Biomedical subjects
Publications and source records attributed to M Ogihara.
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The effects of the alpha 2-adrenergic agonist, clonidine, on the glucagon-stimulated glucose output from serum-free cultures of adult rat hepatocytes were examined in vitro. When hepatocytes were cultured with 10 nM dexamethasone under the serum-free condition, 1 or 10 microM clonidine did not inhibit the glucagon-induced glucose production. In contrast, clonidine dose-dependently inhibited the activity concomitantly with suppression of hepatocyte cAMP production by glucagon when they were cultured with 10 nM dexamethasone and 10 nM insulin. The inhibitory effects of clonidine were completely blocked by prior treatment of hepatocytes with pertussis toxin (100 ng/ml). In addition, forskolin-stimulated cAMP production was also inhibited by alpha 2-adrenergic agonists (clonidine and oxymetazoline) in a dose-dependent manner when hepatocytes were cultured with 10 nM dexamethasone and 10 nM insulin. The inhibitory effects of alpha 2-adrenergic agonists on forskolin-stimulated cAMP production were specifically blocked when they were combined with the alpha 2-adrenergic antagonist yohimbine. Hepatocytes cultured with dexamethasone alone showed no response to the alpha 2-adrenergic agonists. The alpha 2-response was abolished when cycloheximide (0.5 microM) was added to the cultures. These results suggest that insulin develops alpha 2-adrenergic responsiveness through new protein synthesis during the primary culture of adult rat hepatocytes.
A new centrifugal blood pump with a rotor that arranges 6 straight paths radially was developed for open heart surgery and temporary circulatory support. We describe comparative studies of the margin of safety in the practical use of the new pump. This pump was evaluated for temperature increase, cavitation, and pressure sensitivity. Two commercially available centrifugal pumps, the Biomedicus cone type and the Sarns 3M impeller type, were used as control pumps. The temperature increase in the new pump was four times slower than in the impeller pump when the outlet and the inlet of the pump was clamped. No sign of cavitation was observed when 0.1 ml air was introduced to the pump inlet under a negative pressure of 200 mm Hg in fresh bovine blood. As for pressure sensitivity of centrifugal pumps in practical applications, circuit resistance was a more essential factor than flow-pressure curves of the pump.
C3H mice bearing subcutaneously transplanted mouse bladder carcinoma (MBT-2) were treated with intramuscular injection of bleomycin followed by local delivery of electric pulses at the tumor site. The tumors markedly reduced and even disappeared for several days after this treatment. Neither electric pulses nor bleomycin administration alone showed a significant inhibitory effect on the tumor growth. Thus, it is demonstrated that in mouse bladder tumor the antitumor effect of bleomycin can be considerably potentiated by local electric pulses.
A 22-year-old woman had a well differentiated nephroblastic tumor. The tumor was composed of mesenchymal elements with mature tubules and occasionally smooth muscle elements. None of the cellular elements showed any feature indicative of malignancy. Histologically this was similar to congenital mesoblastic nephroma, but the tumor showed an evidence of a uniform expansile growth. It was considered to be a form of mature nephroblastoma.
A 61-year-old man with left renal artery embolus was treated with a continuous selective intra-arterial urokinase (UK) infusion therapy. UK was administered through a 5 Fr. catheter embedded into the occlusive segment of the artery selectively. Continuous low dose UK (15,000 units/hour) was infused following short-term ultra-high dose UK (480,000 units/60 min) infusion. A complete recanalization of the occluded artery was observed by day 7 and also no serious complications were noted during the treatment. Thus, a continuous selective intra-arterial UK infusion therapy seemed to be more effective than conventional methods, especially in patients with complete obstruction.
A patient with Lennox-Gastaut syndrome developed an unusual feature of periodic spasms (PS), intermixed with tonic seizures. At age 14, she began to have unilateral seizures on awaking, followed by series of spasms Each spasm consisted of rotation of the head to the left and global muscle contraction of the whole body lasting for 0.5-1 second. Ictal EEGs revealed diffuse high voltage slow waves (HVSW), sometimes superimposed upon by diffuse low voltage fast activity, which was related to the increase of muscle activity following the spasms. When the duration of the fast activity on EEG became longer than 2 seconds, the peculiar seizures consisting of combination of asymmetrical spasms and tonic seizures occurred. It is speculated that the fast activity superimposed on HVSW seen in PS represents a transition from PS to tonic seizures.
The aim of this study is to evaluate the effects on blood pressure and heart rate of i.v. calcium before the administration of verapamil during the treatment of paroxysmal supraventricular tachycardia (PSVT) in elderly patients. Administration of i.v. verapamil with or without preceding i.v. calcium administration was performed in elderly patients with PSVT. Verapamil (1.0 mg/min) was administered i.v. in 10 patients (Group A) and calcium (3.75 mg/kg for 5 min) followed by verapamil (1.0 mg/min), which was administered i.v. in seven patients (Group B). Blood pressure and heart rate were measured during the study every 5 minutes. Verapamil was effective in suppressing PSVT in both groups. In Group A, i.v. verapamil caused sustained decreases in blood pressure and heart rate over 25 min. In Group B, systolic blood pressure transiently fell immediately after administration of i.v. verapamil, but reversed to the baseline level in 5 min. The absolute and percentage decreases in blood pressure were significantly smaller in Group B than in Group A, whereas changes in heart rate were identical in both groups. Thus, i.v. calcium was effective in preventing hypotension during the treatment of PSVT with verapamil. This regimen was beneficial for elderly patients, since a sufficient dose of verapamil for suppressing PSVT could be administered without causing hypotension.
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The effects of nifedipine and nicardipine on isoproterenol-stimulated gluconeogenesis from 10 mM lactate were examined in serum-free cultures of rat hepatocytes. Nifedipine and nicardipine (10(-7)-10(-5) M) significantly potentiated the isoproterenol-stimulated gluconeogenesis from 10 mM lactate by increasing intracellular cAMP levels. In contrast, diltiazem and verapamil (10(-7)-10(-6) M) did not potentiate it. 1-Methyl-3-isobutylxanthine (IBMX; 10(-6)-10(-4) M), which is known to inhibit phosphodiesterase activity, dose-dependently potentiated isoproterenol-stimulated gluconeogenesis from lactate in serum-free cultures of rat hepatocytes. In parallel, IBMX also increased the isoproterenol-induced intracellular concentrations of cAMP in a dose-dependent manner. These results suggest that the possible mechanism by which nifedipine and nicardipine potentiate the isoproterenol-stimulated gluconeogenesis is related to the increase of cAMP levels through the inhibition of cAMP phosphodiesterase.
The effects of two calcium channel blockers, nifedipine and nicardipine, on glucagon-stimulated glycogenolysis in primary cultures of rat hepatocytes were examined in vitro. When nifedipine and nicardipine (10(-7)-10(-6) M) were added to the incubation mixture with various concentrations of glucagon (10(-10)-10(-6) M), these dihydropyridine calcium channel blockers significantly potentiated the glycogenolytic action of glucagon by increasing intracellular cAMP levels. 1-Methyl-3-isobutylxanthine (IBMX), caffeine and papaverine, which is known to inhibit cAMP phosphodiesterase, also potentiated the stimulatory effect of glucagon on the glycogenolysis in a dose-dependent manner. Parallel to the potentiation of glycogenolysis, IBMX also increased the glucagon-stimulated intracellular cAMP levels in a dose-dependent manner. These results suggest that the mechanism of potentiation of the glucagon-stimulated glycogenolysis by nifedipine and nicardipine is related to the known inhibition of cAMP phosphodiesterase by these agents.
Comparative studies of the differences in elderly patients with and without cardiovascular disorders were made in regard to complications occurring during and after operation. The subjects included 38 patients (6 men and 32 women) aged 70 to 99 years (mean: 84 years) at Nagoya City Kouseiin Geriatric Hospital who had orthopedic surgery under general anesthesia, between March 1990 and October 1992. Diseases identified in these subjects were sequelae of cerebrovascular disease (38 subjects), heart disease (22 subjects), hypertension (9 subjects), senile dementia (6 subjects), Parkinson's disease (5 subjects), malignant disease (3 subjects) and diabetes mellitus (2 subjects). They were initially divided into 2 groups according to ultrasonic cardiography: a normal group comprising 20 patients without cardiovascular abnormalities, and a disorder group comprising 18 patients with reduction of left ventricule function, left ventricular hypertrophy and/or valvular disease (more than moderate). All subjects were examined with regard to age, weight, the nutrition index proposed by Onodera, activity of daily living (ADL), cardiac output, left ventricular ejection fraction, serum level of BUN and albumin etc. Moreover, the disorder group subjects were divided into 2 groups according to the presence or absence of heart failure occurring after surgery. In addition to the above-mentioned, we also studied the duration of surgery and anesthesia, and water balance during and after surgery. Results showed that the ADL and nutrition index in the disorder group were lower compared to the normal group.(ABSTRACT TRUNCATED AT 250 WORDS)
The potential capability of a new dual energy (DE) quantitative computed tomography (QCT) method, 4-equation 4-unknown method (DEQCT4E-4U), was evaluated for estimation of bone mineral density (BMD) as well as bone mineral content/cm width (BMC) in trabecular bone of lumbar vertebrae. Cortical BMD and BMC were also estimated by the single energy QCT method (SEQCT 80 kVp) and the age-related change of cortical BMD and the cortical BMC/trabecular BMC ratio was also studied. The result indicated that the estimation of the BMD combining analysis of BMC in trabecular bone obtained by the present method provides further knowledge concerning vertebral trabecular bone mineral status. The profiles of the age-related changes of the cortical BMD and cortical BMC/trabecular BMC ratio in females were markedly different from those in males. These results indicated that our method combining analysis of BMC (BMD) of cortical bone and trabecular bone was also found to provide valuable information to evaluate the vertebral bone mineral status.
We report a girl 3 years and 6 months old with onset of aphasia at age 3 years and 3 months. There was no evidence of brain damage and there were no seizures. The neuropsychological evaluation showed that the girl tended to be right-handed, that aphasia was global and that other higher cortical functions seemed to be preserved. Isolated spikes and spikes-and-wave were recorded during wake over the right temporal region with rare independent contralateral abnormalities. During polysomnography (PSG), the physiological patterns of sleep were preserved and right temporal epileptiform discharges were significantly increased in all sleep stages. Maximal activation was obtained at sleep onset and during rapid eye movement (REM) sleep periods, when focal abnormalities became continuous and spread contralaterally. Repeat PSGs showed that the activation profile retained this particular trait, although subclinical discharges tended to increase during slow wave sleep (SWS). This pattern of subclinical temporal status epilepticus during REM sleep differs from the characteristic activation profile found in the syndrome of continuous spikes-and-waves during SWS. However, this profile was transient and all epileptiform changes disappeared during clinical recovery at 18 months of follow-up.
The effects of nifedipine and nicardipine on glucagon-stimulated gluconeogenesis from lactate were examined in primary cultures of rat hepatocytes. Nifedipine and nicardipine (10(-7)-10(-5) M) significantly potentiated the glucagon-stimulated gluconeogenesis from lactate by increasing intracellular cAMP levels. In contrast, diltiazem and verapamil did not potentiate the glucagon-stimulated gluconeogenesis. 1-Methyl-3-isobutylxanthine and papaverine also potentiated the glucagon-stimulated gluconeogenesis from lactate. On the basis of these results, possible mechanisms by which nifedipine and nicardipine potentiate the glucagon-stimulated gluconeogenesis will be discussed.
We performed an endocrinological study on three males with persistent pubertal macromastia. The blood testosterone (T) level in these patients was either elevated or at the upper normal limit, estrone (E1) and estradiol (E2) levels were high, and T/E1 and T/E2 ratios were decreased. Persistence of low T/E1 and T/E2 ratios was thought to be the cause of the macromastia. Results of therapy using drugs (cyproterone acetate, tamoxifen citrate, danazol, and clomiphene citrate) were unsatisfactory. Persistent pubertal macromastia is an extreme condition of physiological pubertal gynecomastia, a transient phenomenon in more than half of pubertal males. It is a pathological condition characterized by a great degree of breast enlargement and abnormal endocrinological findings, and its clinical course and treatment are different from those of physiological pubertal gynecomastia.
A chemosensitivity test was carried out on superficial bladder cancer using the dye exclusion assay for the purpose of screening chemosensitive drugs for prophylactic intravesical chemotherapy. Bladder cancer cells of each patients were incubated, in vitro, in the presence of adriamycin, (2"R)-4'-0-tetrahydropyranyladriamycin, mitomycin C, pepleomycin and 4'-epi-adriamycin (500 micrograms/ml) at 5%, CO2, 37 degrees C for 2 hours. The cytotoxic effect of the drugs was evaluated by the ratio of stained cells by trypan-blue. The most effective drug was instilled postoperatively into the bladder 3 times for the first week, and every 2 weeks during the following 14 weeks. In 18 patients followed more than 4 months the prophylactic effect was evaluated. Fifteen of the 18 patients completed the protocol, but the remaining 3 patients failed to complete to the instillation because of severe irritability of the bladder. Tumor recurrence was demonstrated in two patients. Non-recurrence rates of tumors at 12 and 24 months were 93.8% and 82.0%, respectively. These results suggested that this rapid and handy assay was useful for the purpose of screening chemosensitive drugs for the intravesical chemotherapy.
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