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Biomedical subjects

Y Ohno

Publications and source records attributed to Y Ohno.

At least 235 records · Page 13Linked to original sources

Effects of neuroamines and divalent cations on cloned and mutated ATP-gated channels.

Sensitivities to dopamine, 5-hydroxytryptamine, Zn2+ and Cd2+ were studied in P2X1, P2X2, P2X3 and P2X4 purinoceptors and mutants of P2X2 purinoceptors expressed in Xenopus oocytes. Dopamine (10 and 100 microM) and 5-hydroxytryptamine (1 to 100 microM) enhanced the inward current activated by extracellular ATP through P2X2 and P2X4 purinoceptors. Zn2+ (1 to 100 microM) and Cd2+ (10 microM to 1 microM) enhanced the current through P2X2 purinoceptors. As for P2X4 purinoceptors, the ATP-activated current was, however, enhanced after the washout of Zn2+ (100 microM) or Cd2+ (1 mM). Three mutants of P2X2 purinoceptors were constructed by substituting negatively charged amino-acid residues. The magnitude of the enhancement by Zn2+, Cd2+ and dopamine was attenuated when Asp221 was replaced by histidine. The results suggest that dopamine, Zn2+ and Cd2+ require some common motif for the current enhancement.

Adenosine Triphosphate↗

Multivariate evaluation of prognostic determinants for renal cell carcinomas which are metastatic at initial diagnosis.

To clarify the relative importance of clinicopathological factors potentially affecting the survival of individuals initially diagnosed as having metastatic renal cell carcinoma (RCC), univariate and multivariate analyses using Cox's proportional hazards model were performed for 111 RCC patients who were admitted to four hospitals in Nagoya, Japan, between 1978 and 1993. Survival time was calculated from the date of diagnosis to the date of death or the end of May, 1995. Nineteen factors (17 clinically applicable before treatment and 2 histological in nature) were included for assessment. Univariate analysis revealed that 10 of the total 19 factors were significantly associated with patient survival. Multivariate analysis found 7 factors to be statistically significant determinants. Survival was further evaluated by categorizing the patients into three groups according to the number of the 7 factors. These groups showed clearly different survivals (log-rank test, p < 0.0001), confirming the importance of the 7 factors as definite determinants. They should therefore prove to be of advantage for classifying metastatic RCC patients when designing clinical prospective studies of immunotherapy and chemotherapy.

Adult↗

Effects of perospirone (SM-9018), a potential atypical neuroleptic, on dopamine D1 receptor-mediated vacuous chewing movement in rats: a role of 5-HT2 receptor blocking activity.

We compared the acute and subacute effects of perospirone (SM-9018), a novel neuroleptic with potent 5-HT2 and D2 blocking actions, and of haloperidol (HAL) on dopamine D1 receptor-mediated vacuous chewing movement (VCM) in rats. A selective D1 agonist, SKF 38393 (SKF), markedly increased the incidence of VCM, which was blocked by SCH 23390 (a D1 antagonist) but not by sulpiride (a D2 antagonist). Perospirone and HAL inhibited the SKF-induced VCM in a dose-dependent manner. The potency of the inhibitory actions of perospirone was considerably weaker (about 30 times) than that of HAL despite their similar affinities for D1 receptors. Subacute treatment with perospirone for 2 weeks failed to affect the behavioral sensitivity of rats to SKF. However, the HAL treatment markedly enhanced the incidence of the SKF-induced VCM. On the other hand, the selective 5-HT2 antagonists ritanserin and ketanserin significantly reduced the inhibitory actions of HAL and SCH 23390 on the SKF-induced VCM. In addition, combined treatment of ritanserin with HAL for 2 weeks abolished the enhancement of SKF-induced VCM by HAL treatment. These findings suggest that perospirone is weaker than HAL in altering the behavioral sensitivity of D1 receptor-mediated VCM under repeated administration, which may be related to the 5-HT2 blocking activity of perospirone.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Platelet activating factor compromises airway epithelial defense functions.

BACKGROUND: The mechanism of disruption of the epithelial defense function observed in asthmatic airways is considered to be largely the result of mediators involved in allergic responses. Platelet activating factor (PAF) might be a key mediator involved in this mechanism. OBJECTIVE: This study was designed to determine whether PAF is capable of compromising the epithelial defense functions, such as tight junctional barriers and the mucociliary system. METHODS: A total of 120 healthy rabbits were used. Twenty of them were used as normal controls. Eighty rabbits were treated with inhalation of 10 ml of PAF (200 microg/ml), and 20 animals were used for the examination of epithelial defense functions of the trachea at 1, 10, 20, and 30 days after inhalation of PAF. Epithelial defense functions of the trachea were evaluated by ciliary activity, mucociliary transport velocity, epithelial permeability to fluorescein isothiocyanate dextrans (70,000 d), and electron microscopy of the epithelial structure. RESULTS: PAF inhalation induced a significant decrease in ciliary activity and mucociliary transport velocity, which persisted for up to 20 days. PAF inhalation also caused a significant 7.4-fold increase in epithelial permeability to fluorescein isothiocyanate dextrans at I and 10 days. This increased epithelial permeability returned to the normal level 20 days after PAF inhalation. However, electron microscopy demonstrated no apparent evidence of epithelial shedding. CONCLUSIONS: PAF-induced prolonged dysfunction of both the epithelial junctional barrier and the mucociliary system may allow enhanced entry of allergen molecules, as well as bronchoactive agonists to the airway parenchyma and may also significantly contribute to an increased airway responsiveness.

Administration, Inhalation↗

Epidemiological features of moyamoya disease in Japan: findings from a nationwide survey.

To estimate an annual number of patients treated for Moyamoya disease in Japan and to describe the clinico-epidemiological features, a nationwide epidemiological survey was conducted in 1995. The study consisted of two questionnaires, which were distributed to departments randomly selected, of neurosurgery, neurology and pediatrics in hospitals throughout Japan. The first questionnaire inquired the number of the patients treated in 1994 and the second one detailed clinico-epidemiological information of each patient reported. Following major epidemiological findings emerged from the study: (a) The total annual number of patients treated for Moyamoya disease was estimated as 3900 (95% confidence interval (CI) 3500-4400) in Japan 1994, with the prevalence and incidence rates of 3.16 and 0.35 per 100,000 population, respectively; (b) the sex ratio (females to males) of the patients was 1.8; (c) the peak of age distribution of the patients was observed in 10-14 years old and a smaller peak in their forties; (d) the age at onset was under 10 years old in 47.8% of the patients, but some had developed the disease at the age of 25-49 years; (e) family history of Moyamoya disease was found in 10.0% of the patients; and (f) about 75% of the patients had normal activity of daily life or working ability even before treatment. The present findings were quite comparable with those obtained in the previous nationwide epidemiological survey in 1990.

Adolescent↗

Selective depression of the spinal polysynaptic reflex by the NMDA receptor antagonists in an isolated spinal cord in vitro.

1. The effects of N-methyl-D-aspartate (NMDA) receptor glycine-binding site antagonists 7-chlorokynurenate (7-Clkyn) and (+/-)-3-amino-1-hydroxy-2-pyrrolidone (HA-966) on spinal reflexes in an isolated spinal cord that was maintained in Mg(2+)-free medium in vitro were examined. The actions of 7-Clkyn and HA-966 were compared with those of the channel-site antagonist (i.e., dizocilpine) and NMDA-binding site antagonists--that is, 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonate (CPP) and DL-2-amino-5-phosphonovalerate (APV). 2. 7-Clkyn and HA-966 produced a selective depression of the polysynaptic reflex (PSR) while negligibly affecting the activity of the monosynaptic reflex (MSR). The PSR was also differentially suppressed by dizocilpine, CPP and APV. The PSR inhibitory activity of the NMDA antagonists was in the following order: dizocilpine > CPP > APV = 7-Clkyn > HA-966. 3. The inhibitory effects of 7-Clkyn on PSR were markedly antagonized by the simultaneous application of D-serine, an agonist for the NMDA receptor glycine-binding sites. However, PSR inhibition by dizocilpine and CPP was unaffected. 4. Inhibition of the PSR by 7-Clkyn persisted in the presence of strychnine, which markedly increased the PSR activity by itself. 5. These findings suggest that the NMDA receptor glycine-binding sites play a role in generating the NMDA receptor-mediated PSR in the spinal cord in vitro.

Animals↗

Risk factors for sudden deafness: a case-control study.

In order to investigate risk factors for idiopathic sudden sensorineural hearing loss (sudden deafness), a case-control study was done in 109 patients with sudden deafness who visited our hospital between 1992 and 1994, with 109 controls matched to each patient by gender and age. Odds ratio (OR) and 95% confidence interval (CI) for smoking habits, drinking habits, dietary habits, environmental noise, past history of disease, sleeping hours, appetite, fatigue, incidence of common cold were obtained. Fatigue (OR: 3.28; 95% CI: 1.36-7.90) and loss of appetite (OR: 8:00; 95% CI: 1.00-64.0) elevated the risk for sudden deafness. Those who ate many fresh vegetables were at a decreased risk (OR: 0.48; 95% CI: 0.24-0.96 for light-colored vegetables, OR: 0.55; 95% CI: 0.30-1.02 for green-yellow vegetables). Personal histories of hypertension and thyroid disease, and susceptibility to colds appeared to be positively associated with the risk (0.05 < P < 0.10). Smoking habits, drinking habits and environmental noise had no significant association with sudden deafness. These results suggested that environmental factors, including diet, may be importantly involved in the genesis of sudden deafness.

Adolescent↗

Increased intracellular Ca2+ is not coinherited with an inferred major gene locus for hypertension (ht) in the spontaneously hypertensive rat.

Hypertension is characterized by a complex mode of inheritance, consisting of the accumulation and interaction of major and minor genes. The existence of a single major gene locus (ht) has been demonstrated in the backcross analysis of spontaneously hypertensive rats (SHR) and normotensive Donryu rats. Intracellular Ca2+ concentration ([Ca2+]i) determines the tonus of vascular smooth muscle. It has been hypothesized that abnormal Ca2+ transport is an inheritable trait with profound influence on the development of hypertension. Backcross analysis between SHR and Donryu rats was performed to demonstrate ht and to dissect polygenic hypertensive traits through ht and abnormal intracellular Ca2+ metabolism. Among the parental strains, systolic blood pressure and thrombin-stimulated [Ca2+]i in platelets were significantly greater in SHR than in Donryu and F1 rats. The backcrossed rats were distributed into two clusters on a scattergram of blood pressure versus [Ca2+]i, demonstrating the existence of ht. The blood pressure level was correlated with thrombin-stimulated [Ca2+]i in each cluster. Increased [Ca2+]i in platelets was not coinherited with ht and was considered to be a minor inheritable hypertensive trait discriminated from ht. Therefore, [Ca2+]i in platelets is an inadequate marker for searching ht.

Animals↗

Ovariectomy aggravated sodium induced hypertension associated with altered platelet intracellular Ca2+ in Dahl rats.

Our purpose was to determine the effect of ovariectomy on intracellular Ca2+ mobilization and platelet aggregation in sodium induced hypertension. At the age of 12 weeks ovariectomy or sham operation was performed in female Dahl-Iwai salt sensitive rats on a 0.3% NaCl diet. Four weeks later we assessed the effects of ovariectomy and an 8% NaCl diet on agonist induced intracellular Ca2+ mobilization in fura-2 loaded platelets and platelet aggregation. Ovariectomy enhanced the increase of systolic blood pressure and heart to body weight ratio on an 8% NaCl diet. However, thrombin evoked intracellular Ca2+ was not correlated with systolic blood pressure (r = -0.338, P = .17), and was lowered by sodium loading and ovariectomy (360+/-23 to 285+/-9, 296+/-10 nmol/L, P < .05). Furthermore, the ionomycin induced intracellular calcium fraction in the absence of external Ca2+ that reflected internal Ca2+ discharge capacity was reduced in ovariectomized rats compared with sham operated rats on an 8% NaCl diet (648+/-15 v 768+/-35 nmol/L, P < .05). The internal Ca2+ discharge capacity was inversely correlated with systolic blood pressure (r = -0.506, P = .03). In addition to the decreased internal Ca2+ discharge capacity, intracellular Ca2+-independent platelet aggregation by phorbol 12-myristate 13-acetate, a protein kinase C activator, was significantly enhanced in hypertensive rats. We concluded that ovariectomy enhanced sodium induced hypertension associated with the decreased internal Ca2+ discharge capacity and increased platelet aggregation in Dahl-Iwai salt-sensitive rats.

Animals↗

Serum levels of specific IgE, soluble interleukin-2 receptor, and soluble intercellular adhesion molecule-1 in seasonal allergic rhinitis.

BACKGROUND: There is increasing evidence that soluble interleukin-2 receptor (sIL-2R) might reflect T cell activation in vivo and soluble intercellular adhesion molecule-1 (sICAM-1) might reflect the ongoing inflammatory response in the inflamed site. OBJECTIVE: The aim of this study was to determine the effect of antihistamine tablets and allergen-specific immunotherapy on the seasonal changes in specific IgE, sIL-2R, and sICAM-1 in the serum of patients with seasonal allergic rhinitis. METHODS: This prospective study included 99 patients with seasonal allergic rhinitis due to Japanese cedar pollens and 27 nonatopic healthy volunteers. The patients were divided into an antihistamine-treated group and an immunotherapy group. Serum samples were collected before and during the pollen season from each patient to determine specific IgE, sIL-2R, and sICAM-1. RESULTS: Levels of sIL-2R before the pollen season did not differ significantly among the nonatopic group, the antihistamine-treated group, and the immunotherapy group. The levels of sICAM-1 before the pollen season were significantly higher in the antihistamine-treated group and in the immunotherapy group than in the nonatopic group. Seasonal increase in specific IgE was significant in the antihistamine-treated group regardless of their clinical outcomes. In contrast, significant increase in specific IgE was observed during the pollen season in poor responders but not in good responders to immunotherapy. Serum levels of sIL-2R and sICAM-1 were significantly increased during the pollen season in poor responders of the antihistamine-treated group and the immunotherapy group. On the other hand, neither seasonal increase in sIL-2R nor sICAM-1 was significant in good responders of the antihistamine-treated group and the immunotherapy group. CONCLUSIONS: Serum levels of sICAM-1 are higher in patients with seasonal allergic rhinitis, even outside of the pollen season when the allergen does not naturally exist. Seasonal changes in serum sICAM-1 as well as sIL-2R and specific IgE are probably objective markers to indicate the clinical efficacy of antihistamines and immunotherapy on seasonal allergic rhinitis.

Adult↗

Report on the nationwide epidemiological survey of exudative age-related macular degeneration in Japan.

The research Committee on Chorioretinal Degeneration, in cooperation with the Research Committee on the Epidemiology of Intractable Diseases, performed the second nationwide epidemiological survey of exudative age-related macular degeneration (AMD) in 1993. The number of exudative AMD patients in all ophthalmology departments throughout Japan was estimated to be 14,400 in 1993. This number was estimated to have almost doubled over the six year period since the initial survey in 1987. The number of people visiting ophthalmology departments due to exudative AMD was 53 males and 20 females per 100,000 population aged 50 years or over. The percentage of patients with bilateral disease increased with age and accounted for nearly 50% of those aged 80 years or over.

Age Distribution↗

Potent and voltage-dependent block by philanthotoxin-343 of neuronal nicotinic receptor/channels in PC12 cells.

1. Block by philanthotoxin-343 (PhTX-343), a neurotoxin from wasps, of ionic currents mediated through neuronal nicotinic acetylcholine (ACh) receptor/channels was characterized in rat phaeochromocytoma PC12 cells, by use of whole cell voltage-clamp techniques. 2. In the cells held at -60 mV, PhTX-343 at 0.1 and 1 microM inhibited an inward current activated by 100 microM ACh. The current inhibition was relieved by depolarizing steps, and augmented at negative potentials, suggesting that PhTX-343 blocks the channel in a voltage-dependent manner. Joro spider toxin-3 (JSTX-3) also exerted voltage-dependent inhibition of ACh-activated currents in a similar concentration range, but argiotoxin636 did not affect the currents. 3. Analysis of the current decay during hyperpolarizing steps indicated that the current inhibition by 100 nM PhTX-343 develops in an order of several hundres of milliseconds. On the other hand, the recovery from the current inhibition during depolarizing steps developed in an order of about 100 ms. 4. The results suggest that PhTX-343 blocks neuronal nicotinic receptor channels in PC12 cells at concentrations lower than those required for channel block in non-mammalian cells, and the block exhibits clear voltage-dependence. Estimated from the voltage-dependence, the binding site of PhTX-343 may be located near the outer mouth of the channel.

Acetylcholine↗

The effects of a simplified method for cryopreservation and thawing procedures on peripheral blood stem cells.

A simplified method for cryopreservation at -80 degrees C of peripheral blood stem cells (PBSC) has been increasingly used for autologous PBSC transplantation in Japan. Although this method, using 6% hydroxyethyl starch (HES) and 5% dimethyl sulfoxide (DMSO) as a cryoprotectant without rate-controlled freezing, has several advantages over the conventional method using 10% DMSO with rate-controlled freezing, little is known about effects of long-term cryopreservation for years and thawing process on hematopoietic progenitors. We examined the recovery rates of BFU-E and CFU-GM in sample tubes cryopreserved by the simplified method under various conditions as follows: (1) long-term storage for 1-5 years; (2) DMSO exposure for 1 h after rapid thawing; and (3) thawing at a lower temperature other than 37 degrees C. In our study, we found that the recovery rates of BFU-E and CFU-GM were not affected by the length of cryopreservation period; they remained at more than 70% on average for 16-61 months. In our hands, a 1-h exposure to DMSO after rapid thawing was not toxic for hematopoietic progenitors. Furthermore, there was no significant difference in the recovery rates of BFU-E and CFU-GM between thawing at 37 degrees C and 20 degrees C. These observations indicate that PBSC cryopreserved for at least 5 years by the simplified method can be used clinically without losing hematopoietic activity, and suggest that hematopoietic activity of the thawed PBSC may be unaffected when PBSC are infused slowly within 60 min or even when PBSC are thawed gradually at room temperature.

Blood Preservation↗

Autologous peripheral blood stem cell transplantation for acute myelogenous leukemia.

The safety and efficacy of myeloablative therapy followed by autologous peripheral blood stem cell transplantation (ABSCT) for acute myelogenous leukemia (AML) were evaluated in 60 patients. Peripheral blood stem cells (PBSC) were collected during recovery after consolidation chemotherapy. High-dose chemotherapy consisting of busulfan (16 mg/kg), etoposide (40 mg/kg), and cytosine arabinoside (3 g/m2 x 4) (BEA regimen) was used for pretransplant conditioning in 13 patients. For the remaining 47 patients, granulocyte colony-stimulating factor (G-CSF) was administered concurrently with the BEA regimen during conditioning. Unpurged, cryopreserved PBSC containing a median number of 5.4 x 10(8) MNC/kg or 12 x 10(4) CFU-GM/kg were reinfused at transplantation. The median number of days to granulocytes exceeding 500/microl and last platelet transfusion were 15 (8-44) and 24 (0->180), respectively. The 3-year probabilities of disease-free survival (DFS) and relapse were 78.6 and 21.4% for patients transplanted in first remission, 29.6 and 64.4% for those in second or third remission, and 11.1 and 77.8% for those in relapse, respectively. There were no transplant-related deaths within 100 days of transplantation. Age, disease status at transplantation, and number of induction chemotherapies to first complete remission were risk factors affecting the outcome of ABSCT. These results of ABSCT for AML in first remission warrant a prospective study of ABSCT as post-remission therapy.

Acute Disease↗

Genetic analysis of 8;21 chromosomal translocation without AML1 gene involvement in MDS-AML.

We have investigated a case of acute myelocytic leukaemia derived from myelodysplastic syndrome (MDS-AML) with an 8;21 translocation. In this case the AML1/MTG8 (ETO) fusion transcript was not detected by reverse transcriptase-polymerase chain reaction (RT-PCR), and the rearrangement of the AML1 gene locus was not detected by Southern blot nor pulse field gel electrophoresis (PFGE) analyses using specific probes for the AML1 gene. Fluorescence in-situ hybridization (FISH) study using cosmid probes for 21q22 revealed that the breakpoint of 21q22 was telomeric to the AML1 gene locus and centromeric from D21S259, 351, 3421 loci. This is the first report concerning the t(8;21)(q22;q22) carrying AMLs (de novo AML, MDS-AML and therapy-related AML) to show that the breakpoint at 21q22 is located outside the AML1 gene locus. It is also noteworthy that the cell-surface antigen expression pattern of the bone marrow (BM) blasts was changed from CD7+ CD2+ CD13+ CD33+ CD19- CD11b+ CD14+ CD36+ to CD7- CD2- CD13+ CD19+ CD11b- CD14- CD33+ CD34+ CD36- CD56+ during leukaemic progression, and the pattern in leukaemic phase was similar to the characteristic phenotype of de novo AML cases with t(8;21), when the AML1/MTG8 fusion transcripts are always detected by RT-PCR.

Blotting, Southern↗

The effect of immunotherapy on the serum levels of eosinophil cationic protein in seasonal allergic rhinitis.

The role of serum eosinophil cationic protein levels in allergic rhinitis is controversial. It is also unclear whether with immunotherapy it is possible to reduce these serum levels in allergic diseases. We studied serum eosinophil cationic protein levels in patients with cedar-induced allergic rhinitis and compared them with non-atopic controls. The second aim of this study was to elucidate whether immunotherapy is capable of decreasing the seasonal elevation in serum eosinophil cationic protein levels in seasonal allergic rhinitis. The serum eosinophil cationic protein levels of the untreated patient group were significantly higher than those of the non-atopic controls. The levels in patients who received immunotherapy for 2 yr were also significantly higher than those of the non-atopic controls. However, the levels were not different between the patients undergoing immunotherapy for over 3 yr and the non-atopic controls. The serum levels of the 31 patients treated with immunotherapy correlated with the duration of immunotherapy. In conclusion, the serum eosinophil cationic protein levels are higher in untreated patients with seasonal allergic rhinitis and this seasonal activation in circulating eosiohophils decreases gradually during immunotherapy, but this inhibitory effect becomes apparent only after a number of years of immunotherapy. This prevention of seasonal eosinophil activation is one of the mechanisms responsible for the clinical effect of immunotherapy.

Adolescent↗

Serum level of soluble interleukin-2 receptor in patients with seasonal allergic rhinitis.

The rate of release of the soluble form of interleukin-2 receptor (soluble IL-2R) reflects T cell activation in vivo. Since T lymphocytes play a central role in respiratory allergic disorders, the measurement of serum levels of soluble IL-2R may be useful in analysing the disease state of allergic disorders. The study has aimed at investigating the seasonal changes in serum soluble IL-2R in 81 patients with seasonal allergic rhinitis due to Japanese cedar pollens, with special reference to the effect of anti-allergic pharmacotherapy and immunotherapy. Serum samples were obtained twice from each patient, before and during the pollen season, and all the serum samples were simultaneously used for determination of soluble IL-2R and cedar pollen-specific immunoglobin E (IgE). Seasonal elevation in soluble IL-2R was not associated with the good clinical outcome but was associated with the poor clinical outcome, irrespective of pharmacotherapy or immunotherapy. Additionally, successful immunotherapy suppressed seasonal elevation of serum soluble IL-2R more strongly than successful pharmacotherapy, and seasonal increase rates in soluble IL-2R were inversely correlated with the duration of immunotherapy. Seasonal increase rates in soluble IL-2R were significantly correlated with seasonal increase rates in specific IgE in both the medication group and the immunotherapy patients. These results may suggest that seasonal changes in serum soluble IL-2R may serve as an indicator for clinical outcome of seasonal allergic rhinitis, that the magnitude of T cell activation could affect specific IgE production, and that T cell activation could be gradually modulated as immunotherapy proceeds. In conclusion, seasonal changes in serum soluble IL-2R may serve as an objective indicator for clinical outcome of seasonal allergic rhinitis.

Adolescent↗