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Biomedical subjects

Y Asano

Publications and source records attributed to Y Asano.

At least 289 records · Page 16Linked to original sources

Early viral complications following CD34-selected autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

A patient with non-Hodgkin's lymphoma who received a CD34-selected autologous peripheral blood stem cell transplant (PBSCT) developed cytomegalovirus retinitis, adenovirus-associated haemorrhagic cystitis (HC) and fatal herpes simplex virus pneumonia. Depletion of mature T cells from the graft and a persistent decrease in CD4+ lymphocytes following PBSCT may have predisposed this patient to such viral infections. Infusion of cryopreserved autologous PBSC (containing mature T cells) was effective for adenovirus-associated HC. Immunosuppression and resultant viral infections may affect patients receiving CD34-selected autologous transplantation.

Adenoviridae Infections↗

Action of interleukin-3 on the proliferation of leukaemic progenitor cells from patients with acute myeloblastic leukaemia.

In the present study, we examined the effects of interleukin-3 (IL-3) on the proliferation of leukaemic progenitor cells from 11 Japanese patients with acute myeloblastic leukaemia (AML), including the effect of its combination with granulocyte/macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF). The results showed that IL-3 sufficiently stimulated the proliferation of AML progenitor cells in almost all the cases examined, and that the stimulation pattern of IL-3 was similar to that of GM-CSF, although different from that of G-CSF. Furthermore, IL-3 worked synergistically with G-CSF, whereas IL-3 and GM-CSF together were less actively synergistic (P < 0.05). These findings suggest the possibility of IL-3/G-CSF/cytosine arabinoside (Ara-C) combination therapy, which may be able to enhance the cytotoxic effect of Ara-C on AML progenitor cells powerfully in a wider range of patients including cases refractory for IL-3/Ara-C combination therapy.

Adolescent↗

Corticosterone and 11-dehydrocorticosterone stimulate Na,K-ATPase gene expression in vascular smooth muscle cells.

BACKGROUND: In mineralocorticoid target tissues such as kidney and colon, the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta OHSD) catalizes the reversible conversion of corticosterone (CS) to inactive 11-dehydrocorticosterone (DHCS) in rats, and cortisol to inactive cortisone in humans. This enzyme is also expressed in vascular smooth muscle cells (VSMC). METHODS: In cultured VSMC from rat thoracic aortae, we examined the effects of CS and DHCS on Na,K-ATPase alpha 1- and beta 1-mRNA accumulation by Northern blot analysis, on alpha 1- and beta 1-subunit protein accumulation by Western blot analysis, and on Na,K-ATPase activity by the coupled assay method. RESULTS: In VSMC, CS and DHCS (10(-6) M) increased alpha 1-mRNA level 2.6- and 2.5-fold at 48 hours and beta 1-mRNA level 9.2- and 9.1-fold at 12 hours, respectively. The RNA transcription inhibitor (actinomycin D) abolished both CS- and DHCS-mediated alpha 1- and beta 1-mRNA induction. The glucocorticoid receptor antagonist (RU38486) and the mineralocorticoid receptor antagonists (ZK91587) inhibited both CS- and DHCS-mediated alpha 1- and beta 1-mRNA induction. The 11 beta OHSD inhibitor (carbenoxolone) inhibited DHCS-mediated alpha 1- and beta 1-mRNA induction, whereas it caused no effect on CS-mediated alpha 1- or beta 1-mRNA induction. The addition of CS or DHCS to VSMC significantly increased alpha 1- and beta 1-subunit protein levels and Na,K-ATPase activity. When adrenalectomized rats were treated with CS or DHCS for 12 hours, aorta alpha 1- and beta 1-mRNA levels increased 3.0- and 8.7-fold or 3.4- and 8.4-fold, respectively. CONCLUSIONS: In VSMC, both CS and DHCS stimulate Na,K-ATPase alpha 1- and beta 1-mRNA accumulation, alpha 1- and beta 1-subunit protein accumulation, and Na,K-ATPase activity. The CS-mediated alpha 1- and beta 1-mRNA induction occurs independently of 11 beta OHSD, whereas the DHCS-mediated alpha 1- and beta 1-mRNA induction occurs through 11 beta OHSD-dependent mechanisms, possibly via conversion of inactive DHCS into active CS.

Animals↗

Fas/Fas ligand and hematopoietic progenitor cells.

Fas antigen is a receptor that crosslinks with a ligand or antibody initiating a signal transduction cascade that leads to apoptosis. During normal hematopoiesis, Fas antigen is not expressed on CD34+ cells, including premature hematopoietic progenitor cells. Functioning Fas antigen expression is induced by several hematopoietic regulators. These changes may appear not only in the process of differentiation of hematopoietic progenitor cells, but also as a negative feedback mechanism that controls chaotic proliferation of these cells. These findings suggest that the Fas/Fas ligand system is closely related to the maintenance of homeostasis during the process of normal hematopoiesis. Furthermore, increased Fas antigen expression is observed on CD34+ cells from patients with aplastic anemia, suggesting that it might cause bone marrow suppression. The use of Fas-mediated apoptosis of malignant cells as a tool for eliminating hematologic malignancies is promising. Increased Fas ligand expression is observed on natural killer lymphoma cells and may be associated with the pathogenesis of failure of several organs. The Fas/Fas ligand system plays an important role in the physiologic and pathologic processes of hematopoiesis. The development of treatments using this system are forthcoming.

Antigen-Antibody Reactions↗

Five cases of thrombocytopenia induced by primary human herpesvirus 6 infection.

Five patients suffering from exanthem subitum with thrombocytopenia were confirmed as primary human herpesvirus 6 (HHV-6) infection by serological test. All cases had thrombocytopenia during the acute phase of exanthem subitum. The clinical features of these cases were benign, and all recovered without any specific treatment. Moreover, 4 of the 5 cases showed a mild elevation of hepatic transaminase during the same period, and other viral infections including cytomegalovirus, Epstein-Barr virus, and human herpesvirus 7 were ruled out in these patients. It was speculated that direct inhibition of platelet production by the virus or cytokine induced by the virus-infected cells was the mechanism of the thrombocytopenia induced by primary HHV-6 infection.

Acute Disease↗

NER rat strain: a new type of genetic model in epilepsy research.

PURPOSE: We characterized and evaluated as an animal model of epilepsy NER, a new epileptic rat strain, which was developed by inbreeding rats with spontaneous tonic-clonic seizures in a stock of Crj:Wistar. METHODS: Animals were monitored through the inbreeding course, and video-EEGs were recorded selectively. External seizure-provoking stimuli were applied to NER and to a control parental strain. F1, F2, and backcross progenies were produced between NER and a nonepileptic unrelated strain. Pathologic study included hematoxylin-and-eosin (HE), Klüver-Barrera's, modified Bodian silver, and neo-Timm's staining. RESULTS: After the F9 generation, 94%-98% of NER exhibited spontaneous tonic-clonic convulsions, beginning with neck and forelimb clonus, wild jumping/running, opisthotonic posturing, and evolving to tonic, then clonic convulsion, followed by postictal flaccidity. Most seizure onsets occurred between 2-4 months of age, and the incidence was 0.45 +/- 0.21 seizures in 12 h. Ictal cortical and hippocampal EEGs were characterized by high-voltage spikes followed by diffuse spike-and-wave or polyspike-and-wave complexes. NER revealed seizure susceptibility to pentylenetetrazol, tossing, and transcorneal electroshock, but not to tactile, photic, or acoustic stimuli, or to transauricular electroshock. Mating experiments revealed that 0% (0/46) of the animals in F1, 25.5% (13/51) in F2, and 63.6% (56/88) in backcross progenies exhibited spontaneous tonic-clonic convulsions without sex difference. For all these epileptic traits, no pathologic changes were demonstrated in the CNS. CONCLUSIONS: NER frequently exhibited spontaneous convulsions, controlled by a major autosomal recessive gene for epilepsy, that are comparable to generalized tonic-clonic seizures in humans. This can serve as a new genetic model in epilepsy research.

Animals↗

Analysis of the granulocyte colony-stimulating factor receptor gene structure using PCR-SSCP in myeloid leukemia and myelodysplastic syndrome.

The membrane-proximal cytoplasmic region of the granulocyte colony-stimulating factor receptor (G-CSFR) is known to be essential for the proliferation signal, with a more distal region being required for the differentiation signal. Such a separation of functional domains raises the possibility that mutations occurring at these regions may contribute to cell proliferation in the absence of differentiation, this being the most important characteristic in acute leukemia cells. Therefore, we analysed the structural abnormalities at the transmembrane and cytoplasmic region of G-CSFR in a significant number of patients with various myeloid malignancies. When we examined the genomic DNA of G-CSFR obtained from 41 patients with acute myelogenous leukemia (AML), 18 with chronic myelogenous leukemia (CML), 7 with myelodysplastic syndrome (MDS), 2 with chronic myelomonocytic leukemia and 1 with chronic neutrophilic leukemia, we found a polymorphism in 3 patients, but no significant pathogenic mutations in any patients. The screening for this polymorphism in 100 hematologically normal controls revealed that it may be useful as a linkage marker for population and family studies, because the heterozygosity index is at a high level (0.055). While there have been several reports discussing the leukemogenic potential of mutations in the cytokine/hematopoietin receptor superfamily, genetic alterations in the transmembrane and cytoplasmic region of G-CSFR do not seem to play a pathogenic role in leukemia.

Humans↗

Persistence of protective immunity after postexposure prophylaxis of varicella with oral aciclovir in the family setting.

The persistence of protective immunity after postexposure prophylaxis against varicella using oral aciclovir was evaluated in the family setting. Sixty one of 78 recipients of oral aciclovir were assessed by questionnaire, and 13 of 61 were evaluated for serum antibody to varicella zoster virus (VZV) using the fluorescent antibody to membrane antigen method. The observation period ranged from 33 to 50 months. None of those (n = 44) who had initially seroconverted to VZV after aciclovir prophylaxis developed breakthrough varicella. All 13 who had serology repeated still had titres > or = 4. Antibody titres in those who had histories of re-exposure to the virus were significantly higher than in those who had not (p < 0.01).

Acyclovir↗

Effect of cross-linked hemoglobin transfusion on endothelial-dependent dilation in cat pial arterioles.

We determined whether addition of hemoglobin to the plasma would inhibit endothelial-dependent dilation in brain where tight endothelial junctions limit hemoglobin extravasation. Pial arteriolar diameter was measured by intravital microscopy through closed cranial windows in anesthetized cats either without transfusion (hematocrit = 32%) or after exchange transfusion with an albumin or sebacyl-cross-linked human hemoglobin solution (hematocrit = 18%). Dilation of small, medium, and large arterioles to acetylcholine and ADP was not significantly altered by hemoglobin transfusion. The dilatory responses were inhibited by the nitric oxide synthase inhibitor NG-nitro-L-arginine, although significant dilation to 30 microM acetylcholine persisted in small arterioles in the control and albumin-transfused group but not in the hemoglobin-transfused group. The dilatory response to the nitric oxide donor 3-morpholinosydnonimine was unaffected by albumin or hemoglobin transfusion, but the response to nitroprusside was reduced by one-third after hemoglobin transfusion. When cross-linked hemoglobin was superfused through the cranial window, the acetylcholine response became inhibited at a hemoglobin concentration of 0.1 microM and was completely blocked at 10 microM. Because this concentration is substantially less than the 500 microM hemoglobin concentration in plasma after transfusion when there was no inhibition of the acetylcholine response, hemoglobin permeation of the blood-brain barrier was considered negligible. We conclude that exchange of red cell-based hemoglobin with plasma-based hemoglobin does not produce a more effective sink for endothelial-derived nitric oxide evoked by agonist receptor-mediated activation. Furthermore, decreased hematocrit does not affect agonist-evoked endothelial-dependent dilation.

Acetylcholine↗

Atrial natriuretic peptide enhances IL-1 beta-stimulated nitric oxide production in cultured rat vascular smooth muscle cells.

OBJECTIVE: To elucidate the effect of atrial natriuretic peptide (ANP) on cytokine-induced nitric oxide (NO) production, we examined whether ANP affects IL-1 beta-stimulated NO production and inducible NO synthase (iNOS) mRNA expression in cultured rat vascular smooth muscle cells (VSMC). METHODS: VSMC were incubated with test agents for 24 h. The nitrite concentration of the culture medium, a stable-end product of NO, was measured by the column reduction method. NOS mRNA expression was analyzed by Northern blotting. The intracellular cAMP content was measured by enzyme immunoassay. cAMP-dependent kinase (PKA) activity was determined by a PKA assay system. RESULTS: IL-1 beta stimulated nitrite production in VSMC. ANP (10 nM to 1 mM) enhanced the nitrite production and iNOS mRNA expression in the presence of IL-1 beta. Both 8-bromo-guanosine 3',5'-cyclic monophosphate (8-br-cGMP) and dibutylyl adenosine 3',5'-cyclic monophate enhanced IL-1 beta-induced nitrite production. The effects of these two nucleotide donors on the nitrite production were not additive, suggesting a common pathway. KT 5720, an inhibitor of PKA, abolished the enhancement of nitrite production by ANP and 8-br-cGMP, while KT 5823, an inhibitor of cGMP-dependent protein kinase, did not inhibit the enhancement. In the in vitro assay 8-br-cGMP increased PKA activity. CONCLUSIONS: ANP and cGMP enhanced IL-1 beta-induced NO production in VSMC. PKA rather than PKG may be involved in the enhancement.

Animals↗

Haematological and serum biochemical values in spontaneously epileptic male rats and related rat strains.

Haematological and serum biochemical measurements in male spontaneously epileptic rats (SER; double mutants homozygous for zitter and tremor genes) were compared with the values for related rat strains. Some haematological values were low in TRM rats and total leukocyte counts were high in ZI and TRM rats. TRM rats showed higher total cholesterol, phospholipid, high-density lipoprotein cholesterol and calcium values, and lower albumin value than Kyo: Wistar rats. Zitter homozygous rats including SER exhibited low total cholesterol, phospholipid and high-density lipoprotein cholesterol values. The SER showed an increase in urea nitrogen, aspartate aminotransferase and alanine aminotransferase values, and a decrease in glucose value, suggesting deterioration of the whole body with age.

Animals↗

Non-dipolarity of heart potentials estimated by magnetocardiography in normal subjects.

We studied non-dipolarity characteristics during ventricular excitation in normal adults and children by magnetocardiography (MCG) by recording magnetic field on the thorax. The source and currents of the electrical dipole from the onset up to 60 ms of ventricular excitation were analyzed in 16 adults and 5 children. A single equivalent current dipole (ECD) was estimated by Sarvas' formula for the sphere model at 1 ms intervals. The non-dipole value (NDV) was calculated from the magnetic field strength at each recording point and theoretically estimated by ECD, representing an index for the non-dipolarity. At 32-34 ms from the beginning of QRS, the mean NDV was a minimum in all subjects suggesting at least a non-dipole component during this period. High NDV (over 5%) were present in most subjects in both the early and late phase compared to this period. Thirteen of 16 adults had a high NDV in the early phase (9.3 +/- 3.0%, mean +/- SD) and all 16 subjects had a high NDV in the late phase (21.5 +/- 10.5%). All 5 children had high NDV in both the early (10.5 +/- 5.4%) and late phases (16.8 +/- 7.9%). A single ECD estimation by MCG showed a relatively low non dipolar component and MCG could be applied to the clinical evaluation of cardiac excitation in both normal and pathological conditions.

Adult↗

Prospective study of persistence and excretion of human herpesvirus-6 in patients with exanthem subitum and their parents.

OBJECTIVE: To elucidate persistence of human herpesvirus-6 (HHV-6) in the blood and excretion of the virus into several body fluids of patients with exanthem subitum (ES), and to examine serologic and virologic findings of the parents caring for the patients in the family setting. MATERIALS AND METHODS: During a 15-month period, 20 infants from 20 families (11 boys and 9 girls; mean age, 7.7 months; range, 4-11 months) with primary HHV-6 infection and a typical clinical course of ES, and 15 parents from the 20 families (2 males and 13 females; mean age, 28.2 years; range, 21-34 years) were enrolled in the study and examined clinically and virologically. Primary infection with HHV-6 was confirmed by isolation of the virus from peripheral blood mononuclear cells (MNCs), and seroconversion or a significant increase in the antibody titers to HHV-6 by a neutralization test. Viral persistence or excretion was examined by amplifying the viral deoxyribonucleic acid (DNA) in serially collected peripheral blood MNCs, plasma, saliva, stool, and urine samples with a nested polymerase chain reaction method. Data on saliva from the parents were compared with those of 21 age-matched controls. RESULTS: Twenty infants with virologically confirmed ES had HHV-6 DNA in MNCs persistently during and after the disease but in plasma only in the first 5 days of ES. The viral DNA was also detected persistently or intermittently in saliva and stool during and after the disease but rarely in urine. On the other hand, the 15 parents examined of the 20 infants had no HHV-6 viremia nor viral DNA in peripheral blood MNCs and plasma except 1, but half of them excreted viral DNA in saliva during and after ES. The frequency of excretion of viral DNA into saliva was not significantly different from that of 21 control parents. Only 1 of the 15 showed a fourfold increase in antibody titers to HHV-6 after possible exposure from their children. CONCLUSIONS: After systemic replication of HHV-6 in the blood of patients with ES during the first 5 days of the disease, the virus is excreted into saliva and stool persistently or intermittently but rarely into urine. The presence of HHV-6 DNA in plasma suggested active infection with the virus. Excretion of the virus into the saliva of infants with ES and their parents suggests the source and transmission route of infection with HHV-6.

Adult↗

Color-coded Doppler imaging of subclavian steal syndrome.

We examined the usefulness of color-coded Doppler echography for evaluating hemodynamics in patients with subclavian steal syndrome. Eighteen patients with subclavian steal syndrome, aged 54 to 77 years, were investigated. The diagnosis was confirmed by conventional angiography and pulsed-wave Doppler sonography. Using color-coded Doppler echography, the common, internal and external carotid and vertebral arteries and the subclavian artery on the affected side were visualized. In all patients, color-coded images of the antegrade common carotid arterial flow and the retrograde vertebral arterial flow on the affected side were obtained. Rapid flow through stenotic lesions and reflux from vertebral to subclavian arteries at the vertebral arterial ostia were observed. Color-coded Doppler echography is superior to duplex echography without the color-coded mode, because the flow through the affected vertebral and subclavian arteries can be easily traced in detail and the images are persuasive. This method is beneficial for diagnosing subclavian steal syndrome.

Aged↗

Trans-activating activity of the E6 proteins of the human papillomavirus (HPV) type-11 and -16 on the PE1E4 promoter of HPV-11 in C33A cells.

We investigated trans-activating effects of the full-length E6 protein of HPV-16 (16E6) and the E6 protein of HPV-11 (11E6) on the PE1E4 promoter of HPV-11 in C33A cells which lack normal function of p53. 16E6 showed no significant activation of the reporter plasmid containing PE1E4 and the upstream sequence, including the long control region (LCR). In contrast, 11E6 activated the promoter in a dose dependent manner, while relatively high doses of 11E6 were required to activate the promoter. When a reporter plasmid, which lacked LCR was used, however, both 16E6 and 11E6 activated the promoter, though high doses of 16E6 suppressed activity. Using deletion plasmids we further showed that 11E6 activated transcriptions from any mutant reporter plasmids as far as the constructs have promoter activities. Finally, we showed that 11E6 enhanced the expression levels of c-fos protein by infection of C33A cells with 11E6-expressing recombinant adenovirus. These findings suggested that E6 proteins of both HPVs would induce similar protein(s) which is required for an efficient transcription of minimum promoter of viral and cellular genes, and that the 16E6 induce additional protein(s) which suppress PE1E4 in the presence or absence of LCR.

Base Sequence↗

[Clinical features of primary HHV-6 and HHV-7 infections].

Human herpesvirus-6 (HHV-6), a T-lymphotropic herpesvirus, belongs to one of two variants, A or B (HHV-6A and HHV-6B). HHV-6B is the cause of exanthem subitum (ES) which had a wide spectrum of related illnesses in the central nervous system, gastrointestinal tract, respiratory tract, and blood cells including fatal outcome, however, a clear etiologic role has not been identified for HHV-6A. HHV-6 is ubiquitous and primary infection with the virus almost always occurs before the age of 2 years. On the other hand, human herpesvirus-7 (HHV-7), isolated from CD4+ T lymphocytes from the peripheral blood of a healthy individual has been recognized as a new lymphotropic herpesvirus. The virus was distinct from the six previously identified human herpesviruses and had limited homology to human cytomegalovirus and HHV-6 by both molecular and immunological analyses. Healthy adults frequently shed the virus into saliva, and children are infected at a young age but somewhat later than HHV-6B. The primary infection with HHV-7 is linked to febrile illness with or without rash that resembles ES. A consensus is needed on whether the term should be used only for clinical features by primary infection with HHV-6 or for clinical syndromes featuring febrile exanthem by various infectious agents including HHV-6, HHV-7, enteroviruses, etc.

Adult↗