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Biomedical subjects

M Mayumi

Publications and source records attributed to M Mayumi.

At least 55 records · Page 3Linked to original sources

Marked genomic heterogeneity and frequent mixed infection of TT virus demonstrated by PCR with primers from coding and noncoding regions.

A nonenveloped, single-stranded, and circular DNA virus designated TT virus (TTV) has been reported in association with hepatitis of unknown etiology. TTV has a wide sequence divergence (approximately 52%), by which it is classified into at least 16 genotypes separated by an evolutionary distance of >0.30. Therefore, the detection of TTV DNA by polymerase chain reaction would be influenced by primers deduced from conserved or divergent regions of the genome. Of the 30 sera from healthy individuals, up to 17% tested positive with primers deduced from coding region, much less frequently than up to 93% testing positive with primers from noncoding region. These differences were not attributable to the sensitivity of detection, because a cloned TTV DNA of genotype 1a was detected sensitively (up to 1 copy per test) with primers deduced from either the coding or the noncoding region of the same genotype. Sera testing positive only with noncoding region primers, or those showing higher titers with noncoding than coding region primers, contained TTV DNA strains with sequence divergence of 47-53% from the TA278 isolate of genotype 1a within the N22 region spanning 222-231 nucleotides. Some of the sera contained two or three TTV DNA strains of distinct genotypes. These results indicate TTV strains with extremely high sequence divergence prevailing in healthy individuals and frequent mixed infection with TTV strains of distinct genotypes.

Amino Acid Sequence↗

Distinct genotypes of a nonenveloped DNA virus associated with posttransfusion non-A to G hepatitis (TT virus) in plasma and peripheral blood mononuclear cells.

TT virus (TTV) is a nonenveloped, single-stranded DNA virus with little sequence homology to known viruses, and associated with elevated transaminase levels in the patients with posttransfusion hepatitis of unknown etiology. The DNA of TTV was detected, by semi-nested polymerase chain reaction, in peripheral blood mononuclear cells (PBMC) from the 30 healthy individuals with circulating virus in plasma. A sequence of 222 bases was determined on 6-10 TTV DNA clones each from plasma and 6 clones -each from PBMC from eight individuals selected at random from this group. TTV can be classified into genotypes separated by an evolutionary distance > 0.30, which can be divided further into subtypes separated by that of 0.15. Three individuals possessed two different TTV variants of distinct genotypes, with predominant genotypes different between plasma and PBMC. Another possessed TTV of the same genotype in both the plasma and PBMC, but clones with a subtype not seen in plasma were observed in PBMC. A third individual had TTV variants with or without a deletion mutation, and those with the deletion mutation abounded only in PBMC. The remaining three individuals were infected with TTV with the same sequence both in plasma and PBMC. These results indicate that TTV variants with phylogenetic differences could infect the same individual, and that some variants would have a predilection for PBMC. It remains to be seen, however, if TTV replicates in PBMC or whether it has been sequestered before its evolution in the host.

Base Sequence↗

Effect of interferon on a nonenveloped DNA virus (TT virus) associated with acute and chronic hepatitis of unknown etiology.

An unenveloped DNA virus named TT virus (TTV) has been reported in association with acute and chronic hepatitis of unknown etiology. The effect of interferon on TTV was evaluated in the patients with chronic hepatitis C who were coinfected with TTV. TTV DNA was determined by a polymerase chain reaction with heminested primers in the 96 patients with chronic hepatitis C who received interferon-alpha (516 million units in 26 weeks) and followed for 24 months thereafter. TTV DNA was detected in 31 (32%) patients before therapy. TTV DNA became undetectable during interferon therapy and remained absent in 14 (45% of the 31 patients) through 24 months thereafter. The four patients with pretreatment TTV DNA titer > or =10(3)/ml did not respond. These results indicate that TTV is sensitive to interferon, and the response would be inversely correlated with pretreatment viral titers.

Acute Disease↗

Gas-phase oxidation of nitric oxide: chemical kinetics and rate constant.

Inhaled nitric oxide (NO) is gaining popularity as a selective pulmonary vasodilator. Because of the potential toxicity of NO and its oxidizing product nitrogen dioxide (NO2), any system for the delivery of inhaled NO must aim at predictable and reproducible levels of NO and at as low concentrations of NO2 as possible. This review describes the chemical kinetics and rate constant values k for the reaction 2NO + O2 = 2NO2. This reaction has been well established as a third-order homogeneous reaction. Published data support two equally plausible two-step mechanisms for the reaction between NO and O2 over a wide range of temperature and pressure. The Arrhenius equation k (L2 x mol(-2) x s(-1)) = 1.2 x 10(3) e(530/T) (=1.2 x 10(3) x 10(230/T)) gives the best fit to the experimental values of the rate constant thus far reported in a temperature range of 273 to 600 K. Using the reaction mechanism and the rate constant k, one can make reliable predictions about NO2 formation in any set of NO inhalation therapy conditions. It is also pointed out that NO3, the intermediate of one of the two mechanisms, deserves serious attention in NO inhalation therapy.

Administration, Inhalation↗

Prominent medial hypertrophy of renal arterioles in an infant with hyporeninemic hypoaldosteronism.

We describe an 11-month-old boy who presented clinically with hyperkalemic renal tubular acidosis due to hyporeninemic hypoaldosteronism. Persistent hyperchloremic acidosis and mild azotemia were present. All abnormal laboratory values were corrected by the administration of fludrocortisone. Renal biopsy showed prominent medial hypertrophy of renal arterioles and interstitial fibrosis, which closely resemble those of the gene-targeted mice with disruption of the renin angiotensin system. This is the first case report raising the possibility that a defective renin angiotensin system in infancy may lead to tubulointerstitial damage with medial hypertrophy of intrarenal arterioles.

Arterioles↗

Determination of antibodies to TT virus (TTV) and application to blood donors and patients with post-transfusion non-A to G hepatitis in Japan.

Recently, a nonenveloped single-stranded DNA virus named TT virus (TTV) has been reported in association with non-A to G post-transfusion as well as sporadic acute and chronic liver disease. A method was developed for the detection of antibody to TTV (anti-TTV) by means of immune precipitation and detection of TTV DNA by the polymerase chain reaction. The test serum was incubated with TTV, recovered from feces of a carrier, and after incubation, the formed immune complexes were precipitated with goat antiserum to human IgG. TTV DNA was sought for by the polymerase chain reaction in both precipitate and supernatant. The detection of TTV DNA in the precipitate, but not in the supernatant, was considered to represent anti-TTV in the test serum. Of the 44 healthy blood donors in Japan, anti-TTV was detected in one of the six (17%) with TTV DNA and 11 of the 38 (29%) without TTV DNA. In the two patients with post-transfusion non-A to G hepatitis, free anti-TTV developed as they cleared TTV in serum. Anti-TTV complexed with TTV in serum, detectable by precipitating sera with goat anti-human IgG and testing for TTV DNA, elicited while the patients had elevated alanine transaminase levels. The determination of anti-TTV would be useful for detecting resolved infection in surveys for exposure to TTV in the general population, and for establishing the mechanism of liver injury associated with TTV infection.

Adult↗

Serological detection of hepatitis B virus genotypes by ELISA with monoclonal antibodies to type-specific epitopes in the preS2-region product.

An ELISA was developed for serological determination of the six genotypes of hepatitis B virus (HBV) designated A, B, C, D, E, and F. Monoclonal antibodies were raised against genotype-specific epitopes in the preS2-region product, and labeled with horseradish peroxidase. Hepatitis B surface antigen (HBsAg) in sera was captured by immobilized antibodies against the common determinant, and evaluated for reactivity with genotype-specific monoclonal antibodies labeled with the enzyme. Serological genotyping was in complete accord with genotypes determined by S-gene sequences in a panel of 68 sera containing HBV/HBsAg of different genotypes. Of 514 sera with HBsAg from Japan, 507 (98.6%) were genotyped serologically: genotype A was identified in 24 (4.7%); B in 196 (38.1%); C in 282 (54.9%); D in 2 (0.4%); and F in 3 (0.6%). There were no sera containing HBV of genotype E. Likewise, 425 of 446 (95.3%) sera with HBsAg from Brazil, China, India, Indonesia, Kenya, Korea, Nepal, Papua New Guinea, the Philippines, and Thailand were classified into A (25.6%), B (24.2%), C (33.9%), and D (11.7%) genotypes; there were no sera with HBsAg of genotype E or F among them. Some sera unclassifiable by ELISA revealed mixed infection with HBV of distinct genotypes, or contained HBsAg deprived of genotype-specific epitopes by point mutations. The ELISA would be useful for large-scale surveys, because it allows serological detection of HBV genotypes without sequencing nucleotides.

Amino Acid Sequence↗

Infection with an unenveloped DNA virus (TTV) in patients with acute or chronic liver disease of unknown etiology and in those positive for hepatitis C virus RNA.

BACKGROUND/AIMS: An unenveloped single-stranded DNA virus (TTV) has been reported in association with elevated transaminase levels in patients with posttransfusion hepatitis and in those with acute or chronic liver disease of unknown etiology. To further evaluate the association of TTV with liver disease, TTV DNA was searched for in patients with acute or chronic liver disease of various etiologies. METHODS: TTV DNA was determined by polymerase chain reaction with hemi-nested primers in 64 patients with acute or chronic liver disease of unknown etiology and in 100 with acute or chronic liver disease positive for antibody to hepatitis C virus (HCV) as well as HCV RNA. RESULTS: TTV DNA was detected in two of the seven (29%) patients with acute hepatitis of unknown etiology, but in none of the four patients with acute HCV-associated hepatitis. It was detected in 27 of the 57 (47%) patients with chronic liver disease of unknown etiology at a frequency significantly higher (p<0.001) than that in 17 of the 96 (18%) patients with chronic HCV-associated liver disease. By contrast, RNA of hepatitis G virus was detected in none of the patients with acute hepatitis, and only in one of the 57 (2%) patients with chronic liver disease of unknown etiology as well as in six of the 96 (6%) patients with chronic HCV-associated liver disease. CONCLUSIONS: Based on the obtained results, TTV has a role in the development of acute and chronic liver disease of unknown etiology.

Acute Disease↗

Further characterization of memory T cells existing in a case of CD8 deficiency.

CD8 deficiency is a rare primary immunodeficiency caused by a defect of ZAP-70, which plays a pivotal role in T cell activation. We previously reported the existence of memory phenotype-CD4+ T cells in a case of CD8 deficiency, which demonstrates that activation signals through ZAP-70 are not essential to the phenotypic conversion of T cells from "naive" to "memory." In this study, we further characterized CD45RO+ T cells in a CD8 deficient patient. We showed that the patient's CD45RO+ T cell population had a wide variety of T cell receptor Vbeta-chain gene usage, and contained few clonally expanded T cells, while many clonally expanded T cells were present in the memory T cell population of age-matched healthy children. These results suggest that various kinds of antigens were involved in the differentiation of the patient's T cells, and that the differentiation into memory T cells was not accompanied by profound T cell proliferation. Moreover, our findings confirmed that the patient's CD45RO+CD4+ T cells had acquired effector-cytokine producing ability, indicating that there exists an alternative activation pathway which is independent of ZAP-70 for the acquisition of effector-cytokine producing ability.

CD8 Antigens↗

Assessment of bone turnover in term and preterm newborns at birth: measurement of urinary collagen crosslink excretion.

We measured urinary excretion of collagen crosslinks, pyridinoline and deoxypyridinoline, in term and preterm newborns at birth and evaluated the developmental changes in bone turnover. Collagen crosslink excretion in newborns was more than 10 times higher than reported adult values and several times higher than those of older children. The values were significantly higher in preterm newborns than in term newborns. In addition, a significant and inverse correlation was found between urinary collagen crosslinks and gestational age in preterm newborns. Excretion of crosslinks during this period did not correlate with beta2-microglobulin, suggesting that the excretion was not directly influenced by renal function in newborns. We conclude that bone turnover assessed by measurement of collagen crosslink excretion is high at birth and that preterm newborns have higher bone turnover than term newborns.

Adult↗

Existence of activated and memory CD4+ T cells in peripheral blood and their skin infiltration in CD8 deficiency.

CD8 deficiency is a rare primary immunodeficiency caused by the defect of a tyrosine kinase, ZAP-70, which transduces signals from the T cell receptor. We report here a case of CD8 deficiency, having CD4+ T cells with a unique phenotype. The patient's T cells did not respond to anti-CD3 stimulation in vitro, suggesting that they were naive. However, many CD4+ T cells with activated and memory phenotypes, which expressed CD45RO+, HLA-DR+ and CD25+, were present in the peripheral blood, and these cells accumulated in the perivascular area of his infiltrative erythematous skin lesions. The patient's T cells could be activated by a high concentration of phytohaemagglutinin (PHA), indicating the presence of an alternate signalling pathway which bypasses ZAP-70 and activates CD4+ T cells in vivo. The origin and role of activated CD4+ T cells in the pathogenesis involved in the skin lesions are discussed.

CD4-Positive T-Lymphocytes↗

Vesicoureteral reflux in male and female neonates as detected by voiding ultrasonography.

BACKGROUND: Vesicoureteral reflux (VUR) is assumed to be congenital, and its early diagnosis is desired in order to prevent acquired renal damage. However, the incidence of VUR in neonates remains to be revealed. METHODS: Two thousand newborn babies (1048 boys and 952 girls) underwent voiding ultrasonography (an ultrasound examination of urinary tract during provoked voiding). Those who showed transient renal pelvic dilation during voiding, who had small kidneys, or who subsequently developed urinary infection underwent voiding cystourethrography. RESULTS: Transient renal pelvic dilation was observed in 16 babies (0.8%), including one boy with small kidneys. Among the rest of the babies, one boy had a small kidney, and nine babies subsequently developed urinary infection. Voiding cystourethrography revealed VUR in 24 ureters of 16 children (11 boys and 5 girls). Dimercaptosuccinate renoscintigraphy confirmed small kidneys, with generally reduced tracer uptake in a total of three boys, all having VUR. Voiding ultrasonography detected transient renal pelvic dilation in 17 (71%) of the 24 kidneys with VUR and, strikingly, 16 of the 17 (94%) kidneys with high-grade VUR (grade III or more). CONCLUSION: This study effectively detected VUR in 0.8% of the neonates (mostly of high grades and predominantly in males) and voiding ultrasonography showed a decided usefulness for the detection of VUR. The male preponderance of VUR in neonates was considered to be due to the occurrence of congenitally small kidneys, with reflux found exclusively in males and easier ultrasound detection of VUR in male neonates because the majority of diagnoses are reported to be high grades of VUR.

Dilatation, Pathologic↗

Voiding function study with ultrasound in male and female neonates.

BACKGROUND: The neonatal period has been characterized as a time when males have a much higher incidence of urinary infection and severe ureteral reflux than females. However, little information about the voiding function in the neonatal period is available. METHODS: The bladder urine volumes, before and after voiding, and urinary flow rates were determined with the use of noninvasive voiding-provocation maneuvers and ultrasound in the apparently normal neonates. RESULTS: There was no significant difference in the prevoid bladder urine volume between the two sexes. After they were stimulated to enhance the tension of their abdominal wall musculature, 65 of 118 females (55.1%) and 64 of 115 males (55.7%) voided. The voiding was observed in 94 (81.0%) of the 116 neonates who had had a prevoid volume above 12 ml. The residual urine expressed as a percentage of the prevoid volume was significantly higher in the males (median, 12.0% in males vs. 3.0% in females, P < 0.01), with the values being above 20% in 26 (41%) of the 64 males compared with 10 (15%) of the 65 females (P < 0.01). Urinary flow rates, determined in 52 neonates, were significantly smaller in males than in females (mean +/- SD, 2.6 +/- 0.9 g/second vs. 3.8 +/- 1.3 g/second, respectively, P < 0.001). CONCLUSION: This voiding function study with ultrasound using noninvasive voiding-provocation maneuvers successfully revealed that male neonates have a larger residual urine volume and smaller urinary flow rates than female neonates. This study should be useful for the diagnosis of voiding dysfunction in children with abnormal urinary symptoms.

Female↗

Infection by an unenveloped DNA virus associated with non-A to -G hepatitis in Japanese blood donors with or without elevated ALT levels.

BACKGROUND: An unenveloped, single-stranded DNA virus named TT virus has been found in association with elevated alanine aminotransferase (ALT) levels in recipients of transfusions and has been detected frequently in patients with acute or chronic hepatitis of non-A to -G etiology in Japan. DNA of the TT virus was searched for in blood donors with or without elevated ALT levels. STUDY DESIGN AND METHODS: A total of 861 blood donors without previous transfusions and who were negative for markers of hepatitis B or C virus infection were tested. DNA of the TT virus was detected by polymerize chain reaction with hemi-nested primers. RESULTS: TT virus DNA was detected in 62 of 280 (22.1% [95% CI: 18.1-26.6]) donors with elevated ALT levels (mean +/- SD, 89.3 +/- 36.4 U/L; range, 61-301 U/L), which is significantly more frequently (p<0.02) than its detection in 91 of 581 (15.7% [95% CI: 13.2-18.4]) donors with normal ALT (< or = 45 U/L). The frequency of TT virus DNA increased with age, in donors with and without elevated ALT. CONCLUSION: The detection of TT virus DNA, at a frequency higher in donors with elevated ALT than in those without, strengthens the association of TT virus with non-A to -G hepatitis.

Adolescent↗

Excretion into bile of a novel unenveloped DNA virus (TT virus) associated with acute and chronic non-A-G hepatitis.

Recently, an unenveloped, single-stranded DNA virus named TT virus (TTV) has been reported in association with hepatitis of non-A-G etiology. Five patients with TTV viremia, who received bile drainage or cholecystectomy, were tested for TTV DNA in bile by polymerase chain reaction with heminested primers. TTV DNA was detected in bile from all patients; titers were 10-100 times higher than in serum in 4 and at a comparable level in the remaining 1 patient. TTV DNA was detected in feces, also, in 1 of the 2 patients tested. The buoyant density of TTV in bile from 1 tested patient (1.33-1.35 g/cm3) was the same as that in feces (1.32-1.35 g/cm3). TTV may be secreted via bile into feces in a transmissible form and would spread by a fecal-oral route for deep and wide penetration into the general population.

Acute Disease↗

Quasispecies of TT virus (TTV) with sequence divergence in hypervariable regions of the capsid protein in chronic TTV infection.

Three hypervariable regions were identified in a central portion of open reading frame 1 of TT virus DNA, which codes for a putative capsid protein of 770 amino acids. TT virus circulates as quasispecies, with many amino acid substitutions in hypervariable regions, to evade immune surveillance of the hosts and to establish a persistent infection.

Acute Disease↗

Early (4-7 days of age) dexamethasone therapy for prevention of chronic lung disease in preterm infants.

We conducted a comparative study to evaluate whether early (4-7 days of age) low-dose dexamethasone (DEX) therapy in preterm infants with surfactant-pretreated respiratory distress syndrome (RDS) would facilitate extubation and improve the clinical outcome. Twenty-six preterm infants with surfactant-pretreated RDS who were oxygen- and ventilator-dependent at 4 days of postnatal age were enrolled. Twelve infants were in the historical comparison group, and 14 infants were assigned to receive DEX 0.125 mg/kg i.v., every 12 h, for a total of 6 doses. At study entry, the two groups had a comparable clinical status. DEX therapy significantly facilitated weaning from mechanical ventilation (median interval, 6 vs. 24 days, p < 0.005) and shortened duration of oxygen supplementation (9 vs. 28 days, p < 0.05) as compared with the historical comparison group. At 28 days of age, the occurrence of chronic lung disease (CLD) was significantly lower (1/14 vs. 6/12, p < 0.05) and there was a significant decrease in the incidence of ventilator dependence (0/14 vs. 5/12, p < 0.05) in the DEX group. DEX therapy did not influence the incidence of significant complications such as infection, periventricular leukomalacia or retinopathy of prematurity. We conclude that in a selected high-risk group of preterm infants, early low-dose DEX treatment results in improvement in pulmonary outcome without significant side effects.

Apgar Score↗