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Biomedical subjects

Y Asano

Publications and source records attributed to Y Asano.

At least 433 records · Page 24Linked to original sources

Clinical features of infants with primary human herpesvirus 6 infection (exanthem subitum, roseola infantum).

OBJECTIVE: To clarify clinical features of patients with primary human herpesvirus 6 (HHV-6) infection (roseola infantum, exanthem subitum) in a large-scale study. SUBJECTS AND METHODS: Clinical signs and symptoms were analyzed in 176 infants in whom exanthem subitum was initially suspected and primary HHV-6 infection was later confirmed. The infection was proved by isolation of the virus from blood, a significant increase in the neutralizing antibody titers to the virus, or both. RESULTS: The primary HHV-6 infection, which occurred throughout the year, was observed in 94 boys and 82 girls (mean age, 7.3 months). Fever developed in 98% (mean maximum fever, 39.4 degrees C) and lasted for 4.1 days. Macular or papular rashes appeared in 98%, on face, trunk, or both, mostly at the time of subsidence of the fever, and lasted for 3.8 days. Other clinical manifestations occurred as follows: mild diarrhea in 68%, edematous eyelids in 30%, erythematous papules in the pharynx in 65%, cough in 50%, and mild cervical lymph node swelling in 31%. Twenty-six percent had bulging of the anterior fontanelle and 8% had convulsions. CONCLUSIONS: Clinical features of patients with virologically confirmed exanthem subitum were comparable with those described before discovery of HHV-6.

Exanthema Subitum↗

Phorbol ester 12-O-tetradecanoylphorbol-13-acetate down-regulates expression of the c-kit proto-oncogene product.

Modulation of expression of the c-kit proto-oncogene product, the receptor for the recently identified stem cell factor, was studied on 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated cultures of CD34+ normal bone marrow progenitor cells, blast cells from patients with primary acute myelogenous leukemia, cells from the leukemia cell lines HEL and MO7E, as well as cultured HMC-1 mast cells. Expression of c-kit was assessed on both RNA and protein level employing standard Northern blotting, reverse transcription, and polymerase chain reaction-based Southern blotting, as well as cell surface labeling with anti-c-kit mAb YB5.B8. Treatment of virtually all cell types with nontoxic concentrations of TPA (10(-9) M) for at least 48 h was associated with down-regulation of synthesis of c-kit transcripts and stem cell factor-receptor surface expression. Studies on the mechanism of action of TPA utilizing the HEL erythroleukemia line showed that TPA was primarily acting by accelerating the turnover of c-kit RNA most likely through induction of a destabilizing protein. The effect of TPA on c-kit expression levels was independent of TPA-mediated induction of differentiation since other compounds including IFN-gamma, vitamin D3, retinoic acid, arabinofuranosylcytosine, butyric acid, and camptothecin, which also effectively induced differentiation of HEL cells, failed to alter levels of c-kit expression.

Base Sequence↗

Transforming growth factor-beta 1 interferes with the proliferation-inducing activity of stem cell factor in myelogenous leukemia blasts through functional down-regulation of the c-kit proto-oncogene product.

Blast cells, obtained from patients with acute myelogenous leukemia (AML), that express surface binding sites for human stem cell factor (SCF) respond proliferatively upon exposure to this molecule. In the presence of human transforming growth factor-beta 1 (TGF-beta 1) the capacity of SCF to augment the proliferative state of AML blasts was, however, almost completely abolished. This inhibitory action of TGF-beta 1 could be reversed by a neutralizing anti-TGF-beta 1 antibody. Studies on the mechanism of TGF-beta 1 inhibition of SCF-induced proliferation of AML blasts revealed that TGF-beta 1 treatment of these cells was associated with down-regulation of SCF receptor surface expression, as detected with a specific monoclonal antibody, which appeared to be preferentially due to an acceleration of decay of mRNA for the c-kit proto-oncogene encoding the SCF receptor, without an effect on the overall transcriptional activity of the c-kit gene. Direct evidence to prove the importance of c-kit down-regulation in the inhibitory effect of TGF-beta 1 on AML growth came also from experiments demonstrating that signal transduction of SCF could be significantly diminished in the presence of TGF-beta 1, as demonstrated by measuring c-kit kinase-associated phosphorylation of target proteins.

Cell Division↗

Ionizing radiation induces expression of interleukin 6 by human fibroblasts involving activation of nuclear factor-kappa B.

We here report that human lung fibroblasts respond to x-ray treatment (XRT) with release of interleukin (IL)-6. Synthesis of IL-6 upon ionizing radiation is preceded by an increase of IL-6 transcript levels resulting from transcriptional activation of the IL-6 gene. Analysis of deleted fragments of the IL-6 promoter indicated that transcriptional activation of the IL-6 promoter was due to enhanced binding activity of the transcription factor nuclear factor (NF)-kappa B. Although AP-1 did not participate in the rapid induction of the IL-6 promoter, its binding activity was also enhanced by XRT. In contrast to binding kinetics observed with NF-kappa B, AP-1 binding following XRT was biphasic with the second peak being dependent on de novo protein synthesis. In contrast, however, NF-IL-6 activity was not enhanced by XRT in fibroblasts. The introduction of both the NF-kappa B- and the AP-1 recognition sequence conferred inducibility by XRT to a heterologous promoter, with reporter gene activity being maximal 24 or 48 h following XRT, respectively. Sequential activation of two distinct transcription factors might thus contribute to synchronize transcriptional activation of different genes participating in the x-ray response.

Base Sequence↗

Distinction of mouse CD8+ suppressor effector T cell clones from cytotoxic T cell clones by cytokine production and CD45 isoforms.

Mouse CD8+ T cell clones could be subdivided into two subgroups by the pattern of cytokine production and CD45 isoforms that exactly corresponded with the functionally assigned cytotoxic (CTL) and suppressor (Ts) subsets. All the Ts clones invariably produced IL-10 after stimulation with immobilized anti-CD3, whereas none of CTL clones expressed mRNA of IL-10 by the same stimulation. All the CTL clones were positive for CD45RA Ag, a product of exon 4 of CD45 gene, whereas none of the Ts clones were positive for this Ag. The results are analogous to the situation within CD4+ T cell clones in which Th1 and Th2 subtypes can be distinguished by CD45 isoforms and cytokines they produce. Ts clones could suppress the proliferative responses of both Th1 and Th2 type CD4+ clones by the production of two different cytokines, IL-10 and IFN gamma, respectively, but none of the CTL clones could suppress the proliferation of CD4+ T cells. The participation of an additional nonspecific molecule in the suppression of antibody response is suggested.

Animals↗

Clinical and virological analyses of 21 infants with exanthem subitum (roseola infantum) and central nervous system complications.

Twenty-one infants who had virologically confirmed exanthem subitum and central nervous system (CNS) complications were studied to elucidate the clinical features, laboratory and virological findings, and outcome. The primary infection with human herpesvirus 6 was confirmed by isolation of the virus from blood, a significant rise in the antibody titers to the virus, or both. All convulsive seizures (15 generalized and 6 focal) occurred during the pre-eruptive stage of exanthem subitum. Four infants with encephalitis/encephalopathy had more severe clinical features with abnormalities demonstrated on electroencephalograms and cerebral computed tomograms. All infants except those with encephalitis/encephalopathy recovered without any sequelae. One infant with encephalitis/encephalopathy developed epilepsy and another one died. Human herpesvirus 6 DNA amplified by the nested polymerase chain reaction method was detected in the cerebrospinal fluid of 6 infants, including 3 with encephalitis/encephalopathy, of 11 patients examined by the fifth day of the illness. These findings suggest that CNS complications including encephalitis/encephalopathy occur at the pre-eruptive stage of exanthem subitum, that human herpesvirus 6 invades the CNS in some patients, and that the outcome is not always benign.

Base Sequence↗

Protein 1: its purification and application in clinical medicine.

Protein 1 (P1) is a low-molecular-weight protein recently isolated from the urine of patients with chronic renal failure. Its molecular weight is 14 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis and pI 4.7 on isoelectric focusing. We purified this protein, characterized its physicochemical properties, and analyzed its amino acid sequences to show that it is probably identical to human lung Clara cell 10 kDa protein. Its monoclonal antibody was prepared, and a reliable enzyme-linked immunosorbent assay employing the sandwich method was developed and used to investigate distribution and variation in concentration of P1 in various body fluids under an array of physiologic and pathologic conditions. Clinical studies indicated that, as is the case with other proteins of low molecular weight, the main catabolic site of P1 of plasma origin is the kidney: P1 is filtered by the renal glomeruli and reabsorbed by the renal tubules. Unabsorbed P1 is thus excreted into the urine. This protein is also synthesized in the genital tissues of males, however, from which it is also excreted into the urine. Clinical data obtained in our study of this protein is summarized here, and an attempt is made to determine the potential value of this protein in laboratory medicine.

Adolescent↗

Seroepidemiology of human herpesvirus 7 in healthy children and adults in Japan.

The isolation of human herpesvirus 7 (HHV-7) from saliva and blood, and the prevalence of antibodies to the virus in healthy individuals were investigated in Japan. By cocultivating samples with phytohemagglutinin-P-stimulated cord blood mononuclear cells, HHV-7 was isolated from the saliva of 1 of 20 children and from 4 of 38 adults but not from their blood. The isolates were confirmed as closely related to RK strain of HHV-7, but not to U1102 (human herpesvirus 6, HHV-6 type A) or Z29 (HHV-6 type B) strains by restriction cleavage patterns of the DNA. The virus antibody of 330 healthy children and adults was measured with an indirect immunofluorescence assay, using one of our isolates (FG7-6). The positivity rate of antibody was 40% in the first 2 months of life, declined during the first 6 months, then gradually increased and was 45% at 1-4 years of age. It reached the highest level (60%) at 11-13 years of age and was maintained until the end of the third decade, then decreased thereafter. Additionally, no simultaneous rise in the antibody titers was observed in 7 virologically confirmed exanthem subitum patients.

Adolescent↗

Negative selection of thymus-dependent CD4+8+ intestinal intraepithelial lymphocytes by internal superantigens.

CD4 and CD8 double-positive (DP) T cells were transiently found in the Peyer's patch of mice 2 to 3 weeks after birth and preceded the appearance of DP intestinal intraepithelial lymphocytes (iIEL). DP iIEL were detected in euthymic-specific pathogen-free mice, but not in athymic and germ-free mice. The pattern of V beta genes expressed on these DP iIEL was similar to that of CD4 single-positive peripheral T cells, which reflected the negative selection by internal superantigens, M1s, and I-E. CD8 SP T cells did not receive such a strict negative selection with these antigens. DP iIEL expressed a high density of T cell receptor alpha beta and CD3 and responded to immobilized anti-CD3 to undergo blastogenesis and de novo IL2 receptor expression. These results indicate that DP iIEL are mature thymus-dependent T cells immigrated to intraepithelial space via the Peyer's patch in response to intestinal antigenic stimulation.

Animals↗

Cecoureterocele: experience of three cases with special reference to the relevance of endoscopic incision.

We report three cases of cecoureterocele to emphasize the salient features of this rare clinical entity. The differentiation of it from the usual ectopic ureterocele requires careful examination of the urethra by voiding cystourethrography and cystourethroscopy. We describe the management of these three cases with special reference to the endoscopic incision of the obstructing tissue.

Child↗

Human herpesvirus-6 and parvovirus B19 infections in children.

It was proved in the 1980s that human herpesvirus-6 and human parvovirus B19 cause diseases in humans. Human herpesvirus-6, a newly recognized herpesvirus, is a causative agent of exanthem subitum. The virus produces broad clinical features; complications, including fatal outcome, are frequently activated in immunosuppressed conditions such as organ transplantation. Parvovirus B19, a small-DNA virus, infects erythroid progenitor cells. Systemic infection with parvovirus B19 is responsible for several clinical entities, such as erythema infectiosum, arthropathy, aplastic crisis, fetal death, and other disease conditions, including those in immunosuppressed hosts. Reliable diagnostic technologies and carefully designed clinical, immunologic, and virologic studies will fully delineate the clinical significance of both viral infections.

Child↗

Varicella infection complicated with meningitis after immunization.

A healthy 45 month old boy who had received varicella vaccine 21 months previously developed aseptic meningitis along with an episode of varicella. The presence of viral DNA in cerebrospinal fluid (CSF) detected by polymerase chain reaction (PCR) with Southern blot hybridization confirmed the relationship between the symptoms and the CSF pleocytosis. This is the first reported case of this complication of varicella meningitis occurring in a child with documented immunization and seroconversion.

Antibodies, Viral↗

Varicella-zoster virus replication site in internal organs of an otherwise healthy child with varicella and sudden death.

Pathological findings of an otherwise healthy 17 month old boy who was exposed to Varicella-zoster virus (VZV) in his family and unexpectedly died 3 days after onset of varicella are reported. They showed a disseminated VZV infection with involvement of skin, lung, liver, spleen, gastrointestinal tract and other organs where VZV antigen was detected by the enzyme-immunoassay with monoclonal antibodies to VZV. Since the subject was the full-term product of an uncomplicated pregnancy, who grew and developed normally, and had no symptoms or laboratory findings suggestive of immunodeficiency until his death, these findings suggest that many organs are involved as major internal sites of viral replication before or during infection of skin with VZV in the immunocompetent host.

Antibodies, Monoclonal↗

Effect of nafamostat mesilate on Na+ and K+ transport properties in the rabbit cortical collecting duct.

1. To determine the mechanism(s) of hyperkalemia caused by nafamostat mesilate (NM), a serine-protease inhibitor, we investigated the effects of the drug on Na+ and K+ transport properties of the collecting duct (CD) cell in the isolated and perfused cortical collecting duct from rabbit kidneys. 2. NM at 10(-4) M in the lumen, hyperpolarized the apical membrane in parallel with increases in transepithelial resistance (RT) and fractional apical membrane resistance (fRA). 3. These effects were completely inhibited by pretreatment with 50 microM luminal amiloride, whereas they were not affected by luminal addition of 2 mM Ba2+. 4. NM at 10(-4) M in the bath slightly but significantly depolarized the basolateral membrane without any changes in RT or fRA, although NM at 10(-5) M in the bath had no effect on the electrical parameters. 5. It is concluded that NM mainly acts on the apical membrane of the CD cell and inhibits the amiloride-sensitive Na+ conductance in the apical membrane.

Amiloride↗