of a developmentally regulated gene in the mouse central nervous system which encodes a novel proline rich protein.

A full length cDNA whose corresponding mRNA is down-regulated during the mouse embryonic brain development was isolated. The cDNA contains a single long open reading frame which could encode a protein with relative molecular mass of 41 kDa. The predicted gene product contains long stretches of prolines towards the NH2-terminus, followed by a leucine/proline rich region. The cDNA probe detected a number of mRNA species in Northern blot analysis. The reverse transcriptase-polymerase chain reaction analysis of mRNA from adult mouse tissues indicated that heart and testis expressed this gene (named NDPP-1) at relatively high levels, while lower levels of mRNA were detected in a number of other tissues. Expression of NDPP-1 was also detected in embryonic carcinoma and pheochromocytoma cell lines, but not in fibroblasts. The cDNA hybridized to genomic DNA from several vertebrates species in Southern blot analysis indicating interspecies conservation of this gene. The interesting pattern of expression of the NDPP-1 gene during mouse brain development and the structure of its putative protein product indicate that this gene may play an important biological role in the development of mouse central nervous system.

Animals↗
PubMed1992

Identification of a set of genes with developmentally down-regulated expression in the mouse brain.

Using a subtraction cloning approach, we have isolated a set of cDNA clones from mouse neural precursor cells whose respective mRNA levels are down-regulated during the development of mouse brain. Single stranded DNA prepared from neuronal precursor cell cDNA library in lambda Zap vector was subtracted with poly (A)+ RNA prepared from postnatal and adult mouse brain to obtain several clones which show developmental down-regulation of expression. Their patterns of expression indicate that these genes may play important roles during the embryonic development and differentiation of central nervous system.

Aging↗
PubMed1992

Ion selectivity of Ba2+ inward current oscillations in ras-transformed fibroblasts that elicit cytoplasmic Ca2+ oscillations by bradykinin.

Ion selectivity of divalent cations on Ba2+ inward current oscillations was examined by voltage-clamp recording in v-Ki-ras-transformed NIH/3T3 (DT) fibroblasts where repetitive transient increases in cytoplasmic Ca2+ concentration were evoked by bradykinin. Application of bradykinin onto DT cells in 50 mM Ba2+ solution initiated Ba2+ inward current oscillations. The inward currents were inhibited in equimolar Sr2+ or Ca2+ solutions. Ba2+ current oscillations were dependent upon extracellular Ba2+ concentration. The results suggest that inward current oscillations are highly selective to Ba2+.

3T3 Cells↗
PubMed1992

Id gene expression and its suppression by 1,25-dihydroxyvitamin D3 in rat osteoblastic osteosarcoma cells.

Id is one of the helix-loop-helix family of proteins that regulate differentiation in several types of cells, including myoblasts. We found that Id mRNA was constitutively expressed in ROS17/2.8 rat osteoblastic osteosarcoma cells and that the level of Id message in these cells was suppressed by 1,25-dihydroxyvitamin D3 (vitamin D), a calcitropic hormone known to enhance expression of differentiation-related phenotypes in these cells. The vitamin D suppression was dose-dependent, starting at 10(-11) M and saturating at 10(-8) M. This vitamin D effect was seen within 6 hr after the initiation of the treatment and lasted at least 48 hr. Cycloheximide did not block the vitamin D suppression of Id message level. Vitamin D reduced the rate of Id gene transcription by approximately 80% as estimated by nuclear run-on assay. Electrophoretic mobility-shift assay indicated the specific binding of nuclear factors from ROS17/2.8 cells to an E-box DNA sequence, and the binding signal was enhanced in nuclear extracts of the cells treated with vitamin D. The suppressive effect was specific to vitamin D, since another calcitropic hormone, the synthetic compound dexamethasone, did not suppress Id message expression. These observations indicate the presence of helix-loop-helix proteins in osteoblastic cells and indicate that vitamin D, a potent regulator of differentiation in several types of cells, controls the expression of the helix-loop-helix molecules.

Animals↗
PubMed1992

Binding of two growth factor families to separate domains of the proteoglycan betaglycan.

Cell surface proteoglycans help present some polypeptide growth factors such as basic fibroblast growth factor (bFGF) to their receptors and may act as reservoirs for others such as transforming growth factor-beta (TGF-beta). Betaglycan, a cell surface heparan sulfate/chondroitin sulfate proteoglycan that binds TGF-beta via its core protein, is shown here to bind bFGF via its heparan sulfate chains. We investigated the potential for regulation of betaglycan by its ligands in osteoblasts, a system in which bFGF and TGF-beta have complementary effects. We report here that the apparent molecular mass of betaglycan from an osteoblast-enriched primary culture of fetal rat calvaria is decreased in response to bFGF, as detected by an increased electrophoretic migration of betaglycan. The betaglycan forms expressed in bFGF-treated osteoblasts have a reduced content of heparan sulfate GAGs, without detectable changes in the content of chondroitin sulfate GAGs or the size of the core protein. bFGF did not affect the overall population of cell-surface-associated proteins identified by sulfate labeling, which contained primarily heparan sulfate, and had only small effects on the major secreted proteoglycans, which were, by contrast, chondroitin sulfate proteoglycans. The effect of bFGF on betaglycan is therefore a selective one. These results suggest that cells can interact with members of the TGF-beta and FGF families through separate domains of the same membrane proteoglycan, and can selectively regulate the bFGF-binding carbohydrate chains of this proteoglycan in response to bFGF.

3T3 Cells↗
PubMed1992

Ba2+ current oscillations modulated by cyclic AMP and phorbol esters in ras-transformed fibroblasts.

An oscillatory influx of divalent cations was measured as Ba2+ inward currents (Ba2+ current oscillations) by voltage-clamp recording in v-Ki-ras-transformed NIH/3T3 (DT) fibroblasts after activation with bradykinin or serum. Application of forskolin or dibutyryl cyclic AMP onto DT cells initiated Ba2+ current oscillations. Increasing intracellular cyclic AMP reduced the amplitude but increased the frequency of the Ba2+ current oscillations. Activation of protein kinase C by phorbol esters terminated Ba2+ current oscillations. No inhibition of Ba2+ current oscillations by phorbol esters was observed in down-regulated cells that had been pretreated with phorbol esters for 24 hrs. The results suggest that Ba2+ current oscillations are regulated by intracellular second messengers.

3T3 Cells↗
PubMed1992

Epoxyeicosatrienoic acid stimulates ADP-ribosylation of a 52 kDa protein in rat liver cytosol.

In rat liver cytosol, rapid ADP-ribosylation of a 52 kDa protein by endogenous ADP-ribosyltransferase(s) was observed. This ADP-ribosylation was stimulated dose-dependently by 14,15-epoxyeicosatrienoic acid (14,15-EET), one of the metabolites of arachidonic acid by NADPH-dependent cytochrome P-450 mono-oxygenase. This stimulatory effect required the presence of GTP or its non-hydrolysable analogues, guanosine 5'-[beta gamma-imido]triphosphate or guanosine 5'-[gamma-thio]triphosphate. Of four regioisomeric EETs, 14,15-EET was the most potent. No stimulatory effect was observed with addition of 14,15-dihydroxyeicosatrienoic acid, a stable metabolite of 14,15-EET. The 52 kDa protein was not ADP-ribosylated by cholera toxin A subunit and pertussis toxin, and was not recognized by anti-Gs alpha and anti-Gi alpha antibodies. However, the 52 kDa protein could be photoaffinity-labelled with 8-azidoguanosine 5'-[alpha-32P]triphosphate. These results suggest that the 52 kDa protein is neither Gs nor Gi, though it may have a GTP-binding site. These results contribute to the understanding of the role of mono-oxygenase metabolites of arachidonic acid in intracellular signal transduction.

8,11,14-Eicosatrienoic Acid↗
PubMed1992

Distinct downstream signaling mechanism between erythropoietin receptor and interleukin-2 receptor.

Erythropoietin receptor (EPOR) and interleukin-2 receptor beta chain (IL-2R beta) belong to the same cytokine receptor superfamily and have highly conserved sequences in their intracellular signaling domain. However, common downstream signaling pathways of these receptors have not been demonstrated. In the present study, we introduced and expressed the murine EPOR in murine IL-2-, IL-3- and IL-5-dependent cell lines and analyzed their growth response to EPO. We found that the expression of EPOR induced EPO dependence in IL-3-dependent BAF-B03 and IL-5-dependent Y16 cells but not in IL-2-dependent CTLL-2 cells, although the EPOR-expressing CTLL-2 cell lines could bind and internalize EPO as efficiently as the BAF-B03-derived cell lines. Additional expression of AIC2B, a common signal transducer for IL-3R, IL-5R and GM-CSFR, made no difference to the EPO responsiveness of the EPOR-expressing CTLL-2 cell lines. These results suggest that the cellular components required for the transduction of EPOR signal and IL-2R signal are at least partially different, and this difference cannot be explained solely by the absence of AIC2B.

Animals↗
PubMed1992

Partial suppression of tumorigenicity in a human lung cancer cell line transfected with Krev-1.

A human non-small-cell lung carcinoma cell line, Calu-6 (from an anaplastic carcinoma), was transfected with the Ki-ras-related anti-oncogene Krev-1. Several transfectant lines were obtained that showed a reduced tumorigenicity in nude mice with respect to the parental and control transfected cell lines. This decrease was approximately 50% in tumor incidence at 4 wk after subcutaneous inoculation of the transfected cells. In addition, the volume of the Calu-6 revertant-derived tumors was three to 10 times smaller than that of the equivalent tumors produced by inoculation of the control cell line transfected with the neomycin-resistance gene. Krev-1--transfected cells that exhibited reduced tumorigenicity expressed Krev-1 mRNA and had variable numbers of copies of the Krev-1 gene. Moreover, Krev-1--transfected cells exhibited a more differentiated squamous epithelial morphology than the parental and control cell lines did. Moderately elevated levels of protein kinase C activity were detected in some revertant clones. Such activity correlated with the level of expression of Krev-1 mRNA in most cases. In summary, Krev-1 induced important morphological and biological changes in transfected Calu-6 cells that we interpreted as partial reversion of the malignant phenotype.

Animals↗
PubMed1992

Immunoglobulin idiotype expression in reactive lymphoid tissues and B-cell lymphomas.

In an investigation of the immunoglobulin idiotypic expression of non-tumour and neoplastic B lymphocytes in situ, fresh-frozen specimens of reactive tonsils, lymph nodes and B-cell malignant lymphomas (B-MLs) from Japanese patients were studied immunohistochemically with 39 different anti-idiotype antibodies. In reactive lymphoid tissues, while idiotype-bearing cells were largely distributed sparsely in follicles and perifollicular areas, some were heavily crowded in particular germinal centres (GCs), suggesting the presence of oligoclonal proliferations of B-cells in GCs. Forty-eight out of 100 B-MLs reacted with anti-idiotype antibodies. This proportion was significantly higher than those reported in Western cases (27-36%), indicating that Japanese B-MLs share public idiotypes much frequently than western cases. The idiotypes demonstrated in these lymphomas, in contrast to those not expressed in any B-ML, were found much commonly in non-tumour lymphocytes, suggesting that such public idiotypes as were common in B-MLs were frequently shared by normal B-lymphocytes.

Antibodies↗
PubMed1992

Isolation of Fukuoka virus, a member of the Kern Canyon serogroup viruses of the family Rhabdoviridae, from cattle.

Four virus strains with identical antigenic properties were isolated from blood samples of 4 sentinel calves having a fever and leukopenea in cultures of HmLu-1 cells derived from baby hamster lung. The virus was identified as Fukuoka virus, classified as a member of the Kern Canyon serogroup viruses of the family Rhabdoviridae, on the basis of its antigenic properties.

Animals↗
PubMed1992

The characteristics of hepatic venous flow velocity pattern in patients with pulmonary hypertension by pulsed Doppler echocardiography.

To determine the characteristic change in the Doppler hepatic venous flow velocity pattern in patients with pulmonary hypertension (PH), 21 patients with PH in sinus rhythm were examined with pulsed Doppler echocardiography. The control group included 13 subjects with chest pain syndrome and normal pulmonary arterial pressure. The hepatic vein Doppler signal was biphasic with one peak during ventricular systole (S wave) and the other in diastole (D wave). A reversed signal was recorded after contraction (A wave). The peak velocity of the A wave (Va), S wave (Vs), and D wave (Vd), the time velocity integral of these waves (VIa, VIs, and VId), the acceleration time (t-AC), and the slope of acceleration (s-AC) in the S wave were measured. Compared with controls the PH group had a higher value of Va (26.88 +/- 10.30 vs 13.41 +/- 3.69 cm/sec; p less than 0.01), VIa (2.55 +/- 1.18 vs 1.20 +/- 0.34 cm; p less than 0.01), VIa/(VIs+VId) (0.34 +/- 0.22 vs 0.14 +/- 0.06; p less than 0.01), and s-AC (372 +/- 156 vs 203 +/- 103 cm/sec2; p less than 0.01). They also had a shorter t-AC (101 +/- 32 vs 136 +/- 27 msec; p less than 0.01). There was a weak correlation between the reversed atrial flow and the right heart pressures (r = 0.43 to 0.66). Thus, the hepatic venous flow velocity pattern by Doppler echocardiography is clinically useful in evaluating pulmonary hypertension.

Adult↗
PubMed1992

Soluble interleukin 2 receptors in patients with sarcoidosis. Possible origin.

We determined levels of soluble interleukin 2 receptors (IL-2R) in patients with sarcoidosis and further examined their origin. Thirty-nine patients with sarcoidosis and 18 healthy control subjects were studied. Soluble IL-2R levels in serum were significantly higher (p < 0.01) in sarcoidosis than in control subjects. In sarcoidosis, levels of soluble IL-2R in serum were significantly higher (p < 0.05) in patients with active disease than those with inactive disease and were significantly (p < 0.01) correlated with serum angiotensin-converting enzyme (ACE) levels. IL-2R expression on monocytes and alveolar macrophages (AMs) was significantly (p < 0.01) increased in patients with sarcoidosis as compared with control subjects. Soluble IL-2R levels in the supernatants of cultured monocytes and AMs were higher in patients with sarcoidosis than in control subjects. Those of cultured T lymphocytes obtained from peripheral blood and bronchoalveolar lavage fluid were detected in some patients with sarcoidosis, while undetected in control subjects. Furthermore, soluble IL-2R in serum was significantly correlated with soluble IL-2R in the supernatants of cultured monocytes and AMs (p < 0.01 and p < 0.05, respectively). These results demonstrate that soluble IL-2R in serum is a useful index of the disease activity of sarcoidosis and is mainly derived from monocytes and AMs.

Adult↗
PubMed1992

Type A-insulin resistance with lipopexia on extremities: a case report.

We present the unusual case of a 17-year-old female with insulin-resistant diabetes, acanthosis nigricans, hirsutism, amenorrhea, dental dysplasia and lipopexia on the extremities. She had been diagnosed as having border line diabetes with hyperinsulinemia at age 12 when she was not obese and diabetes mellitus at age 13. On admission, she was obese and had lipopexia only on the extremities. The presence of hyperinsulinemia and poor response to exogenous insulin suggested severe insulin resistance. Insulin binding to transformed B-lymphoblasts derived from her was extremely low compared to the normal control, showing decreased receptor affinity. Her parents and sister exhibited hypersecretion of insulin in response to a 75 g oral glucose tolerance test. Her mother was diabetic, and her father and sister had border line diabetes, whereas her brother had a normal response. These findings support strongly the diagnosis of a type A syndrome with severe insulin resistance associated with lipopexia on the extremities. A genetic defect in the insulin receptor gene may be responsible.

Absorptiometry, Photon↗