Search PubMed⌕ Search

Biomedical subjects

M Omata

Publications and source records attributed to M Omata.

At least 217 records · Page 12Linked to original sources
PubMed1998

Gene therapy for hepatic micrometastasis of murine colon carcinoma.

BACKGROUNDS/AIMS: Pit cells are located in the hepatic sinusoids and are organ-associated natural killer cells that contribute to immune surveillance in the liver. In the present study, the interleukin-2 gene was introduced into hepatocytes using an adenovirus vector to induce interleukin-2 production in an attempt to enhance the natural killer activity of pit cells, leading to inhibition of metastasis of colon carcinoma. METHODS: The recombinant adenovirus vector "Adex1CAmIL2" was constructed by inserting an expression unit which was composed of the CAG promotor (cytomegalovirus enhancer plus chicken beta-actin promotor), murine interleukin-2 cDNA, and a rabbit beta-globin polyadenylation signal. After administration of Adex1CAmIL2 to mice (4x10(7) pfu per animal), the expression of murine interleukin-2 in hepatocytes was examined by immunostaining and in situ hybridization, and the natural killer activity of hepatic mononuclear cells was measured. Inhibition of hepatic metastasis of colon carcinoma was examined after infusion of colon 38 tumor cells into the superior mesenteric vein. RESULTS: After administration of Adex1CAmIL2, interleukin-2 mRNA expression was demonstrated in hepatocytes until day 7, and the serum interleukin-2 level was increased. The natural killer activity of hepatic mononuclear cells was markedly enhanced for 7-10 days. Hepatic metastasis was inhibited by administration of Adex1CAmIL2 until day 7 after tumor cell inoculation. CONCLUSION: These results suggest that gene therapy using Adex1CAmIL2 could be potentially useful for inhibiting hepatic micrometastasis by enhancing the natural killer activity of pit cells.

Actins↗
PubMed1998

Impaired myocardial vasodilation during hyperemic stress with dipyridamole in hypertriglyceridemia.

OBJECTIVES: This study sought to investigate the specific role of hypertriglyceridemia in the myocardial hyperemic stress with dipyridamole/rest flow ratio (MDR). BACKGROUND: Reduced MDR has been reported in hypercholesterolemic patients without evidence of ischemia. However, the specific role of hypertriglyceridemia in MDR has not been studied. METHODS: Fifteen nondiabetic normocholesterolemic hypertriglyceridemic patients and 13 age-matched control subjects were studied. Myocardial blood flow (MBF) during dipyridamole administration and baseline MBF in hypertriglyceridemic patients and control subjects were measured using positron emission tomography and nitrogen-13 ammonia, after which the MDR was calculated. RESULTS: Baseline MBF (ml/min per 100 g heart weight) in hypertriglyceridemic patients (mean +/- SD 73.6 +/- 24.1) did not differ significantly from that in control subjects (81.6 +/- 37.2). MBF during dipyridamole loading in hypertriglyceridemic patients (198 +/- 106) was significantly reduced compared with that in control subjects (313 +/- 176, p < 0.05), as was the MDR (2.71 +/- 1.07 vs. 3.73 +/- 1.14, respectively, p < 0.05). Spearman rank-order correlation analysis showed a significant relation between plasma triglyceride concentration and MDR (r = -0.466, asymptotic SE 0.157, p = 0.0125); however, no such significant relation was seen between total plasma cholesterol concentration and MDR (r = -0.369, asymptotic SE 0.130, p = 0.059). CONCLUSIONS: Impaired myocardial vasodilation was suggested in hypertriglyceridemic patients without symptoms and signs of ischemia.

Adult↗
PubMed1998

Quantitative analysis of ras gene mutation in pancreatic juice for diagnosis of pancreatic adenocarcinoma.

It has recently been demonstrated that mutant ras gene was also detected in patients with mucinous cell hyperplasia without adenocarcinoma, indicating that the presence of the mutation could not be a definite marker for pancreatic adenocarcinoma. The present study was performed to differentiate pancreatic adenocarcinoma from others by quantification of mutant ras gene in pancreatic juice. By measuring mutant ras gene by polymerase chain reaction (PCR) during its logarithmic phase, the amount was semiquantitatively evaluated between 0.1 and 10% of total DNA that was extracted from pancreatic juice obtained via endoscopy. Semiquantitative analysis revealed that the mutant gene occupied more than 1% of total DNA in eight of 15 patients (53%) with pancreatic adenocarcinoma, and in all three patients (100%) with intraductal papillary neoplasm of the pancreas, but in only two of 19 cases (11%) without neoplasm. Semiquantitative analysis may provide a clinical tool for the differential diagnosis of pancreatic carcinoma.

Adenocarcinoma↗
PubMed1998

The two different states of hepatitis B virus DNA in asymptomatic carriers: HBe-antigen-positive versus anti-HBe-positive asymptomatic carriers.

During the course of hepatitis B virus (HBV) infection, there exists a long period of normal liver function tests with different states of HBeAg/Ab. As the state of HBV in asymptomatic carriers was not well characterized, we quantitatively and qualitatively examined HBV in both HBeAg-positive and anti-HBe-positive asymptomatic carriers. Sera from 10 HBeAg-positive and 27 anti-HBe-positive asymptomatic carriers were analyzed. The amount of HBV DNA was determined by dot-blot hybridization and polymerase chain reaction. The mutations in precore and core regions, spanning 636 nucleotides, of hepatitis B virus were examined by directly sequencing the amplified HBV DNA. HBV DNA was detected in all 10 HBeAg-positive cases, whereas it was found in only 7 of 27 (26%) anti-HBe-positive cases by the nested PCR method. The mean amount of HBV DNA in HBeAg-positive cases was 10(9.1 +/- 0.7) copies/ml, while that in anti-HBe-positive cases was 10(1.0 +/- 1.5) copies/ml. There were no missense mutations in the entire precore and core genes of HBV DNA taken from HBeAg-positive asymptomatic carriers. In contrast, many mutations (mean 9.0 +/- 3.3, range 6-14) were detected in the core gene of seven anti-HBe-positive asymptomatic carriers including two cases with increments of the mutations. Analysis of the precore region revealed three wild-type and four mutant-type (including one coexisting with wild-type) cases. These data suggest that HBV exists in quite different ways in "asymptomatic" carriers; in the HBeAg-positive phase HBV probably coexists with the host and remains as the wild type, whereas in the anti-HBe-positive phase a drastically reduced amount of HBV with many mutations remains, probably as a consequence of the long-lasting interaction with the host. Nevertheless, such small amount of virus could cause fulminant hepatic failure. It is important to make further clinical and virological investigations in order to understand the state of asymptomatic carrier.

Adult↗
PubMed1998

Hepatocyte nitric oxide production is induced by Kupffer cells.

To investigate the cellular communication in the liver, nitric oxide (NO) production by sinusoidal cells and hepatocytes by stimulation with cytokines and Kupffer cell-conditioned medium was quantitatively analyzed. NO production by the cells was measured by the Griess reaction, and nitric oxide synthase (iNOS) transcription level by a competitive RT-PCR assay using mutant iNOS mRNA as a standard. NO production and iNOS mRNA transcriptional levels in Kupffer cells were markedly increased by stimulation with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma), and moderately by interleukin-1beta (IL-1beta). NO production by hepatocytes was not significantly enhanced by LPS, but was markedly enhanced by IL-1beta or the combination of tumor-necrosis factor-alpha (TNF-alpha) and IFN-gamma. Hepatocyte NO production and iNOS mRNA levels were markedly enhanced by the LPS-activated Kupffer cell conditioned medium, but these effects were reduced by heat treatment or anti-TNF antibody. Although NG-monomethyl-L-arginine acetate and dexamethasone reduced NO production by the cells, the iNOS mRNA level was reduced by dexamethasone only. Gel-shift assay showed NF-kappaB activation in hepatocytes during this activation. These data reinforce the importance of cellular communication between sinusoidal cells and hepatocytes.

Animals↗
PubMed1998

Interleukin-8 production in primary cultures of human gastric epithelial cells induced by Helicobacter pylori.

Interleukin-8 (IL-8) production by the gastric mucosa is increased in Helicobacter pylori infection. Previous studies indicated that H. pylori induces IL-8 synthesis in cancer cell lines, and the ability of H. pylori to stimulate IL-8 production is supposed to be associated with cagA and other cag pathogenicity island genes, including picB gene. In the present study, we investigated the induction of IL-8 in primary cultures of normal human gastric epithelial cells to elucidate the IL-8 induction by wild type strains and by the picB knockout strain. Human gastric epithelial cells were obtained from surgically resected specimens from four patients. Three H. pylori strains (TN2F4; type 1 clinical isolate, TN2F4m1; isogenic picB mutant of TN2F4, Tx30a; type 2 strain) were cocultured with the normal gastric epithelial cells or the transformed MKN-28. IL-8 levels in culture medium were determined by enzyme immunoassay. Human gastric epithelial cells produced IL-8 at a 10-50 times higher level than MKN-28 did when cocultured with TN2F4. The mutant TN2F4m1 induced IL-8 at significantly lower levels than the parent strain. Cells from four patients behaved similarly on IL-8 production. The results of the present study demonstrated the induction of IL-8 in normal gastric epithelial cells, suggesting that picB gene product may play an essential role in vivo.

Bacterial Proteins↗
PubMed1998

Functional evaluation using motor scores after cervical spinal cord injuries.

Patient evaluation using Zancolli's classification for cervical cord injuries uses easily understood criteria and accurately defines the state of disability in Frankel grade A or B patients. However, this classification cannot be used in Frankel grade C patients even though they also cannot walk. We compared the Zancolli classification with American Spinal Injury Association (ASIA) motor scores in evaluating self-care in Frankel grade C patients. The Zancoli classification was found to correlate closely with the ASIA motor score. The threshold of ability to perform self-care in areas such as urinary toileting and wheelchair mobility occurred approximately between C6A and C6B 1 in the Zancolli classification in Frankel grade A and B patients and at the level of about 30 points in the ASIA motor score in Frankel grade C patients. The ASIA motor score is helpful in defining functional motor status in Frankel grade C patients with cervical spinal cord injuries.

Activities of Daily Living↗
PubMed1998

Relevance of periglomerular myofibroblasts in progression of human glomerulonephritis.

To clarify the pathological and clinical significance of periglomerular alpha-smooth muscle actin (alpha-SMA)-positive cells, we examined 51 needle-biopsy specimens from patients with human glomerulonephritis. Immunoelectron microscopy confirmed these cells were myofibroblasts showing characteristic features with abundant alpha-SMA-positive thin myofilaments. Nonsclerotic glomeruli with periglomerular myofibroblasts were larger in the Bowman's capsular planar area than nonsclerotic glomeruli without periglomerular myofibroblasts (24.7 +/- 6.0 x 10(3) microm2 v 19.9 +/- 8.5 x 10(3) microm2; P < 0.01). We studied the correlation between the clinical prognosis and the extent of periglomerular myofibroblasts in 24 patients with IgA nephropathy. Patients were divided into two groups; those with plasma creatinine levels within normal range at biopsy and significantly elevated at follow-up were designated group 1 (poor prognosis), and patients with plasma creatinine levels within normal range at biopsy and not significantly elevated at follow-up were designated group 2 (fair prognosis). In the kidneys of group 1 patients, periglomerular alpha-SMA was expressed more intensively than it was in the kidneys of group 2 patients (alpha-SMA expression score, 1.0 +/- 0.48 v 0.52 +/- 0.54; P < 0.05). These findings indicate that periglomerular myofibroblasts appeared surrounding the nonsclerotic hypertrophic glomeruli, which may lead finally to glomerulosclerosis. This report suggests that interaction between the glomerular cells and the periglomerular myofibroblasts may have a role in the progression of glomerular diseases.

Actin Cytoskeleton↗
PubMed1998

Endoscopic papillary balloon dilation for the management of common bile duct stones: experience of 226 cases.

BACKGROUND AND STUDY AIMS: Endoscopic sphincterotomy is a widely accepted technique for the treatment of patients with common bile duct stones. However, it is still associated with occasional complications. The recently developed technique of endoscopic papillary balloon dilation seems to be a safe and effective procedure, and to have great potential for replacing endoscopic sphincterotomy. However, few reports have been published on the use of this technique for bile duct stones. The present study was undertaken to evaluate its safety and efficacy. PATIENTS AND METHODS: Endoscopic papillary balloon dilation was used to remove common bile duct stones in 226 consecutive patients including 41 patients of ASA classification III/IV, 41 elderly patients (> 80 years) 24 with liver cirrhosis, and 86 with periampullary diverticulum. After dilation of the papilla with a balloon diameter of 8 mm, the stones were retrieved. RESULTS: In conjunction with the use of a mechanical or/and electrohydraulic lithotriptor in 79 patients (35%) with large stones (> 10 mm in diameter), clearance of the common bile duct was achieved in 225 of 226 patients (99%) without serious complications, such as hemorrhage or severe pancreatitis; mild (n = 13) or moderate (n = 2) pancreatitis occurred in 7% of cases. CONCLUSIONS: Endoscopic papillary balloon dilation is a safe and effective technique for the treatment of common bile duct stones, even in high-risk patients.

Adult↗
PubMed1998

Etiologic considerations of fulminant non-A, non-B viral hepatitis in Japan: analyses by nucleic acid amplification method.

The etiology of fulminant non-A, non-B hepatitis has remained unclear, even after the identification of hepatitis C and E viruses. To study the possible involvement of hepatitis B, C, D, and E virus infections, viral genomes were amplified by a sensitive polymerase chain reaction method in sera and liver tissues obtained from 20 patients serologically diagnosed with non-A, non-B fulminant hepatitis (n = 14), acute hepatitis severe type (n = 2), and ordinary acute hepatitis (n = 4). Hepatitis C or E virus RNA could not be detected in sera obtained at admission from these patients. Hepatitis B virus DNA was detected in sera from 3 patients with fulminant hepatitis and in liver from 9 patients with fulminant hepatitis or acute hepatitis severe type. These results suggest that HCV might not be involved in fulminant non-A, non-B hepatitis, and HBV might be related to some of the serologic "non-A, non-B" viral hepatitis cases in Japan.

Adult↗
PubMed1998

The possible role of vascular endothelial growth factor (VEGF) in gastric ulcer healing: effect of sofalcone on VEGF release in vitro.

Angiogenesis plays an important role in gastric ulcer repair. Several growth factors are involved in angiogenesis and, of these, vascular endothelial growth factor (VEGF) has received considerable attention because it is the only factor that acts specifically on endothelial cells and, unlike other angiogenic growth factors, has the hydrophobic signal peptide required for extracellular transport according to classical secretory pathways. We have lately demonstrated the role of VEGF in gastric ulcer repair. Previous reports confirmed that sofalcone has remarkable effects on gastric ulcer healing, which may be mediated by its stimulatory effect on prostaglandin (PG) release in gastric cells. Our data indicate that PGs stimulate VEGF expression in gastric fibroblasts. In this report we hypothesize that the clinical effect of sofalcone is mediated by VEGF expression and we demonstrate that sofalcone stimulates VEGF release by gastric fibroblasts in primary culture.

Anti-Ulcer Agents↗
PubMed1998

Ostensible day-night difference of QT prolongation during long-term treatment with antiarrhythmic drugs: reappraisal of the law of "regression to the mean".

This study was designed to test whether the law of regression to the mean explains the diurnal variation in the modulation of electrocardiographic variables during the treatment with antiarrhythmic agents. In part 1, in 34 subjects, ambulatory ECG monitorings were repeated twice, and the corrected QT interval (QTc) at a heart rate of 60 beats/min was calculated separately for the daytime and night. The individual diurnal QTc variation (day-night difference) of the first recording (4.4 +/- 3.3%) was significantly correlated with that of the second recording (5.0 +/- 3.1%; r = 0.61; p < 0.0001), and naturally, the second measurement tended to be lower than the first value in those with relatively greater baseline diurnal QTc variation and vice versa (p < 0.005). In part 2, 30 subjects undertook ambulatory ECG recordings before and during treatment with class Ia antiarrhythmic drugs. Mean QTc changes in the daytime and in the night with the drugs were comparable (18 +/- 17 ms and 19 +/- 15 ms). However, the day-night difference of postdrug QTc changes in each subject was inversely correlated with baseline diurnal QTc variation (r = -0.64; p < 0.0001). These observations in part 2 were comparable with those in part 1, and individual day-night difference in QT prolongation with antiarrhythmic drugs seemed to be a chance occurrence. It was suggested that the law of regression to the mean is appreciably reflected in the ostensible intraday variation of pharmacologic modulation of electrocardiographic variables.

Anti-Arrhythmia Agents↗
PubMed1998

Identification and characterization of a cytotoxic T cell epitope of hepatitis C virus presented by HLA-B*3501 in acute hepatitis.

In order to clarify the role of cytotoxic T lymphocytes (CTL) in hepatitis C virus (HCV) infection, an HLA-B35-restricted cytotoxic T cell epitope of HCV was identified using a strategy called reverse immunogenetics. Twenty-eight of 53 HCV peptides carrying two anchor residues were selected as HLA-B*3501 binding peptides. These peptides were used to induce the specific cytotoxic T cells in peripheral blood lymphocytes from a patient with acute hepatitis C. Six HLA-B*3501 binding peptides induced the peptide-specific CTL. One (HPNIEEVAL) of five peptides was confirmed as the epitope by the specific T cell clones. A sequence identical to the epitope was detected in isolates of the virus from the patient and a strong CTL response to this epitope was observed in the acute phase of hepatitis C but not in the recovery phase. The specific CTL for this epitope were not detected in peripheral blood lymphocytes from patients with chronic hepatitis C. Together these results suggest that the CTL specific for this epitope have an important role in the elimination of the virus in the patient.

Acute Disease↗
PubMed1998

In vivo adenovirus-mediated prodrug gene therapy for carcinoembryonic antigen-producing pancreatic cancer.

In gene therapy for malignancy, the herpes simplex virus thymidine kinase (HSVtk)-ganciclovir (GCV) system has been widely used. For pancreatic cancer targeting, we estimated the therapeutic efficacy of gene transduction by an adenovirus-carrying HSVtk gene under the control of a carcinoembryonic antigen (CEA) promoter (AdCEAtk) followed by systemic administration of GCV. Four cell lines, CEA-producing Su.86.86. BxPC-3 (pancreatic cancer cells), MKN45 (gastric cancer cells) and CEA-nonproducing HeLa, were used for analysis of GCV sensitivity induced by adenoviral gene transduction. To evaluate the therapeutic efficacy of AdCEAtk and GCV administration in human CEA-positive pancreatic cancer in vivo, a subcutaneously implanted tumor-bearing nude mouse model was used. When the HSVtk gene was transduced with a ubiquitous promoter into these cells, increase of the GCV sensitivity was independent of CEA-production. In contrast, when the cells were transduced with a CEA promoter, the cell-killing effect of GCV was increased in only CEA-producing cells. For in vivo analysis, AdCEAtk was delivered into subcutaneously established tumors of Su.86.86 cells. Immunohistochemical staining of the tumor showed that HSVtk protein was expressed only in tumor cells, and tumor growth was markedly suppressed by administration of GCV. These results suggest that the adenovirus-mediated transfer of HSVtk gene with CEA promoter specifically increases the GCV sensitivity of CEA-producing pancreatic cancer cells in vitro and in vivo. This strategy may provide a useful tool for treating pancreatic cancer, especially CEA-producing tumor cells.

Adenoviridae↗
PubMed1998

Do the effects of antiarrhythmic drugs on defibrillation efficacy vary among different shock waveforms?

This study was designed to extend our knowledge on how pharmacological modification of defibrillation efficacy is associated with shock waveform. In 35 anesthetized dogs, the baseline transcardiac DFT was determined using 12-ms monophasic and three biphasic waveforms (10 ms-2 ms, 8 ms-4 ms, and 6 ms-6 ms). Twenty-eight dogs were then treated with either lidocaine (n = 7), mexiletine (n = 7), dofetilide (n = 7), or MS-551 (n = 7), while 7 dogs were left untreated to confirm the reproducibility of DFT data. Subsequently, DFT measurements were repeated in all dogs. Waveform related differences of the baseline DFT were significant, and the monophasic DFT was higher than any of the biphasic DFTs. Lidocaine increased DFT by 11% +/- 12% (12-ms monophasic), 20% +/- 20% (10 ms-2 ms, P < 0.05), 13% +/- 20% (8 ms-4 ms), and 12% +/- 10% (6 ms-6 ms, P < 0.05). With infusion of mexiletine, the DFT increased by 17% +/- 16% (P < 0.05), 9% +/- 12%, 10% +/- 10% (P < 0.05), and 4% +/- 15%, respectively. Both dofetilide and MS-551 significantly decreased the DFT regardless of the pulse waveform (dofetilide: from -18% +/- 19% to -24% +/- 19%, MS-551; from -18% +/- 11% to -32% +/- 6%). In all drug groups, waveform related differences in DFT remained significant. These results support the view that the advantages of biphasic shock waveforms are not lessened by treatment with antiarrhythmic drugs.

Animals↗
PubMed1998

Postshock recovery interval of relatively refractory myocardium as a possible explanation for disparate defibrillation efficacy between monophasic and biphasic waveforms.

We investigated the electrophysiological background for the waveform related variability of defibrillation efficacy. In 22 open-chest dogs, a localized potential gradient was created using an 8-V or 16-V field stimulus across a pair of plate electrodes separated by 5 mm. The post shock recovery interval of the nondepolarized myocardium adjacent to the excited area was estimated by the residual refractory period after an appropriately timed field stimulus. The postshock recovery interval and the defibrillation threshold were compared among six different waveforms but with the same total duration of 12 ms (n = 11) or 16 ms (n = 11). Six defibrillation thresholds in individual hearts showed a significant inverse correlation with postshock recovery intervals in most dogs (8/11) tested with a total pulse duration of 12 ms (8 V stimulus: r = -0.80 +/- 0.20 [n = 11]). In contrast, waveforms with a total duration of 16 ms failed to reveal this distinct relationship. We conclude that the waveform related variability of defibrillation efficacy is associated with the refractoriness of relatively refractory myocardium when the total pulse duration is within a certain range. However, the mechanisms responsible for waveform performance may vary as the total pulse duration changes.

Animals↗
PubMed1998

Effect of atrial natriuretic peptide on electrical defibrillation efficacy.

INTRODUCTION: In vitro studies have suggested that human atrial natriuretic peptide (ANP) modulates the electrophysiologic properties of myocardial cells. This study assessed whether ANP could influence defibrillation efficacy. METHODS AND RESULTS: In 35 anesthetized dogs, the transcardiac defibrillation threshold (DFT) as well as hemodynamic and electrophysiologic variables were determined before and during treatment with ANP (n = 11), hydralazine (n = 11), or saline (n = 13). ANP (1.5 microg/kg + 0.2 microg/kg per min) increased the plasma concentration of cyclic GMP (a second messenger for ANP) and significantly decreased aortic blood pressure (mean 100+/-11 mmHg to 83+/-15 mmHg). ANP also prolonged ventricular repolarization (effective refractory period 157+/-7 msec to 165+/-11 msec) and markedly reduced DFT (5.4+/-1.2 J to 3.8+/-0.7 J [P < 0.01]) without changing pulmonary artery pressure or sinus cycle length. Neither saline nor hydralazine (1.5 mg/kg) had a significant effect on DFT (saline 4.7+/-2.1 J to 4.6+/-2.4 J; hydralazine 4.3+/-2.0 J to 4.2+/-1.9 J), although hydralazine caused pronounced hypotension (mean aortic pressure 103+/-9 mmHg to 74+/-13 mmHg). CONCLUSION: These results suggest that ANP increases defibrillation efficacy, and that this effect is not necessarily shared by other vasodilating agents.

Animals↗