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Biomedical subjects

M Mayumi

Publications and source records attributed to M Mayumi.

At least 91 records · Page 5Linked to original sources
PubMed1997

Prostaglandin E2 and IL-4 provide naive CD4+ T cells with distinct inhibitory signals for the priming of IFN-gamma production.

We investigated the effects of prostaglandin E2 and IL-4 on the acquisition of cytokine-producing ability by naive CD4(+) T cells in human umbilical cord blood. The presence of PGE2 or IL-4 at primary stimulation inhibited the production of IFN-gamma at secondary stimulation, and the combination of these stimuli resulted in cooperative effects. During primary stimulation with anti-CD3, the intracellular cAMP level was elevated in PGE2-treated cells but not in IL-4-treated or control cells. The signal provided by PGE2, but not by IL-4, was inhibited with RpcAMP, indicating that it was mediated by cAMP. After differentiation into Th2-like cells, cAMP levels in PGE2- and IL-4-treated cells were not different. Our results suggest that both PGE2 and IL-4 play important roles with distinct mechanisms in inhibiting the priming of IFN-gamma production of naive CD4(+) T cells.

CD4-Positive T-Lymphocytes↗
PubMed1997

Mutation rate of GB virus C/hepatitis G virus over the entire genome and in subgenomic regions.

A patient on maintenance hemodialysis was infected with a recently discovered putative non-A to -E hepatitis virus designated GB virus C (GBV-C) or hepatitis G virus (HGV) by transfusion. The viral isolate was recovered from the patient soon after she turned positive for GBV-C/HGV RNA in serum (GS185) and 8.4 years thereafter (GS193), and the entire nucleotide sequences were determined. They both had a genomic length of 9391 nucleotides with a defective C gene made of only 42 nucleotides. Between GS185 and GS193, 31 (0.33%) nucleotides were different, which changed 5 (0.18%) of the encoded 2842 amino acids. Thus, GBV-C/HGV was estimated to have a mutation rate of 3.9 x 10(-4) base substitutions per site per year. Nucleotide conversions were distributed over subgenomic regions, except in the 5' untranslated region of 552 nucleotides and a defective short C gene, which were conserved in sequence. The change in the putative envelope genes (E1 and E2) was no different from that in the entire genome with only 6 (0.35%) nucleotide substitutions among the 1730, just 1 of which induced an amino acid conversion. Taken along with the comparison of the two isolates with the reported five GBV-C or HGV isolates, these results indicate that GBV-C/HGV would not have hypervariable regions and would use a strategy for viral persistence that is different from immune escape.

Amino Acid Sequence↗
PubMed1997

Infection with GB virus C and hepatitis C virus in drug addicts, patients on maintenance hemodialysis, or with chronic liver disease in Nepal.

Infection with GB virus C (GBV-C) and hepatitis C virus (HCV) was surveyed in various populations in Kathmandu, Nepal. GBV-C RNA and HCV RNA were detected in four (2%) and none, respectively, of 181 normal controls. Viral RNAs were detected significantly more frequently (P < 0.001) in 32 (44%) and 43 (60%), respectively, of 72 users of illicit intravenous drug, and in three (14%) and one (5%) of 22 patients on maintenance hemodialysis. The three hemodialysis patients with GBV-C RNA had been transfused with more blood units than the 19 without GBV-C RNA (51 +/- 21 vs. 5 +/- 3 units, P < 0.01), and one was co-infected with HCV. Of 145 patients with chronic liver disease, GBV-C RNA was detected in four (3%) and HCV RNA in 12 (8%); only one patient with GBV-C RNA was without markers of HCV or hepatitis B virus infection. In the 32 drug addicts infected with GBV-C, genotypes were G1 in two (6%), G2 in 26 (81%), G3 in three (9%), and the remaining one (3%) was coinfected with G2 and G3. GBV-C genotypes in the 13 individuals in the populations other than drug addicts were G2 in 11 (85%) and G3 in two (15%). HCV genotypes in the 43 drug addicts with viremia were l/1a in 21 (49%), V/3a in 19 (44%) and l/1a plus V/3a in two (5%); these genotypes were not prevalent in normal controls and patients with chronic liver disease in Nepal. These results indicate that GBV-C infection is prevalent in healthy subjects in Nepal at a frequency (2%) comparable with those in the other countries and that GBV-C transmits efficiently by intravenous drug abuse among drug addicts and by transfusion in hemodialysis patients.

Adult↗
PubMed1997

IL-7 induces proliferation, variable cytokine-producing ability and IL-2 responsiveness in naive CD4+ T-cells from human cord blood.

We investigated the effects of IL-7 on the proliferation and acquisition of cytokine-producing ability of naive CD4+ T-cells from human cord blood. Naive CD4+CD45RA+ T-cells from human cord blood expressed CDw127 (IL-7R) at higher levels than adult CD4+ CD45RA+ T-cells and produced IL-2 and a small amount of IFN-gamma upon stimulation with PMA and ionomycin. IL-7 induced IL-2-independent proliferation and both Th1- and Th2-type cytokine-producing abilities in cord blood CD4+CD45RA+ T-cells without stimulation via TCR. These results suggest that this IL-7-induced antigen-independent activation mechanism could contribute to maintaining the clonal size of naive T-cells with the potential to differentiate into either Th1 or Th2 cells at the sites of IL-7-expression.

Adult↗
PubMed1997

A monoclonal antibody against a hepatitis B e antigen epitope borne by six amino acids encoded by the precore region.

Hepatitis B e antigen (HBeAg) polypeptide in the circulation (p17e) is composed of ten amino acids (aa) coded for by the precore region and 149 aa by the core gene of hepatitis B virus. A monoclonal antibody (Y0583A) was raised against the N-terminal ten amino acids (SKLCLGWLWG) encoded by the precore region. The binding of Y0583A with a panel of 203 decapeptides on multipins, which covered the precursor of HBeAg polypeptide made of 212 aa shifting by one aa, recognized an epitope sequenced LGWLWG representing the C-terminal six aa coded for by the precore region. This HBeAg epitope was not readily accessible on HBeAg in serum, but it became exposed and bound with Y0583A by treatment with 0.2 N NaOH. Using Y0583A, an enzyme-linked immunosorbent assay was developed for specific determination of HBeAg. The test sample was incubated with the monoclonal antibody to an HBeAg determinant encoded by the core gene (904) that had been immobilized on a solid support. Captured HBeAg was treated with 0.2 N NaOH, neutralized and released into the fluid phase. The reactant was then tested for a sandwich between monoclonal antibody (C33) to the C-terminus of the HBeAg polypeptide immobilized on a solid support and Y0583A labeled with horseradish peroxidase.

Amino Acid Sequence↗
PubMed1997

The molecular basis of hepatitis B e antigen (HBeAg)-negative infections.

Hepatitis B e antigen (HBeAg)-negative infections are an unusual form of chronic hepatitis B virus (HBV) infection in which viral replication and liver damage persist despite antibodies against HBeAg. This form of HBV may be associated with fulminant hepatitis. The molecular basis for an HBeAg-minus phenotype has been extensively studied and is most often a result of mutations in the precore region. However, other mutations can give rise to this phenotype and their investigation and characterization may reveal new insights into the pathogenesis of chronic viral hepatitis.

Codon, Terminator↗
PubMed1997

Identification of genetic mutations in Japanese patients with fructose-1,6-bisphosphatase deficiency.

Fructose-1,6-bisphosphatase (FBPase) deficiency is an autosomal recessive inherited disorder and may cause sudden unexpected infant death. We reported the first case of molecular diagnosis of FBPase deficiency, using cultured monocytes as a source for FBPase mRNA. In the present study, we confirmed the presence of the same genetic mutation in this patient by amplifying genomic DNA. Molecular analysis was also performed to diagnose another 12 Japanese patients with FBPase deficiency. Four mutations responsible for FBPase deficiency were identified in 10 patients from 8 unrelated families among a total of 13 patients from 11 unrelated families; no mutation was found in the remaining 3 patients from 3 unrelated families. The identified mutations included the mutation reported earlier, with an insertion of one G residue at base 961 in exon 7 (960/961insG) (10 alleles, including 2 alleles in the Japanese family from our previous report [46% of the 22 mutant alleles]), and three novel mutations--a G-->A transition at base 490 in exon 4 (G164S) (3 alleles [14%]), a C-->A transversion at base 530 in exon 4 (A177D) (1 allele [4%]), and a G-->T transversion at base 88 in exon 1 (E30X) (2 alleles [9%]). FBPase proteins with G164S or A177D mutations were enzymatically inactive when purified from E. coli. Another new mutation, a T-->C transition at base 974 in exon 7 (V325A), was found in the same allele with the G164S mutation in one family (one allele) but was not responsible for FBPase deficiency. Our results indicate that the insertion of one G residue at base 961 was associated with a preferential disease-causing alternation in 13 Japanese patients. Our results also indicate accurate carrier detection in eight families (73%) of 11 Japanese patients with FBPase deficiency, in whom mutations in both alleles were identified.

Amino Acid Substitution↗
PubMed1997

Molecular investigation of GB virus C infection in hemophiliacs in Japan.

RNA of a putative non-A, -B, -C, -D, or -E hepatitis virus named GB virus C (GBV-C) was detected by reverse transcription-polymerase chain reaction with primers deduced from the 5' untranslated region in 15 (24%) of 63 men with hemophilia in Japan at a frequency higher (P < .001) than that in 2 (0.6%) of 337 controls. By phylogenetic analysis, GBV-C isolates from some patients were similar in sequence, indicating infection with closely related strains, and those from certain patients resembled sequences reported from foreign countries. All patients were infected with hepatitis C virus, and genotypes that are rare in Japan were detected in 36 (57%) of them. These results indicate that patients with hemophilia in Japan would be at increased risk for infection with GBV-C and hepatitis C virus, some of which would have been transmitted via imported coagulation factor concentrates in the past.

Adolescent↗
PubMed1997

Response to interferon-alpha 2a in patients with e antigen-negative chronic hepatitis B.

Sixty-eight consecutive patients with chronic hepatitis B received 702 million units of recombinant interferon-alpha 2a. Of the 24 patients negative for hepatitis B e antigen (HBeAg) in serum, the normalization of serum transaminase occurred in 14 (58%) at the completion of interferon therapy and in 13 (54%) at 12 months thereafter; it was normalized in 17 (39%) and 13 (30%), respectively, of the 44 HBeAg-positive patients. Of the HBeAg-negative patients, hepatitis B virus DNA was cleared from serum in six (25%) at the completion and in one (4%) at 12 months thereafter, in contrast to only one (2%, p < 0.05) and none of the HBeAg-positive patients, respectively. The 1896th nucleotide of G (G1896) for codon 28 for tryptophan or A (A1896) for the stop codon 28 in the precore region was determined by restriction fragment length polymorphism. The ten HBeAg-negative patients with A1896 only in the precore region had lower pretreatment levels of viral markers, which decreased more rapidly and extensively after interferon than in the 14 HBeAg-negative patients with a mixture of G1896 and A1896 or in the 44 HBeAg-positive patients. These results indicate that patients with HBeAg-negative chronic hepatitis B may respond better to interferon than HBeAg-positive patients, and that the precore mutant with the stop codon 28 may be sensitive to interferon.

Adult↗
PubMed1997

The entire nucleotide sequences of two GB virus C/hepatitis G virus isolates of distinct genotypes from Japan.

Recently, putative viral agents responsible for human non-A to E hepatitis have been independently reported by two groups of investigators and designated GB virus C (GBV-C) and hepatitis G virus (HGV), respectively. The entire nucleotide sequences were determined for two viral genomes isolated from Japanese blood donors with GBV-C RNA. One of them (GT230) had a total genomic length of 9390 nucleotides (nt) with 5' and 3' untranslated regions of 551 and 313 nt, while the other (GT110) had genomic lengths of 9395, 281 and 315 nt, respectively. They both had a single long open reading frame, encoding 2842 amino acids (aa) in GT230 and 2933 aa in GT110. Surprisingly, they both lacked a clearly identifiable core gene, and possessed the E1/E2 gene with only four potential N-linked glycosylation sites. Pairwise comparison and phylogenetic analysis of the entire sequence indicated that the prototype GBV-C and two HGV isolates reported, as well as GT230 and GT110, are the same virus possibly of different genotypes. The five GBV-C/HGV isolates were variable up to 13.8% in the genomic nucleotide sequence, and contained deletions and insertions within the 5'-terminal 518-593 nt, which resulted in four different sizes of predicted polyproteins encoded by genomes of individual isolates. By contrast, the 3' untranslated region was well conserved. The high degree of sequence conservation within this region would favour it as a target for sensitive detection of GBV-C/HGV RNA.

Amino Acid Sequence↗
PubMed1997

Assessment of endogenous nitric oxide formation in newborns: measurement of urinary nitrite and nitrate concentrations.

We measured the urinary nitrite and nitrate (NOx-) excretion, an index of endogenous nitric oxide formation, in term and preterm newborns on the 1st and 4th days of age. In the infants of both groups, the urinary NOx- excretion significantly increased from the 1st to the 4th day. The urinary NOx- excretion in preterm infants was significantly higher as compared with term babies on both days. Furthermore, the urinary NOx- excretion was significantly elevated in preterm infants with respiratory distress syndrome as compared with those without cardiopulmonary complications on the 4th day. These changes of urinary NOx- excretion in newborns strongly suggest the presence of an active physiological role for nitric oxide in the circulatory adaptation to extrauterine life.

Female↗
PubMed1997

Infection with GB virus C in patients with chronic liver disease.

Infection with putative non-A to E hepatitis virus, designated GB virus C (GBV-C), was surveyed in 286 patients with chronic liver disease in Japan. RNA of GBV-C was detected, by reverse-transcription polymerase chain reaction with nested primers from the 5'-noncoding region, in 19 patients (6.6%) at a frequency higher (P < 0.001) than in three of 275 (1.1%) normal controls. It was detected in three of 83 (4%) patients with hepatitis B virus infection, 15 of 188 (8%) patients with hepatitis C virus infection, and one of 12 (8%) patients without evidence of ongoing infection with hepatitis B or C virus. GBV-C RNA was detected in nine of 186 (5%) patients with chronic hepatitis aged 51.2 +/- 13.3 years, six of 64 (9%) with liver cirrhosis aged 62.9 +/- 11.4 years, and four of 36 (11%) with hepatocellular carcinoma aged 62.0 +/- 11.1 years. Nucleotide sequences of 100 base pairs in the helicase region of GBV-C isolates from the 19 patients varied up to 21%, while sequences of 33 deduced amino acids were conserved and differed only by up to 6%. These results indicate that infection with GBV-C in patients with non-B, non-C chronic liver disease would not be frequent, although the sensitivity of the detection method could be improved. Coinfection of GBV-C with hepatitis B or C virus, as well as the duration of infection, might accelerate the progression of chronic liver disease.

Amino Acid Sequence↗
PubMed1997

X-linked severe combined immunodeficiency with gamma delta T cells.

A patient with X-linked severe combined immunodeficiency (X-SCID) was found to have a deletion mutation of a four base pair in the transmembrane domain of the IL-2 receptor gamma chain gene, a subunit shared by the receptors for IL-4, IL-7, IL-9, and IL-15 (common gamma chain; gamma c). He had very few alpha beta T cells but had a considerable number of gamma delta T cells in his peripheral blood. Fluorescence in situ hybridization (FISH) analysis showed that the gamma delta T cells in his peripheral blood were not of maternal origin. He had received a Bacillus Calmette-Guerin (BCG) vaccination before recognition of the disease, and the BCG infection remained quiescent with no reaction for 19 months. After successful bone marrow transplantation, the site of the BCG vaccination showed a reaction, and live BCG were detected. It is useful to consider the relationship between the existence of gamma delta T cells and BCG in this case, and it is suggested that gamma delta T cells may be, in a given situation, less dependent on the gamma c chain than are alpha beta T cells.

Gene Deletion↗
PubMed1997

Response to interferon of GB virus C and hepatitis C virus in patients with chronic hepatitis.

OBJECTIVES: To evaluate the response to interferon and capacity to induce liver disease of a putative non-A to E hepatitis virus designated GB virus C (GBV-C). METHODS: RNA of GBV-C was detected by reverse transcription polymerase chain reaction with nested primers deduced from the 5'-noncoding region. It was titrated, along with RNA of hepatitis C virus (HCV), in 16 co-infected patients (11%) out of 140 patients who received interferon. RESULTS: At the completion of a 6-month course of interferon (total dose: 516-774 million units), GBV-C RNA disappeared from serum in seven (44%) and HCV RNA from serum in 11 (69%) patients. At 6 months after interferon treatment ended, GBV-C RNA remained cleared in three patients (19%), and HCV RNA was persistently undetectable in four (25%). One patient lost both GBV-C and HCV RNAs. The three patients whose serum was cleared of GBV-C RNA had pretreatment titers of the virus (two with 10[1]/ml and one with 10[2]/ml) that were considerably lower than the titers of 13 patients (one with 10[2]/ml, eight with 10[3]/ml, and four with > or = 10[4]/ml) without such clearance. The decrease in alanine aminotransferase levels paralleled the response of HCV RNA but not that of GBV-C RNA to interferon. The response of HCV at 6 months after interferon in the co-infected patients (4/16 or 25%) did not differ significantly from that in patients without GBV-C infection (44/124 or 35%). CONCLUSIONS: The sensitivity of GBV-C to interferon is comparable to but independent of HCV. Co-infection with GBV-C does not influence the response to interferon of patients with chronic hepatitis C.

Antiviral Agents↗
PubMed1996

Association of circulating hepatitis G virus with lipoproteins for a lack of binding with antibodies.

Buoyant density of a recently discovered putative non-A to E hepatitis virus designated hepatitis G virus (HGV) was estimated in plasma or serum samples from three symptom-free carriers and two hepatitis patients. HGV RNA was detected by reverse-transcription polymerase chain reaction in sucrose density fractions with a low density at 1.05-1.10 g/cm3, and the density shifted to 1.23-1.26 g/cm3 after a treatment of peak fractions with Tween 80. Fractionated HGV was precipitated with antibodies to apolipoproteins, but not at all with antibodies to IgG; it was retained by affinity columns of lectins. These results indicate that the circulating HGV would be covered with lipoproteins of the host and has sugar moieties on the surface. The association of HGV with lipids would be responsible for the observed low density and prevent the binding with antibodies for viral persistence.

Antibodies↗