Biomedical subjects

N Nishimura

Publications and source records attributed to N Nishimura.

At least 55 records · Page 3Linked to original sources

PubMed2000

Experience with live attenuated varicella vaccine (Oka strain) in healthy Japanese subjects; 10-year survey at pediatric clinic.

Live attenuated varicella vaccine (Oka strain, Biken Institute, Osaka, Japan) was administered to 973 healthy individuals over a 10-year period (1987-1997) at the pediatric clinic of Showa Hospital in Japan. We evaluated the relevant serological and clinical data, which were collected by questionnaire. Seroconversion by the immune adherence hemagglutination method was documented in 94% (805/860) of the initially seronegative subjects. Of the initially seropositive subjects, 56% (63/113) showed enhancement of antibody after vaccination. Reactions to the vaccine were generally insignificant, except for a rash at the injection site, seen in the first 3 days post-administration in 17% (41/241) of the recently vaccinated subjects. In March 1998, we conducted a survey of 559 of the initially seronegative subjects who had received the vaccine 0.6-10. 8 (mean 5.4) years earlier. Of these subjects, 21% (119/559) contracted breakthrough varicella. However, their symptoms were milder than those caused by natural varicella seen in unvaccinated children. Seroconversion was demonstrated in 92% (109/119) of these cases. The incidence of breakthrough disease decreased with a rise in postvaccination antibody titer to >==32. Four of the subjects (0.7% of 559) developed herpes zoster following vaccination, two of whom had earlier exhibited breakthrough varicella. Lesions in one case of zoster, without breakthrough varicella, appeared on the cervical dermatome at the injection site. The vaccine was safe and effective. However, there was a relatively high incidence of rash at the injection site with certain lot numbers used in recent years which warrants investigation.

Adolescent↗

PubMed2000

Role of IL-6 in the induction of hepatic metallothionein in mice after partial hepatectomy.

Metallothioneins (MT) are induced upon partial hepatectomy (PH), possibly mediated by various cytokines. In the present study, we studied cytokine-dependent MT synthesis in partially hepatectomized IL-6 gene knock-out (GKO) mice in the remaining lobe of the liver. We focused on IL-6, TNFalpha and IL-1beta, the major cytokines thought to be involved in MT synthesis. The IL-6 GKO mice and B6J129Sv (wild-type control) mice were subjected to 70% PH or laparotomy. We found that MT was significantly decreased in IL-6 GKO mice, although PH induced hepatic MT in both strains of mice. Laparotomy induced MT in the liver of wild-type mice but not in IL-6 GKO mice. Pretreatment of IL-6 GKO mice with rIL-6 (5 microg/mouse) restored hepatic MT synthesis. Serum IL-6 level in wild-type mice was maximal at 6 h after surgery and decreased thereafter. Serum IL-1beta was the same in both strains of mice. Serum TNFalpha basal level in IL-6 GKO mice was higher than in wild-type mice. PH caused an increase in serum TNFalpha level in both strains of mice, and it was two times higher in IL-6 GKO mice than in wild-type mice at 18 h after surgery. We conclude that IL-6 plays a predominant role in hepatic MT synthesis after PH, but that IL-6 GKO mice still reserve the capacity to synthesize MT by an as yet unidentified mechanism.

Animals↗

PubMed2000

Down-regulation by a new anti-inflammatory compound, FR167653, of differentiation and maturation of human monocytes and bone marrow CD34+ cells to dendritic cells.

FR167653 (1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8 (4-pyridyl) pyrazoro [5-1-c] [1,2,4] triazin-2-yl]-2-phenylethanedion sulfate monohydrate), one of the pyridinyl imidazoles, is an immunosuppressive agent which was developed to inhibit proinflammatory cytokine production. We examined the effect of FR167653 on the differentiation and maturation phases of both human bone marrow-derived dendritic cells (BM-DC) and blood monocyte-derived DC (Mo-DC). DC induced from either BM-DC or Mo-DC progenitors in the presence of FR167653 had lower expression of CD1a, CD83 and CD86 (B7.2). FR167653 also significantly suppressed the ability of Mo-DC to produce both TNF-alpha and IL-1beta in response to LPS stimulation. Mixed lymphocyte reaction (MLR) stimulation was significantly lower in FR167653-treated Mo-DC than in control Mo-DC, although the suppressive effect of FR167653 was much less on BM-DC. These results indicate novel immunosuppressive properties of FR167653, which may be therapeutically useful in controlling chronic immune and/or inflammatory diseases through down-regulation of DC differentiation and maturation.

Anti-Inflammatory Agents↗

PubMed2000

Lack of metallothionein-I and -II exacerbates the immunosuppressive effect of ultraviolet B radiation and cis-urocanic acid in mice.

The effect of a null mutation for the metallothionein (MT)-I and -II isoforms in mice on the immunosuppressive action of ultraviolet B (UVB; 280-320 nm) radiation has been examined. Mice were exposed to a series of increasing daily UVB doses, each dose administered to the dorsum on 3 consecutive days. Erythema was assessed, and measured as its oedema component by the post-irradiation dorsal skinfold thickness, but there was no effect of the null mutation (MT-/-) observed after 3 x 3.4 kJ/m2 of UVB radiation. Immune function was assessed by the contact hypersensitivity (CHS) response, which was initiated by sensitization on unirradiated abdominal skin, and thus demonstrated the systemic effects of dorsal treatments. In comparison with the wild-type MT+/+ mouse, the MT-/- mouse was significantly more immunosuppressed by moderate daily UVB doses (1. 75-5.9 kJ/m2). When topically applied cis-urocanic acid (cis-UCA) replaced UVB radiation as the immunosuppressive agent, contact hypersensitivity in MT-/- mice was again markedly more suppressed than in MT+/+ mice, in a dose-responsive manner. The results infer that MT, which was shown immunohistochemically to be strongly induced in the epidermis of MT+/+ mice, but to be absent in MT-/- epidermis, has the potential to protect from photoimmunosuppression, and that the mechanism of action may be via the inactivation of the epidermal UVB-photoproduct, cis-UCA.

Animals↗

PubMed2000

Cutaneous metallothionein induction by ultraviolet B irradiation in interleukin-6 null mice.

The mediators of cutaneous metallothionein induction by ultraviolet radiation have not been defined. In this study we sought to identify cytokines that might be involved. We examined the role of interleukin-6, using the IL-6 null (IL-6-/-) mouse, which has been observed to be highly sensitive to ultraviolet radiation damage. Whereas cutaneous metallothionein concentration, measured by radioimmunoassay, began to rise in wild-type (IL-6+/+) mice by 12 h after ultraviolet irradiation, there was a significant delay in the IL-6-/- mice until 48 h after UV irradiation. Immunohistologically, metallothionein appeared in IL-6+/+ mice at 24 h in dermal fibroblasts, and then by 48 h in epidermal basal keratinocytes, with intensity increasing until 72 h, and was coincident with proliferating cell nuclear antigen-positive staining. Corresponding metallothionein expression in IL-6-/- mouse skin was significantly delayed. Serum interleukin-6 was elevated in IL-6+/+ mice following ultraviolet irradiation, with peak concentration at 4 h, but no increase in serum interleukin-1beta was found in either IL-6+/+ or IL-6-/- mice. Interestingly, tumor necrosis factor alpha concentration in serum was elevated at 12 h postirradiation in IL-6+/+ mice, but there was an earlier (at 4 and 8 h) time-dependent increase in tumor necrosis factor alpha in serum of the IL-6-/- mice. Skin zinc and copper concentrations were not altered by ultraviolet irradiation in either IL-6+/+ or IL-6-/- mice. The results suggest that interleukin-6 may be a very early mediator of cutaneous metallothionein induction by ultraviolet radiation, but that this role is possibly assumed by alternative cytokines like tumor necrosis factor alpha when interleukin-6 is deficient.

Animals↗

PubMed2000

Direct polymerase chain reaction from whole blood without DNA isolation.

Blood and other animal fluids contain a variety of substances that inhibit the polymerase chain reaction (PCR), so that isolation of DNA is generally necessary prior to PCR. We have developed a novel reagent cocktail that effectively suppresses these inhibitory substances and makes DNA isolation from blood unnecessary for PCR. When this reagent was included in the PCR mixture, DNA fragments of the beta-globin gene could be efficiently amplified directly from human blood samples treated with various anticoagulants or PCR-inhibitory substances. We confirmed the usefulness of this cocktail by examining a large number of blood samples with various PCR primer sets. In addition to fresh blood, this method enabled PCR amplification from blood samples stored at 4 degrees C, -20 degrees C or -80 degrees C for a minimum of 1 year.

Animals↗

PubMed2000

Plasma cholesterol-lowering effect on rats of dietary fiber extracted from immature plants.

Crude dietary fiber samples were prepared from beet, cabbage, Japanese radish, onion and mung bean sprouts (BF, CF, RF, OF and MF, respectively). These samples contained total dietary fiber at the levels of 814, 699, 760, 693 and 666 g/kg, respectively. To examine the effect of these dietary fiber sources on the plasma cholesterol concentration, male Sprague-Dawley rats were fed on a fiber-free (FF) diet or on an FF diet supplemented with 5% or 10% dietary fiber. Dietary fiber extracted from vegetables, wood cellulose (CL), pectin (PE) and guar gum (GG) were used as the fiber sources. Compared with the rats fed on the FF diet, a significant reduction in the plasma cholesterol concentration was observed in the rats fed on BF, CF, RF, MF, PE or GG after a 21-d feeding period. Cecal acetate, n-butyrate and total short-chain fatty acids were significantly higher in the rats fed on these dietary fibers, except for CF, than in those fed on the FF diet. A negative correlation was apparent between the total dietary fiber content, hemicellulose content and pectin content of each dietary fiber source and the plasma cholesterol concentration. These results suggest that some vegetable fibers exert a plasma cholesterol-lowering effect through cecal fermentation of these fibers.

Animals↗

PubMed2000

Liquid chromatography mass spectrometric analysis of ouabainlike factor in biological fluid.

Ouabainlike factor (OLF), assayed as ouabainlike immunoreactivity (OLI), is a probable endogenous digitalislike factor (EDLF). Liquid chromatography/mass spectrometry (LC/MS) is one of the most highly sensitive tools for obtaining structural information regarding low-molecular weight materials in a target compound, and to measure the concentrations of these materials. We have previously reported that OLI can be isolated from the culture supernatant of the rat pheochromocytoma cell line, PC12, by several reverse-phase chromatography and LC/MS techniques. The present study was performed to characterize OLF from biological fluids such as plasma and culture supernatant of PC12 cells by LC/MS. The previous applications of LC/MS to OLI in plasma have been limited to structural identification at the final stages of isolation, in which the starting volume of plasma has been over 10 I. In the present study, we tried to minimize the volume of plasma, and to develop a new preclearing step to gain adequate LC/MS characterization using MS/MS analysis. The plasma was acidified, and OLI was purified by ODS column chromatography. OLI in chromatographic fractions from plasma was assayed by a sensitive enzyme-linked immunosorbent assay for ouabain. After Sep-Pak treatment and two rounds of ODS column chromatography, OLI was identified from 80 ml of plasma. The structure of the purified OLI was identical to authentic ouabain and digoxin, as assessed by LC/MS. In conclusion, we identified the chemically or structurally clarified ouabain and digoxin as the circulating form in plasma by LC/MS.

Animals↗

PubMed2000

Low-intensity pulsed ultrasound accelerates bone maturation in distraction osteogenesis in rabbits.

We investigated the effects of low-intensity pulsed ultrasound on distraction osteogenesis in a rabbit model. Callotasis of the right tibia was performed in 70 male Japanese white rabbits using mini-external fixators. In the first part of the study in 64 animals using normal distraction (waiting period seven days; distraction rate 0.5 mm/12 hours; distraction period ten days), we evaluated the distraction site by radiography, measurement of the bone mineral density (BMD), mechanical testing, and histology. In the second part in six rabbits using fast distraction (waiting period 0 days; distraction rate 1.5 mm/12 hours; distraction period seven days) the site was evaluated radiologically. Half of the animals (35) had received ultrasound to their right leg (30 mW/cm2) for 20 minutes daily after ceasing distraction (ultrasound group), while rigid fixation only was maintained in the other half (control group). With normal distraction, the hard callus area, as shown by radiography, the BMD, and the findings on mechanical testing, were significantly greater in those receiving ultrasound than in the control group. Histological analysis showed no tissue damage attributable to exposure to ultrasound. With fast distraction, immature bone regeneration was observed radiologically in the control group, while bone maturation was achieved in the ultrasound group. We conclude that ultrasound can accelerate bone maturation in distraction osteogenesis in rabbits, even in states of poor callotasis.

Animals↗

PubMed2000

Callotasis for post-traumatic shortening and deformity of leg.

We have been performed callotasis, including hemicallotasis, in cases of more than 30 mm limb lengthening and more than 15 degrees angular deformity. There were 21 cases in this series. The mean age was 29.8 years old. Ilizarov external fixator (EF) was used in 13 cases and Orthofix EF in 8. The operation site was femur in 12 cases and tibia in 9 cases. Pre-existed complications were noted to occur in 10 cases. Callotasis was indicated in 17 cases, and the average length gain was 28.4 mm. Hemicallotasis was indicated in 5 cases, and the mean degree of correction angle was 18 degrees. Among available types of EF, Orthofix EF was suitable for proximal femoral callotasis, while Ilizarov EF was suitable for corrective deformity using hemicallotasis and tibial callotasis. The bone healing process of callotsis was better in the absence than presence of pre-existed complication. Also, we performed bone transportation using Ilizarov EF in cases of pseudoarthrosis with leg shortening and in all cases where bone grafting was unnecessary.

Adolescent↗

PubMed1999

Procedural and late outcomes following MULTI-LINK DUET coronary stent deployment.

The MULTI-LINK DUET is the next generation MULTI-LINK stent with modified strut geometry. Safety and efficacy of the MULTI-LINK DUET were evaluated in a prospective multicenter registry and were compared with prior MULTI-LINK stent experience from the ASCENT randomized trial. A total of 270 patients received 302 MULTI-LINK DUET stents and were evaluated using a composite primary end point of major cardiac events (death, Q-wave and non-Q-wave myocardial infarction, and requirement for coronary revascularization) attributable to the target stenosis cumulative to 30 days following enrollment. Quantitative coronary angiography was performed at a mean follow-up of 6 +/- 2 (+/-SD) months. No difference in primary end point or in angiographic restenosis to 6 months was observed between MULTI-LINK DUET and MULTI-LINK experiences. The MULTI-LINK DUET demonstrated improved device and procedural success, less postprocedural in-stent stenosis, larger postprocedural minimal lumen diameter, and fewer postprocedural marginal dissections compared with the MULTI-LINK stent. Multivariate regression modeling identified stent length, diabetes mellitus, poststent minimal lumen diameter, lesion eccentricity, and current smoking as independent predictors of in-stent restenosis. Thus, the MULTI-LINK DUET Registry demonstrates enhanced procedural performance with clinical and angiographic outcomes similar to those previously observed for the MULTI-LINK stent in the ASCENT randomized trial.

Aged↗

PubMed1999

Combined therapy with anti-P-glycoprotein antibody and macrophage colony-stimulating factor gene transduction for multiorgan metastases of multidrug-resistant human small cell lung cancer in NK cell-depleted SCID mice.

Our aim was to determine the antimetastatic potential of anti-P-glycoprotein (P-gp) antibodies (Abs) against multidrug-resistant (MDR) human small cell lung cancer (SCLC) cells expressing P-gp. Human SCLC cells H69 (P-gp negative) and its etoposide-resistant variant H69/YP (P-gp positive) were used. H69 and H69/VP cells injected i.v. metastasized to the liver, kidneys and systemic lymph nodes of NK cell-depleted severe combined immunodeficient (SCID) mice. H69/VP cells, but not H69 cells, were resistant to treatments with vindesine. Treatment with mouse-human chimeric anti-P-gp Ab (MH162) and its mouse counterpart (MRK-16) reduced metastasis of H69/VP cells in various organs and prolonged the survival of tumor-bearing mice, although they were less effective if injected at late times (after 28 days). Treatment with another mouse anti-Pgp Ab, MRK-17, was effective only against liver metastasis. MH162 and MRK-16 efficiently induced Ab-dependent cellular cytotoxicity (ADCC) by peritoneal macrophages against H69/VP cells in vitro, but MRK-17 was less effective, in accordance with their in vivo antimetastatic potential. Gene transfection of macrophage colony-stimulating factor (M-CSF) into H69/VP cells to augment macrophage-mediated ADCC resulted in inhibition of metastasis to the liver and lymph nodes, but not kidneys. Combined treatment with a low dose of MRK-16 completely cured metastasis of M-CSF transfectant, but not of the mock transfectant. Our findings suggest that while anti-P-gp Abs had antimetastatic potential against SCLC cells expressing P-gp, combined treatment with M-CSF gene transduction to augment the therapeutic efficacy of anti-P-gp Abs may be beneficial for eradicating metastatic MDR SCLC in humans.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Synthesis of 5-hydroxy-2-(beta-D-ribofuranosyl)pyran-4-one from a pyranulose glycoside.

The synthesis of 5-hydroxy-2-(beta-D-ribofuranosyl)pyran-4-one (9) is described. Treatment of pyranulose glycoside with bromine in carbon tetrachloride afforded brompyranulose glycoside in 90% yield. The reaction of (6S)- and (6R)-4-bromo-6-hydroxy-6-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-6H- pyran-3-one (2) in acidic media was examined with the following results: the reaction of 2 with trifluoroacetic acid (TFA) in dioxane afforded a mixture of 5-hydroxy-2-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)pyran-4-one (3) and its furan derivative 5-hydroxy-2-{5-(benzoyloxy)methyl]furan-2-yl}pyran-4-one (4), but the use of hydrochloric acid formed the bromofurfural, 3-bromo-5-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-2-furancarboxyal dehyde only. Acetylation of a mixture (3 and 4) with acetic anhydride facilitated product separation to give the corresponding acetates 5-acetoxy-2-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)pyran-4-one (5) and 5-acetoxy-2-{5-[(benzoyloxy)methyl]furan-2-yl}pyran-4-one (6). Treatment of 5 with hydrazine afforded 3-hydroxymethyl-6-(beta-D-ribofuranosyl)-1H-pyridazin-4-one in 43% yield. Debenzoylation of 5 with aq ammonia gave 9 in 50% yield.

Anti-Bacterial Agents↗

PubMed1999

A di-acidic (DXE) code directs concentration of cargo during export from the endoplasmic reticulum.

Efficient export of vesicular stomatitis virus glycoprotein (VSV-G), a type I transmembrane protein, from the endoplasmic reticulum requires a di-acidic code (DXE) located in the cytosolic carboxyl-terminal tail (Nishimura, N., and Balch, W. E. (1997) Science 277, 556-558). Mutation of the DXE code by mutation to AXA did not prevent VSV-G recruitment to pre-budding complexes formed in the presence of the activated form of the Sar1 and the Sec23/24 complex, components of the COPII budding machinery. However, the signal was required at a subsequent concentration step preceding vesicle fission. By using green fluorescence protein-tagged VSV-G to image movement in a single cell, we found that VSV-G lacking the DXE code fails to be concentrated into COPII vesicles. As a result, the normal 5-10-fold increase in the steady-state concentration of VSV-G in downstream pre-Golgi intermediates and Golgi compartments was lost. These results demonstrate for the first time that inactivation of the DXE signal uncouples early cargo selection steps from concentration into COPII vesicles. We propose that two sequential steps are required for efficient export from the endoplasmic reticulum.

Animals↗

PubMed1999

Trizygotic pregnancy consisting of two fetuses and a complete hydatidiform mole with dispermic androgenesis.

A triplet pregnancy in a 23-year-old woman was terminated at 15 weeks of gestation because of her severe hypertension, lung edema, and secondary hyperthyroidism. The pregnancy consisted of a hydatidiform mole with a 46,XY karyotype and two fetuses each with 46,XX and a 46,XY karyotype. To determine the zygosity and genetic origin of the mole and fetuses, PCR- and computer-assisted genotyping were performed at 27 CA-repeat marker loci that were distributed evenly over the genome. As a result, genotypes of the three pregnancy products were distinct from each other, indicating that the triplets were trizygotic. The mole lacked any maternal alleles but inherited both of the paternal alleles and/or one paternal allele in duplicate. This, along with the XY sex chromosome constitution, indicated that the mole resulted from dispermic androgenesis. The mother developed a persistent trophoblastic tumor thereafter.

Abortion, Therapeutic↗

PubMed1999

Cytolysis of human dendritic cells by autologous lymphokine-activated killer cells: participation of both T cells and NK cells in the killing.

Dendritic cells (DC) play a key role in the initiation of immune response by stimulating the naive T cells. The fate of DC after the initiation of immune response is not clearly understood. Although there are few reports implicating natural killer (NK) cells in the elimination of DC, killing of DC by LAK cells, and specifically by T cells, has not been studied. In this study, we observed that DC, generated from monocytes, in vitro in the presence of granulocyte-macrophage colony-stimulating factor, interleukin-4 (IL-4), and tumor necrosis factor alpha were susceptible to cytolysis by lymphokine-activated killer (LAK) cells induced in the presence of IL-2 and IL-15 but not IL-12 alone. However, LAK cells induced by a combination of IL-12 and suboptimal dose of IL-2 were cytotoxic to DC. When purified lymphocytes were activated with IL-2, the CD8+/CD57- fraction (T-LAK), but not the CD8-/CD57+ fraction (NK-LAK) was cytotoxic to autologous DC. However, when unseparated peripheral blood mononuclear cells were used to generate LAK cells, both T-LAK and NK-LAK fractions showed equal cytotoxicity against autologous DC. Monoclonal antibodies against CD54, CD11a, and CD18 significantly inhibited the cytolysis, indicating that the killing involves the engagement of CD54 with its ligands.

Antibodies, Blocking↗

PubMed1999

Heterogeneity of multiorgan metastases of human lung cancer cells genetically engineered to produce cytokines and reversal using chimeric monoclonal antibodies in natural killer cell-depleted severe combined immunodeficient mice.

Lung cancer is a major cause of cancer deaths, most of which can be attributed to distant multiorgan metastases. To examine the cellular and molecular mechanisms of lung cancer metastasis to distant organs, we have established novel models of human lung cancer (small cell and non-small cell lung cancer) metastasis in natural killer cell-depleted severe combined immunodeficient (SCID) mice. We investigated whether local production of the cytokines responsible for regulation of macrophage function at tumor growth sites affects the pattern of lung cancer metastasis in distant organs. Several lung cancer cell lines were genetically engineered to produce human macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein-1 (MCP-1), and their metastatic potentials were assessed. Interestingly, M-CSF gene transduction had an antimetastatic effect for the liver and lymph nodes, but not the kidneys. In contrast, MCP-1 gene-modified lung cancer cells and their parent cells had identical metastatic potentials. These findings indicate a possible role for cytokines and suggest that lung cancer has metastatic heterogeneity. Examining ways of controlling human lung cancer metastases, we investigated the antimetastatic effect of chimeric monoclonal antibodies (MAbs) against P-glycoprotein and ganglioside GM2 (MH162 and KM966, respectively). Both MAbs, when given on days 2 and 7, inhibited the development of distant metastases of lung cancer in a dose-dependent fashion. Combined use of anti-P-glycoprotein MAb with M-CSF or MCP-1 gene transduction caused complete inhibition of metastasis of H69/VP cells. The antimetastatic effect of these MAbs in vivo was mainly due to an antibody-dependent cell-mediated cytotoxicity reaction mediated by mouse macrophages. These findings suggest that the mouse-human chimeric MAb in combination with cytokine gene transduction may be useful for the eradication of lung cancer metastases in humans.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

The prevalence of TT virus (TTV) infection and its relationship to hepatitis in children.

TT virus (TTV) is a newly discovered virus from a patient with post-transfusion hepatitis. We investigated the frequency and pathogenesis of TTV infection in children. A semi-nested PCR assay was used to amplify TTV-DNA in serum samples from 254 ambulatory children without liver disease, 20 with hepatitis of unknown etiology, and 18 transfusion recipients or hemophiliacs. In positive samples, TTV-DNA was quantified by real-time quantitative PCR using a fluorescent probe. We detected TTV-DNA in 20% of children with hepatitis of unknown etiology, which was not statistically different from the 23% prevalence in ambulatory children. In transfusion recipients or hemophiliacs, the frequency was higher (50%) than that in ambulatory children (P = 0.01). Among ambulatory children, TTV-DNA was frequently detected in children with acute gastroenteritis (36%). TTV-DNA was detected in 10% of the infants under 6 months old, and 20% of the children from 7 to 12 months old. The prevalence was constant after the age of 1 year; however, the copy number of TTV-DNA was significantly higher in children under 1 year of age (mean: 10(5.4) versus 10(3.8) copies/ml, P= 0.008). Finally, TTV-DNA was quantified serially in three children with chronic hepatitis who were positive for TTV-DNA. The presence or amount of TTV-DNA was unrelated to the serum alanine aminotransferase level. These results indicate that TTV infection is common in children. The larger quantity of TTV-DNA in infants and the high prevalence of TTV in children of all ages suggest that TTV may be transmitted in early childhood. Its relationship to hepatitis is doubtful in children.

Adolescent↗