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Biomedical subjects

M Omata

Publications and source records attributed to M Omata.

At least 253 records · Page 14Linked to original sources
PubMed1997

Expression of vascular endothelial growth factor at the human gastric ulcer margin and in cultured gastric fibroblasts: a new angiogenic factor for gastric ulcer healing.

Angiogenesis plays a pivotal role in gastric ulcer repair. Several growth factors are involved in angiogenesis, and of these, vascular endothelial growth factor (VEGF) has received considerable attention, since it is the only factor that specifically acts on endothelial cells. However, the role of VEGF in gastric ulcer repair is not known. In the present study, we demonstrate the specific expression of VEGF at the gastric ulcer margin, using immunohistochemistry and RT-PCR. The specific receptors of VEGF, flt-1 and KDR were also detected in gastric mucosa. We further demonstrate the expression of VEGF by cultured human gastric fibroblasts which is enhanced by tumor necrosis factor-alpha. These data suggest that VEGF may play a role in angiogenesis in the process of gastric ulcer healing.

Base Sequence↗
PubMed1997

Effect of caffeine on mucus secretion and agonist-dependent Ca2+ mobilization in human gastric mucus secreting cells.

Caffeine is known to stimulate gastric acid secretion, but, the effects of caffeine on gastric mucus secretion have not been clarified. To elucidate the action of caffeine on gastric mucin-producing cells and its underlying mechanism, the effects of caffeine on mucus glycoprotein secretion and agonist-induced [Ca2+]i mobilization were examined in human gastric mucin secreting cells (JR-I cells). The measurement of [Ca2+]i using Indo-1 and the whole cell voltage clamp technique were applied. Mucus glycoprotein secretion was assessed by release of [3H]glucosamine. Caffeine by itself failed to increase [Ca2+]i and affect membrane currents, while it dose-dependently inhibited agonist (acetylcholine (ACh) or histamine)-induced [Ca2+]i rise, resulting in inhibiting activation of Ca2+-dependent K+ current (I(K.Ca)) evoked by agonists. The effect of caffeine was reversible, and the half maximal inhibitory concentration was about 0.5 mM. But, caffeine did not suppress [Ca2+]i rise and activation of I(K.Ca) induced by A23187 or inositol trisphosphate (IP3). Theophylline or 3-isobutyl-1-methyl-xanthine (IBMX) did not mimic the effect of caffeine. Caffeine failed to stimulate mucus secretion, while it significantly decreased ACh-induced mucus secretion. These results indicate that caffeine selectively inhibits agonist-mediated [Ca2+]i rise in human gastric epithelial cells, probably through the blockade of receptor-IP3 signaling pathway, which may affect the mucin secretion.

Caffeine↗
PubMed1997

Can a class III antiarrhythmic drug improve electrical defibrillation efficacy during ventricular fibrillation?

OBJECTIVES: We tested whether a new class III drug (MS-551) administered during ventricular fibrillation (VF) could decrease the defibrillation threshold (DFT) in anesthetized canine hearts. BACKGROUND: Pretreatment with class III antiarrhythmic agents is known to enhance electrical defibrillation efficacy. METHODS: In a preliminary study (n = 10), we ascertained the validity of DFT determination by a sequence of incremental defibrillation shocks in a single fibrillation/defibrillation episode. We then compared the DFTs after 130 s of VF with and without administration of MS-551 (2 mg/kg body weight) at 10 s after the onset of VF in 12 open chest dogs and 8 closed chest dogs. RESULTS: MS-551 decreased the DFT in both experimental models (open chest [mean +/- SD]: from 416 +/- 106 to 318 +/- 92 V, p < 0.05; closed chest: from 714 +/- 75 to 615 +/- 112 V, p < 0.05). The change (delta) in DFT in each heart was inversely correlated with the drug-induced prolongation of VF cycle length before the defibrillation attempt (delta DFT vs. delta VF cycle length 10 s before the first discharge: r = -0.58 and -0.81, p < 0.05). CONCLUSIONS: MS-551 given after the induction of VF improved defibrillation efficacy. Class III antiarrhythmic agents deserve consideration when VF is resistant to electrical defibrillation during cardiopulmonary resuscitation.

Action Potentials↗
PubMed1997

Characterization of mutant myosins of Dictyostelium discoideum equivalent to human familial hypertrophic cardiomyopathy mutants. Molecular force level of mutant myosins may have a prognostic implication.

Recent studies have revealed that familial hypertrophic cardiomyopathy (FHC) is caused by missence mutations in myosin heavy chain or other sarcomeric proteins. To investigate the functional impact of FHC mutations in myosin heavy chain, mutants of Dictyostelium discoideum myosin II equivalent to human FHC mutations were generated by site-directed mutagenesis, and their motor function was characterized at the molecular level. These mutants, i.e., R397Q, F506C, G575R, A699R, K703Q, and K703W are respectively equivalent to R403Q, F513C, G584R, G716R, R719Q, and R719W FHC mutants. We measured the force generated by these myosin mutants as well as the sliding velocity and the actin-activated ATPase activity. These measurements showed that the A699R, K703Q, and K703W myosins exhibited unexpectedly weak affinity with actin and the lowest level of force, though their ATPase activity remained rather high. F506C mutant which has been reported to have benign prognosis exhibited the least impairment of the motile and enzymatic activities. The motor functions of R397Q and G575R myosins were classified as intermediate. These results suggest that the force level of mutant myosin molecule may be one of the key factors for pathogenesis which affect the prognosis of human FHC.

Actins↗
PubMed1997

Adenovirus-mediated gene therapy of gastric carcinoma using cancer-specific gene expression in vivo.

The carcinoembryonic antigen (CEA) is a glycoprotein which overexpressed in the majority of human gastric cancers. We demonstrated that recombinant adenoviral vector (AdCEAtk), containing the CEA promoter, could transfer the herpes simplex virus thymidine kinase (HSVtk) gene into CEA-producing gastric cancer cells to confer sensitivity to ganciclovir (GCV) in vivo. In an ex vivo experiment, the tumor growth was inhibited after GCV treatment when the tumor contained more than 20% of AdCEAtk infected cells, indicating an efficient bystander killing effect. With intra-tumoral injection of AdCEAtk, the HSVtk were selectively expressed in approximately 30% of CEA producing cancer cells. By AdCEAtk injection and GCV administration, the growth of tumors was significantly inhibited by 20% as compared to untreated tumors. It is hoped that these results provide a strategy of tumor specific gene transfer for CEA producing gastric cancers.

Adenoviridae↗
PubMed1997

Extracellular Mg2+ inhibits receptor-mediated Ca(2+)-permeable non-selective cation currents in aortic smooth muscle cells.

The effects of extracellular Mg2+ on receptor-mediated Ca(2+)-permeable non-selective cation currents were investigated in a cultured aortic smooth muscle cell line (A7r5) from rat thoracic aorta, using the whole-cell voltage-clamp technique. Under the Cs(+)-containing internal solution, both vasopressin and endothelin-1 (100 nM) activated a long-lasting inward current with a high noise level. The reversal potential of these agonists-induced current was approximately +0 mV, and was not significantly altered by the replacement of [Cl-]i or [Cl-]o, suggesting that the inward current was a cation-selective channel. La3+ and Cd2+ (1 mM) almost completely abolished the vasopressin or endothelin-induced non-selective cation current; however, nifedipine (10 microM) failed to inhibit it significantly. Extracellular Mg2+ (3-20 mM) also markedly inhibited the vasopressin- or endothelin-induced non-selective cation current in a concentration-dependent manner. When a non-hydrolysable GTP-analogue, GTP gamma S (1 mM), was applied from the patch pipette, the non-selective cation current was gradually activated even in the absence of agonist (vasopressin or endothelin-1), probably due to the direct activation of GTP-binding proteins coupled to the receptors. Extracellular Mg2+ (3-20 mM) also suppressed the activation of non-selective cation current induced by GTP gamma S, suggesting that the inhibitory sites of Mg2+ are not located on the receptors. These results suggest that extracellular Mg2+ inhibits receptor-mediated non-selective cation current, which may contribute to the relaxation effects of Mg2+ in vascular smooth muscle cells.

Animals↗
PubMed1997

Incidence of induced atrial fibrillation/flutter in complete atrioventricular block. A concept of 'atrial-malfunctioning' atrio-hisian block.

BACKGROUND: Atrial fibrillation/flutter (Af) has been considered to occur coincidentally with atrioventricular (AV) block. However, a case with complete AV block was reported to histologically show fibrotic changes solely in the atrial muscles but neither in the AV node nor in the His bundle, indicating a possible relation between AV block and atrial tachyarrhythmias. To test a hypothesis that AV block and Af are causally interrelated, we investigated the incidence and electrophysiological characteristics of Af in complete AV block. METHODS AND RESULTS: Forty-two patients with persistent complete AV block underwent the electrophysiological study. Patients with spontaneous/electrically induced Af were compared with the other patients with respect to their electrophysiological variables. Of the 42 patients, Af was transiently induced by electrical stimulation in 5 patients (11.9%), while persistent Af was observed in 2 patients (4.8%, AH and HV block). AV block in the 5 patients with induced Af was invariably due to AH block. AH block complicated by persistent/induced Af was marked by relatively short RR intervals, significantly short junctional recovery time, and impaired intra-atrial conduction. CONCLUSIONS: Electrically induced Af in complete AV block was associated frequently with complete AH block. These patients were characterized differently from the commonly recognized AV block and therefore may stand as a unique subgroup of AH block.

Adult↗
PubMed1997

In vivo gene therapy for alpha-fetoprotein-producing hepatocellular carcinoma by adenovirus-mediated transfer of cytosine deaminase gene.

The alpha-fetoprotein (AFP) gene is normally expressed in fetal liver and is transcriptionally silent in adult liver but overexpressed in human hepatocellular carcinoma (HCC). Here, we demonstrate that replication defective recombinant adenoviral vectors, containing the human AFP promoter/enhancer, can be used to express the Escherichia coli cytosine deaminase (CD) gene (AdAFPCD) and the beta-galactosidase gene (AdAF-PlacZ) in AFP-producing HCC cell lines. Expression of the CD gene by adenovirus from the AFP promoter/enhancer (AdAFPCD) induced cells sensitive to 5-fluorocytosine (5FC) in the AFP-producing cells but not in the AFP-nonproducing cells. Transduction by an adenoviral vector harboring an ubiquitous strong promoter and CD gene showed enzymatic activity and 5FC killing in all cell lines. When AdAFPlacZ was injected into the s.c. established hepatoma in vivo, expression of the beta-galactosidase gene was confined to AFP-producing HCC xenografts. Moreover, HCC xenografts regressed by transduction with AdAFPCD and subsequently with 5FC treatment in vivo. These findings suggest that utilization of the AFP promoter/enhancer in an adenoviral vector can confer selective expression of a heterologous suicide gene in hepatocellular carcinoma cells in vitro and in vivo.

Adenoviridae↗
PubMed1997

Detection of GBV-C RNA in patients with non-A-E fulminant hepatitis by reverse-transcription polymerase chain reaction.

GBV-C might be a causative agent of fulminant hepatitis of unknown etiology. Fulminant hepatitis is an indication for liver transplantation. However, in Japan, because of the legal difficulties associated with cadaveric donation, patients with fulminant hepatitis are still treated by plasmapheresis and multiple transfusions of fresh frozen plasma. So, the possibility that GBV-C might be transmitted by transfusions after the onset of fulminant hepatitis is real. Therefore, we have examined the possible role of GBV-C in non-A-E fulminant hepatitis. Nine patients with non-A-E fulminant hepatitis and one with non-A-E late onset hepatic failure were examined. Sera were obtained from the patients at admission before any blood or blood products were given, and again after transfusions. GBV-C RNA was detected by nested reverse transcription polymerase chain reaction with primers based on the reported sequence. GBV-C RNA was negative in all 10 pretransfusion patients with non-A-E fulminant hepatitis or late onset hepatic failure. Then, fresh frozen plasma was transfused to these patients, and four of them became seropositive. GBV-C is unlikely to be a major etiologic agent for non-A-E fulminant hepatitis in Japan.

Adult↗
PubMed1997

Direct detection of Mycobacterium tuberculosis using polymerase chain reaction assay among patients with hepatic granuloma.

BACKGROUND: In liver tuberculosis, demonstration of acid bacilli by conventional methods remains futile. Since the definitive diagnosis of liver tuberculosis is based on the histologic evidence of granulomatous process with caseation necrosis, seen in only a third of cases, the diagnosis is made retrospectively by response to empirical anti-tuberculous drug therapy. AIMS: Our objective is to establish a polymerase chain reaction assay for detection of Mycobacterium tuberculosis affecting the liver using the paraffin-embedded liver biopsy specimens obtained from patients with hepatic granulomas. METHODS: As positive control, patients having either "definitive" (n=8) or "presumptive" (n=9) tuberculosis on the basis of clinical, microbiological, histologic data and their positive response to empirical treatment of anti-tuberculous drugs were used. Patients with hepatic granulomas secondary to schistosomiasis (n=6), sarcoidosis (n=2) and other liver diseases (n=10) were used as negative control. RESULTS: Of those patients who were diagnosed as having "definitive" and "presumptive" liver tuberculosis, positivity by one-step polymerase chain reaction was 100% and 44%, respectively. Using the nested polymerase chain reaction, positivity increased to 78% with "presumptive" liver tuberculosis. In contrast, the polymerase chain reaction assays were negative among all patients with hepatic granuloma due to non-tuberculous-in-origin and other liver diseases. CONCLUSIONS: The overall positivity of this polymerase chain reaction assay (88%) compares favorably with that of other conventional methods (12%). Thus, this polymerase chain reaction assay may be a reliable diagnostic tool for liver tuberculosis in a patient population in which the prevalence of diseases associated with hepatic granuloma is common.

Adolescent↗
PubMed1997

Quantitative assays for hepatitis C virus in serum as predictors of the long-term response to interferon.

BACKGROUND/AIMS: Interferon therapy has a beneficial effect in patients with chronic hepatitis C who have a low viral load. The aim of this study was to compare the core protein level with HCV RNA levels and to analyze whether virus quantitation predicts the efficacy of interferon therapy. METHODS: HCV core protein level assessed by the recently developed assay was compared with HCV RNA levels measured by three different methods (Amplicor-HCV monitor, competitive RT(CRT)-PCR, and bDNA probe assay) in 352 patients with chronic hepatitis C in relation to viral serotype. RESULTS: From 91% (320/352) to 93% (299/322) of patients with viremia were detected by Amplicor-monitor and CRT-PCR, in contrast to 60% (187/312) and 74% (191/258) by bDNA and HCV core protein assay, respectively. The HCV core protein level was positively correlated with HCV RNA levels measured by the three assays (r = 0.680 to 0.731). Serum HCV RNA and core protein levels were significantly lower in patients with serotype 2 than in those with serotype 1. Viral eradication after interferon therapy was observed in 60-70% of the patients with < 1 x 10(4) copies/ml of HCV RNA by Amplicor-monitor assay, < 2 x 10(5) copies/ml by CRT-PCR, < 0.5 Meq/ml by bDNA assay, and < 20 pg/ml of core protein by HCV core protein assay. Viral eradication was uncommon (< 11%) among the patients with higher viral loads. Bivariate analysis revealed that the outcome of interferon therapy was more closely associated with both HCV core protein and RNA levels than the HCV serotype. CONCLUSIONS: Quantitation of HCV core protein and HCV RNA in useful for prediction of the interferon response.

Adolescent↗
PubMed1997

GB virus-C RNA in Japanese patients with hepatocellular carcinoma and cirrhosis.

BACKGROUND/AIMS: The involvement of non-B, non-C virus in the incidence of hepatocellular carcinoma (HCC) is not yet known. We have therefore examined the occurrence of GBV-C RNA in such patients. METHODS: One hundred and eleven patients diagnosed as having HCC and 67 patients with cirrhosis without HCC were examined for the prevalence of GBV-C RNA by nested reverse transcription polymerase chain reaction with primers located at the helicase region. Sera were obtained and kept at -20 degrees C until analysis. RESULTS: GBV-C RNA was positive in 11/111 (9.9%) cases with HCC, in 10/74 (13.5%) anti-HCV positive cases, in 1/25 (4%) HBsAg positive cases, and in 0/8 (0%) anti-HCV and HBsAg negative cases. GBV-C RNA was also positive in 7/67 (10.4%) cases with cirrhosis, in only 1/18 (5.6%) anti-HCV and HBsAg negative cases, in 4/33 (12.1%) anti-HCV positive, and in 2/14 (14.3%) HBsAg positive cases. The clinical background of patients with anti-HCV positive HCC who were also positive for GBV-C RNA did not differ from the background of those negative for GBV-C RNA. CONCLUSIONS: GBV-C is unlikely to be a major etiologic agent of non-B, non-C chronic liver diseases and HCC in Japan.

Adult↗
PubMed1997

Present status of autoimmune hepatitis in Japan--correlating the characteristics with international criteria in an area with a high rate of HCV infection. Japanese National Study Group of Autoimmune Hepatitis.

BACKGROUND/AIMS: A nationwide survey of autoimmune hepatitis (AIH) was carried out in Japan. METHODS: Four hundred and ninety-six patients were enrolled by questionnaires sent to 101 hospitals with hepatology specialists. RESULTS: The clinical features of Japanese AIH were as follows: most patients were middle-aged women; serum autoantibodies, especially antinuclear antibody, were frequently positive, serum IgG level was high, and HLA-DR4 was the major HLA allotype. Liver-kidney microsomal type 1 antibody was positive in nine of 79 patients tested. Eight of these antibody positive patients were also positive for antinuclear antibody and five for anti-smooth muscle antibody. Ninety-two percent of the patients showed piecemeal necrosis and 60% bridging necrosis; plasma cell infiltration in the portal areas was observed in 50% of the patients. Only 12.3% were diagnosed as having liver cirrhosis. A favorable effect of corticosteroid, normalization of serum transaminases, was observed in 89% of 317 patients, who were treated with an initial dose of over 30 mg/day. Sixty-two patients were positive for hepatitis C virus (HCV) markers. In these patients, however, only one patient was liver-kidney microsomal type 1 antibody positive. Corticosteroid was effective in 30 (81%) of 37 HCV-marker-positive patients treated with this agent. Thus the efficacy of corticosteroid did not differ from that in AIH patients without HCV infection (90%). Similarly, interferon treatment was used in 20 patients, all of whom were positive for HCV-RNA, and resulted in 50% efficacy as determined by normalization of the serum transaminase level 6 months after treatment. The International Diagnostic Scoring System for the diagnosis of AIH worked well in these patients, except for HCV-infected individuals, that is, approximately 10% of the total of AIH patients.

Adolescent↗
PubMed1997

Relation of 24-h ambulatory blood pressure with plasma potassium in essential hypertension.

The established associations between blood pressure (BP) and electrolytes are mostly based on either dietary intake or urinary excretion data. We measured office BP, ambulatory BP (ABP) using the automated oscillometric ABPM-630 device, and plasma electrolytes in 82 essential hypertensive patients to examine the relation between BP and plasma electrolytes. Significant negative correlations were observed between plasma potassium concentration and 24-h systolic BP (r = -0.336) and diastolic BP (r = -0.298) in our patients. Plasma potassium concentration inversely correlated also with both daytime and nighttime systolic and diastolic BPs. There was no relation between office BP and plasma potassium concentration. These findings indicate that in essential hypertensives plasma potassium concentration is inversely related to ABP including daytime and nighttime BPs and suggest that potassium may be a factor determining the whole day BP in essential hypertension.

Adult↗