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Biomedical subjects

Y Shiratori

Publications and source records attributed to Y Shiratori.

At least 109 records · Page 6Linked to original sources
PubMed1999

How soon can a virological sustained response be determined after withdrawal of interferon therapy in chronic hepatitis C? Tokyo-Chiba Hepatitis Research Group.

Hepatitis C virus (HCV)-RNA status and alanine aminotransferase (ALT) levels determined shortly after interferon (IFN) therapy in patients with chronic hepatitis C do not predict long-term response. To determine the virological sustained response after the completion of IFN therapy, HCV-RNA was measured at the end of treatment and at 3-4 months and 12 months after the completion of therapy in 537 patients with chronic hepatitis C. In 347 patients, HCV-RNA was not detected by polymerase chain reaction (PCR) at the completion of therapy and 175 of these patients (50%) were still PCR negative 12 months later. In contrast, of the 180 patients who were HCV-RNA negative at 3-4 months after completion of therapy, 99% remained negative at 12 months. Normal ALT levels were found in 80, 93 and 95% of patients who were negative for HCV-RNA either at the end of treatment or at 3-4 months and 12 months after the completion of therapy, respectively. Of patients who were HCV-RNA positive, 30, 15 and 20% were found to have normal ALT levels at the same respective time points. To determine a sustained virological response shortly after the completion of therapy, serum HCV-RNA was serially examined in 66 patients negative for HCV-RNA at the end of therapy. Of 31 patients who relapsed, HCV-RNA reappeared in 33, 80, 97 and 100% of patients by 1, 2, 4 and 8 weeks after the completion of therapy. In conclusion, a sustained virological response could be determined with 97 and 99% certainty at 4 weeks and at 3-4 months after the completion of therapy, respectively.

Adult↗
PubMed1999

Endoscopic variceal ligation is a sufficient procedure for the treatment of oesophageal varices in patients with hepatitis C liver cirrhosis: comparison with injection sclerotherapy.

AIMS: Endoscopic variceal ligation (EVL) is a recently developed alternative to endoscopic injection sclerotherapy (EIS) for the treatment of oesophageal varices. Endoscopic variceal ligation and EIS were compared in an attempt to clarify the efficacy and safety of EVL for patients with cirrhosis due to hepatitis C. METHODS: Endoscopic variceal ligation was performed in 60 patients and EIS in 30. Varices were eradicated in all patients by EVL and 87% (26 out of 30) by EIS. RESULTS: There was no significant difference between EVL and EIS in relation to the incidence of bleeding and the 5 year survival rate after treatment. There were no severe complications except mild substernal pain after EVL, while pulmonary embolism occurred in one patient receiving EIS. CONCLUSIONS: Endoscopic variceal ligation is a safe and effective technique for eradicating oesophageal varices in patients with hepatitis C cirrhosis.

Esophageal and Gastric Varices↗
PubMed1999

Mutational inactivation of mitotic checkpoint genes, hsMAD2 and hBUB1, is rare in sporadic digestive tract cancers.

Genetic instability is a key mechanism of tumorigenesis, and the instability exists at two distinct levels, the nucleotide and the chromosome levels. Disruption of the mitotic spindle checkpoint is one of the underlying mechanisms leading to aneuploidy and alterations of hsMAD2 and hBUB1, assumed to take part in the spindle checkpoint in human cells, have been found to be associated with chromosomal instability in some tumor cell lines. Therefore, we investigated the mutational status of the hsMAD2 and hBUB1 genes in 32 sporadic digestive tract cancers by reverse transcription-polymerase chain reaction-single strand conformation polymorphism analysis. The entire coding sequence of the hsMAD2 gene, and conserved regions (codons 21-152 and codons 732-1043) presumed to be functionally important in the hBUB1 gene were analyzed. Mutation of the hsMAD2 gene was not observed at all and missense mutation of the hBUB1 gene was noted in one rectal cancer case. Sequencing analysis revealed an AGT-to-GGT missense mutation, substituting glycine for serine, at codon 950, which is conserved between budding yeast and human. These results indicate that mutations of the hsMAD2 and hBUB1 genes are very rare and presumably play a very restricted role in tumor development of sporadic cancers.

Adenocarcinoma↗
PubMed1999

Strategy of liver-directed gene therapy: present status and future prospects.

The liver is particularly amenable to gene therapy as it is the site of many metabolic diseases and malignancies. Thus, liver-directed gene therapy is being actively pursued and developed as a method of treatment for various liver diseases. Strategies of liver-directed gene therapy include drug delivery to the liver, compensation of the defective gene(s), anti-tumor activity, anti-viral therapy, and immunomodulation. The strategy chosen for liver-directed gene therapy depends on the genetic basis of the disease. Many aspects are key factors to the success of the chosen strategy: intervention of genes, efficient gene delivery system, stable transgene expression, transgene regulation, target cell transfection, and timing of transgene expression. Several tactics can be used to overcome problems in the above, and these include the use of a gene switch to exogenously regulate transgene expression, targeting at the transcriptional level, circumvention of the immune response (as in the use of adenovirus vector to achieve long-term correction of genetic diseases), and genetically engineered antibodies in gene transfer. At the present rate of research activity and development, gene therapies may soon be more efficient than current standard treatments for some liver diseases.

Animals↗
PubMed1999

Potential utility of magnetic resonance cholangiography in the management of endoscopic biliary drainage tubes.

An 80-yr-old woman with advanced hilar cholangiocarcinoma underwent a placement of endoscopic biliary drainage (EBD) tube from the common hepatic to common bile duct through the stricture. Magnetic resonance cholangiography clearly demonstrated the later dislocation and obstruction of the EBD tube. The present case suggests that magnetic resonance cholangiography may be a potentially useful tool in the management of EBD tubes.

Aged↗
PubMed1999

Structure of cag pathogenicity island in Japanese Helicobacter pylori isolates.

BACKGROUND: cag pathogenicity island (PAI) is reported to be a major virulence factor of Helicobacter pylori. AIM: To characterise cagA and the cag PAI in Japanese H pylori strains. METHODS: H pylori isolates from Japanese patients were evaluated for CagA by immunoblot, for cagA transcription by northern blot, and for cagA and 13 other cag PAI genes by Southern blot. cagA negative strains from Western countries were also studied. Induction of interleukin-8 secretion from gastric epithelial cells was also investigated. RESULTS: All Japanese strains retained cagA. Fifty nine of 63 (94%) strains had all the cag PAI genes. In the remaining four, cag PAI was partially deleted, lacking cagA transcripts and not producing CagA protein. Details of the PAI of these strains were checked; three lacked cagB to cagQ (cagI) and continuously cagS to cag13 (cagII), and the remaining one lacked cagB to cag8. Western cagA negative strains completely lacked cag PAI including cagA. Nucleotide sequence analysis in one strain in which the cag PAI was partially deleted showed that the partial deletion contained 25 kb of cag PAI and the cagA promoter. Interleukin-8 induction was lower with the cag PAI partial deletion strains than with the intact ones. All Japanese cag PAI deleted strains were derived from patients with non-ulcer dyspepsia, whereas 41 of 59 (70%) CagA-producing strains were from patients with peptic ulcers or gastric cancer (p<0.05). CONCLUSIONS: Most Japanese H pylori strains had the intact cag PAI. However, some lacked most of the cag PAI in spite of the presence of cagA. Thus the presence of the cagA gene is not an invariable marker of cag PAI related virulence in Japanese strains.

Adult↗
PubMed1999

Adenovirus mediated p53 tumour suppressor gene therapy for human gastric cancer cells in vitro and in vivo.

BACKGROUND/AIMS: Gastric cancer is one of the most prevalent forms of cancer in East Asia. Point mutation of the p53 gene has been reported in more than 60% of cases of gastric cancer and can lead to genetic instability and uncontrolled cell proliferation. The purpose of this investigation was to evaluate the potential of p53 gene therapy for gastric cancer. METHODS: The responses of human gastric cancer cell lines, MKN1, MKN7, MKN28, MKN45, and TMK-1, to recombinant adenoviruses encoding wild type p53 (AdCAp53) were analysed in vitro. The efficacy of the AdCAp53 treatment for MKN1 and MKN45 subcutaneous tumours in nude mice was assessed in vivo. RESULTS: p53-specific growth inhibition was observed in vitro in two of four gastric cancer cell lines with mutated p53, but not in the wild type p53 cell line. The mechanism of the killing of gastric cancer cells by AdCAp53 was found, by flow cytometric analysis and detection of DNA fragmentation, to be apoptosis. In vivo studies showed that the growth of subcutaneous tumours of p53 mutant MKN1 cells was significantly inhibited by direct injection of AdCAp53, but no significant growth inhibition was detected in the growth of p53 wild type MKN45 tumours. CONCLUSIONS: Adenovirus mediated reintroduction of wild type p53 is a potential clinical utility in gene therapy for gastric cancers.

Adenoviridae↗
PubMed1999

High proportion of mutant K-ras gene in pancreatic juice of patients with pancreatic cystic lesions.

BACKGROUND/AIMS: It was recently reported that the quantitative analysis of mutant K-ras gene in pancreatic juice could be useful for the diagnosis of pancreatic cancer. This methodology was applied to patients with pancreatic cystic lesions. METHODS: DNA was extracted from pancreatic juice collected at the time of endoscopy with injection of secretin. The ratio of the K-ras mutant allele to the wild-type allele was measured by two methods to detect and semiquantify mutant K-ras gene: polymerase chain reaction/preferential homoduplex formation assay and enriched polymerase chain reaction/enzyme linked mini-sequence assay. RESULTS: A high frequency of K-ras mutation was detected (more than 2% of all K-ras genes) in six of 14 patients (43%) with pancreatic cysts. This frequency was similar to those detected in patients with pancreatic adenocarcinoma and in intraductal papillary neoplasms of the pancreas. In contrast, the frequency of mutation was low (less than 2%) in patients without either pancreatic cysts or pancreatic neoplasms. CONCLUSIONS: K-ras gene mutation may be derived from duct cells in the pancreas with a high potential for tumorigenesis. Therefore careful follow up of patients with a pancreatic cyst is recommended if they are found to have a high level of the mutant gene in the pancreatic juice.

Adenocarcinoma↗
PubMed1999

Susceptibility of lamivudine-resistant hepatitis B virus to other reverse transcriptase inhibitors.

The emergence of resistant hepatitis B virus (HBV), with mutations in the YMDD motif of the polymerase gene after treatment with lamivudine, is becoming an important clinical problem. In this study, susceptibility of wild-type and lamivudine-resistant HBV M552I, M552V, and L528M/M552V mutants to other reverse transcriptase inhibitors was investigated by transient transfection of full-length HBV DNA into human hepatoma cells. HBV DNA replication was monitored by Southern blot hybridization, which showed the presence of a single-stranded band (representative of the HBV replicative intermediates) in the drug-free, wild-type HBV-transfected cells. This band was diminished in the samples of wild-type HBV DNA treated with either lamivudine, adefovir, or lobucavir. The band intensities from the lamivudine-resistant mutants were not decreased by treatment with lamivudine, but were decreased by the treatments with adefovir or lobucavir. In contrast, penciclovir and nevirapine did not diminish the intensity of the single-stranded band of wild-type HBV or the lamivudine-resistant mutants. These results demonstrate that lamivudine-resistant HBV is susceptible to adefovir and lobucavir. Lamivudine-resistant HBV should be treated with adefovir or lobucavir, and combination therapy with lamivudine and adefovir/lobucavir may prevent the emergence of lamivudine-resistant HBV.

Acyclovir↗
PubMed1999

Acquired factor VIII inhibitor in a non-hemophilic patient with chronic hepatitis C viral infection.

Production of coagulation factor VIII inhibitor is rarely encountered in non-hemophilic patients. A 63-year-old Japanese male suffered from severe bleeding tendency caused by this inhibitor. Although he did not have malignancy or collagen disease, he had chronic hepatitis C virus (HCV) infection. Although HCV is known to induce production of various autoimmune antibodies, this may be the first report of a case with both acquired factor VIII inhibitor and HCV infection.

Blood Coagulation Factors↗
PubMed1999

[Carotenoids].

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Carotenoids↗
PubMed1998

Adenovirus-mediated transduction of Escherichia coli uracil phosphoribosyltransferase gene sensitizes cancer cells to low concentrations of 5-fluorouracil.

5-fluorouracil (5-FU), although a widely used chemotherapeutic agent, has a limited effect in the treatment of human solid tumors due to their resistance to the cytotoxic effects of 5-FU. Escherichia coli uracil phosphoribosyltransferase (UPRT) is a pyrimidine salvage enzyme that catalyzes the synthesis of UMP from uracil and 5-phosphoribosyl-alpha-1-diphosphate. The present study demonstrates that adenovirus-mediated transduction of E. coli UPRT gene results in marked sensitization of colon, gastric, liver, and pancreas cancer cell lines to low concentration of 5-FU in vitro. The in vitro bystander effect was observed when only 10% of the hepatoma Hep3B cells were infected with UPRT-expressing adenovirus. In addition, 5-FU treatment of human hepatoma or gastric cancer xenografts in nude mice transduced with UPRT was demonstrated to result in significant in vivo antitumor effects. The adenovirus vector transduction of the UPRT gene followed by 5-FU administration is representative of a new chemosensitization strategy for cancer gene therapy.

Adenoviridae↗