Biomedical subjects

M Noda

Publications and source records attributed to M Noda.

At least 415 records · Page 23Linked to original sources

PubMed1993

Stimulation of mono-ADP ribosylation in rat liver plasma membranes after long-term alcohol intake.

ADP ribosylation is considered one of the important covalent modifications of cellular proteins catalyzed by ADP ribosyltransferase, which transfers ADP ribose moiety of NAD to an acceptor protein. Because a growing body of evidence has suggested significant biological roles for mono-ADP ribosylations in transmembrane signal transduction and other cell metabolism, how alcohol intake alters them is of interest. Cholera toxin and pertussis toxin have been widely used as probes to investigate the roles of GTP-binding proteins (G-proteins) in the transduction of hormonal and sensory signals. We first tested effects of long-term alcohol intake on these toxin-catalyzed ADP ribosylations of G-proteins in rat liver plasma membranes. Treatment of rat liver plasma membrane with [32P]NAD and thiol-preactivated cholera toxin resulted in the labeling of a 44-kD band, most likely an alpha-subunit of the stimulatory GTP-binding protein, the extent of which was much greater in alcohol-fed rats than in pair-fed controls. Analogous experiments with pertussis toxin also demonstrated enhancement of toxin-catalyzed ADP ribosylation of the inhibitory GTP-binding protein after long-term alcohol intake. More interesting was that long-term alcohol intake remarkably stimulated endogenous mono-ADP ribosylation of a 58-kD protein in a GTP-dependent manner. In vitro, ethanol (50 mmol/L) or a single load of ethanol (3 gm/kg) did not stimulate the reaction. Thus long-term alcohol intake stimulated both toxin-catalyzed and endogenous mono-ADP ribosylations of proteins in rat liver plasma membranes. Pursuit of alcohol interaction with mono-ADP ribosylation may provide an interesting approach to the study of alcohol's effects on the liver.

Adenosine Diphosphate Ribose↗

PubMed1993

Endothelin modulates osteopontin and osteocalcin messenger ribonucleic acid expression in rat osteoblastic osteosarcoma cells.

Endothelins (ETs) are vasoconstrictive peptides produced mainly by endothelial cells. The ET receptors are expressed in many types of cells including osteoblast-like cells. The purpose of this study was to examine the effects of endothelin on the expression of osteoblastic phenotype-related genes. We found that endothelin-1 (ET-1) enhanced approximately two-fold the mRNA expression of both osteopontin and osteocalcin genes in rat osteoblastic osteosarcoma ROS17/2.8 cells. These effects were dose-dependent, peaking at 10(-7) M. The ET-1 enhancement of the abundance of osteopontin and osteocalcin mRNAs was time-dependent, with a maximal effect at 24 h. ET-1 modulation of the expression of the two phenotype-related gene products of osteoblasts suggests that endothelin is one of the cytokines which modulate osteoblastic functions and that this molecule may play a role in the regulation of bone metabolism.

Animals↗

PubMed1993

Decrease in coupling of Gs in v-src-transformed NIH-3T3 fibroblasts: possible involvement of tyrosine phosphorylation of Gs by pp60v-src.

In Rous sarcoma virus (RSV)-transformed NIH-3T3 fibroblasts expressing pp60v-src as tyrosine protein kinase, isoproterenol-stimulated cAMP accumulation was much lower than in normal cells. The reduction in v-src-transformed cells seemed to be mainly due to a decrease in the number of beta 2-adrenoceptors. When the membranes were phosphorylated with ATP, however, the binding affinity of isoproterenol to beta 2-adrenoceptors was reduced in transformed cell membranes by 34% compared to that in normal cell membranes. The reduction in transformed cell membranes was restored to the level of normal cell membranes by treatment of membranes with anti-pp60v-src antibody. GTP gamma S- and cholera toxin-stimulated adenylyl cyclase activities were reduced with no change in forskolin-stimulated adenylyl cyclase activity in transformed cell membranes. The reduced effect of GTP gamma S was also restored by treatment with anti-pp60v-src antibody or by adding staurosporine, which inhibits a variety of protein kinases, including tyrosine protein kinase. One of the 32P-phosphoproteins phosphorylated with [gamma-32P]ATP in v-src-transformed cell membranes was bound to GTP-agarose, and was a 46-kDa molecule on a sodium dodecyl sulfate-polyacrylamide gel. This 46-kDa 32P-labeled phosphoprotein was immunoprecipitated with anti-phosphotyrosine antibody or anti-stimulatory GTP-binding protein (anti-Gs) antibody. These results suggest that pp60v-src phosphorylates the alpha-subunit of Gs and consequently causes a decrease in the coupling of beta 2-receptors to Gs and in the coupling of Gs to adenylyl cyclase.

3T3 Cells↗

PubMed1993

Post-exercise oxygen uptake kinetics in patients with left ventricular dysfunction.

We assessed the kinetics of oxygen uptake (VO2) after symptom-limited maximal exercise by use of cardiopulmonary exercise testing with a bicycle ergometer in normal subjects and patients with left ventricular dysfunction due to dilated cardiomyopathy. During the first few minutes after the cessation of exercise, the VO2-time relationship showed an exponential-like decrease. A monoexponential curve was fitted to this relationship of the first 3 min after exercise to obtain the time constant of the decrease in VO2 (T(VO2)). The results of exercise testing in 37 normal subjects (25 male and 12 female) revealed that T(VO2) was relatively independent of age and gender. Then, 30 male patients with dilated cardiomyopathy (10 in New York Heart Association functional class I, 12 in class II, and 8 in class III) were evaluated and the results were compared with those of 16 age-matched male control normal subjects. Although the amount of the estimated oxygen debt was smaller in the patient group, the time constant T(VO2) was 117 +/- 8 s for the controls as compared with 130 +/- 14 s for the patients in class I, 153 +/- 13 s for those in class II, and 219 +/- 49 s for those in class III. There were significant correlations between T(VO2) and anaerobic threshold (r = -0.68, p < 0.001), peak VO2 (r = -0.74, p < 0.001), and the increase in VO2 per work rate (r = -0.88, p < 0.001). T(VO2) also correlated with the ventilatory equivalent for carbon dioxide output (VE/VCO2) at peak exercise (r = 0.70, p < 0.001) and the time course of minute ventilation during the early phase of the post-exercise period (r = 0.67, p < 0.001). Thus, the time course of VO2 decrease after symptom-limited exercise is considered to be closely related to exercise capacity and also to the degree of exercise-induced hyperpnea in patients with left ventricular dysfunction.

Adult↗

PubMed1993

The clinical course and prognosis of patients with severe, moderate or mild sarcoidosis.

During 1978-1990, 346 patients with sarcoidosis were enrolled in our institute. Of 346 patients, 295 patients were eligible for evaluation on the clinical course and prognosis. According of their clinical presentations, they were classified into 3 groups; severe, moderate and mild sarcoidosis. Of the 295 patients, 27 (9.2%) were classified as severe sarcoidosis who developed serious illness including involvement of the heart (8), lung (6), muscles (5), eyes (3), central nervous system (CNS) (3) or liver (2). The mean interval between the onset of disease to severe disability was 58.3 months. The interval was particularly long in those patients who presented with either pulmonary (100.8 months) or liver sarcoidosis (108 months). Of the 27 patients with severe sarcoidosis, 8 (29.6%) gradually became worse towards the end of their clinical course despite only mild clinical signs and symptoms at the first presentation. Therefore, the initial clinical symptoms and findings, including ocular involvement. ECG abnormalities, negative reaction to PPD, high value of serum angiotensin converting enzyme (ACE) and a small number of lymphocytes in peripheral blood, were not useful in predicting prognosis. The relationship between the maximum serum ACE value during the clinical course and the duration of the active phase was statistically significant in the 123 patients who were monitored throughout their course, suggesting that the maximum serum ACE may be a marker for assessing prognosis. Corticosteroid was administered to 76 patients (22%) with serious systemic involvement. They included 26 (96.4%) of the 27 severe sarcoidosis and 50 (37.9%) of the 132 moderate sarcoidosis. Patients with mild sarcoidosis did not receive corticosteroids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

Cholera toxin directly stimulates pregnenolone generation with increasing Ca2+ efflux in bovine adrenocortical mitochondria.

The present experiments demonstrated that the holotoxin as well as the A- and B-subunits of cholera toxin were able to directly enhance pregnenolone synthesis when isolated intact mitochondria, prepared from bovine adrenocortical tissue, were incubated; they were not, however, able to enhance pregnenolone synthesis when the inner mitochondrial fraction was similarly incubated, suggesting that the conformational structure of mitochondria is very important for activation of cholesterol side-chain cleavage by cholera toxin. Data are also presented demonstrating that cholera toxin can enhance Ca2+ release from isolated mitochondria, while pertussis toxin could activate neither pregnenolone generation nor increase Ca2+ efflux from mitochondria. Thus it is suggested that cholera toxin may activate pregnenolone synthesis by regulating Ca2+ movement in mitochondria.

Adrenal Cortex↗

PubMed1993

Simultaneous measurements of twenty-four-hour whole-body retention of 47Ca-chloride and 99mTc-MDP: early differentiation of metabolic bone diseases in rat models.

The 24-h whole-body retention (24-h WBR) of 47Ca-chloride and 99mTc-MDP was measured in four rat models over a 6-week period at 2 week intervals. Fine detail bone radiographs of the femurs and histologic bone specimens were also obtained simultaneously. In the osteomalacic (M) and steroid-induced osteoporotic (S) groups the 24-h WBR values of 47Ca were significantly lower, and in the osteoporotic (P) group were higher than in the control (C) group from the second week. The 24-h WBR values of 99mTc-MDP were significantly higher in the M group and were lower in the S group from the second week. Simultaneous measurements of 24-h WBR of these two radiopharmaceuticals facilitated the early differentiation of metabolic bone diseases in the animal models prior to the detection of radiologic bone changes.

Animals↗

PubMed1993

Postaortic left innominate vein: radiological assessment and pathogenesis.

Postaortic left innominate vein (PALIV) is a rare venous anomaly and the findings on plain chest radiographs have not been well described. Plain chest radiographs, CT and MR of nine adults known to have PALIV were reviewed. They all showed a high aortic arch, including four with a right-sided aortic arch and one with a double aortic arch, in postero-anterior radiographs, and seven showed curved shadows in the left upper mediastinum. On all lateral chest radiographs (n = 5), the superior retrosternal region was opacified by the high aortic arch. CT or MR images confirmed the aortic arch and/or innominate artery to be in that part of the retrosternal space, normally occupied by the left innominate vein, in all cases. Association of a curved shadow in the superior mediastinum with a high aortic arch on plain chest radiographs is therefore suggestive of, though not diagnostic for, PALIV. This entity was well documented by CT or MR and the radiological findings were considered to imply that developmentally PALIV is secondary to a high position of the aortic arch.

Adult↗

PubMed1993

Site-directed mutagenesis of the putative active site residues of 3C proteinase of coxsackievirus B3: evidence of a functional relationship with trypsin-like serine proteinases.

Picornavirus 3C proteinases (3Cpro) are cysteine proteinases but recent sequence analyses have shown that they are related to trypsin-like serine proteinases. Two models of 3Cpro structure have been presented. Both models indicate that residues His40 and Cys147 are members of the catalytic triad but the models differ in the designation of the third member of the catalytic triad, which is assigned as either Glu71 or Asp85. To test the importance of these four residues in the catalytic activity of 3Cpro of coxsackievirus B3, a member of the enterovirus subgroup of the picornavirus family, single amino acid substitutions were introduced at each of the four sites. All of these mutations resulted in the reduction or inactivation of autocatalytic cleavage of the 3C precursor protein expressed in Escherichia coli, suggesting that all of these residues are essential for the proteolytic reaction. The substitution of Cys147 with Ala abolished 3Cpro activity while the mutant in which Cys147 was replaced with Ser retained reduced proteolytic activity both in cis and in trans. Our results strongly support the proposal that Cys147 of 3Cpro functions as a nucleophile analogous to Ser195 of trypsin-like serine proteinases.

3C Viral Proteases↗

PubMed1993

Mechanisms of reversion.

Reversion of transformed cells provides biological system useful in multiple areas of cancer research. First, reversion can be induced by inhibiting the activities of specific oncogenes or replacing intact tumor suppressor genes, and such experiments yield important insights into the roles of these genes in carcinogenesis and normal growth regulation as well as the functional relationships between these genes and other known genes. Second, novel genes involved in growth regulation can be discovered by isolating revertants from transformed cells after mutagenesis or DNA transfection and then characterizing the genes responsible for the non-transformed phenotype. Third, potential anti-cancer drugs can be screened by reversion assay using cells transformed by specific oncogenes. The novel genes and chemicals discovered through these studies serve as valuable tools that help our understanding of how cells regulate their growth and differentiation.

Animals↗

PubMed1993

Priming effect of pseudomonal leukocidin on chemiluminescence response of rabbit polymorphonuclear leukocytes.

To clarify effects of pseudomonal leukocidin (42.5 kd) on chemiluminescence (CL) production of polymorphonuclear leukocytes (PMNs), rabbit PMNs were stimulated by zymosan or phorbol myristate acetate (PMA) after pretreatment with the leukocidin, which by itself stimulated little chemiluminescence response. The extent of CL responses stimulated by zymosan or PMA was respectively 5.3- or 3.5-fold greater in leukocidin (1.5 micrograms/ml)-pretreated PMNs than in non-pretreated ones. The priming effect of the leukocidin was greater than that of G-CSF and related to some steps before NADPH oxidase activation. The increased CL productions might be related to tissue damages caused by pseudomonal infections in vivo.

Acridines↗

PubMed1993

Changes in the susceptibility of 12-O-tetradecanoylphorbol 13-acetate (TPA)-treated HL-60 cells to staphylococcal leukocidin.

Susceptibility of human promyelocytic leukemia HL-60 cells to staphylococcal leukocidin following treatment of cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) was examined. TPA treatment for 6 hr rendered the cells very resistant transiently to leukocidin. There was no change in binding of leukocidin to the cells, but leukocidin-induced 45CaCl2 influx, phospholipase A2 and C activities were inhibited. Further incubation with TPA rendered the cells sensitive again and then more sensitive than original HL-60 cells following increase of the binding, and leukocidin-induced activities described above appeared again. Those cells treated with TPA for more than 18 hr started to differentiate to macrophages morphologically and functionally. These data suggest that the differentiated cells were more sensitive than original HL-60 cells because of increased binding of leukocidin and that treatment of TPA for 6 hr may transiently impair the signal transduction system of leukocidin after binding of leukocidin to the specific receptor of the cell membrane. Using these TPA-treated cells, it was shown in this report that calcium influx, phospholipase A2 and C activities were important to induce cytotoxic action of leukocidin after binding of leukocidin to specific receptors on the cells.

Calcium Chloride↗

PubMed1993

Effect of heparin on hemagglutinin of herpes simplex virus type 1.

Heparin inhibited the hemagglutinin activity of herpes simplex virus (HSV) type 1. The minimal inhibitory concentration of heparin required to inhibit 8 hemagglutination (HA) U of HSV ranged from 0.005 to 0.01 U/ml. Mouse erythrocytes failed to combine with the HA inhibitory factor of heparin. On the other hand, mouse erythrocytes treated with heparinase had greatly reduced agglutinability by HSV. Virus-heparin complex formation was observed by sedimenting heparin with the virus particles.

Animals↗

PubMed1993

Comparative study of the cellular fatty acids of methicillin-resistant and -susceptible Staphylococcus aureus.

The cellular fatty acid compositions of 26 strains of methicillin-resistant Staphylococcus aureus (MRSA) and 17 strains of methicillin-susceptible S. aureus (MSSA) were analyzed by gas-liquid chromatography. The fatty acid compositions of the two groups were very similar with 16 identified components. The major fatty acids were Ci14 = 0, Ci15 = 0, C18 = 0 and C20 = 0. Among these fatty acids, the percentage of the Ci15 = 0 fatty acid component of MRSA strains (11.4 +/- 3.9%) was statistically higher than that of MSSA strains (6.2 +/- 2.4%) (p < 0.001). On the other hand, the percentage of the C20 = 0 fatty acid components of MRSA strains (20.2 +/- 8.8%) was statistically lower than that of MSSA strains (30.7 +/- 10.4%) (p < 0.001). The production of beta-lactamase and beta-hemolysin in both groups' strain was also unrelated to the relative amounts of the fatty acid components. These results indicated a statistical tendency for the percentage fatty acid compositions of the MRSA strains to be quantitatively different from those of the MSSA for both the Ci15 = 0 and C20 = 0 fatty acid components. Analysis of the fatty acid compositions may have an application in the differentiation of MRSA and MSSA strains.

Anti-Bacterial Agents↗

PubMed1993

Mapping of the KREV1 transformation suppressor gene and its pseudogene (KREV1P) to human chromosome 1p13.3 and 14q24.3, respectively, by fluorescence in situ hybridization.

The chromosomal location of the transformation suppressor gene KREV1 and its pseudogene (KREV1P) on R-banded human prometaphase chromosomes was determined by fluorescence in situ hybridization. The KREV1 gene mapped to chromosome 1p13.3, whereas the KREV1P pseudogene mapped to 14q24.3. Our results substantiate the previous mapping data of Rousseau-Merck et al. (1990) and further confine the position of the RAP1A/KREV1 gene to a narrower region.

Chromosome Mapping↗

PubMed1993

[Tissue concentration of intravesically instilled (2"R)-4'-o-tetrahydropyranyl-adriamycin or adriamycin in superficial bladder cancer].

Twenty-one patients with superficial bladder cancer entered an analysis of single dose (2'R)-4'-O-tetrahydropyranyladriamycin (THP) or adriamycin (ADM) administration. The patients in each group that have been or not have been treated previously with anti-cancer drugs were randomized into two groups, one was given THP and the other ADM. Thirty-mg of THP or ADM dissolved in 30 ml of physiologic saline was instilled into the bladder, and retained for 1 hour. After 1 hour retention of the drugs, tumor tissues and normal mucosas were removed by punch biopsy forceps transurethrally. The tissue concentrations of THP and ADM were estimated by high performance liquid chromatography. The tissue concentrations of THP and ADM in the tumors were significantly greater (p < 0.05) than those in the normal bladder mucosas. The tissue concentration of THP in the tumors were greater than that of ADM. The tissue concentrations of THP and ADM in the tumor of patients who have been treated with anti-cancer drugs previously were less than those of patients who have not. This results demonstrated that prior therapy with anti-cancer drug may cause a resistance for intravesical instillation chemotherapy. However in patients with prior therapy, the tissue concentration of THP in the tumors were greater than that of ADM. Based on these findings, THP has been shown to be were effective as an intravesical instillating agent especially, in cases with prior chemotherapy.

Administration, Intravesical↗

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↗

PubMed1993

Pharmacological profile of a highly potent and long-acting angiotensin II receptor antagonist, 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4- yl]methyl]-1H-benzimidazole-7-carboxylic acid (CV-11974), and its prodrug, (+/-)-1-(cyclohexyloxycarbonyloxy)-ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5- yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate (TCV-116).

The angiotensin II (AII) antagonistic action of 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl-1H-benzi mid azole-7 - carboxylic acid (CV-11974) was examined in in vitro assay systems, including AII receptor binding assay using membrane fractions of bovine adrenal cortex or rabbit aorta and AII-induced contraction assay using rabbit aortic strips, and CV-11974 and its prodrug, (+/-)1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H- benzimidazole-7-carboxylate (TCV-116), were examined in an in vivo system of AII-induced pressor response in conscious rats. DuP 753 or EXP3174 (the main active metabolite of DuP 753) was used as the reference compound. CV-11974 inhibited the binding of [125I] AII to the bovine adrenal cortical membrane and rabbit aortic membrane with IC50 values of 1.12 x 10(-7) and 2.86 x 10(-8) M, respectively. Similar results were obtained with EXP3174. CV-11974 interacted with AII in these membrane fractions with subtype 1 receptor in a competitive manner. CV-11974 at 10(-5) M did not affect the binding of [125I]AII to subtype 2 (AT2) receptor in bovine cerebellum. CV-11974 selectively inhibited the AII-induced contraction of rabbit aortic strips in a noncompetitive manner (pD' 2, 9.97); it had no effects on the contraction induced by norepinephrine, KCl, serotonin, prostaglandin F2 alpha or endothelin. EXP3174 showed a pD'2 value of 8.95 for the AII-induced contraction. CV-11974 given intravenously and TCV-116 given orally inhibited the AII-induced pressor response in rats with ID50 values of 0.033 mg/kg and 0.069 mg/kg, respectively. These effects of CV-11974 and TCV-116 were 12 and 48 times more potent than those of EXP3174 and DuP 753, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗