GBV-C infection among patients with hepatitis C virus in the Islamic Republic of Iran: a preliminary report.
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Blood Donors↗
Biomedical subjects
M Mayumi
Publications and source records attributed to M Mayumi.
Urinary excretion of aquaporin-2 in term and preterm infants.
Aquaporin-2 (AQP-2) is a vasopressin-regulated water channel of the renal collecting duct and is excreted in human urine. We measured the urinary excretion of AQP-2 by radioimmunoassay in 14 term and 12 preterm infants aged 1 month. Excretion of AQP-2 was low compared with adults, and correlated significantly with urine osmolality in preterm infants. Our results demonstrate that AQP-2 water channels are expressed in the renal collecting duct of both term and preterm infants.
Aquaporin 2↗
Clinical and molecular virological differences between fulminant hepatic failures following acute and chronic infection with hepatitis B virus.
Clinical and molecular biological characteristics were compared between patients who presented with fulminant hepatic failure following acute infection with hepatitis B virus (HBV) and those who developed hepatic failure during they carried HBV. The 11 patients with acute HBV infection had higher levels of alanine aminotransferase (mean +/- SD: 4943 +/- 2867 vs 1157 +/- 678 IU/L, P < 0.01), more often with a single peak (91% vs. 0%, P < 0.001), and lower total bilirubin level (15.3 +/- 4.4 vs 28.1 +/- 14.3 mg/1000 ml, P < 0.01) than the 13 patients with chronic HBV infection. Hepatitis B surface antigen was detected less often (55% vs. 100%, P < 0.05) and viral DNA polymerase less frequently (0% vs. 46%, P < 0.05) in the patients with acute than chronic HBV infection. Hepatitis B e antigen was detected in one (9%) patient with acute infection, less frequently than in six (46%) patients with chronic infection (P < 0.05). Mutations in the precore region was detected in HBV DNA clones from ten (91%) patients with acute infection and only in those from eight (62%) patients with chronic infection. All HBV DNA clones from the five (38%) patients with chronic infection that did not have precore mutations, however, possessed mutations in the core promoter. These results indicate that HBV mutants incapable of translating hepatitis B e antigen would play a major role in fulminant hepatic failure occurring after acute HBV infection. In contrast, HBV variants with core promoter mutations for reducing the transcription of hepatitis B e antigen would play an additional role in fulminant hepatic failure developing during chronic infection.
Acute Disease↗
Infection with an unenveloped DNA virus (TTV) associated with posttransfusion non-A to G hepatitis in hepatitis patients and healthy blood donors in Thailand.
An unenveloped single-stranded DNA virus (TTV) has been reported in association with posttransfusion and acute and chronic hepatitis of unknown etiology. DNA of TTV was tested for by polymerase chain reaction with heminested primers in 127 patients with chronic liver disease and 105 healthy blood donors in Thailand. TTV DNA was detected in 23 (59%) of the 39 patients without hepatitis B surface antigen or RNA of hepatitis C virus, at a frequency significantly higher than the detection in 21 (36%) of the 59 patients with HBsAg (P < 0.05) or in 38 (36%) of the 105 blood donors (P< 0.05). Among patients with chronic liver disease, TTV DNA occurred in those with liver cirrhosis and hepatocellular carcinoma more frequently than in those with chronic hepatitis (35 of 65 or 54% vs. 20 of 62 or 32%, P< 0.05). There were no differences in age, sex, or markers of infection with hepatitis B, C and GBV-C/HGV viruses, indicating a mode of transmission of TTV different from those of the other hepatitis viruses. Phylogenetic analysis indicated three different genotypes of TTV with six distinct subtypes in Thailand. Based on these results, TTV would have a role in the development of chronic liver disease of unknown etiology in Thailand.
Base Sequence↗
Ataxia-telangiectasia in the Japanese population: identification of R1917X, W2491R, R2909G, IVS33+2T-->A, and 7883del5, the latter two being relatively common mutations.
We analyzed the data regarding six Japanese ataxia-telangiectasia (A-T) patients from four unrelated families, at the DNA level, to search for possible common mutations in the Japanese population. Among eight mutant alleles in the four families, c. 4612del165 (exon 33 skipping) was identified in two alleles, and c. 5749A to T (R1917X), c. 7471T to C (W2491R), c.7883de15, and c. 8725A to G (R2909G) were identified in one allele each. We found no mutations in the other two alleles. The IVS33 + 2T-->A mutation was identified at the genomic level as the cause of exon 33 skipping. We also identified the IVS33 + 2T-->A mutation in a Japanese patient ATL105 who was previously found to be a homozygote of c. 4612del165. W2491R and R2909G mutations were not detected in more than 100 control Japanese alleles. The latter is located in a highly conserved PI-3 kinase domain and is a completely conserved residue among ATM-related proteins. Taken together with previously documented mutations in five other Japanese A-T patients, IVS33 + 2T-->A and 7883del5 were identified in four and five alleles, respectively, in a total of 18 mutant alleles of Japanese A-T patients. These results suggest that these two mutations are relatively common mutations in the Japanese population.
Adolescent↗
Nicotine administration decreases the number of binding sites and mRNA of M1 and M2 muscarinic receptors in specific brain regions of rat neonates.
Nicotine has been shown to delay the developmental increase of muscarinic receptors in brain of rat neonates. In this study, we have examined the muscarinic receptor binding sites and corresponding messenger RNA in rat neonates, whose mothers received nicotine in the drinking water, using competition binding study and northern blot analysis. On postnatal 14th day, nicotine treatment led to a 61% reduction in the proportion of high-affinity sites for pirenzepine (M1-subtype) to total [3H]quinuclidinyl benzilate binding sites in cerebral cortex in rat neonate. Nicotine treatment also decreased that for 11-2[[2-[(diethylamino)methyl]-1-piperidinyl]-5,11-dihydro-6H-pyrido [2,3-b] [1,4] benzodiazepin-6-one (AF-DX 116) (M2-subtype) by 77% in cerebellum on postnatal 14th day. The levels of m1 and m2 muscarinic receptor messenger RNAs in the same brain regions were also decreased in the same day after nicotine treatment. On postnatal 35th day, no difference was observed in binding sites or in messenger RNA levels of the brain regions tested (cerebral cortex, midbrain, hippocampus, cerebellum and brainstem). Our results show that nicotine reduces muscarinic receptor subtypes in developing rat brain, in part, through suppression of the messenger RNA expression, but that the effects are different among brain regions and subtypes.
Animals↗
High-turnover osteopenia in preterm infants: determination of urinary pyridinium cross-links of collagen.
Osteopenia is a frequent condition in preterm infants, but its pathogenesis is uncertain. In the present study, we measured longitudinal changes in the excretion of pyridinium cross-links of collagen (specific markers of bone resorption) and evaluated the relationship between collagen cross-links and other indexes of bone and renal function in preterm infants. In these infants, urinary collagen cross-links were markedly increased on day 7 and day 30 of life and at estimated full-term gestation. The values were several times higher than those of older children and almost comparable to those of healthy full-term infants. Cross-link excretion did not correlate with beta2-microglobulin (B2M) or N-acetyl-beta-D-glucosaminidase (NAG) activity (markers of renal function), indicating that cross-link excretion is not influenced directly by infantile renal function. High serum osteocalcin and low bone mineral density (BMD) in the lumbar spine were also observed at estimated full-term gestation. There was no significant correlation between collagen cross-link excretion and either serum osteocalcin or spine BMD. We conclude that a state of high bone turnover underlies the development of osteopenia in preterm infants.
Aging↗
Renal water channel expression in newborns: measurement of urinary excretion of aquaporin-2.
Aquaporin-2 (AQP-2) encodes the vasopressin-regulated "water channels" of the renal collecting duct and is excreted in human urine. We measured urinary excretion of AQP-2 by radioimmunoassay in 15 term and 10 preterm infants on day 1 and day 4 of life to determine the molecular basis of water balance during the newborn period. AQP-2 was detectable in the urine of term and preterm newborns, but AQP-2 excretion was severalfold less than the reported level in normal adults. Urinary excretion of AQP-2 significantly decreased postnatally, in parallel with a reduction in urine osmolality and arginine vasopressin (AVP) excretion. Urinary AQP-2 correlated positively and significantly with urine osmolality on days 1 and 4 and with AVP on day 1 in both groups. No significant differences were detected in AQP-2 levels between term and preterm newborns. Our findings suggest that vasopressin-regulated water channels are expressed in the renal collecting duct of both term and preterm newborns, although to a lesser extent as compared with adults, and these channels encoded by AQP-2 contribute to the urine concentrating power of the newborn kidney.
Acetylglucosaminidase↗
Endothelin subtype A receptor antagonist induces osteopenia in growing rats.
Previous studies suggested that endothelin (ET) peptides are involved in bone metabolism. We examined the effects of long-term blockade of the ET(A) receptor, a receptor subtype primarily involved in the anabolic actions of ET, on bone mineral status in growing rats. Eight-week-old rats injected intraperitoneally with FR139317 50 mg/kg body weight, a specific ET(A) receptor antagonist, for 2 or 4 weeks were compared with control rats injected with vehicle only. Treatment with FR139317 caused a significant decrease in bone mass in the lumbar spine as determined by dual-energy x-ray absorptiometry (DXA). FR139317-induced osteopenia was associated with a significant decrease in the serum osteocalcin concentration but no change in the urinary excretion of pyridinium cross-links of collagen. Our findings indicate that long-term blockade of the ET(A) receptor reduces bone formation and induces osteopenia in growing rats. Our results suggest that ET produced by vascular endothelial cells plays an important role in bone growth and metabolism in vivo.
Absorptiometry, Photon↗
IL-4 and prostaglandin E2 inhibit hypomethylation of the 5' regulatory region of IFN-gamma gene during differentiation of naive CD4+ T cells.
We have previously shown that prostaglandin E2 (PGE2) and IL-4 inhibit the priming of IFN-gamma-production during the differentiation of naive CD4+ T cells from human cord blood by different signal-transducing mechanisms. To compare and analyse the molecular mechanisms by which PGE2 and IL-4 inhibit the priming of IFN-gamma production, we investigated the effects of PGE2 and IL-4 on the methylation of the IFN-gamma gene during the in vitro differentiation of naive CD4+ T cells. In human naive CD4+ T cells, which produce primarily IL-2 and a little amount of IFN-gamma, the IFN-gamma gene was methylated. After stimulation via TCR, CD4+ T cells produced IFN-gamma and the CpG dinucleotide contained within the TATA proximal regulatory element of the IFN-gamma gene was partially hypomethylated. Both IL-4 and PGE2 inhibited the hypomethylation of this site and the acquisition of IFN-gamma-producing ability. In contrast to the SnaBI site in the TATA proximal regulatory element, the HpalI site in the first intron of the IFN-gamma gene of the CD4+ T cells from cord blood was completely methylated even after stimulation via TCR. 5-azacytidine restored the IFN-gamma-producing ability of these cells treated with IL-4 and PGE2. These findings suggest that, although the signal transduction that inhibits the priming of IFN-gamma-production is different for each reagent, the protection from hypomethylation of the regulatory region of the IFN-gamma gene is involved in the molecular mechanisms by which these reagents inhibit the priming of IFN-gamma-production during the differentiation of human naive CD4+ T cells.
Azacitidine↗
Incidence and influence of GB virus C and hepatitis C virus infection in patients undergoing bone marrow transplantation.
Markers of GB virus C (GBV-C) and hepatitis C virus (HCV) were sought in 80 patients before and after they underwent BMT in a metropolitan hospital in Tokyo between 1990 and 1996. RNA of GBV-C was detected in 14 (18%) patients before BMT. Of the 55 patients who had been transfused, 14 (25%) possessed GBV-C RNA at a frequency significantly higher than in the 25 untransfused patients who were all negative (P < 0.01). HCV RNA was detected in three of the 55 (5%) transfused patients, but in none of the 25 untransfused patients. Sera at 3 months after BMT were available for 57 patients. GBV-C RNA persisted in all 10 patients who were infected before BMT, while it was detected in five of the remaining 47 (11%) patients who were not. However, persistent and/or ongoing GBV-C infection had no appreciable influence on patient morbidity or mortality. Two of the 57 patients were positive for HCV RNA before BMT and this persisted after BMT in both. HCV RNA became positive in eight of the remaining 55 (15%) patients who were negative before BMT. Of the 14 patients who received transfusions screened by the first-generation test at BMT, seven (50%) became positive for HCV RNA, a rate significantly higher than the one of 41 (2%) patients who received transfusions screened by the second-generation test (P < 0.001). These results indicate that BMT patients are at increased risk of GBV-C infection transmitted by transfusions received before and at the time of BMT, and that the risk of HCV infection has decreased after the implementation of the second-generation anti-HCV test.
Adolescent↗
Nitric oxide in septic and aseptic meningitis in children.
To investigate the involvement of nitric oxide (NO) in childhood meningitis, we measured the concentrations of NO2- (a stable metabolite of NO) in serial samples of cerebrospinal fluid (CSF) from 11 children with septic and 7 with aseptic meningitis and 26 control patients without meningitis. The mean concentration of NO2- in samples obtained during the early stages of septic meningitis, but not aseptic meningitis, was significantly higher than in control samples. Clinical and laboratory improvement following administration of antibiotics and dexamethasone was associated with a fall in CSF [NO2-] to normal levels in these patients. CSF [NO2-] remained almost consistently within the normal range in patients with aseptic meningitis. Our findings indicate that NO production is enhanced in the CSF compartment of children with septic meningitis and support the hypothesis that NO is involved in the pathophysiology of septic meningitis.
Alanine↗
The entire nucleotide sequences of three hepatitis C virus isolates in genetic groups 7-9 and comparison with those in the other eight genetic groups.
We have proposed that hepatitis C virus should be classified into eleven genetic groups (types) which further divide into more than 80 genotypes (subtypes). However, only eight genetic groups (1-6, 10 and 11) have been defined on the basis of the full-length sequence. Hence, the entire nucleotide sequences of three HCV isolates in genetic groups 7-9 have now been determined. Phylogenetic analysis over the full-length sequences of these three isolates, along with 30 more in the other eight genetic groups, indicated that genetic groups 6-9 and 11 have bifurcated from a common branch and groups 3 and 10 from another. In the former branch groups 7 and 11, and groups 8 and 9, are closely related. Consequently, HCV can be classified into either eleven (1-11) or six groups (1; 2; 3 and 10; 4; 5; 6-9 and 11), allowing a clear separation of group and genotype similarity within the NS5b region or a subregion of 1093 nt. When pairwise comparison of 1093 nt in the NS5b sequence was performed on 106 HCV isolates of 36 genotypes in eleven genetic groups, they were classified into either eleven (1-11) or six (1; 2; 3 and 10; 4; 5; 6-9 and 11) genetic groups. However, group and genotype similarities were not clearly separable in either classification. The overlapping range was smaller using the classification into eleven genetic groups as compared to six genetic groups (2.7 vs 4-7%). These results indicate that HCV might not have evolved in the two-tiered fashion, at least in a strict sense.
Base Sequence↗
Role of endothelin in erythropoietin-induced hypertension in rats.
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Animals↗
[A patient with EDTA-dependent pseudothrombocytopenia who underwent emergent clipping surgery for a ruptured aneurysm].
A 42-year-old female with EDTA-dependent pseudothrombocytopenia underwent emergent clipping surgery for a ruptured aneurysm. On admission, the platelet count was low, but bleeding time and coagulation test were within normal limits. The blood smear anticoagulated with EDTA revealed remarkable agglutination of platelets, while heparinized blood showed a normal level. Diagnosis of EDTA-dependent pseudothrombocytopenia was made. The progressive drop in platelet count occurred within 10 minutes in the presence of EDTA. The autocounter misjudged the agglutination of platelets as red or white blood cells. The earlier study reported the incidence of this diseases as 0.07%. This disease is often misdiagnosed. Therefore, thrombocytopenia without any clinical symptom should be considered as showing a possible symptom of EDTA-dependent pseudothrombocytopenia.
Adult↗
An enzyme-linked immunosorbent assay with monoclonal antibodies for the determination of phosphorylated hepatitis B core protein (p21c) in serum.
An enzyme-linked immunosorbent assay (ELISA) was developed for the determination of hepatitis B virus (HBV) core protein (p21c) using monoclonal antibody (mAb) directed to a phosphorylated C-terminal amino acid sequence that is not present in hepatitis B e antigen (HBeAg). HBV virions in the test serum were precipitated with horse polyclonal antibody to hepatitis B surface antigen (HBsAg), dissolved with Tween 20 and NaOH, and then neutralized. HBV core protein (p21c), released from HBV cores by this procedure, was sandwiched between immobilized mAb C33 directed to amino acids (aa) 133-140 of the core protein, fixed on a solid support and labeled mAb T2212 that recognizes aa 165-175, only when they are phosphorylated. The method was applied for the detection of phosphorylated p21c in sera from symptom-free carriers and patients with chronic hepatitis. The results indicated a higher extent of phosphorylation in p21c of HBV cores from symptom-free carriers than hepatitis patients.
Animals↗
Fecal excretion of a nonenveloped DNA virus (TTV) associated with posttransfusion non-A-G hepatitis.
Five patients with type B or C hepatocellular carcinoma were found to be infected with a nonenveloped DNA virus (TTV) associated with posttransfusion hepatitis of non-A-G etiology. Paired feces and serum samples from these patients were tested for TTV DNA by polymerase chain reaction with seminested primers and their sequences were compared. TTV DNA was detected in sera from all of the patients, while it was detected in feces from three patients, including two with high viral titers in serum. When feces and serum from one patient were subjected to floatation ultracentrifugation in CsCl, TTV in feces banded at a peak density of 1.35 g/cm3 and that in serum at 1.31-1.32 g/cm3. TTV isolates in three pairs of feces and serum had the identical sequence of 222 base pairs. The excretion of TTV into feces indicates that TTV would be transmitted not only parenterally but also nonparenterally by a fecal-oral route.
Base Sequence↗
A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology.
By means of representational difference analysis, a viral clone (N22) of 500 nucleotides was isolated from serum of a patient (TT) with posttransfusion hepatitis of unknown etiology. The N22 clone showed a poor homology to any reported sequences. Oligonucleotide primers were deduced from the N22 sequence for detecting it by polymerase chain reaction. N22 sequence in serum banded at a sucrose density of 1.26 g/cm3, indicating its association with a viral particle which was designated TT virus (TTV). Since nucleic acids of TTV were sensitive to DNase I, it would be a DNA virus. TTV DNA was detected in sera from three of the five patients with posttransfusion non-A to G hepatitis, including the index case (TT). TTV DNA titers closely correlated with aminotransferase levels in the three patients. These results indicate that TTV would be a novel DNA virus with a possible capacity to induce posttransfusion non-A to G hepatitis.
Aged↗