Search PubMed⌕ Search

Biomedical subjects

M Omata

Publications and source records attributed to M Omata.

At least 451 records · Page 25Linked to original sources
PubMed1992

High incidence of ras gene mutation in intrahepatic cholangiocarcinoma.

The DNA sequences around codons 12, 13, and 61 of the ras gene were analyzed by polymerase chain reaction and direct sequencing in 18 intrahepatic cholangiocarcinomas. The ras gene mutations were found in 9 of 18 (50%): 6 in K-ras codon 12, 1 in K-ras codon 13, 1 in K-ras codon 61, and 1 in N-ras codon 12. The incidence of mutations was higher in the hilar type of intrahepatic cholangiocarcinomas, especially when these tumors were large. The incidence and spectrum of the mutations were almost the same as those reported in colon cancers, possibly indicating similar etiologic agent(s) in the carcinogenesis of both cancers.

Adenocarcinoma↗
PubMed1992

Nucleotide sequence of prothrombin gene in abnormal prothrombin-producing hepatocellular carcinoma cell lines.

A protein induced by vitamin K absence or antagonist II, PIVKA-II is synthesized in the liver and possesses a structure similar to prothrombin except that ten glutamic acid residues in amino-terminal Gla domain are not completely gamma-carboxylated and are functionally inactive. This protein can be detected in the plasma of patients with hepatocellular carcinoma (HCC) and used as a new tumor marker. To analyze the mechanism of PIVKA-II production in HCC tissue, the prothrombin gene of PIVKA-II-secreting HCC cell lines was sequenced to detect the mutation in the Gla domain and carboxylase recognition site of leader sequence located on exons I and II that may cause the inhibition of carboxylation. Exons I and II and donor and acceptor site of intron I of the prothrombin gene in two HCC cell lines, PLC/PRF/5 and huH-2, were analyzed by polymerase chain reaction (PCR), and the product was sequenced directly. In addition, RNA samples of these cell lines were used for complementary DNA synthesis, followed by PCR and sequencing. The nucleotide sequences of the Gla domain in both HCC cell lines were conserved. One nucleotide change was detected at nt.554 (adenine to guanine), but this did not influence the amino acid sequence. Splicing sites between exons I and II, the leader sequence of the precursor prothrombin, and protease target sites also were conserved as the reported prothrombin gene, and mutations reported for other des-gamma-carboxy coagulation factors were not detected. These results also were confirmed by DNA analysis of seven human fresh-frozen samples (three PIVKA-II-positive HCC samples and four control specimens). The mechanism of PIVKA-II production in HCC is still unclear, but it is not caused by mutation in the prothrombin gene.

Amino Acid Sequence↗
PubMed1992

Non-A, non-B chronic hepatitis is chronic hepatitis C: a sensitive assay for detection of hepatitis C virus RNA in the liver.

To study the role of hepatitis C virus in non-A, non-B chronic hepatitis, 49 liver biopsy samples from 40 patients with non-A, non-B chronic hepatitis and 9 control patients were analyzed by complementary DNA/polymerase chain reaction. Two segments of the HCV genome, one in the nonstructural region and the other in the noncoding region, were amplified by two sets of primer pairs. With use of the nonstructural region primers, hepatitis C virus RNA was detected in 24 (60%) of 40 patients with non-A, non-B chronic hepatitis. Of these 40 patients, RNA was detected in 19 (70%) of 27 patients positive for antibody to hepatitis C virus and in 5 (38%) of 13 patients negative for antibody to hepatitis C virus. However, with the noncoding region primers, hepatitis C virus RNA was detected in 38 (95%) of 40 patients with non-A, non-B chronic hepatitis. Of these patients, the RNA was detected in 26 (96%) of 27 patients positive for antibody to hepatitis C virus and also in 12 (92%) of 13 patients positive for antibody to hepatitis C virus. Hepatitis C virus RNA was not detected in any of the control patients. Sequence analysis showed homology between our samples and the prototype to be only 66% to 77% in the nonstructural region but 99% to 100% in the noncoding region. We conclude that almost all patients with non-A, non-B chronic hepatitis in Japan are currently infected with hepatitis C virus, regardless of the presence or absence of antibody to hepatitis C virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1992

Inhibition of hepatic metastasis of colon carcinoma by asialo GM1--positive cells in the liver.

This study investigates the role of hepatic asialo GM1-positive cells in inhibiting hepatic metastasis of colon carcinoma (colon adenocarcinoma 38) in mice after administration of a biological response modifier, streptococcal derivative (OK432). Administration of OK432 increased the number of asialo GM1-positive cells in the liver, enhanced natural killer activity of hepatic mononuclear cells and reduced the number of hepatic metastases of colon carcinoma inoculated into the superior mesenteric vein. Administration of antiserum against asialo GM1 reduced the number of hepatic asialo GM1-positive cells, abolished natural killer activity of hepatic mononuclear cells and increased the number of hepatic metastases. In addition, administration of antiserum against asialo GM1 even after OK432 treatment also decreased the number of asialo GM1-positive cells, reduced natural killer activity of hepatic mononuclear cells and increased the number of hepatic metastases of colon carcinoma. However, administration of gadolinium chloride, which suppresses phagocytic function of Kupffer cells, did not influence the natural killer activity of hepatic mononuclear cells or the number of hepatic metastases. In vivo tumor-neutralization assay revealed that tumor growth was inhibited by the hepatic mononuclear asialo GM1-positive cells, but not by T lymphocytes or Kupffer cells after OK432 administration. These results suggest that an increased number of hepatic asialo GM1-positive cells after administration of OK432 plays an important role in protecting against metastasis of colon carcinoma in the liver.

Animals↗
PubMed1992

Effects of antiviral agents on chronic hepatitis B. Analysis using Cox proportional hazard model.

Two hundred fifteen courses of antiviral treatment including interferon with or without steroid withdrawal, adenine arabinoside with steroid withdrawal, and steroid withdrawal alone were given to 175 patients with HBe-antigen positive chronic hepatitis B. The effectiveness was judged on loss of HBe antigen and formation of anti-HBe, and was compared with 80 controls. According to cumulative HBe seronegative and seroconversion rates as analyzed by the Kaplan-Meier method, interferon with steroid withdrawal increased both the cumulative HBe seronegative and seroconversion rates significantly (P < 0.0001). Adenine arabinoside with steroid withdrawal and interferon alone increased the cumulative HBe seronegative rate only (P < 0.001). The Cox proportional hazard regression model was fitted to the data of 188 cases whose pretreatment liver biopsy specimens were obtained. Among treatment protocols, interferon with steroid withdrawal shortened both the HBeAg-positive period and the duration until anti-HBe becomes reactive significantly (P < 0.0001). Interferon without steroid withdrawal and adenine arabinoside with steroid withdrawal shortened the HBeAg positive interval only (P < 0.05). Among patients' characteristics, female and advanced liver histology were favorable factors. Effects of treatment protocols were analyzed after averaging each parameter of the patients' characteristics. Interferon and adenine arabinoside with steroid withdrawal shortened the HBeAg-positive interval significantly (P < 0.0001 and P < 0.05, respectively), and interferon alone showed a tendency to shorten the interval. In particular, interferon with steroid withdrawal increased the chance of losing HBeAg 7.3 times more than control. The effectiveness of antiviral treatment on chronic hepatitis B, especially the priority of interferon with steroid withdrawal, was thought to be established through this study.

Antiviral Agents↗
PubMed1992

p53 gene mutations in gastric and esophageal cancers.

The presence of point mutation of the p53 gene in exons 5, 6, 7, and 8 was examined in 10 cases of gastric adenocarcinoma and 5 cases of esophageal squamous cell carcinoma by polymerase chain reaction and direct nucleotide sequencing. Mutations of the p53 gene were found in 5 cases of gastric cancer and 4 cases of esophageal cancer. The mutations in the stomach cancers consisted of four missence mutations (exons 5 and 8) and one frame shift (exon 7). In the esophageal cancers, three missence mutations (exons 6, 7, and 8) and one point mutation within the splice donor site of intron 5 were found. Of the seven missence mutations in the two cancers, five showed the transition from G to A and two from G to T. All these changes occurred in the highly conserved region of the p53 protein. These results suggest that mutations of the p53 gene are genetic events in the pathogenesis of gastric adenocarcinoma and esophageal squamous cell carcinoma.

Adult↗
PubMed1992

Nucleotide sequences of 5-1-1 of hepatitis C virus in patients with chronic liver disease.

The discovery of hepatitis C virus (HCV) has led to the development of an assay against a viral peptide (C100-3), which is now used worldwide. It has been shown that the majority of HCV-infected individuals are positive for the antibody. However, there are patients who are repeatedly seronegative for the antibody despite the presence of HCV RNA in the serum. The nucleotide sequences of 5-1-1 (a major epitope of C100-3) obtained from five antibody-positive patients and five negative patients with chronic liver disease were studied. The nucleotide identities of the seropositive and seronegative patients with HCV prototype sequence were 80.6% and 81.8%, respectively, not showing much difference in the nucleotide sequence of the 5-1-1 region. Moreover, no marked differences were noted in the deduced amino acid residues and the hydropathy profiles between the two groups. These data suggest that absence of the antibody in HCV carriers are not due to variations of major epitopes but are probably due to immunological incompetence against the synthetic C100-3 peptide.

Amino Acid Sequence↗
PubMed1992

Posttransfusion hepatitis in Japan.

The incidence of posttransfusion hepatitis and the rate of chronicity were investigated in a program devised at our hospital in December, 1982. Out of 2,596 blood recipients between January, 1982, and December, 1987, 451 (22.7%) developed posttransfusion hepatitis. Seventy-seven patients out of 217 (35.3%) whose course was closely followed progressed to chronicity. The incidence of posttransfusion hepatitis increased with the volume of transfused blood without any evident limitation. Recipients of elevated-ALT donor blood (greater than 26 Karmen units) were found to be more susceptible to posttransfusion hepatitis than those who had received only normal-ALT donor blood. Packed red blood cells, whole blood and fresh whole blood were high-risk components, and fresh frozen plasma a low-risk component of blood. The carrier rate of non-A, non-B hepatitis agents in Japanese healthy blood donors was determined to be 1.2% using the Frost-Reed model of infectious diseases. Anti-hepatitis C virus was detected in 62% of the cases of posttransfusion hepatitis 1 year after transfusion.

Acute Disease↗
PubMed1992

Variations in codons 84-101 in the core nucleotide sequence correlate with hepatocellular injury in chronic hepatitis B virus infection.

Individuals with chronic hepatitis B virus (HBV) infection are generally divided into asymptomatic healthy carriers and patients with chronic liver disease. Several studies have suggested that the hepatitis B core antigen could be an immunological target of cytotoxic T lymphocytes (CTL). To investigate the possible pressure site from CTL, the entire core region of HBV DNA was sequenced in 30 subjects (10 asymptomatic healthy carriers and 20 patients with chronic liver disease). No significant changes in the nucleotide sequence and deduced amino acid residue were noted in the 10 healthy carriers. In contrast, a cluster of changes in a small segment of 18 amino acids (codons 84-101 from the start of the core gene) was found in 15 of the 20 chronic liver disease patients. All these 15 patients had advanced liver diseases (chronic active hepatitis and cirrhosis), whereas only mild liver disease (chronic persistent hepatitis) was found in the five patients without mutations. These data suggest that the region with mutation clustering is the major target of CTL, and that the mutations evolve under the pressure of immune selection.

Adult↗
PubMed1992

A multi-institute case-control study on the risk factors of developing pancreatic cancer.

A multi-institute, hospital-based, case-control study on pancreatic cancer was carried out to examine its association with preceding diseases, cigarette smoking, alcohol drinking and dietary factors. Analyses were based on 124 newly diagnosed exocrine pancreatic cancer cases and sex-, age- and institute-matched hospital controls in seven hospitals in Japan. Cigarette smoking showed a positive association with the risk of developing pancreatic cancer. Especially among smokers, a risk enhancing effect of involuntary/passive smoking prior to twenty years of age was observed (P < 0.05). No consistent associations were found with coffee, black tea or alcohol consumption. Among dietary factors, favoring food of a salty taste and drinking green tea five cups per day or more were positively associated with the risk. Drinking milk and eating fish everyday were inversely associated with the risk.

Adult↗
PubMed1991

Resolution of acute hepatitis C after therapy with natural beta interferon.

To test whether interferon can prevent acute non-A, non-B hepatitis from becoming chronic, a prospective controlled trial was conducted in 25 patients; 11 were treated for an average of 30 days with a mean of 52 megaunits of interferon and 14 acted as controls. 4 patients in the treatment group who continued to have raised serum aminotransferase concentrations after a year's follow-up were given a second course of interferon. Follow-up at 3 years has revealed that all but 1 of those treated showed normal serum aminotransferase, whereas only 3 controls showed such change (p less than 0.02). Serum hepatitis C virus RNA became undetectable in 10 of 11 treated and in only 1 of 12 control patients, which suggests that interferon prevents the progression of acute non-A, non-B hepatitis to chronicity by eradicating HCV.

Acute Disease↗
PubMed1991

Mutations in the precore region of hepatitis B virus DNA in patients with fulminant and severe hepatitis.

BACKGROUND: The presence of the hepatitis B e antigen (HBeAg) in serum is known to be a marker of a high degree of viral infectivity. However, fulminant hepatitis may occur in persons who are negative for HBeAg. A single point mutation has been reported to produce a stop codon in the precore region of hepatitis B virus DNA and prevent the formation of the precore protein required to make HBeAg. To determine whether a precore-mutant virus is causally related to severe liver injury, we analyzed the entire precore region in viral strains isolated from patients with fatal cases and uncomplicated cases of hepatitis B. METHODS: Serum was obtained from 9 patients with fatal hepatitis B (5 with fulminant and 4 with severe exacerbations of chronic hepatitis) and 10 patients with acute, self-limited hepatitis B. Serum samples from a sex partner implicated as the source of the virus in one case of fulminant hepatitis were also studied. The 87 nucleotides in the precore region of the hepatitis B virus were amplified by the polymerase chain reaction and then directly sequenced. RESULTS: Of the nine patients with fatal hepatitis, seven had retrievable hepatitis B DNA: In all seven there was a point mutation from G to A at nucleotide 1896 of the precore region, converting tryptophan (TGG) to a stop codon (TAG). In contrast, this mutation was not found in the 10 patients with acute, self-limited hepatitis B. The hepatitis B DNA from the implicated source contained a sequence with the stop-codon mutation that was identical to the sequence in her partner, who had fulminant hepatitis. CONCLUSIONS: The presence of a mutant viral strain is associated with and may be involved in the pathogenesis of fulminant hepatitis B and severe exacerbations of chronic hepatitis B.

Acute Disease↗
PubMed1991

Ras gene mutations in intraductal papillary neoplasms of the pancreas. Analysis in five cases.

Five intraductal papillary neoplasms of the pancreas were analyzed for the presence of the Ras gene mutations. Three (60%) of the five neoplasms showed point mutations at K-ras codon 12. This incidence of the mutations was rather low compared with that found with ordinary pancreatic adenocarcinoma. The presence of the mutations did not correlate with the severity of cellular atypia, but was apparently related to the size of the tumor. The two neoplasms that had no mutations were smaller than the others that had mutations. The analysis suggested that Ras gene mutation is not the first genetic alteration of tumor progression, but that it occurs during the development of neoplasms of the pancreas.

Adenocarcinoma, Papillary↗
PubMed1991

Randomized, double-blind, placebo-controlled trial of eight-week course of recombinant alpha-interferon for chronic non-A, non-B hepatitis.

Forty-nine Japanese patients were enrolled in a randomized, placebo-controlled, double-blind trial of alpha-interferon for chronic non-A, non-B hepatitis: 24 patients received 3 million units of recombinant human alpha alpha-interferon (alpha-2a) thrice weekly for eight weeks, and 25 patients received placebo in a similar schedule. The mean serum alanine aminotransferase (ALT) dropped from 155 +/- 91 (SD) to 69 +/- 72 during interferon treatment, but remained unchanged (158 +/- 140 to 147 +/- 130) during placebo treatment (P less than 0.001). Serum ALT level fell to the normal range in 29% of interferon-treated patients, but in only 4% of placebo-treated patients. Pre- and posttreatment liver biopsies were obtained in all but one case. Average histological activity indices (HAI) were markedly improved in the interferon-treated group (9.5 +/- 3.7 to 7.0 +/- 4.3), but were unchanged in the placebo group (8.5 +/- 4.3 to 8.5 +/- 4.9). In addition, we compared the efficacy of interferon treatment between anti-hepatitis C virus (HCV) antibody positive and negative groups. Biochemical and histological improvements were similar and statistically significant in patients with and without antibody to hepatitis C virus. These data indicate that a eight-week course of alpha-interferon induces biochemical and histological improvement in more than half the patients with chronic non-A, non-B hepatitis.

Alanine Transaminase↗
PubMed1991

Detection and partial sequencing of hepatitis C virus RNA in the liver.

To detect hepatitis C virus RNA, total RNA was extracted from liver tissue, reverse transcribed to complementary DNA, and amplified by polymerase chain reaction. The reaction products were analyzed by ethidium bromide staining in acrylamide gel and hybridization with a radiolabeled probe. Hepatitis C virus RNA was thereby detected in 17 of 27 (63%) liver tissue specimens obtained from patients with non-A, non-B chronic liver diseases. Of these 27 patients, viral RNA was detected in 12 of 17 (71%) liver tissues from anti-hepatitis C virus-positive patients and in 5 of 10 (50%) liver tissues from anti-hepatitis C virus-negative patients. Direct sequencing of amplified complementary DNA (35 nucleotides) of the 17 RNA-positive samples showed only 66% to 77% homology to the reported hepatitis C virus complementary DNA sequence. These results indicate that the majority of anti-hepatitis C virus-positive patients are currently infected with hepatitis C virus, and some of the anti-hepatitis C virus-negative patients with non-A, non-B hepatitis are harboring hepatitis C virus in the liver. Detection of hepatitis C virus RNA appears to provide a useful indicator in the study of hepatitis C virus infection.

Base Sequence↗