Biomedical subjects

M Omata

Publications and source records attributed to M Omata.

At least 325 records · Page 18Linked to original sources

PubMed1996

Nonreentrant supraventricular tachycardia due to double ventricular response via dual atrioventricular nodal pathways.

Narrow and wide QRS tachycardias associated with various rhythm disturbances were recognized during 24-hour ambulatory eletrocardiographic monitoring in a 65-year-old man with coronary artery disease. Laddergram analysis revealed the presence of dual atrioventricular nodal pathways. Non-reentrant supraventricular tachycardia due to simultaneous fast and slow conduction through the dual atrioventricular nodal pathways was confirmed by electrophysiologic study. The atrial rate determined the occurrence of simultaneous conduction, and extrastimulation failed to induce a double ventricular response. Enhanced vagal activity was thought to play a critical role in provoking this phenomenon. Radiofrequency catheter ablation of the slow pathway eliminated the arrhythmias.

Aged↗

PubMed1996

Gene expression and active virus replication in the liver after injection of duck hepatitis B virus DNA into the peripheral vein of ducklings.

BACKGROUND/AIMS: Duck hepatitis B virus is a member of the hepadnavirus family, which possesses strong hepatotropism. Duck hepatitis B virus DNA serves as a replicative template for producing biologically active virus particles after transfection into cell lines established from human hepatocellular carcinoma or into duck liver by direct injection of calcium phosphate-precipitated DNA. Our aim was to develop a new method of liver-specific gene expression after intravenous DNA delivery. METHODS/RESULTS: We inoculated duck hepatitis B virus DNA with and without cationic liposomes, Lipofectin or LipofectAMINE, as DNA carries. Two weeks after a single intravenous injection of 10 or 50 micrograms of plasmid DNA containing a head-to-tail dimer of duck hepatitis B virus DNA into 25 one-day old ducklings, duck hepatitis B virus RNA transcripts including the pregenome replicative intermediate were detected by Northern blot in the liver of eight ducks (100%) of the Lipofectin group, five ducks (63%) of the LipofectAMINE group, and three ducks (50%) of the group which received DNA without carrier. Duck hepatitis B virus RNA transcription was almost exclusively liver specific, even though the liposomes had no tissue specificity. Replicative forms of duck hepatitis B virus DNA were detected in the liver and DHBsAg was observed in the cytoplasm of the hepatocytes by immunostaining. The serum of transfected ducklings contained virus particles which were infectious in other ducklings. CONCLUSION: The efficient and liver-specific expression of inoculated DNA was due to the amplification of nucleic acids by active virus replication process under the control of hepatocyte specific regulation.

Animals↗

PubMed1996

Expression of a nonmuscle myosin heavy chain in glomerular cells differentiates various types of glomerular disease in rats.

To characterize the phenotypic modulation of mesangial and glomerular epithelial cells, we investigated the expression of a nonmuscle type myosin heavy chain, SMemb, and alpha-smooth muscle actin (alpha-SM actin) in rat experimental glomerular diseases, which included anti-Thy 1 nephritis, 5/6 nephrectomy, diabetes, and anti-glomerular basement membrane nephritis. SMemb was only slightly expressed in normal glomerular epithelial cells but not in mesangial cells. In the anti-Thy 1 nephritis rats, both SMemb and alpha-SM actin were most conspicuously induced in mesangial cells. However, the expression profile was shifted from alpha-SM actin to SMemb dominant pattern over the course of glomerulonephritis. The expression of SMemb was also increased in epithelial cells in this model. In the other three models, glomerular cells did not express alpha-SM actin, but did so for SMemb. In the nephrectomized and the diabetic rats SMemb was newly expressed in mesangial cells at earlier stages, but at later stages was remarkably enhanced in epithelial cells when severe glomerular hypertrophy developed. In the anti-GBM nephritis rats, SMemb expression was increased in epithelial cells. In all models examined, mesangial and epithelial expression of SMemb was confirmed by immunoelectron microscopy, and enhanced expression of SMemb mRNA in glomeruli was verified by RNase protection assay. We conclude from these results that glomerular cells change their phenotypes differently depending on various types of glomerular diseases. These phenotypic changes in glomerular cells can be revealed by the combined immunostaining for SMemb and alpha-SM actin. SMemb is especially useful to detect both mesangial and glomerular epithelial cell activation in these glomerular disease models. Understanding the functional difference and regulatory mechanisms of these cytoskeletal proteins will provide insight into the pathogenesis and progression of glomerular diseases.

Actins↗

PubMed1996

Analysis of K-ras gene mutation in hyperplastic duct cells of the pancreas without pancreatic disease.

BACKGROUND & AIMS: We and others have previously shown that the mutation of K-ras codon 12 was found in the majority of pancreatic adenocarcinomas. The mutation has also been identified in the pancreatic duct with mucous cell hyperplasia in association with chronic pancreatitis. Ductal hyperplasia is also frequently found in the pancreas free from pancreatic carcinoma or chronic pancreatitis. The aim of this study was to assess the incidence and types of mutations in hyperplastic foci in these cases. METHODS: The nucleotide sequence of the K-ras gene at codon 12 of the DNA extracted from microdissected hyperplastic epithelium of the pancreatic duct obtained at autopsy in patients without pancreatic adenocarcinoma or chronic pancreatitis was analyzed. RESULTS: Of 38 patients with 79 hyperplastic foci, 12 patients (with 19 hyperplastic foci) had mutations. None of the 16 normal ducts in 12 specimens had this mutation. The nucleotide sequence of the codon in 53% of ductal hyperplastic foci was TGT or AGT, both of which were not found in 30 cases of adenocarcinoma. CONCLUSIONS: These results suggest that the ras gene mutation occurs frequently in multifocal hyperplastic foci of pancreatic duct and that the mutations may not have direct relevance to the carcinogenesis of pancreatic cancer.

Adult↗

PubMed1996

Expression of variant CD44-messenger RNA in colorectal adenocarcinomas and adenomatous polyps in humans.

BACKGROUND & AIMS: Recent studies have shown that some variant forms of CD44, a transmembrane glycoprotein expressed on various cell surfaces, might be involved in tumor progression or tumor metastasis. The aim of this study was to analyze the expression of CD44-messenger RNA (mRNA) in colorectal cancer and colorectal adenoma to further elucidate the role of CD44 in colorectal tumorigenesis. METHODS: The expression of CD44-mRNA was examined in 90 specimens from 44 patients with colorectal cancer or colorectal adenomatous polyps and in the peripheral blood leukocytes from 7 healthy volunteers by reverse transcription-polymerase chain reaction and Southern blot hybridization. RESULTS: Strong expression of the epithelial form and variant forms containing exons 11 or 12 of the CD44 gene, which conferred metastatic behavior to rat cells, was detected in primary and metastatic tumor tissues, whereas it was very weak or not detectable in normal colonic mucosae, normal liver tissue, or peripheral blood leukocytes. However, adenomatous colorectal polyps also showed as strong an expression of epithelial and variant forms of CD44 as primary and metastatic tumor tissues. CONCLUSIONS: These results suggest that variant forms of CD44-mRNA might be expressed in an early stage of colorectal carcinogenesis.

Adenocarcinoma↗

PubMed1996

Tumor-specific gene expression in carcinoembryonic antigen--producing gastric cancer cells using adenovirus vectors.

BACKGROUND & AIMS: An increase of carcinoembryonic antigen (CEA) expression is noted in about 40% of patients with gastric cancer. Adenovirus-mediated gene therapy using the CEA promoter was investigated as a way to specifically target human CEA-producing gastric tumors. METHODS: Recombinant adenovirus vectors carrying a CEA promoter linked to the lacZ gene (AdCEA lacZ) or the cytosine deaminase gene (AdCEA-CD) were constructed. After infection with these vectors, CEA-producing (MKN45 and MKN28) and non-CEA-producing (MKN1) gastric cancer cells were analyzed for transgene expression and sensitivity to 5-fluorocytosine. RESULTS: The lacZ gene was expressed selectively in CEA-producing AdCEA-lacZ-infected cells in vitro and in vivo. Transduction of the vector containing the CEA-regulated cytosine deaminase gene (AdCEA-CD) resulted in extraordinary sensitivity of MKN45 and MKN28 cells to 5-fluorocytosine. This effect was not observed in MKN1 cells. Moreover, AdCEA-CD-infected MKN45 cells showed a profound in vitro neighbor cell killing effect in the presence of 5-fluorocytosine. This effect was attributed to the diffusion of 5-fluorouracil, resulting from conversion of 5-fluorocytosine to 5-fluorouracil by the cytosine deaminase-expressing cells. CONCLUSIONS: The results of this study suggest that use of a CEA promoter in an adenovirus vector could confer selective expression of the cytosine deaminase gene in CEA-producing gastric cancer cells, rendering the transduced cells susceptible to 5 fluorocytosine. This system may be useful in gene therapy that targets CEA-producing gastric carcinomas.

Adenoviridae↗

PubMed1996

High incidence of ADH21/ALDH21 genes among Japanese alcohol dependents and patients with alcoholic liver disease.

In an attempt to clarify the genetic factors in alcoholism among the Japanese, polymorphism of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) genes has been investigated. Genetic polymorphism of ADH2/ALDH2 in 66 cases of normal subjects, 90 cases of alcohol dependent, and 31 patients with alcoholic liver disease among Japanese has been analyzed using a polymerase chain reaction assay followed by a direct sequencing method, because ethanol is mainly catabolized by ADH and ALDH and less by cytochrome P450IIE1 and catalase. The incidence of both ADH2*1/*1 and ALDH2*1/*1 was significantly higher in patients with alcohol dependence and in patients with alcoholic liver disease when compared with that in control subjects. In addition, the incidence of ALDH2*1/*2 and ALDH2*2/*2 was significantly reduced in alcoholics compared with control subjects. Genetic polymorphism of ADH2/ALDH2 in patients with alcoholic liver disease was not different from that of alcohol dependents. According to these results, not only ALDH2 gene, often claimed to be responsible for alcohol dependence among Japanese, but also ADH2 gene polymorphism, which modulates the metabolism of ethanol, play important roles in habitual alcohol intake behavior in Japanese patients and in some patients leads to alcoholic liver diseases.

Adult↗

PubMed1996

Cytokine-induced neutrophil chemoattractant release from hepatocytes is modulated by Kupffer cells.

To clarify the role of intercellular communication in the liver during accumulation of neutrophils, the release of cytokine-induced neutrophil chemoattractant (CINC) (interleukin-8 [IL-8] related protein in rodents) by hepatocytes was investigated in the presence of Kupffer cell-conditioned medium in vitro. Kupffer cells were prepared by perfusion of rat liver with collagenase followed by centrifugation on a metrizamide gradient and were cultured in the presence or absence of lipopolysacharide (LPS). The conditioned medium was collected after 24 hours, and rat hepatocytes were cultured in the presence or absence of Kupffer cell-conditioned medium. An amount of CINC in the culture supernatant was measured by western blotting analysis and enzyme-linked immunosorbent assay (ELISA), and expression of its messenger RNA (mRNA) was assessed by the polymerase chain reaction. LPS-stimulated Kupffer cell-conditioned medium enhanced an expression of CINC mRNA in hepatocytes and increased the production of CINC by hepatocytes. Enhanced production of CINC was not shown when the Kupffer cell-conditioned medium was pretreated with heat (56 degrees C, 30 minutes). The production of CINC by hepatocytes in the presence of the LPS-stimulated Kupffer cell-conditioned medium was reduced by an antibody against interleukin 1 beta (IL-1 beta), but not by antibodies against tumor necrosis factor alpha (TNF-alpha) or LPS. These results suggest that production of CINC by hepatocytes could be regulated by IL-1 beta released from Kupffer cells, leading to neutrophil accumulation during liver injury, because this protein is a strong chemoattractant for neutrophils.

Animals↗

PubMed1996

Prospective assessment of donor blood screening for antibody to hepatitis C virus by first- and second-generation assays as a means of preventing posttransfusion hepatitis.

In November 1989, the Japanese Red Cross began screening blood donors for the hepatitis C virus antibody (anti-HCV) by first-generation assay and high-titer hepatitis B virus core antigen antibody. A significant reduction in the incidence of acute posttransfusion hepatitis was reported; however, the incidence still ranged from 2 percent to 4 percent. The Red Cross changed to the second-generation assay in February 1992, the objective being the complete elimination of potential posttransfusion hepatitis. The aim was to elucidate the advantage of second-generation assay as a blood-donor screening test. The incidence of posttransfusion hepatitis after the introduction of second-generation assay was compared with that before the introduction of the first-generation assay and with that during its use. The incidence of posttransfusion hepatitis was 9.6 percent (216/2,240) before anti-HCV-s donor screening. It was 3.7 percent (24/655) and 0.9 percent (3/326) after the introductions of the first- and second-generation hepatitis C virus (HCV) assays, respectively (chi (2) = 50.0, P < .01). Blood-donor screening by second-generation anti-HCV provided a significant benefit compared with the first-generation assay.

Adult↗

PubMed1996

Quantitation of alpha-fetoprotein and albumin messenger RNA in human hepatocellular carcinoma.

To analyze gene expression of alpha-fetoprotein (AFP) and albumin in hepatocellular carcinoma (HCC), messenger RNAs (mRNAs) of these proteins in six human hepatoma cell lines and in 30 cases of HCC were quantitatively analyzed by competitive reverse transcription (RT) followed by polymerase chain reaction (PCR). The transcriptional levels of both AFP and albumin genes in HepG2 and Huh 7 cell lines were 10(10) copies/microgram RNA, in contrast to approximately 10(5) copies/microgram RNA in HLE and HLF cell lines. AFP and albumin mRNA levels in three normal livers were 10(5) and 10(10) transcripts/microgram RNA, respectively. In 30 cases with HCC AFP mRNA level in neoplasm was 10 to 10(5)-fold enhanced as compared with that of nonneoplastic portion, and correlated with serum AFP level and tumor size (P < .01). In contrast, albumin mRNA level was not reduced in the neoplasms presenting enhanced AFP mRNA levels, indicating that AFP and albumin gene expression in situ is not necessarily mutually exclusive. Prospective analysis revealed that an increased serum AFP was shown at the time of recurrence among patients with enhanced AFP mRNA levels in neoplasm only, indicating that AFP mRNA levels in neoplasm could be a clinically predictable tool.

Aged↗

PubMed1996

Endoscopic papillary balloon dilation in cirrhotic patients: removal of common bile duct stones without sphincterotomy.

BACKGROUND AND STUDY AIMS: Endoscopic papillary balloon dilation (EPBD) is a less invasive alternative to endoscopic sphincterotomy (EST). This study reviews a series of cirrhotic patients with bile duct stones who were treated with EPBD. PATIENTS AND METHODS: EPBD was used to remove common bile duct stones in nine cirrhotic patients (one in Child-Pugh grade A, four in grade B, and four in grade C). After the papilla was dilated with balloon-tipped catheter, the stones were removed with a retrieval basket catheter or a retrieval balloon, or both. Mechanical lithotripsy was required in two patients with stones of more than 1 cm in diameter. RESULTS: Clearance of the common bile duct was achieved in all patients without any serious complications such as hemorrhage or perforation. CONCLUSIONS: These results suggest that EPBD is a safe and effective technique for the treatment of common bile duct stones in patients with liver cirrhosis.

Aged↗

PubMed1996

Keratinocyte growth factor is an endogenous stimulant of rabbit gastric epithelial cell proliferation and migration in primary culture.

Mesenchymal-epithelial interactions are important in the gastric mucosal repair. However, specific factors responsible for such interactions have not been established. In the present study, keratinocyte growth factor (KGF) significantly stimulated proliferation of gastric epithelial cells dose dependently and synergistically with hepatocyte growth factor (HGF), epidermal growth factor (EGF) and insulin. Restitution of gastric epithelial monolayers was also assessed, using a round wound restitution model. Keratinocyte growth factor facilitated the restitution of gastric epithelial cells significantly but did not have any effects on gastric fibroblasts. Keratinocyte growth factor receptor mRNA was expressed by gastric epithelial cells, indicating that these effects were elicited by the specific receptor mediated pathway. Northern blot analysis revealed the expression of KGF mRNA in gastric fibroblasts but not in gastric epithelial cells, indicating the production of KGF. These results suggest that KGF might be involved in gastric mucosal repair, through mesenchymal-epithelial interaction.

Animals↗

PubMed1996

Real-time monitoring of HCV-RNA by single tube assay kit and potential importance for predicting virological sustained response in patients with chronic hepatitis C.

In an attempt to predict virological sustained responders among patients with chronic hepatitis C after interferon therapy, HCV-RNA in serum was measured by a one tube RT-PCR assay kit using the RNA corresponding to 5 microL serum (standard assay) or 300 microL serum (enhanced-sensitivity assay). Dilution analysis revealed that sensitivity of the 'enhanced-sensitivity assay' increased by 10-100-fold when compared with a 'standard assay'. Using these assays, prospective study of interferon therapy on 38 HCV-RNA seropositive cases with chronic hepatitis (total amount 702 MU; duration of treatment 5-6 months) was performed. At the end of treatment, six were still positive and 32 became negative by the "standard assay', whereas an additional eight cases became positive (total 14 cases positive; the remaining 24 cases negative) by the 'enhanced-sensitivity assay'. Hepatitis C viral RNA state at the end of treatment remained the same 6 months later in 23 cases (61%) by a 'standard assay' and in 31 (82%) by the 'enhanced-sensitivity assay'. Of importance was that all patients (14 cases) demonstrating HCV-RNA in serum at the end of therapy, even by the "enhanced-sensitivity assay', did not show the disappearance of HCV-RNA in serum despite the long follow up. From these results, in order to improve our treatment efficacy, we should try to modify our treatment protocol to the extent that at least HCV-RNA becomes undetectable. That can be only feasible during treatment by real-time monitoring of HCV-RNA.

Adult↗

PubMed1996

Point mutation in precore region of hepatitis B virus: sequential changes from 'wild' to 'mutant'.

One point mutation to make a stop codon in the precore (pre-C) region of the hepatitis B virus DNA in anti-HBe-positive patients has been reported recently. This mutation disturbs the formation of the pre-C protein that is processed to make HBeAg. The relationship between the point mutation and HBe antigen antibody status was investigated in B-viral liver diseases. The pre-C region was amplified by a polymerase chain reaction (PCR) method and the nucleotide sequences were determined by a direct sequencing method. In seven cases who were persistently HBeAg-positive, the wild type (no mutation in pre-C region) was detected in all. In 20 cases who were anti-HBeAg-positive at diagnosis, the mutant type (point mutation at nucleotide 1896 in pre-C region, which makes a stop codon) was detected in 16 cases and the wild type in two cases. In HBe seroconversion (SC) cases, the types of virus were investigated in serial blood samples. No mutant type was detected in initial sera during the HBeAg-positive period. In two 'natural' SC cases, the mutant type appeared before anti-HBe formation. However, in three anti-viral 'drug-induced' SC cases, the mutant type appeared after the formation of anti-HBe. In two 'reversed' seroconversion cases only the wild type was detected throughout the follow-up period. These data suggest that the appearance of a pre-C mutant may help to predict seroconversion from HBeAg to anti-HBe and may help distinguish 'natural' and 'drug-induced' seroconversion of HBeAg.

Adult↗

PubMed1996

Effects of a class III antiarrhythmic drug and biphasic shocks on the postdefibrillation refractory period of relatively refractory myocardium.

INTRODUCTION: This study was designed to test whether the refractory state of nondepolarized myocardium is a major determinant of electrical defibrillation. METHODS AND RESULTS: Postshock recovery interval (PSRI) was estimated by measuring the residual refractory period after an appropriately timed field stimulus (1 to 16 V). The PSRI and transcardiac defibrillation threshold (DFT) were compared before and during the administration of E-4031, a new Class III antiarrhythmic drug (group 1, n = 10), or between monophasic and biphasic shocks (group 2, n = 14) in anesthetized open chest dogs. Group 1: E-4031 reduced the DFT from 2.6 +/- 0.6 J to 1.8 +/- 0.6 J (P < 0.01). The PSRI increased with the increase of the applied voltage and was almost always greater during E-4031 infusion than at baseline. There was an inverse correlation between the changes of DFT and PSRI measured with a 14-V stimulus (r = -0.80, P < 0.01) and a 16-V stimulus (r = -0.80, P < 0.01). Group 2: Mean DFTs were not statistically different between the two waveforms (3.3 +/- 1.0 J vs 2.9 +/- 1.4 J). However, there also was an inverse correlation between the differences in individual PSRIs and DFTs of the two waveforms (10-V stimulus: r = -0.62, P < 0.05; 16-V stimulus: r = -0.75, P < 0.01). CONCLUSIONS: Modulation of defibrillation efficiency by E-4031 infusion or by changes of the shock waveform was related to the effect of these interventions on PSRI. These results suggest an independent role for the refractoriness of nondepolarized myocardium in the mechanism of defibrillation.

Animals↗

PubMed1996

[Development of a detection system for Helicobacter pylori DNA in gastric juice].

A rapid and sensitive PCR-based microwell plate assay (PCR-MWP) system to detect the 16 S ribosome RNA gene of Helicobacter pylori was developed. Analytical sensitivity, evaluated with purified recombinant plasmid DNA and genomic DNA of H. pylori, was one copy of DNA per PCR. Specificity was validated with a panel of DNA from 75 kinds of microorganisms including Helicobacter showed weak positives, when 1 pg of DNA was input. Other microorganisms gave negative signals even when 100 pg of DNA was used for PCR. When compared with a Nested-PCR system to detect the urease A-subunit gene performed by a commercial reference laboratory, the results obtained (sensitivity 93.3% and specificity 73.3%) was almost equivalent. The PCR-MWP was rapid and easy for the detection of H. pylori DNA in gastric juice specimen.

DNA, Bacterial↗

PubMed1996

Hachimi-jio-gan extract protects the kidney from hypertensive injury in Dahl salt-sensitive rat.

We investigated whether the Chinese herbal remedy, Hachimi-jio-gan extract, attenuates the renal injury seen in salt-induced hypertension in Dahl salt-sensitive (Dahl S) rats. Administration of this extract for 5 weeks dose-dependently decreased systolic blood pressure in Dahl S rats fed with a high-salt (2% NaCl) diet. This blood pressure reduction was associated with a decrease in cardiac mass and in thickness of the aortic wall. Urinary excretion of prostaglandin E2 was increased and glomerular filtration rate was improved with this treatment. Glomerulosclerosis and arterial injury in the kidney were morphologically improved. These data suggest that Hachimi-jio-gan extract exhibits an antihypertensive effect, which is associated with partial resolution of renal injury in salt-induced hypertension.

Animals↗

PubMed1996

Electrophysiological background of individual variability in electrical defibrillation efficacy.

This study was performed to test whether heart-to-heart variability of defibrillation efficacy is attributable to differences in postshock refractory state of nondepolarized myocardium. In 30 anesthetized dogs, a localized potential gradient was created using 1-16 V of stimulus across a pair of platinum plate electrodes on the right ventricle (5-mm interelectrode distance). The postshock recovery interval (PSRI) of the relatively refractory myocardium directly adjacent to the excited area was estimated by measuring the recovery interval after an appropriately timed field stimulus. The transcardiac defibrillation threshold (DFT) was also determined. The results showed that DFT normalized by the weight of the heart was inversely correlated with the PSRI measured with a field stimulus of 6 V (local shock intensity approximately 5 V/cm) or more (6 V: r = -0.502, P < 0.005; 16 V: r = -0.635, P < 0.0005). This observation suggests that variability of defibrillation efficacy in intact hearts is largely due to differences in the postshock refractory state of the nondepolarized myocardium.

Animals↗