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Biomedical subjects

H Ninomiya

Publications and source records attributed to H Ninomiya.

At least 145 records · Page 8Linked to original sources

Physiological role of Ca2+-permeable nonselective cation channel in endothelin-1-induced contraction of rabbit aorta.

We previously showed a role for a nonselective cation channel (NSCC) in the ETA-dependent action of endothelin-1 in mouse fibroblast and rabbit aortic smooth-muscle cell. To clarify the physiological significance of NSCCs in endothelin-1 (ET-1)-induced vasocontraction, we examined the effects of NSCC blockers such as mefenamic acid and SK&F 96365 on the contractions of deendothelialized rabbit aortic rings induced by a low (10[-10] M) or high (10[-8] M) concentration of ET-1. Mefenamic acid (< or =10[-3] M) had little effect on the contraction induced by 45 x 10(-3) M K+ or 1 x 10(-6) M Bay K-8644 in combination with 15 x 10(-3) M K+, indicating that it does not affect voltage-operated calcium channels (VOCs) and contractile mechanisms. The contraction by a low concentration of ET-1 was abolished after removal of extracellular Ca2+, but it was reduced only to 50% by a maximally effective concentration (10[-5] M) of nifedipine, an inhibitor of L-type VOCs (L-VOC). Mefenamic acid and SK&F 96365 inhibited the ET-1-induced contraction with 50% inhibitory concentration (IC50) values of 10(-4) M and 2 x 10(-5) M, respectively, and abolished it at 10(-3) M and 10(-4) M. By contrast, nifedipine, mefenamic acid, or SK&F 96365 had little effect on the contraction by a high concentration of ET-1. The contraction induced by a low or high concentration of ET-1 was abolished by an ETA antagonist, BQ-123, but not by an ETB antagonist, BQ-788. These results demonstrate that the contraction induced by ET-1 is totally mediated exclusively by ETA, but that Ca2+ entry through NSCCs in addition to L-VOCs plays an important role in contractions induced by low concentrations of ET-1, whereas it plays only a minor role in contractions induced by high concentrations of ET-1.

Animals↗

Influence of reference electrodes, stimulation characteristics and task paradigms on auditory P50.

To clarify the nature of auditory P50, middle latency auditory evoked potentials were recorded by using different conditions of reference electrodes (linked earlobes, LE; balanced non-cephalic, BN), stimulation characteristics (tone burst, human voice) and tasks (counting, simple reaction) in 10 right-handed males (aged 21-36 years). EEG was recorded from Fz, Cz, Pz, C3, C4, T3 and T4 according to the 10-20 system. Two groups of electrode sites were made for the statistical analysis: a midline group, Fz, Cz and Pz, and a lateral group, T3, C3, Cz, C4 and T4. The results were that the P50 amplitudes with BN electrodes were significantly higher than those with LE in both groups (midline, P < 0.01; lateral, P < 0.01); the P50 amplitudes by voice stimulation were significantly higher than those by tone stimulation in the lateral group (P < 0.05), and the P50 latencies under a simple reaction paradigm were significantly shorter than those under a counting task in both groups (midline, P < 0.05; lateral, P < 0.05). These results suggest that various factors including motor response affect the P50 amplitudes and latencies.

Acoustic Stimulation↗

Negative correlation of reaction times and the auditory P50 in a Go, No-Go paradigm.

We investigated the relationship between reaction times in a Go, No-Go paradigm and various components of the auditory event-related potentials. The P50 latencies in the Go trials were significantly earlier than those in the No-Go trials. The N200 and P300 were positively associated with the reaction times. However, the P50 latencies showed negative correlation with the reaction times, and the negative correlation at F3 was the largest. Referring to source studies on P50, it is suggested that the activation of either the ascending activating system or the left premotor area through that system might affect the speed of reaction.

Adult↗

A study of verbal and spatial information processing using event-related potentials and positron emission tomography.

The activated cerebral regions and the timing of information processing in the hemispheres was investigated using event-related potentials (ERP) and regional cerebral blood flow (rCBF) as the neurophysiological indicators. Seven men and one woman (age 19-27 years) were asked to categorize two-syllable Japanese nouns (verbal condition) and to judge the difference between pairs of rectangles (spatial condition), both tests presented on a monochrome display. In the electroencephalogram (EEG) session, EEG were recorded from 16 electrode sites, with linked earlobe electrodes as reference. In the positron emission tomography (PET) session, rCBF were measured by the 15O-labeled H2O bolus injection method. Regions of interest were the frontal, temporal, parietal, occipital and central lobes, and the entire cerebral hemispheres. When the subtracted voltages of the ERP in homologous scalp sites were compared for the verbal and spatial conditions, the significant differences were at F7.F8 and T5.T6 (the 10-20 system). The latencies of the differences at T5.T6 were around 200, 250 and 320 ms. A significant difference in rCBF between the verbal and spatial conditions was found only in the temporal region. It was concluded that early processing of information, that is, registration and simple recognition, may be performed mainly in the left temporal lobe for verbal information and in the right for spatial information.

Adult↗

[Reproductive and developmental toxicity studies of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a novel drug for urinary frequency and incontinence (1). Fertility study in rats by oral administration].

Fertility and developmental toxicity study of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was conducted in Crl:CD rats. Male rats were given NS-21 orally from 60 days before mating to the day of necropsy, and female rats were given NS-21 orally from 14 days before mating to day 7 of pregnancy. The dose levels for both males and females were 0 (control), 2, 30 and 500 mg/kg. On day 20 of pregnancy, the females were sacrificed and their fetuses examined. At the 500 mg/kg dosage level, one male and one female died. Salivation and dilated pupils occurred at the 30 and 500 mg/kg dosage levels, and rales occurred at 500 mg/kg. Body weights and food consumption were decreased, and water consumption was increased in both males and females at the 500 mg/kg dosage level. Decreases in the numbers of corpora lutea and implantations per litter and a lower number of live fetuses per litter were found at the 500 mg/kg dosage level. However, the incidence and number of postimplantation loss per litter were comparable among the treatment and control groups. These results demonstrate that the NOAEL (no observed adverse effect level) of NS-21 is 2 mg/kg for general toxicity in parental animals, and 30 mg/kg for reproductive function of the parent animals and for embryo-fetal development.

Administration, Oral↗

[Reproductive and developmental toxicity studies of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a novel drug for urinary frequency and incontinence (2). Teratogenicity study in rats by oral administration].

A study of teratogenicity and developmental toxicity of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was conducted in Crl:CD rats. Female rats were given NS-21 orally at dose levels of 0 (control), 2, 25 and 300 mg/kg from day 7 to day 17 of pregnancy. Twenty-two female rats per dose level were sacrificed on day 20 of pregnancy for examination of their fetuses, and the remaining pregnant rats (twenty-three per dose level) were allowed to deliver naturally for postnatal examination of their offspring. At the 300 mg/kg dosage level, rales, partially closed eyes and reduced activity were observed in pregnant rats. Decreases in body weight gain, food consumption and water consumption were observed in the dams at the 300 mg/kg dosage level. Fetal body weights were decreased at the 300 mg/kg dosage level. The drug never altered the numbers of corpora lutea and implantations, fetal mortality, the number of live fetuses, sex ratio, placental weight, and external, visceral and skeletal development of fetuses. NS-21 did not affect the delivery of dams, the number of live newborns, birth index, body weight or survival index. Nor did NS-21 have any adverse effect on the postnatal development of the offspring, including physical and functional development, emotionality, motor activity, learning ability and reproductive performance. These results demonstrate that the NOAEL (no observed adverse effect level) of NS-21 is 25 mg/kg for general toxicity in mother animals. 300 mg/kg for reproductive function in mother animal and 25 mg/kg for developmental toxicity.

Administration, Oral↗

[Reproductive and developmental toxicity studies of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a novel drug for urinary frequency and incontinence (3). Teratogenicity study in rabbits by oral administration].

A study of the effect of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was conducted in New Zealand White rabbits during the period of fetal organogenesis. Female rabbits were given NS-21 orally at dose levels of 0 (control), 2, 10 and 50 mg/kg from day 6 to day 18 of pregnancy. Female rabbits were sacrificed on day 29 of pregnancy for examination of their fetuses. Five does in the 10 mg/kg dosage group and one doe in the 50 mg/kg dosage group died or were sacrificed in moribund condition. Two does in the control group died. Lacrimation and convulsion were observed in the 10 and 50 mg/kg groups, and no or soft stool was observed in the 50 mg/kg dosage group. Body weight gain, food and water consumptions were decreased in the 50 mg/kg dosage group. There were no effects of NS-21 in necropsy findings at cesarean sections in does at any dosage level. Developmental toxicity of fetuses was not apparent at any dosage level. These results demonstrate that the NOAEL (no observed adverse effect level) of NS-21 is 2 mg/kg for maternal toxicity and 50 mg/kg for fetal toxicity.

Administration, Oral↗

[Reproductive and developmental toxicity studies of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate(NS-21), a novel drug for urinary frequency and incontinence (4). Perinatal and postnatal study in rats by oral administration].

A study of the effect of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was conducted in Crl:CD rats during the perinatal and lactational periods. Female rats(thirty-three per dose level) were given NS-21 orally at dose levels of 0 (control), 2, 25 and 300 mg/kg from day 17 of pregnancy to day 21 after delivery. All pregnant rats were allowed to deliver naturally for postnatal examination of their offspring. At the 300 mg/kg dosage level, reduced activity, salivation and rales were observed in dams, and five dams died. Decreases in body weight gain, food consumption and water consumption were also observed in the dams at the 300 mg/kg. The number of remaining implantation sites was increased at 300 mg/kg, indicating fetal mortality. The number of live newborns, birth index and survival index at the birth were decreased at the 300 mg/kg dosage level. Reduced activity, paleness in color and/or discoloration were observed for many pups at the 300 mg/kg on lactation day 0. Body weights of male and female offspring at the birth were also decreased at the 300 mg/kg dosage group. Survival index at the 4 days was decreased at the 300 mg/kg dosage level. Body weight gains of male and female offspring were decreased at the 300 mg/kg during the lactational period and after weaning. NS-21 did not affect the postnatal development of the offspring, including physical and functional development, motor activity, emotionality, learning ability and reproductive performance. These results demonstrate that the NOAEL (no observed adverse effect level) of NS-21 is 25 mg/kg for general toxicity and reproductive function in mother rats and 25 mg/kg for developmental toxicity of their offspring.

Administration, Oral↗

Interstitial pneumonitis related to granulocyte colony-stimulating factor administration following chemotherapy for elderly patients with non-Hodgkin's lymphoma.

We treated three cases of interstitial pneumonitis (IP) in 26 elderly (> or = 65 years old) patients with non-Hodgkin's lymphoma (NHL) who received the same chemotherapeutic protocol including granulocyte colony-stimulating factor (G-CSF) administration. Fortunately, all three patients recovered from IP spontaneously by discontinuation of G-CSF alone or with administration of corticosteroid. Because the duration and extent of neutrophilia induced by G-CSF administration was not different between the cases complicated by IP and those without IP, underlying pulmonary damage is suggested to be more involved than neutrophil count in the development of IP.

Aged↗

[Effects of ischemic preconditioning on the recovery of myocardial function after unprotected ischemia and cardioplegia in the isolated and crystalloid perfused rat hearts].

Preconditioning with repetitive brief periods of ischemic (IPC) is known to induce myocardial protection against a subsequent more prolonged period of ischemia. We investigated whether IPC can offer similar beneficial effects on myocardial function after cardioplegic preservation in isolated and crystalloid-perfused rat hearts. IPC was produced by 5 periods of 1 min ischemia followed by 5 min reperfusion before 25 min of unmodified ischemia or 40 min of cardioplegia. IPC had no significant effect on the time to contractile arrest (control: 211 +/- 27 sec, IPC: 240 +/- 32 sec) after unmodified ischemia, while the time to electrical asystole was significantly (p < 0.05) shortened by IPC (676 +/- 107 sec) compared to control (1021 +/- 197 sec). However, rapid contractile arrest concomitant with electrical asystole was induced by infusion of St. Thomas' Hospital solution in control as well as in IPC-treated hearts without a significant intergroup difference (control: 33 +/- 7 sec, IPC 39 +/- 9 sec). Although myocardial ATP was significantly reduced by IPC, IPC-treated hearts showed a significantly higher ATP level after 25 min of unprotected ischemia. Accumulation of myocardial lactate after 25 min of unprotected ischemia was significantly (p < 0.05) inhibited by IPC. However, the levels of myocardial ATP and lactate after 40 min of cardioplegia were comparable between control and IPC-treated hearts. Left ventricular developed pressure (LVDP) at 30 min reperfusion after unprotected ischemia was significantly improved by IPC, while the recovery of LVDP at 30 min reperfusion after cardioplegia was comparable between control and IPC-treated hearts. The onset of ischemic contracture, i.e., a rise of left ventricular end-diastolic pressure (LVEDP), was significantly accelerated and its magnitude was significantly greater in IPC-treated hearts during unprotected ischemia and also during cardioplegia. However, a significant decrease of LVEDP during reperfusion compared to control hearts was observed only after unprotected ischemia. The amounts of creatine kinase (CK) released during 30 min reperfusion after unprotected ischemia was significantly greater in control than in IPC-treated hearts, but there was no significant difference in CK release between control and IPC-treated hearts during reperfusion after cardioplegia. These results suggest that IPC-induced cardioprotection may be induced via inhibition of anaerobic energy metabolism through a negative chronotropic effect during unprotected ischemia, but such a beneficial effect is dissipated with cardioplegia by which rapid electrical asystole is induced. It is, therefore, concluded that IPC may not provide additional myocardial protection over conventional hyperkalemic cardioplegia.

Animals↗

[Allopurinol induced pancytopenia in a patient with myeloproliferative disorder].

We reported a rare case of pancytopenia caused by allopurinol. A 61-year-old man was first admitted in May 1993, because of thrombocytosis. He had suffered from chronic glomerulonephritis. He was administered allopurinol for hyperuricemia from March 1993. On first admission the laboratory findings revealed leukocytosis (10,100/microliter) and thrombocytosis (971 x 10(3)/microliter) in the peripheral blood. Myelofibrosis was strongly suspected due to increased number of MgK and reticular fiber in the bone marrow. Two months later, he readmitted due to pancytopenia (WBC 1,300/microliter, Hb 6.2g/dl, Plt 10 x 10(3)/microliter). His bone marrow showed markedly hypocellular. Because we suspected that pancytopenia was induced by allopurinol, we discontinued allopurinol and administered oxymetholone, G-CSF, and EPO, WBC, RBC, and platelet count had been recovered about one and half months later. In vitro co-culture indicated that CFU-G, E, and Meg in the bone marrow cells after recovery from pancytopenia were markedly suppressed in the presence of patient's serum and oxipurinol. Pancytopenia due to allopurinol was reported to be rare, and some authors showed that it will sometimes be fatal. Because pancytopenia of this case had been recovered in a relatively short time with cytokine therapy, it was thought to be effective for pancytopenia due to drug like this case.

Allopurinol↗

[Central sleep apnea syndrome successfully treated with nasal bi-level positive airway pressure and sleep position adjustment].

A 55-year-old obese man was admitted to our hospital because of a severe morning headache. He snored and had recurrent episodes of sleep apnea that began 10 years earlier and had since become much worse. An overnight polysomnographic recording confirmed that he had sleep apnea syndrome, predominantly of the central type. The apneas were more frequent when he lay on his back (apnea index 54.5) than on his side (apnea index 1.2). He was treated with sleep position adjustment and nasal bi-level positive airway pressure, inspiratory positive airway pressure at 5 cmH2O and expiratory positive airway pressure at 2 cmH2O. His snoring, headache, and oxygen desaturation resolved. This case suggests that airway collapse may cause central apnea, and that nasal continuous positive airway pressure, and nasal bi-level positive airway pressure and adjustment of sleep position can be effective in some patients with central-type sleep apnea syndrome.

Humans↗

[NO inhalation therapy for post-operative pulmonary hypertensive crisis of the case of truncus arteriosus].

Two-months-old baby underwent complete correction by Barbero-Marcial's procedure for type I truncus arteriosus. Postoperative hemo-dynamics was fairly stable immediately after the operation. However, the acute rise in pulmonary pressure occurred on the 2nd postoperative day. The pulmonary vasodilation therapy with prostaglandin E1 and amrinone had failed. Thirty ppm of inhaled nitric oxide (NO) was started and it resulted in an immediate decrease in pulmonary arterial pressure. Complete weaning from NO was achieved 9 days after surgery by simultaneous administration of PGE1 and amrinone. Although inhalation of NO reduced pulmonary arterial pressure, combination of PGE1 and amrinone with NO inhalation exerted a pulmonary vasodilation and brought the patient to full recovery in this case with pulmonary hypertensive crisis.

Administration, Inhalation↗

[A surgical case of intrapericardial inferior vena cava injury complicating liver injury caused by a blunt trauma].

A 63-year-old man was brought to our hospital 20 minutes after sustaining blunt injury. He had been struck by a steel frame weighing about 700 kg that had fallen from a height of 2 meters. On admission, he was in cardiogenic shock with a systolic pressure of 70 mmHg and a pulse rate of 130 beats/minute. There was no apparent open wound and no brain injury was suspected. Echocardiography and chest computed tomogram showed cardiac tamponade, and abdominal computed tomogram showed liver injury. We performed emergency operation under cardio-pulmonary bypass standby. Laceration of the inferior vena cava at the right atrium junction was noticed. We had to perform IVC repair under cardio-pulmonary bypass because of massive bleeding. Liver injury was repaired after neutralization of systemic heparinazation. The patient developed respiratory, hepatic and renal failure during his postoperative course; however, he was discharged on postoperative day 39. Intrapericardial IVC injury caused by blunt trauma is a very rare event. Reconstruction can be performed successfully under cardio-pulmonary bypass.

Abdominal Injuries↗

Thromboembolism in a patient with transient eosinophilia.

We report here a case of thromboembolism occurring in a 29-year-old woman with transient eosinophilia. Eosinophilia for at least 11 days was followed by pulmonary embolism. Both reperfusion of pulmonary arteries and disappearance of deep vein thrombi were obtained by treatment with urokinase, tissue plasminogen activator, and heparin. Although the causes of eosinophilia were not specified, we suggested a causative correlation of elevated serum levels of eosinophil granule proteins with the development of thromboembolism.

Adult↗

Negative correlation of P50 peak latencies and reaction times in a simple reaction task.

We investigated the influence of stimulus characteristics and tasks (count and simple reaction tasks) on auditory P50. Ten normal volunteers served as subjects. EEGs and auditory evoked potentials were obtained from Fz, Cz, Pz, C3, C4, T3 and T4 referred to linked earlobes (LE) and balanced non-cephalic (BN) electrodes. In the recordings using a BN reference there were significant negative correlations between the reaction times and P50 peak latencies at Fz, Cz, Pz, C3 and C4. In the LE reference recordings there were negative correlations but these did not reach statistical significance. The results are discussed with reference to the activation of the LE reference and the neural sources of P50. The findings suggest the possibility that reaction times are determined at the very early stage of auditory information processing.

Adult↗

Clinicopathological characteristics of primary Ki-1 anaplastic large cell lymphoma.

The clinical findings and prognosis in 15 patients with primary Ki-1 anaplastic large cell lymphoma (ALCL) were analyzed and compared with those of patients with T cell and B cell lymphoma and Hodgkin's disease. Clinical data revealed lymphadenopathy in 13 patients (87%) and skin lesions in eight (53%). Other organic involvements were hepatomegaly in two patients (13%), splenomegaly in five (33%), and bone marrow involvement in three (20%). The rate of skin involvement was significantly higher than that in B cell lymphoma and Hodgkin's disease. In laboratory findings the gamma-globulin concentration was significantly higher than that in T cell lymphoma, and the erythrocyte sedimentation rate (ESR) was significantly higher than that in B cell lymphoma. Complete remission was achieved in 11 patients (73%) and the five-year relapse-free survival was 27%. The overall survival was 4.0-69.8 months (mean 30.6 months). The mean survival was compatible with that of T cell lymphoma and was significantly shorter than that in Hodgkin's disease. Ki-1 ALCL can be distinguished from other lymphomas clinically as well as pathologically. Because Ki-1 ALCL is chemosensitive and the prognosis is as poor as that of T cell lymphoma, aggressive chemotherapy should be employed for the treatment of this disease.

Hodgkin Disease↗