Efficacy of nifekalant hydrochloride on the treatment of life-threatening ventricular tachyarrhythmias during reperfusion for acute myocardial infarction.
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Angioplasty, Balloon, Coronary↗
Biomedical subjects
S Nishiyama
Publications and source records attributed to S Nishiyama.
The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT): initial aims and impact of the family history of type 1 diabetes mellitus in Japanese children.
The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) was established in July 1994 with the chief aim to improve the quality of therapy for type 1 diabetes in children, an entity far less common in Japan than in Europe. We proposed four initial research topics: (i) to determine the current status of medical care and glycemic control in Japanese children with type 1 diabetes mellitus; (ii) to standardize the measurement of hemoglobin A1c; (iii) to establish a registry of a large cohort of patients in order to enable prospective studies to improve the quality of therapy for children with type 1 diabetes in Japan; and (iv) to enable participants of the JSGIT to hold a workshop twice annually. We registered a total of 736 patients from 45 hospitals throughout Japan. Intervention via insulin treatment was instituted after 2 yr for those patients whose hemoglobin A1c level was more than 8.1%. The proportion of patients receiving multiple insulin injections increased after intervention; however, average hemoglobin A1c in females remained significantly higher than in males. We identified two forms of diabetes in Japanese children: a rapidly progressive form and a more slowly progressive form. There was a significantly higher prevalence of a family history of diabetes in first-degree relatives in the slowly progressive form. These preliminary findings are the result of the first collaborative study of childhood diabetes in Japan.
Journal Article↗
Real time visualization of 13N-translocation in rice under different environmental conditions using positron emitting Ttacer imaging system.
The ammonium ion is an indispensable nitrogen source for crops, especially paddy rice (Oryza sativa L. cv Nipponbare). Until now, it has been impossible to measure ammonium uptake and nitrogen movement in plants in real time. Using the new technologies of PETIS (positron emitting tracer imaging system) and PMPS (positron multi-probe system), we were able to visualize the real time translocation of nitrogen and water in rice plants. We used positron-emitting 13N-labeled ammonium (13NH4+) and 15O-water to monitor the movement. In plants cultured under normal conditions, 13NH4+ supplied to roots was taken up, and a 13N signal was detected at the discrimination center, the basal part of the shoots, within 2 minutes. This rapid translocation of (13)N was almost completely inhibited by a glutamine synthetase inhibitor, methionine sulfoximine. In general, nitrogen deficiency enhanced 13N translocation to the discrimination center. In the dark, 13N translocation to the discrimination center was suppressed to 40% of control levels, whereas 15O-water flow from the root to the discrimination center stopped completely in the dark. In abscisic acid-treated rice, 13N translocation to the discrimination center was doubled, whereas translocation to leaves decreased to 40% of control levels. Pretreatment with NO3- for 36 hours increased 13N translocation from the roots to the discrimination center to 5 times of control levels. These results suggest that ammonium assimilation (from the roots to the discrimination center) depends passively on water flow, but actively on NH4+-transporter(s) or glutamine synthetase(s).
Biological Transport↗
Case report. Lymphatic vessel-type sporotrichosis: immunohistochemical evaluation and cytokine expression pattern.
A 57-year-old male carpenter living in Sagamihara, Kanagawa Prefecture, visited the Department of Dermatology of Kitasato University Hospital because an ulcer which appeared in his left forearm around May 1992 had spread gradually. An oval, shallow ulcer measuring 39 mm x 18 mm was found on the flexor aspect of the left forearm. Histopathological examination showed partial ulceration on the epidermis and marked cell infiltration throughout the entire dermal layer with an abscess in the centre and granulomatous reactions around it. PAS-positive spores were present between infiltrating cells and in giant cells in abscess and in granulomatous reactions. The skin lesion rapidly disappeared after beginning treatment with 125 mg day(-1) terbinafine and only a slight redness remained 14 weeks after starting the treatment. At this time the culture was negative. We conducted immunohistochemical examinations of the affected skin before, during and after starting treatment with terbinafine and studied local expression of cytokines at the affected lesion.
Arm↗
FK506 attenuates early ischemic neuronal death in a monkey model of stroke.
UNLABELLED: FK506 is an immunosuppressive agent that has been reported to have neuroprotective effects in several kinds of rodent models of stroke. The purpose of this study was to evaluate the neuroprotective effects of FK506 in a monkey model of stroke. METHODS: Cynomolgus monkeys underwent 3 h of occlusion followed by 5 h of reperfusion of the right middle cerebral artery (MCA) through a transorbital approach. A single bolus dose of FK506 (0.1 mg/kg) was injected intravenously 5 or 175 min after MCA occlusion. Eight hours after ischemia, a neuropathologic study was performed and the volume of ischemic damage was determined. To measure local cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO(2)), and the oxygen extraction fraction during the experiments, PET scans were obtained using a steady-state (15)O continuous-inhalation method. Four consecutive PET scans (before and 2 h after ischemia and immediately and 3 h after reperfusion) were obtained on each monkey. RESULTS: Treatment with FK506 (0.1 mg/kg) 5 or 175 min after ischemia significantly reduced cortical damage 8 h after ischemia by 82% (P < 0.05) and 73% (P < 0.05), respectively. In PET studies, FK506 did not affect CBF or physiologic parameters in any treatments. In the FK506-treated group, a volume of >40% CMRO(2) reduction 3 h after reperfusion decreased significantly (P < 0.05). CONCLUSION: This study showed that FK506 showed a powerful neuroprotective effect in a nonhuman primate model of stroke. The therapeutic time window of FK506 was at least 3 h after onset. PET studies detected neuroprotective effects only in areas with >40% CMRO(2) reduction 3 h after reperfusion.
Animals↗
[An elderly woman with breast cancer and multiple liver metastasis that responded well to combination therapy of fadrozole and tamoxifen].
Few reports suggest a clinical benefit from combination treatment of fadrozole and tamoxifen for advanced breast cancer in elderly patients. We report the case of an 82-year-old breast cancer patient with multiple liver metastasis. After mastectomy, combination treatment of fadrozole and tamoxifen was added. Two months after the start of this treatment, there was a remarkable reduction in the size of metastatic lesions that continued over 6 months. CT examination revealed the largest lesion was reduced from 8.0 cm to 5.0 cm in largest diameter. The other two lesions were reduced from 3.0 cm to 2.0 cm. The reduction rate was 36%, indicating PR in the Response Evaluation Criteria in Solid Tumors (RECIST). The tumor marker CEA was remarkably reduced from 318 to 85 (ng/ml), and CA15-3 was reduced from 430 to 150 (U/ml). Tumor marker reduction continued over the 6 months corresponding to CT findings. No adverse effect was experienced. This combination therapy was useful and safe against metastatic breast cancer in a patient over 80 years of age.
Administration, Oral↗
Age-related reduction of [11C]MDL100,907 binding to central 5-HT(2A) receptors: PET study in the conscious monkey brain.
Age-related alterations of serotonin (5-hydroxytryptamine; 5-HT) type 2A receptors (5-HT(2A)) in the living brains of young (6.0+/-1. 3 years old) and aged (19.2+/-3.0 years old) monkeys (Macaca mulatta) were evaluated with [11C]MDL100,907 in the conscious state using high-resolution positron emission tomography (PET). For quantitative analysis of 5-HT(2A) binding in vivo, PET scan of [11C]MDL100,907 was performed with arterial blood sampling in each animal, and the metabolic-corrected arterial input function was used for Logan graphical analysis. Higher cerebral binding of [11C]MDL100, 907 was observed in the hippocampus, cingulate gyrus, frontal, temporal and occipital cortices, regions known to contain high densities of 5-HT(2A), by in vitro assay. Binding was intermediate in the striatum and thalamus, and lower in the pons and cerebellum in both young and aged monkeys. The age-related decrease in [11C]MDL100,907 binding to 5-HT(2A) receptors was prominent in the hippocampus, cingulate gyrus, frontal, temporal and occipital cortices, but not in the striatum, thalamus and pons. These observation demonstrated the usefulness of [11C]MDL100,907 as an labeled compound for assessment of the aging process of the cortical 5-HT(2A) measured by PET.
Aging↗
Cholinergic neuronal modulation alters dopamine D2 receptor availability in vivo by regulating receptor affinity induced by facilitated synaptic dopamine turnover: positron emission tomography studies with microdialysis in the conscious monkey brain.
To evaluate the cholinergic and dopaminergic neuronal interaction in the striatum, the effects of scopolamine, a muscarinic cholinergic antagonist, on the striatal dopaminergic system were evaluated multi-parametrically in the conscious monkey brain using high-resolution positron emission tomography in combination with microdialysis. l-3,4-Dihydroxyphenylalanine (l-[beta-(11)C]DOPA) and 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane ([beta-(11)C]CFT) were used to measure dopamine synthesis rate and dopamine transporter (DAT) availability, respectively. For assessment of dopamine D(2) receptor binding in vivo, [(11)C]raclopride was applied because this labeled compound, which has relatively low affinity to dopamine D(2) receptors, was hypothesized to be sensitive to the striatal synaptic dopamine concentration. Systemic administration of scopolamine at doses of 10 and 100 microg/kg dose-dependently increased both dopamine synthesis and DAT availability as measured by l-[beta-(11)C]DOPA and [beta-(11)C]CFT, respectively. Scopolamine decreased the binding of [(11)C]raclopride in a dose-dependent manner. Scopolamine induced no significant changes in dopamine concentration in the striatal extracellular fluid (ECF) as determined by microdialysis. However, scopolamine dose-dependently facilitated the striatal ECF dopamine induced by the DAT inhibitor GBR12909 at a dose of 0.5 mg/kg. Scatchard plot analysis in vivo of [(11)C]raclopride revealed that scopolamine reduced the apparent affinity of dopamine D(2) receptors. These results suggested that the inhibition of muscarinic cholinergic neuronal activity modulates dopamine turnover in the striatum by simultaneous enhancement of the dynamics of dopamine synthesis and DAT availability, resulting in no significant changes in apparent "static" ECF dopamine level but showing a decrease in [(11)C]raclopride binding in vivo attributable to the reduction of affinity of dopamine D(2) receptors.
Animals↗
Effect of probucol on repeat revascularization rate after percutaneous transluminal coronary angioplasty (from the Probucol Angioplasty Restenosis Trial [PART]).
To address the issue of whether probucol reduces clinical events after percutaneous transluminal coronary angioplasty (PTCA), we surveyed clinical status at 1 year after PTCA of 101 patients who had entered the Probucol Restenosis Angioplasty Trial. Repeat angioplasty at index lesions were required in 5 patients in the probucol group and in 12 in the control group, suggesting that probucol administered beginning 4 weeks before PTCA reduces repeat revascularization rates for 1 year.
Angioplasty, Balloon, Coronary↗
Total Synthesis of Bryostatin 3 This work was supported by the Ministry of Education, Science, Sports, and Culture (Japan). K.O. is grateful to JSPS for a predoctoral fellowship. The authors thank Dr. G. N. Chmurny (NIH) for providing them with (1)H and (13)C NMR spectra of bryostatin 3 and for helpful discussions.
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Journal Article↗
Docosahexaenoic acid (DHA) improves the age-related impairment of the coupling mechanism between neuronal activation and functional cerebral blood flow response: a PET study in conscious monkeys.
The regional cerebral blood flow (rCBF) response to vibrotactile stimulation was compared in conscious young (5.9+/-1.8 years old) and aged (18.0+/-3.3 years old) monkeys using [15O]H(2)O and high-resolution positron emission tomography (PET). In addition, the effects of docosahexaenoic acid (DAH), an n-3 polyunsaturated fatty acid (PUFA), on the rCBF response to stimulation were evaluated in aged monkeys. Soybean milk (SBM) or DHA-containing SBM (DHA/SBM) was supplied to aged monkeys for 1 and 4 weeks. Under control conditions, vibrotactile stimulation elicited an increase in the rCBF response in the contralateral somatosensory cortices of both young and aged monkeys, but the degree of increase in the rCBF response was significantly lower in aged monkeys (116% of corresponding 'rest' condition) than that in young animals (141%). The regional cerebral metabolic rate of glucose (rCMRglc) response to the stimulation, an index of neuronal activation, was not significantly different between young and aged monkeys as measured by [18F]-2-fluoro-2-deoxy-D-glucose (FDG). Supply of DHA/SBM at a dose of 150 mg/kg/day as DHA for 1 week resulted in a significant increase in rCBF response to stimulation (127%) in aged monkeys, and 4-week supply of DHA induced further facilitation of the rCBF response (133%). In contrast, the reduced rCBF response in the aged monkeys was not affected by SBM alone for either 1 or 4 weeks. The neuronal activation itself elicited by the stimulation, as measured by [18F]FDG, was not affected by SBM or DHA/SBM. These results suggested the involvement of DHA in the coupling mechanism between the neuronal activation and rCBF response, possibly by modulation of cholinergic neuronal transmission.
Aging↗
Dose-response and duration effects of acute administrations of cocaine and GBR12909 on dopamine synthesis and transporter in the conscious monkey brain: PET studies combined with microdialysis.
The dose-response and duration effects of acute administration of the dopamine transporter (DAT) blocker cocaine and GBR12909 on dopamine synthesis and transporter availability were evaluated in the brains of conscious monkeys using high-resolution positron emission tomography (PET) in combination with microdialysis. Rate of dopamine synthesis and DAT availability were evaluated using L-[beta-11C]DOPA and [11C]beta-CFT (WIN35,428), respectively. Administration of cocaine (0.5, 2 and 5 mg/kg) resulted in dose-dependent elevation of dopamine level in the striatal extracellular fluid (ECF) at 0.5 h after injection, and returned to the baseline level within 1.5 h post-injection. At 0.5 post-injection, cocaine reduced dopamine synthesis rate and DAT availability in a dose-dependent manner. The reduction of DAT availability by cocaine (2 mg/kg) returned to baseline level at 3 h post-injection and thereafter. Interestingly, dopamine synthesis rate was significantly higher at 3 h than baseline level and returned to baseline level 5.5 h post-injection. When GBR12909 (0.5, 2 and 5 mg/kg) was administered 0.5 h before tracer injection, dopamine synthesis rate and DAT availability were significantly decreased in a dose-dependent manner. These reductions induced by GBR12909 (2 mg/kg) lasted at least until 5.5 h post-injection. GBR12909 induced dose-dependent elevation of dopamine level in ECF, and the elevation lasted up to 7 h. The present results indicated that cocaine and GBR12909 affect dopamine synthesis rate and DAT availability in the striatum with difference time courses as measured by PET in the conscious monkey brains.
Animals↗
Impaired glucose tolerance as a determinant of early deterioration of left ventricular diastolic function in middle-aged healthy subjects.
To clarify the determinants of an abnormal relaxation diastolic pattern assessed by Doppler echocardiography, 131 middle-aged healthy subjects were analyzed. By multivariate logistic regression analysis, fasting insulin levels (p = 0.0016) and peak glucose levels (p = 0.046) were independent predictors of an abnormal relaxation diastolic pattern 2 hours after 75 g OGTT.
Diastole↗
Protective effects of soyasapogenol A on liver injury mediated by immune response in a concanavalin A-induced hepatitis model.
The present study was carried out to analyze the effects of soyasapogenol A on the liver injury mediated by the immune response in concanavalin A-induced hepatitis in mice. Soyasapogenol A reduced the number of infiltrating inflammatory cells in the liver and significantly lowered the elevated level of plasma tumor necrosis factor-alpha (TNF-alpha) 2 h after concanavalin A treatment, and then markedly reduced the elevated plasma alanine aminotransferase activity and decreased the number of apoptotic bodies in the liver parenchymal cells but not in the sinusoidal cells at 24 h. Since the effect of soyasapogenol A on the elevated plasma TNF-alpha level was not appreciable compared to the preventive effect of soyasapogenol A on the elevated plasma alanine aminotransferase level, these results suggest that soyasapogenol A directly prevents apoptosis of hepatocytes, and secondly, inhibits the elevation of plasma TNF-alpha, which consequently resulted in the prevention of liver damage in the concanavalin A-induced hepatitis model.
Alanine Transaminase↗
Age-related impairment of coupling mechanism between neuronal activation and functional cerebral blood flow response was restored by cholinesterase inhibition: PET study with microdialysis in the awake monkey brain.
The effects of three cholinesterase inhibitors (physostigmine, E2020, and Tacrine), all of which are to be cognitive enhancers, on the functional regional cerebral blood flow (rCBF) response were studied in young (5.9+/-1.8 years old) and aged (18.0+/-3.3 years old) monkeys under awake conditions using high-resolution positron emission tomography (PET). Under control condition, vibrotactile stimulation elicited increases in the rCBF response in the contralateral somatosensory cortices of both young and aged monkeys, but the degree of increase in rCBF response was significantly lower in aged (115.8%) than that in young monkeys (139.9%). Regional cerebral metabolic rate of glucose (rCMRglc) response to the stimulation, measured using [18F]-2-fluoro-2-deoxy-Dphysostigmine) were consistent with the data obtained by microdialysis. In contrast, the cognitive enhancers did not alter rCBF response to stimulation in young monkeys. The present results demonstrated that the functional change in rCBF response to the stimulation was induced during the aging process by impairment of the coupling mechanism between the neuronal activation and rCBF response. Furthermore, the observation that cognitive enhancers partly restored the functional rCBF response suggested that the coupling mechanism might be regulated via cholinergic neuronal transmission.
Acetylcholine↗
Synthesis and biological activities of hapalosin derivatives with modification at the C12 position.
Among the hapalosin derivatives synthesized, the compounds carrying methyl (5a), methylthioethyl (5d) and phenylmethyl (5e) groups at the C12 position possess only the cis-peptide structure, in contrast to the cases of 5b and 5c. In addition to their conformational stability, the biological activities of the compounds were determined in relation of the P-glycoprotein-mediated MDR-reversing activity and induction of apoptosis.
Antineoplastic Agents↗
Ketamine decreased striatal [(11)C]raclopride binding with no alterations in static dopamine concentrations in the striatal extracellular fluid in the monkey brain: multiparametric PET studies combined with microdialysis analysis.
The effects of ketamine, a noncompetitive antagonist of NMDA receptors, on the striatal dopaminergic system were evaluated multiparametrically in the monkey brain using high-resolution positron emission tomography (PET) in combination with microdialysis. L-[beta-(11)C]DOPA, [(11)C]raclopride, and [(11)C]beta-CFT were used to evaluate dopamine synthesis rate, D(2) receptor binding, and transporter availability, respectively, in conscious and ketamine-anesthetized animals. Dopamine concentrations in the striatal extracellular fluid (ECF) were simultaneously measured by PET. Thirty minutes prior to PET scan, intravenous administration of ketamine was started by continuous infusion at a rate of 3 or 10 mg/kg/h. Ketamine infusion dose-dependently decreased [(11)C]raclopride binding, but induced no significant changes in dopamine concentration in the striatal ECF as measured by microdialysis at any dose used. In contrast, ketamine increased both dopamine synthesis and DAT availability as measured by L-[beta-(11)C]DOPA and [(11)C]beta-CFT, respectively, in a dose-dependent manner. These results suggest that the inhibition of glutamatergic neuronal activity modulates dopamine turnover in the striatum by simultaneous enhancement of the dynamics of dopamine synthesis and DAT availability to the same extent, resulting in no apparent changes in ECF dopamine concentration as measured by microdialysis. It also suggests that the alteration of [(11)C]raclopride binding in vivo as measured by PET might not simply be modulated by the static synaptic concentration of dopamine.
Animals↗
Impact of Doppler-derived left ventricular diastolic performance on exercise capacity in normal individuals.
BACKGROUND: Doppler-derived left ventricular (LV) diastolic indexes have been shown to correlate with exercise capacity in patients with heart diseases as well as healthy individuals. However, it is uncertain whether they predict exercise capacity independent of noncardiac factors. METHODS: To clarify the impact of the LV diastolic index on exercise capacity, 160 healthy individuals were investigated. All underwent Bruce protocol treadmill stress testing and 2-dimensional and Doppler echocardiography. Estimated metabolic equivalent was calculated from exercise time (metabolic equivalent = 1.11 + 0.016 x exercise time). Diastolic performance was assessed by Doppler transmitral flow velocity pattern. Pulmonary function tests and complete blood cell count were also performed. RESULTS: LV diastolic indexes correlated well with metabolic equivalent (peak transmitral filling velocity (A): r = -0.51, P <.0001; ratio of early and late transmitral filling velocities (E/A): r = 0.58, P <. 0001). However, there was no significant correlation between LV systolic indexes and metabolic equivalent. Independent predictors for a higher metabolic equivalent by multivariate analysis were higher E/A (P <.0001), higher vital capacity (P =.001), smaller body mass index (P =.0003), younger age (P =.0050), and higher hemoglobin concentration (P =.0026). CONCLUSION: Doppler-derived LV diastolic index may help in predicting exercise capacity in normal individuals independent of other cardiac and extracardiac factors.
Adult↗