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Biomedical subjects

Y Asano

Publications and source records attributed to Y Asano.

At least 361 records · Page 20Linked to original sources
PubMed1996

Distribution of human herpesvirus 6 and varicella-zoster virus in organs of a fatal case with exanthem subitum and varicella.

The distribution of human herpesvirus 6 (HHV-6) and varicella-zoster virus (VZV) was examined in autopsy samples from a fatal case with both virus infections. A 9-month-old boy developed convulsive seizures followed by macular skin rashes, rapidly progressed to brain death, and died 15 days after the onset, when signs of varicella were noted. An isolation of HHV-6 from blood and evaluation of antibody activities to various viral agents including HHV-6 were performed before his death. Postmortem examinations included: (i) isolation of HHV-6 and VZV from tissues or organs; (ii) detection of both virus antigens in tissues or organs by an indirect immunofluorescent assay using monoclonal antibodies to both viruses; (iii) amplification of both viruses and human herpesvirus 7 DNA sequences by a nested polymerase chain reaction assay; and (iv) endonuclease digestion of amplified products of HHV-6 DNA for differentation of variants A and B. Human herpesvirus 6 DNA was detected in peripheral blood mononuclear cells (PBMC) and plasma obtained at the eruptive stage but present only in PBMC 15 days after, indicating the primary infection with HHV-6, although the virus was not isolated from the same blood sample and a significant rise in the antibody titers to HHV-6 was not observed. Both virus antigens and DNA were detected in various tissues or organs obtained at autopsy, but only VZV was isolated from these samples, suggesting disseminated infection with both viruses in an infant. All the amplified products of HHV-6 DNA were variant B. Among the findings for the distribution of virus antigens, it was noteworthy that HHV-6 antigen was demonstrated in the endothelial cells of small vessels in the frontal lobe of the brain. There was no evidence of HHV-7 infection. These data indicate that the primary HHV-6 infection closely followed by the primary VZV infection had the potential hazard of an unexpected and apparently life-threatening event, in which disseminated infections with both viruses were noted in multiple tissues or organs including the brain.

Antibodies, Viral↗
PubMed1996

Comparison of specific immunities to varicella-zoster virus following post-exposure prophylaxis of varicella by oral acyclovir observed in a family.

An otherwise healthy 3-year-old girl developed severe varicella complicated by aseptic meningitis and received intravenous acyclovir (ACV) therapy. Her two siblings who were susceptible to varicella-zoster virus (VZV) and closely exposed to VZV in the family received oral ACV (45 or 54 mg/kg per day in four divided doses for 7 days) starting 8 days after onset of the index case for post-exposure prophylaxis of varicella. They showed only five or seven papules over the body without fever 12 days after onset of the index case, while they had one-third or half the level of antibody titer and equal sized skin reactions to VZV antigen of the index case 2.5 months later.

Acyclovir↗
PubMed1996

Dose-dependent effects of oral acyclovir in the incubation period of varicella.

Dose of acyclovir (ACV) and clinical features of varicella were evaluated in 65 household contacts (0.8-9 y) who received oral ACV (5-80 mg/kg daily in four divided doses) during the latter half of the incubation period of varicella. The severity of the disease was compared with that of 23 children who did not receive ACV. Infection was confirmed by a fluorescent antibody to membrane antigen assay. The antibody titers and the rate of apparent infection increased as the dose of ACV administered decreased. The number of skin lesions in patients who received ACV was significantly reduced when compared to the control group. These data suggest dose-dependence of ACV for modification of varicella during secondary viremia in the incubation of the disease.

Acyclovir↗
PubMed1996

Differential regulation of Na+-K+-ATPase gene expression by corticosteriods in vascular smooth muscle cells.

To determine whether gluco- and mineralocorticoids have specific actions on Na+-K+-ATPase gene expression in vascular tissue, we used Northern blot analysis to compare the effects of dexamethasone (Dex) and aldosterone (Aldo) on Na+-K+-ATPase alpha1 and beta1-subunit mRNA expression in cultured vascular smooth muscle cells from rat aortae. Dex at 10(-6)M increased alpha1 -mRNA level 2.5-fold at 24 h and beta1-mRNA level 9.9-fold at 12 h. Aldo at 10(-6)M increased alpha1-mRNA 2.7-fold at 48 h and beta1-mRNA level 10.9-fold at 6 h. The half-maximal stimulation of both alpha1 and beta1-mRNA levels occurred at a concentration of 5-7 X 10(-9)M Dex, whereas it occurred at a concentration of 2-3 X 10(-9)M Aldo. The glucocorticoid receptor antagonist RU-38486 inhibited both Dex- and Aldo-mediated induction of beta1-mRNA. The mineralocorticoid receptor antagonist spironolactone inhibited Aldo-mediated induction of beta1-mRNA, whereas it had no effect on Dex-mediated induction of beta1-mRNA. Removal of Na+ from the extracellular medium (isosmotic replacement with choline) caused no effect on Dex-mediated induction beta1-mRNA, whereas it inhibited Aldo-mediated induction of beta1-mRNA. Addition of a specific inhibitor of the Na+/H+ exchange, ethylisopropylamiloride, had no effect on Dex-mediated induction of beta1-mRNA, whereas it resulted in a significant inhibition of Aldo-mediated induction of beta1-mRNA. We conclude that 1) both Dex and Aldo induce Na+-K+-ATPase alpha1- and beta1-mRNA expression in a time- and dose-dependent manner; 2) Dex-mediated induction of beta1-mRNA occurs only through glucocorticoid receptors, whereas Aldo-mediated induction of beta1-mRNA occurs through both gluco- and mineralocorticoid receptors; and 3) Dex-mediated induction of beta1-mRNA occurs through Na+-independent mechanisms, whereas Aldo-mediated induction of beta1-mRNA, at least in part, occurs through Na+-dependent mechanisms, including stimulation of the Na+/H+ exchange.

Adrenal Cortex Hormones↗
PubMed1996

Hyperosmolality stimulates Na-K-ATPase gene expression in inner medullary collecting duct cells.

Primary cultures of inner medullary collecting duct (IMCD) cells of rats were incubated in hyperosmotic media to determine the effects on Na-K-ATPase alpha 1- and beta 1-subunit mRNA expression. Osmolality of the incubation media was raised from 300 up to 500 mosmol/kgH2O by adding NaCl, mannitol, raffinose, or urea. Hyperosmotic media supplemented with NaCl, mannitol, or raffinose caused two- to fourfold increases in the alpha 1-subunit mRNA accumulation and five- to eightfold increases in the beta 1-subunit mRNA accumulation, with peak elevations of both subunits at 12 h after addition. In sharp contrast, hyperosmolar urea medium had no effect at any time. When NaCl or mannitol was added to the media in amounts ranging from 300 to 600 mosmol/kgH2O, the maximal effects on both alpha 1- and beta 1-subunit mRNA accumulation occurred at 500 mosmol/kgH2O. In urea-supplemented medium, however, there was no significant change at any level of osmolality. The upregulation of alpha 1- and beta 1-subunit mRNA induced by hyperosmotic mannitol- or raffinose-supplemented media was markedly inhibited by removal of Na from the culture medium. Furthermore, pretreatment with a protein synthesis inhibitor cycloheximide partially inhibited the upregulation of alpha 1- and beta 1-subunit mRNA in IMCD cells exposed to hyperosmotic media treated with NaCl or mannitol. When IMCD cells were incubated with hyperosmotic media (500 mosmol/kgH2O) supplemented with NaCl or mannitol for 24 h, Na-K-ATPase activity increased by 78.6 and 82.8%, respectively. In contrast, hyperosmolar urea medium had no significant effect on Na-K-ATPase activity. These results demonstrate that 1) hyperosmolality induced by the poorly permeating solutes (NaCl, mannitol, and raffinose) but not the rapidly permeating solute (urea) stimulates both alpha 1- and beta 1-subunit mRNA accumulations in IMCD cells in a time- and an osmolality-dependent manner, 2) the hyperosmolality-induced upregulation of alpha 1- and beta 1-subunit mRNA leads to an increase in Na- K -ATPase activity; and 3) the above upregulation of alpha1- and beta 1-subunit mRNA in response to hyperosmotic media requires, at least in part, the presence of Na in the extracellular medium and the de novo synthesis of intermediate proteins.

Animals↗
PubMed1996

Inactivation of brain and kidney aspartate aminotransferases by S-(1,2,-dichlorovinyl)-L-cysteine and by S-(1,1,2,2,-tetrafluoroethyl)-L-cysteine.

Long-term exposure to trichloroethylene can cause kidney cancer in experimental animals and humans. In addition, dichloroacetylene (a breakdown product of trichloroethylene) is nephrotoxic and neurotoxic. Both trichloroethylene and dichloroacetylene are metabolized in part to the corresponding cysteine S-conjugate (i.e. S-(1,2-dichlorovinyl)-L-cysteine) which is toxic. Cysteine S-conjugate beta-lyases convert S-(1,2,dichlorovinyl)-L-cysteine to pyruvate, ammonia and a reactive fragment that adds to macromolecules, depletes cellular thiols and causes lipid peroxidation. We now show that S-(1,2-dichlorovinyl)-L-cysteine and another nephrotoxic cysteine S-conjugate, S-(1,1,2,2-tetrafluoroethyl)-L-cysteine, inactive purified cytosolic aspartate aminotransferase and purified alanine aminotransferase. These cysteine S-conjugates also inactive aspartate aminotransferase in cytosolic and mitochondrial fractions of rat brain and kidney. The present results suggest that some halogenated xenobiotics may be toxic in part through their conversion to the corresponding cysteine S-conjugate which inactivates key pyridoxal 5'-phosphate-containing enzyme.

Alanine Transaminase↗
PubMed1996

A study on regulating factors of plasma refilling during hemodialysis.

Hypotension is frequently encountered during hemodialysis (HD). One of the main factors of the HD-induced hypotension is acute reduction of circulating plasma volume by water removal, which is induced by the poor plasma refilling from the extravascular space into vessels. The determinants of plasma refilling, however, have not been clearly identified. Recently, we devised a mathematical model of water transport in HD patients, which can estimate the plasma-refilling coefficient (Kr) during HD. In the present study, we evaluated the factors determining plasma refilling by using this model. In 13 patients undergoing regular HD, the changes of Kr during HD were calculated from the model. Levels of ANP, cGMP, cAMP, endothelin, angiotensin II and vasopressin were measured before and after HD. Kr fell from 750.4 +/- 558.0 to 112.8 +/- 81.9 ml/mm Hg/h during HD. The rate of water removal during HD showed no significant correlation with the changes of Kr. Among the hormones and nucleotides measured here, plasma ANP level and cGMP were significantly correlated with Kr (r = 0.78, p < 001 and r = 0.62, p < 0.01, respectively). Our findings suggest that severe reduction in the level of serum ANP during HD, which is induced by water removal, plays some role in HD-induced hypotension through the attenuation of plasma refilling in HD patients.

Adult↗
PubMed1996

An index of plasma refilling in hemodialysis patients.

During hemodialysis therapy, a large amount of water is removed from the patient's blood in a short time; however, blood pressure remains stable in most patients. As water is removed, the circulating serum proteins become more concentrated, resulting in a marked increase in the driving force which pulls water from the extravascular space into the blood vessels, by a process called plasma refilling. However, since a method for studying plasma refilling has not previously been proposed, it is not known what determines the plasma refilling capacity of hemodialysis patients. To evaluate the plasma refilling capacity of patients, we propose here a method for calculating an index of plasma refilling capacity, which we have called the plasma-refilling coefficient (Kr). In 14 patients receiving maintenance hemodialysis therapy, total serum protein was measured before hemodialysis, and hematocrits were measured hourly during hemodialysis. From the changes in the hematocrits, we estimated the changes in the circulating plasma volume and in the intracapillary oncotic pressure at each time point. The water removal rate was also measured hourly. From these values, we calculated Kr. An averaged volume of 2,692 +/- 219 ml of water was removed from each patient resulting in a decrease in the estimated circulating blood volume, while the hematocrit and the estimated intracapillary oncotic pressure increased gradually. Kr calculated after 1 h of hemodialysis varied widely between patients, 140.3-1,744.2 ml/mm Hg/h, and decreased gradually as water removal continued. The average Kr of 14 patients was 698.9 +/- 15.2 ml/mm Hg/h at the beginning of water removal, and it decreased to 405.3 +/- 75.4, 203.9 +/- 39.5, 130.2 +/- 20.5 and 93.9 +/- 14.3 each hour thereafter. The index of plasma refilling proposed in this paper is useful for examining capillary water permeability and the degree of plasma refilling in hemodialysis patients.

Adult↗
PubMed1996

Calcium signals in helper T cells after interaction with antigen-specific and antigen-nonspecific B cells.

By confocal fluorescence microscopy we have studied the rises of the intracellular free calcium ion concentration ([Ca2+]i) in helper T cells (KLH-specific, I-Ak-restricted Th1 cells, 28-4) after interaction with antigen-specific and antigen-nonspecific B cells (antigen-presenting cells). Antigen-specific and antigen-nonspecific B cells were prepared by the preincubation of TNP (trinitrophenol)-specific B cell hybridomas (TP67.21 I-Ak) with TNP-conjugated KLH and KLH alone, respectively. Calcium signals in Th1 cells (28-4) were induced by antigen-specific B cells one hundred times more efficiently as those by antigen-nonspecific B cells. Herbimycin A, a tyrosine kinase inhibitor, suppressed the former signals but not the latter. These results indicated that tyrosine phosphorylation was involved in the antigen processing of antigen-specific B cells but not in the processing of antigen-nonspecific B cells.

Animals↗
PubMed1996

PMA and ionomycin differently affect atrial natriuretic peptide stimulated cyclic GMP production in rat mesangial cells.

How 4 beta-phorbol 12-myristate 13-acetate (PMA) and ionomycin (Io), a calcium ionophore, affect on the atrial natriuretic peptide (ANP) stimulated cyclic-3',5'-guanosine monophosphate (cGMP) production in cultured rat mesangial cells was examined. Cultured mesangial cells were prepared by isolated glomeruli from Sprague Dawley rats employing the sieving method and were used between the 3rd and 15th passage for experiments. cGMP and protein contents were measured by radioimmunoassay and Lowry method. Incubations with effectors were carried out either in the presence or absence of 0.5 mM 1-methyl-3-isobutyl-xanthine (MIX). The intracellular concentration of calcium ([Ca2+]i) was determined by using the Fura-2 method. Pretreatment with PMA, an activator of protein kinase C (PKC), attenuated ANP stimulated cGMP production in a time- and dose-dependent fashion, while alpha PDD (an inactive analog of PMA) did not inhibit cGMP production. PMA inhibition was reversed by addition of staurosporine, a protein kinase C inhibitor. Io attenuated ANP stimulated cGMP production in the absence but not in the presence of MIX. These findings suggested that PMA acts on ANP receptor or guanylate cyclase via activation of PKC in rat mesangial cells. Io may inhibit ANP stimulated cGMP production via activation of cyclic nucleotide phosphodiesterase.

1-Methyl-3-isobutylxanthine↗
PubMed1996

[A clinical evaluation of fluconazole in deep seated fungal infections associated with hematological disorders].

The effectiveness of fluconazole on deep seated fungal infections associated with hematological disorders was evaluated in a multicenter clinical study. The underlying diseases included acute myeloblastic leukemia, acute lymphocytic leukemia, malignant lymphoma, adult T cell leukemia, multiple myeloma and others. Fluconazole (FLCZ) was administrated 100-400 mg/day intravenously or orally to 79 patients with systemic fungal infections complicated with hematological disorders and it was possible to evaluate clinical efficacies in 60 patients. 27 patients were diagnosed as having determinate systemic fungal infections and 33 patients suspected fungal infections. The clinical efficacies were 81.5% (22/27) in patients with diagnosed fungal infections and 57.6% (19/33) in patients with suspected fungal infections. The overall clinical efficacy was 68.3% (41/60). No side effects such as gastrointestinal symptoms, vascular pain and renal dysfunction were observed in this study. As for abnormal laboratory test, transient increases in GOT, GPT, Al-P, LDH, serum Na, Cl and decrease in serum K were observed in 9 patients (11.4%). These results indicated that FLCZ has a high therapeutic efficacy on deep seated fungal infections in patients with hematological disorders.

Aged↗
PubMed1996

[Human herpesviruses 6 and 7].

By new methods for propagating cells of the immune system and for detecting infectious agents in disease tissue, 4 human herpesviruses have been discovered during the past decade: human herpesvirus 6 variants A and B (HHV-6A and HHV-6B), human herpesvirus 7 (HHV-7), and human herpesvirus 8 (HHV-8). Only HHV-8 has been linked to a disease that might be described as new, that is AIDS-associated Kaposi's sarcoma. No disease has been clearly linked to HHV-6A infection, HHV-6B is the major etiologic agent of exanthem subitum, and HHV-7 infection is associated with febrile exanthem which mimics exanthem subitum cases and occurs somewhat later than primary HHV-6B infection. Over 90% of the population has been infected with either or both HHV-6A and HHV-6B and over 85% with HHV-7. Both history and biology suggest that these viruses have a broad clinical spectrum and that they are each linked with significant and specific clinical entities. The clinical, epidemiological, and viral information has been obtained by new technologies such as virus isolation method, antigen and antibody assays, and molecular virology techniques including polymerase chain reaction amplification and in situ hybridization. However, since the viruses are ubiquitous, special attention will be required for evaluating an association between the results and disease condition.

Exanthema Subitum↗
PubMed1995

Physical dissociation of the TCR-CD3 complex accompanies receptor ligation.

Recent studies indicate that there may be functional uncoupling of the TCR-CD3 complex and suggest that the TCR-CD3 complex is composed of two parallel signal-transducing units, one made of gamma delta epsilon chains and the other of zeta chains. To elucidate the molecular mechanisms that may explain the functional uncoupling of TCR and CD3, we have analyzed their expression by using flow cytometry as well as immunochemical means both before and after stimulation with anti-TCR-beta, anti-CD3 epsilon, anti-CD2, staphylococcal enterotoxin B, and ionomycin. We present evidence that TCR physically dissociates from CD3 after stimulation of the TCR-CD3 complex. Stimulation with anti-CD3 resulted in down-modulation of TCR within 45 min whereas CD3 epsilon was still expressed on the cell surface as detected by flow cytometry. However, the cell surface expression of TCR and CD3 was not affected when cells were stimulated with anti-TCR-beta under the same conditions. In the case of anti-CD3 treatment of T cells, the TCR down-modulation appeared to be due to the internalization of TCR, as determined by immunoelectron microscopy. Immunochemical analysis of cells after stimulation with either anti-TCR or anti-CD3 mAbs revealed that the overall protein levels of TCR and CD3 were similar. More interestingly, the dissociation of the TCR-CD3 complex was observed with both treatments and occurred in a manner that the TCR and the associated TCR-zeta chain dissociated as a unit from CD3. These results provide the first report of physical dissociation of TCR and CD3 after stimulation through the TCR-CD3 complex. The results also suggest that the signal transduction pathway triggered by TCR may differ from that induced by CD3.

Animals↗
PubMed1995

Alteration in relative activities of phenylalanine dehydrogenase towards different substrates by site-directed mutagenesis.

Glycine-124 and leucine-307 of phenylalanine dehydrogenase from Bacillus sphaericus were altered by site-specific mutagenesis to the corresponding residues in leucine dehydrogenase: alanine and valine, respectively. These two residues have previously been implicated from molecular modelling as important in determining the substrate discrimination of the two enzymes. Single and double mutants displayed lower activities towards L-phenylalanine and enhanced activity towards almost all aliphatic amino acid substrates tested compared to the wild-type, thus confirming the predictions made from molecular modelling.

Amino Acid Oxidoreductases↗
PubMed1995

A novel type of cell death of lymphocytes induced by a monoclonal antibody without participation of complement.

A monoclonal antibody, RE2, raised by immunizing a rat with cell lysate of a mouse T cell clone, was found to directly kill interleukin 2-dependent T cell clones without participation of serum complement. Fab fragments of RE2 had no cytolytic activity, while the cross-linking of Fab fragments with anti-rat immunoglobulin reconstituted the cytotoxicity. The cytotoxicity was temperature dependent: the antibody could kill target cells at 37 degrees C but not at 0 degrees C. Sodium azide, ethylenediaminetetraacetic acid, and forskolin did not affect the cytolytic activity of RE2, while the treatment of target cells with cytochalasin B and D completely blocked the activity. This suggested that the cell death involves a cytoskeleton-dependent active process. Giant holes on the cell membrane were formed within 5 minutes after the treatment with RE2, as observed by scanning electron microscopy. There was no indication of DNA fragmentation nor swelling of mitochondria during the cytolysis, suggesting that the cell death is neither apoptosis nor typical necrosis. The antibody also killed T cell lymphomas and T and B cell hybridomas only when these cells were preactivated with concanavalin A, lipopolysaccharide, or phorbol myristate acetate. Preactivated peripheral T and B cells were sensitive to the cytotoxicity of RE2, while resting T and B cells were insensitive. These results provide evidence for a novel pathway of cell death of activated lymphocytes by membrane excitation.

Animals↗