Biomedical subjects
Y Asano
Publications and source records attributed to Y Asano.
[Utilization of a direct sandwich ELISA kit for rapid diagnosis of adenovirus hemorrhagic cystitis in a patient with adult T-cell leukemia].
We report on a case of adenovirus hemorrhagi cystitis that developed in a 49-year-old woman during intensive chemotherapy for adult T-cell leukemia. Although rapid etiologic diagnosis is essential for the effective management of viral hemorrhagic cystitis, the isolation of adenovirus from urine is often too time-cousuming. We detected the adenovirus antigen in the patient's urine using an Adenoclone direct sandwich ELISA kit (Cambridge Bio Science), which is commonly employed for the diagnosis of adenovirus conjunctivitis. Treatment consisted of intravenous vidarabine and bladder irrigation, which resulted in prompt clinical improvement. The Adenoclone kit was useful for the rapid etiologic diagnosis of adenovirus hemmorrhagic cystitis.
Up-regulation of integrin beta 3 expression by cyclic stretch in human umbilical endothelial cells.
The effect of uni-axial cyclic mechanical stretch on the expression of the adhesion protein integrin was investigated. Human umbilical endothelial cells (HUVECs) cultured on fibronectin coated silicon membranes were subjected to uni-axial cyclic stretch. The level of expression of integrin beta 3 mRNA was found to be increased and peaked at 4 hours in response to cyclic stretch using a semiquantitative RT-PCR method. The increased level of the integrin mRNA from stretched HUVECs remained higher than that from non-stretched controls. The amount of integrin beta 3 also increased and peaked at 12 hr. Immuno-fluorescent microscopy revealed that the amount of integrin beta 3 adhesions increased in stretched HUVECs compared with that in non-stretched HUVECs. These results suggest that uni-axial cyclic stretch up-regulates the expression of integrin beta 3. This increase in integrin beta 3 may enhance the adhesiveness to the substratum and contribute to the protection of HUVECs against being peeled off from the vessel wall.
[Progress on diagnosis and therapy of water-electrolyte imbalance--basic knowledge of acid-base equilibrium and arterial blood gas analysis].
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Effect of the chimeric soluble granulocyte colony-stimulating factor receptor on the proliferation of leukemic blast cells from patients with acute myeloblastic leukemia.
The biological roles of the soluble granulocyte colony-stimulating factor (G-CSF) receptor, which arises as a result of alternative RNA splicing, are as yet unknown. In this study, we examined the in vitro effect of a chimeric protein composed of the extracellular region of a murine G-CSF receptor and the human IgG1 Fc region because a human natural soluble G-CSF receptor was not available. First, we found that this chimeric soluble G-CSF receptor could inhibit the biological activity of G-CSF on normal bone marrow colony formation. Because G-CSF also plays an important role in the proliferation of leukemic blast cells, we next examined the effect of the soluble G-CSF receptor on leukemic blast colony formation in 10 acute myeloblastic leukemia cases. Although G-CSF stimulated the proliferation of leukemic progenitor cells to form leukemic blast colonies, the chimeric soluble G-CSF receptor completely inhibited this stimulatory effect. Furthermore, the chimeric soluble G-CSF receptor also inhibited spontaneous leukemic blast colony formation in two cases. Because a high concentration of G-CSF was observed in the supernatants of leukemic blast cells from these two cases, it seems likely that the soluble G-CSF receptor cut off the autocrine growth mechanism of leukemic blast cells mediated by G-CSF. These findings suggest the possibility that the soluble G-CSF receptor could be used in a clinical application for acute myeloblastic leukemia patients in the future.
Optical mapping of drug-induced polymorphic arrhythmias and torsade de pointes in the isolated rabbit heart.
OBJECTIVES: This study sought to 1) test the hypothesis that in the setting of bradycardia and drug-induced action potential prolongation, multiple foci of early afterdepolarizations (EADs) result in beat to beat changes in the origin and direction of the excitation wave front and are responsible for polymorphic arrhythmias; and 2) determine whether EADs may initiate nonstationary reentry, giving rise to the typical torsade de pointes (TDP) pattern. BACKGROUND: In the past, it has been difficult to associate EADs or reentry with the undulating electrocardiographic (ECG) patterns of TDP. METHODS: A voltage-sensitive dye was used for high resolution video imaging of electrical waves on the epicardial and endocardial surface of the Langendorff-perfused rabbit heart. ECG and monophasic action potentials from the right septal region were also recorded. Bradycardia was induced by ablation of the atrioventricular node. RESULTS: Perfusion of low potassium chloride Tyrode solution plus quinidine led to prolongation of the action potential and the QT interval. Eventually, EADs and triggered activity ensued, giving rise to intermittent episodes of polymorphic arrhythmia. In one experiment, triggered activity was followed by a long episode of vortex-like reentry with an ECG pattern characteristic of TDP. However, in most experiments, focal activity of varying origins and propagation patterns was observed. Triggered responses also showed varying degrees of local block. Similar results were obtained with E-4031. Burst pacing both at control conditions and in the presence of quinidine consistently led to vortex-like reentry whose ECG pattern resembled TDP. However, the cycle length of the arrhythmia with quinidine was longer than that for control ([mean +/- SEM] 194 +/- 12 vs. 132 +/- 8 ms, p < 0.03). CONCLUSIONS: Drug-induced polymorphic ventricular arrhythmias may result from beat to beat changes in wave propagation patterns initiated by EADs or EAD-induced nonstationary reentrant activity. In contrast, burst pacing-induced polymorphic tachycardia in the presence or absence of drugs is the result of nonstationary reentrant activity.
beta-Carotene effectively scavenges toxic nitrogen oxides: nitrogen dioxide and peroxynitrous acid.
beta-Carotene absorbed 2 equimolar amounts of NO2 accompanying the complete destruction of beta-carotene. Electron spin resonance study using 2-phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl revealed that no significant amounts of NO were released by the interaction. Nitrogen atoms derived from NO2 were tightly bound to the beta-carotene molecules. Destruction of beta-carotene was inhibited little by alpha-tocopherol and polyunsaturated fatty esters, and slightly by ascorbyl palmitate, indicating that beta-carotene was a more effective scavenger of NO2. ONOOH/ONOO- and 3-morpholinosydononimine similarly destroyed beta-carotene. The results suggest that beta-carotene contributes to the prevention of cytotoxicity and genotoxicity of NO2 and ONOOH/ONOO- derived from NO.
Scintigraphic evaluation along with CT and MR images in a case of huge gravitation abscess.
The authors presented a rare case of huge gravitation abscess. 67Ga scintigraphy was useful in the evaluation of the extent and activity of the disease. CT showed clearly the location and shape of the abscess. Enhanced MRI showed vertebral lesions as characteristic geographic and ring-like enhancement.
3-Methylaspartate ammonia-lyase as a marker enzyme of the mesaconate pathway for (S)-glutamate fermentation in Enterobacteriaceae.
The enzyme 3-methylaspartase (3-methylaspartate ammonia-lyase, EC 4. 3.1.2) was found in the cells of enteric bacteria, especially in the genera Citrobacter and Morganella, that were grown under anoxic and oxygen-limited conditions. The enzymes were purified to homogeneity from the cell-free extracts of 18 active strains and had similar enzymological properties such as action on columns, specific activity, molecular weight, subunit structure, and N-terminal amino acid sequence similarity. The production of the enzyme was dependent on the limitation of oxygen during growth and was arrested by aeration. The addition of external electron acceptors such as dimethylsulfoxide could support cell growth and production of the enzyme. Activities of glutamate mutase (EC 5.4.99.1) and (S)-citramalate hydrolyase (EC 4.2.1.34), key enzymes of the mesaconate pathway of (S)-glutamate fermentation in the genus Clostridium, were detected in the cells of the active strains grown under oxygen-limited conditions. Based on the results, the mesaconate pathway is proposed to explain the (S)-glutamate fermentation process observed in Enterobacteriaceae, and 3-methylaspartase could be a marker enzyme for this pathway.
The tumor-bearing state induces augmented responses of organ-associated lymphocytes to high-dose interleukin-2 therapy in mice.
A high-dose bolus regimen for interleukin(IL)-2 administration to cancer patients frequently causes serious side-effects in which various organs are involved. In order to reveal the mechanism of toxicities associated with this regimen, we compared the augmenting effect of high-dose IL-2 on murine organ-associated lymphocytes between neoplastic and non-neoplastic states. Intraperitoneal administration of IL-2 at a dose of 10(5) JRU (Japanese Reference Units) twice daily for 3 days led to the death of all the syngeneic MH134-hepatoma- or X5563-myeloma-bearing mice, whereas it had no lethal effect on non-tumor-bearing mice. Histological and morphometric analyses demonstrated that tumor-bearing mice displayed more extensive infiltration of large granular lymphocytes and agranular lymphocytes in the liver and lungs than did the non-tumor-bearing mice. Large granular lymphocytes had the ultrastructural characteristics of lymphokine-activated killer cells. Lymphocytes often underwent extravasation into the interstitial space and exhibited local proliferation without causing any direct injury to apposed parenchymal cells. Flow-cytometric analysis of hepatic mononuclear cells demonstrated that IL-2-receptor-beta (IL-2R beta)-bearing lymphocytes, i.e., natural killer cells and intermediate CD3 cells, were increased in number in the neoplastic state before the IL-2 injection. The present study indicates that the tumor-bearing state increases the number of organ-associated IL-2R beta + lymphocytes, which are then greatly amplified by the challenge of high-dose IL-2, leading to the functional disturbance of organs. We have further demonstrated here that an intermittent low-dose IL-2 regimen has a potential therapeutic effect on tumor regression without causing lethal side-effects.
A low-Na+ diet enhances expression of mRNA for epithelial Na+ channel in rat renal inner medulla.
The purpose of the present study was to determine whether the renal inner medulla expresses mRNA for the rat epithelial Na+ channel (rENaC) and, if so, to define its regulatory properties using a low-Na+ diet model. We detected alpha, beta and gamma subunit mRNA in rat renal inner medulla using reverse transcriptase-polymerase chain reaction (RT-PCR) with primers specific for rENaC alpha, beta and gamma subunits. Moreover, we have developed a specific probe for the alpha subunit using RT-PCR with rENaC alpha-subunit-specific primers. The resulting cDNA was verified by sequencing and was then used in Northern blot analysis of distal colon, whole kidney and inner medulla. The probe for the rENaC alpha subunit hybridized not only to distal colon RNA but also to inner medulla RNA derived from rats fed a normal diet. Furthermore, we examined the effect of a low-Na+ diet on alpha, beta and gamma subunit mRNA expression of rENaC using full-length cDNA as a probe. A marked elevation of rENaC alpha subunit mRNA abundance in the inner medulla was observed in response to a high plasma aldosterone concentration induced by dietary Na+ deprivation. On the other hand, neither beta nor gamma subunit mRNA expression was enhanced by a low-Na+ diet. From these results, it is suggested that rENaC is responsible for Na+ transport in the renal inner medulla and that is probably regulated via transcriptional control of the alpha subunit of ENaC.
Precordial leads QRST time integrals for evaluation of right ventricular overload in children with congenital heart diseases.
It was previously shown that body surface QRST isointegral maps of the anterior chest were abnormal in patients with right ventricular overload and that the abnormalities varied with hemodynamic status. The QRST isointegral maps were first characterized by using a departure index map for normal controls. The study group consisted of 14 patients with pulmonary stenosis (PS), 20 with tetralogy of Fallot, (TOF) and 43 with atrial septal defect (ASD). The QRST isointegral maps of these three groups were compared with the data on 23 to 65 age-matched normal children. In mean departure index maps, the patients with right ventricular pressure overload (PS or TOF) showed an increase in departure index on the anterior midchest, while those of right ventricular volume overload (ASD) showed two maxima on the anterior and left lateral chest, with a trough-like negative area between them. Since the abnormal findings were seen on the anterior chest, we evaluated the diagnostic usefulness of QRST time integral values for precordial leads of the routine electrocardiogram (ECG) in a second part of this study. The precordial QRST time integral values from 9 patients with PS and 11 with TOF (0-2 years of age, mean 1.1 years) and 22 ASD patients (6-15 years, mean 10.1 years) were compared with those of the age-matched control children. The QRST time integral values of the precordial leads in right ventricular pressure overload were significantly increased in the right precordial leads (V1, V2). In right ventricular volume overload, the QRST time integral values of the V1, V2, V4, and V6 leads demonstrated a significant deviation from those of the control group. Therefore, a discrimination formula was constructed by using the values of these leads, and the criteria derived from this formula revealed good (98%) diagnostic accuracy. In detection of right ventricular overload, the QRST time integral values of the precordial lead ECG, if confirmed in a larger data set, may be useful as a simple screening method.
Effect of (-)-epigallocatechin gallate on leukemic blast cells from patients with acute myeloblastic leukemia.
Information on the anti-carcinogenic effect of EGCG, the main constituent of the polyphenols present in Japanese green tea leaves, has recently been accumulating. In this report, we evaluate the effect of EGCG on leukemic blast cells from AML patients. The results showed that EGCG inhibited the proliferation of AML cells in all cases examined. Since AML cells might proliferate by autocrine or paracrine growth mechanisms, we also examined the effect of EGCG on the production of GM-CSF from AML cells. Although EGCG did not directly inhibit the production of GM-CSF, it did inhibit the effect of TNF-alpha or TPA, both of which stimulated AML cells to produce GM-CSF. On the other hand, the modulation of receptors for growth factors might play a role in the proliferation or carcinogenesis of AML cells. We also found that EGCG inhibited the modulation of c-kit, a receptor for stem cell factor, on leukemic cells. These findings suggested that EGCG might be available as a new therapeutic tool for AML patients.
Interleukin-10 inhibits the autocrine growth of leukemic blast cells from patients with acute myeloblastic leukemia.
The effect of interleukin-10 (IL-10) on the growth of leukemic blast cells from patients with acute myeloblastic leukemia (AML) is in need of clarification. We therefore examined the effect of IL-10 on AML cells obtained from 10 patients. Although granulocyte colony-stimulating factor (G-CSF) and/or granulocyte/macrophage colony-stimulating factor (GM-CSF) was able to stimulate the growth of AML progenitor cells to form leukemic blast colonies, IL-10 itself demonstrated no leukemic blast colony-forming activity and no synergistic stimulating activity with other cytokines. However, leukemic blast colonies were formed without the addition of exogenous cytokines in four cases and IL-10 suppressed these spontaneous colony formations in two of the four cases. Since the production of G-CSF and GM-CSF was observed in these two cases, the presence of an autocrine growth mechanism mediated by these cytokines was suggested. When serial concentrations of IL-10 were added, the production of G-CSF and GM-CSF was dramatically inhibited in a dose-dependent manner. These findings suggested that IL-10 could suppress the autocrine growth of AML cells by inhibiting their production of G-CSF and/or GM-CSF. In addition, the administration of IL-10 may be harmless to normal hematopoiesis because IL-10 did not suppress the growth of normal hematopoietic progenitor cells. Our study provides experimental support for the clinical application of IL-10 in patients with AML.
Multistage regulation of Th1-type immune responses by the transcription factor IRF-1.
Eradication of a given pathogen is dependent on the selective differentiation of T helper (Th) cells into Th1 or Th2 types. We show here that T cells from mice lacking the transcription factor IRF-1 fail to mount Th1 responses and instead exclusively undergo Th2 differentiation in vitro. Compromised Th1 differentiation is found to be associated with defects in multiple cell types, namely impaired production of interleukin-12 by macrophages, hyporesponsiveness of CD4+ T cells to interleukin-12, and defective development of natural killer cells. These results indicate the involvement of IRF-1 in multiple stages of the Th1 limb of the immune response.
Relationship between a low toxicity of the mutant A subunit of enterotoxigenic Escherichia coli enterotoxin and its strong adjuvant action.
In the work described here it was determined if and how unnicking in the A subunit of Escherichia coli enterotoxin at Arg192 or nearby residues affected biological activities of the toxin. The mutant toxin was constructed to lack the nick site in the A subunit by deleting the tripeptide Arg192-Thr193-Ile194, which is essential for toxicity. The mutant toxin did not exhibit agmatine ADP-ribosyltransferase activity in the presence or absence of the ADP-ribosylation factor and had less diarrhoeal activity and lower induction of cyclic AMP than did LT. The mutant toxin exhibited a much stronger adjuvant action on antibody responses to measles virus, keyhole limpt haemocyanin, bovine immunoglobulin and ovalbumin compared with LT. The altered toxicity of the mutant toxin might be closely related to the potent adjuvant action on antibody responses to antigens. The relationship between two activities is discussed.