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Biomedical subjects

Yoshio Nakamura

Publications and source records attributed to Yoshio Nakamura.

At least 37 records · Page 2Linked to original sources
PubMed2003

Calcineurin is not involved in some mitochondrial enzyme adaptations to endurance exercise training in rat skeletal muscle.

The purpose of this study was to test the hypothesis that calcineurin, a calcium-dependent protein phosphatase recently implicated in the signaling of skeletal muscle hypertrophy and fiber type conversion, is required to induce some mitochondrial enzyme adaptations to endurance exercise training in skeletal muscle. Three- to four-week-old male Sprague-Dawley rats with an initial body weight ranging from 45 to 55 g were used in this study. The rats were randomly assigned to groups injected with either a specific calcineurin inhibitor, cyclosporin A (CsA), (group CI) or vehicle (group VI). CsA was subcutaneously injected into the rats at a rate of 50 mg.kg(-1) body weight per day for 10 days. The CI and VI groups were further assigned to sedentary (SED) or exercise training (EX) groups. In the EX group, the rats were trained for 10 days (90 min.day(-1), approximately 14-20 m.min(-1), 10% grade). The citrate synthase (CS) activities in the soleus and plantaris muscles of the EX group rats were significantly higher than those of the SED group rats ( p<0.001). Furthermore, 3-beta-hydroxyacyl-CoA dehydrogenase (3-HAD) activities in the soleus and plantaris muscles were significantly higher in the EX group rats than in the SED group rats ( p<0.001). However, there were no significant differences in CS and 3-HAD activities between the VI and CI groups. The interactions between CsA injection and exercise training were not statistically significant in any of the parameters. These results may suggest that calcineurin is not involved in some mitochondrial enzyme adaptations to endurance exercise training.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2003

Susceptibility of heat shock protein 70.1-deficient C57BL/6 J, wild-type C57BL/6 J and A/J mice to Trypanosoma congolense infection.

The heat shock protein (HSP) 70.1 gene lies on mouse chromosome 17 among the candidates for Tir1, the major quantitative trait locus associated with response to Trypanosoma congolense infection. To evaluate whether the HSP70.1 gene is involved in the response, we compared the susceptibility of HSP70.1-deficient C57BL/6 J, resistant wild-type C57BL/6 J and susceptible A/J mice. No differences were observed between HSP70.1-deficient and wild-type C57BL/6 J mice in survival time, levels of parasitemia and anemia, suggesting that there is no involvement of the HSP70.1 gene in control of T. congolense infection. The course of infection was markedly different between A/J and C57BL/6 J mice. A/J mice showed a bi-phasic survival pattern, which seemed to be associated with two waves of high parasitemia, but developed only moderate anemia. C57BL/6 J mice controlled parasitemia well but developed severe anemia in the late stage of infection.

Animals↗
PubMed2003

Blood pressure and muscle sympathetic nerve activity during cold pressor stress: fitness and gender.

We examined putative autonomic and hemodynamic mechanisms that might explain our prior finding that cardiorespiratory fitness mitigates blood pressure responses by normotensive women during the hand cold pressor test. We report that fitness level was inversely related to increases in systolic and diastolic blood pressures and muscle sympathetic nerve activity (MSNA) during the cold pressor among women but not men. The pattern of responses among fitter women was consistent with decreased central sympathetic outflow resulting in reduced stroke volume or dampened peripheral resistance in vascular beds other than calf skeletal muscle. Fitter men and women had slightly larger increases in blood pressure during mental arithmetic, but otherwise fitness was not directly related to stress responses. The results further encourage consideration of cardiorespiratory fitness as a modifying covariate when the hand cold pressor test is used as a predictor of future hypertension among women.

Adult↗
PubMed2003

Role of bradykinin in renoprotective effects by angiotensin II type 1 receptor antagonist in salt-sensitive hypertension.

To elucidate whether bradykinin is involved in the renoprotective effect produced by angiotensin II type 1 receptor antagonist (AT1A) in chronic salt-sensitive hypertension, Dahl salt-sensitive rats receiving a high-salt (8%) diet were treated either with an AT1A (candesartan, 1 mg/kg/day), a bradykinin B2 receptor antagonist (BKB2A; FR172357, 30 mg/kg/day) or a combination of AT1A and BKB2A for 7 weeks. None of the treatments changed the markedly increased systolic blood pressure induced by a high-salt diet. However, chronic treatment with AT1A significantly improved the histological hallmarks of renal damage-i.e., glomerular sclerosis and cell proliferation-despite the presence of severe hypertension. This beneficial action of AT1A was abolished by the concomitant administration of BKB2A. In agreement with these histologically based findings, increases in levels of creatinine clearance induced by AT1A were also reversed back to the basal levels when BKB2A was administered in conjunction with AT1A. Furthermore, urinary excretions of nitrate plus nitrite and prostaglandin E2 increased moderately in response to the administration of AT1A alone, but not in combination with BKB2A. Thus, the blockade of bradykinin signaling abrogates the renoprotective actions of the angiotensin II type 1 (AT1) receptor antagonism. Collectively, these data show that when AT1 action is chronically blocked, endogenous bradykinin plays a pivotal role in preventing the progression of glomerular injury in salt-sensitive hypertension.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2003

Remission and regression of diabetic nephropathy.

Diabetic nephropathy has become the single largest cause of end-stage renal disease (ESRD) worldwide. Until recently, it was thought that once a patient developed overt proteinuria, diabetic nephropathy was irreversible and inevitably progressed to ESRD. However, the reversal of lesions caused by diabetic nephropathy (e.g., glomerular basement membrane thickening and mesangial matrix increase) has been demonstrated in a series of patients who underwent a pancreas transplantation 10 years prior to the reversal. Remission of nephrotic range proteinuria has also been reported in some patients with type 1 diabetes from the Collaborative Study Group during a median follow-up of 3 years of angiotensin-converting enzyme (ACE) inhibitor administration; no deterioration of renal function was observed in these patients. Remission and regression in nephropathy of type 1 diabetes patients have also been reported when blood pressure was controlled aggressively. Recent clinical trials have demonstrated that angiotensin II receptor blocker (ARB) preserved renal function and slowed the progression of nephropathy to ESRD in patients with type 2 diabetes. Since many patients with type 2 diabetes manifest with a metabolic syndrome, multifactorial intensive treatment is necessary; such treatment includes behavior modifications, dietary intervention, exercise, and smoking cessation. In this population, pharmacological therapy targeting hyperglycemia, hypertension (including ARB/ACE inhibitor), and hyperlipidemia in cases of type 2 diabetes is also necessary.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

A case of normoreninemic aldosterone-producing adenoma associated with chronic renal failure: case report and literature review.

The diagnosis of aldosterone-producing adenoma (APA) is challenging for endocrinologists, as APA does not always present with the typical constellation of clinical and laboratory features, such as hypertension, hypokalemia, suppressed plasma renin activity (PRA), and high plasma aldosterone concentration (PAC). Very recently, several studies have indicated that APA can be discovered even in normokalemic subjects with normal PRA more frequently than previously considered. Here we report a case of APA associated with chronic renal failure, which showed normokalemia and normal PRA. The patient was referred to our clinic for evaluation of an incidentally discovered adrenal mass with abnormally high PAC. After 6 yr, it was found that the right adrenal tumor showed a marked increase in size. Endocrinological examinations indicated normal PRA and markedly high PAC. Aldosterone showed a better response to the upright posture test than that to ACTH stimulation test. The diagnosis of APA was made based on the markedly high PAC to PRA ratio and the adrenocortical scintigraphy, which showed unequivocal uptake into the tumor. Right laparoscopic adrenalectomy was performed, revealing a right adrenocortical adenoma with massive hemorrhage. Histopathological examinations revealed the presence of two independent adrenocortical adenomas, one APA with predominant clear tumor cells and few c17 (17alpha-hydroxylase) immunoreactivity and the other, cortisol producing adenoma with compact cytoplasm and abundant C17 immunoreactivity. This case indicates a difficulty of diagnosis of "normoreninemic APA" with renal failure. This case is in line with the recent concept that APA is a continuous condition in which only a minority of patients have the classical clinical picture of primary aldosteronism such as hypokalemia. It is possible that normokalemic APA constitutes the most common presentation of the disease.

Adrenal Cortex Neoplasms↗
PubMed2003

Regional differences in blood volume and blood transit time in resting skeletal muscle.

We examined regional differences in blood volume and transit time along the length of a resting skeletal muscle by positron emission tomography. In contrast, blood volume didn't change. The blood transit time increased significantly from proximal to distal portions, suggesting that blood flow velocity slows even though there are no changes in blood volume.

Adult↗
PubMed2003

[Prevention and remission of diabetic nephropathy].

Diabetic nephropathy is the most important cause of end-stage renal failure. Recent clinical trials have postulated the possibility for prevention and remission of the disease once reckoned as irreversible. In DCCT, UKPDS and Kumamoto study, progression to overt proteinuria was prevented by intensive blood glucose control. Lewis study has demonstrated renoprotective effect of ACE inhibitor in type-1 diabetic nephropathy, and RENAAL and IDNT has documented that of angiotensin II type-1 receptor blocker in type-2 diabetes. Moreover, potential efficacy of lipid lowering in prevention of diabetic nephropathy has been postulated in recent Steno-2, multifactorial intervention trial. Thus, simultaneous adjustment on hyperglycemia, hypertension, and dyslipidemia may lead to prevention and remission of diabetic nephropathy.

Angiotensin Receptor Antagonists↗
PubMed2002

Measuring pain: an introspective look at introspection.

The measurement of pain depends upon subjective reports, but we know very little about how research subjects or pain patients produce self-reported judgments. Representationalist assumptions dominate the field of pain research and lead to the critical conjecture that the person in pain examines the contents of consciousness before making a report about the sensory or affective magnitude of pain experience as well as about its nature. Most studies to date have investigated what Fechner termed "outer psychophysics": the relationship between characteristics of an external stimulus and the magnitude and nature of pain experience. In contrast, Fechner originally envisioned that "inner psychophysics" should investigate the relationship between physiological states and subjective experience. Despite the lack of established research tradition, inner psychophysics has a potential utility in elucidating underlying mechanisms for the production of phenomenal self-report. We illustrate this, using causal modeling analyses of the accuracy of self-reported pain ratings from our laboratory. We submit that the results are inconsistent with representationalist assumptions. Converging trends from several domains of consciousness studies seem to suggest that we need to abandon the unquestioned doctrine of representationalism and search for a more viable framework for understanding the generation of subjective self-report.

Adult↗
PubMed2002

Influence of fitness and gender on blood pressure responses during active or passive stress.

We examined hemodynamic and autonomic components of blood pressure responses during active and passive stressor tasks in a sample of young, normotensive men and women who were physically active but differed on fitness (i.e., VO2peak). During the hand cold pressor, increases in systolic blood pressure were inversely related to fitness among women but not men. Regardless of gender, fitter participants had a greater increase in cardiac pace during mental arithmetic, coherent with a decreased cardiac-vagal component of heart rate variability, and a greater compensatory reduction in stroke volume. Fitness was otherwise unrelated to changes in cardiac output and vascular resistance during the stressor tasks. Our findings suggest that cardiorespiratory fitness augments the cardiac-vagal withdrawal that is characteristic of mental arithmetic. The blunted systolic blood pressure response to the hand cold pressor among fitter women suggests that cardiorespiratory fitness should be considered as a covariate in studies that examine the hand cold pressor as a predictor of future hypertension among women.

Adult↗
PubMed2002

A psychophysiological causal model of pain report validity.

The validity of the pain report is vitally important but difficult to assess because pain is a personal experience. Human laboratory research affords an opportunity to investigate validity because one can measure the consistency and sensitivity of pain ratings produced in response to known stimuli. This article presents 2 levels of evidence characterizing the validity of the pain report measure. The within-subject agreement of pain report with known stimulus variation quantifies the criterion validity, or accuracy, of the measure. Causal modeling defines a second, between-subject, level of construct validity by suggesting a psychophysiological mechanism determining the observed individual variation in accuracy. We analyzed pain rating data obtained in a laboratory study where 100 subjects (56 men and 44 women) experienced varied levels of painful fingertip electrical stimulation, delivered in random order across 144 trials. Unknown to the subjects, there were only 3 stimulus intensities. Accuracy, defined operationally as the proportion of variance in pain report explained by stimulus level, ranged from 0.07 to 0.91 with a median of 0.64. Hypothesized determinants of accuracy comprised current intensity, event-related late near field evoked potentials, skin conductance response, heart rate, and pupil diameter change. We limited the evoked potential measures to the amplitude of the negative peak at 150 msec (N150amp) and combined the latter 3 measures to form a single index of overall sympathetic nervous system arousal (Arousal). Although men chose higher stimulus levels for the experiment and had higher Arousal than did women, their mean pain reports and their Accuracy did not differ from those of female subjects. We constructed a sequence of path analysis models designed to clarify the causal contributions of current intensity, N150amp, and Arousal, and to determine whether these relationships differ in men and women. The final model revealed a direct causal chain. Stimulus current determined the amplitude of N150amp (possibly an indicator of attention). N150amp in turn determined Arousal, and Arousal emerged as the sole determinant of the Accuracy of the pain report. In addition, this latter effect differed across the sexes. Men who experienced higher levels of Arousal gave more accurate pain reports than those who had lower levels, but women who had higher levels of Arousal gave less accurate pain reports than those with lower levels. Thus construct validation emerged, not from direct stimulus-response correlation, but from the elucidation of a causal chain that related stimulus to response.

Journal Article↗
PubMed2002

Recombinant tumor necrosis factor alpha does not inhibit the growth of African trypanosomes in axenic cultures.

Mice whose tumor necrosis factor alpha (TNF-alpha) genes were disrupted developed higher levels of parasitemia than wild-type mice following infection with Trypanosoma congolense IL1180 or T. brucei brucei GUTat3.1, confirming the results of earlier studies. To determine whether TNF-alpha directly affects the growth of these and other bloodstream forms of African trypanosomes, we studied the effects of recombinant mouse, human, and bovine TNF-alpha on the growth of two isolates of T. congolense, IL1180 and IL3338, and two isolates of T. brucei brucei, GUTat3.1 and ILTat1.1, under axenic culture conditions. The preparations of recombinant TNF-alpha used were biologically active as determined by their capacity to kill L929 cells. Of five recombinant TNF-alpha lots tested, one lot of mouse TNF-alpha inhibited the growth of both isolates of T. brucei brucei and one lot of bovine TNF-alpha inhibited the growth of T. brucei brucei ILTat1.1 but only at very high concentrations and without causing detectable killing of the parasites. The other lots of mouse recombinant TNF-alpha, as well as human TNF-alpha, did not affect the growth of any of the test trypanosomes even at maximal concentrations that could be attained in the culture systems (3,000 to 15,000 U of TNF-alpha/ml of medium). These results suggest that exogenously added recombinant TNF-alpha generally does not inhibit the growth of African trypanosomes under the culture conditions we used. The impact of TNF-alpha on trypanosome parasitemia may be indirect, at least with respect to the four strains of trypanosomes reported here.

Animals↗
PubMed2002

Rapidly progressive glomerulonephritis due to rifampicin therapy.

A 60-year-old man was treated with rifampicin, isoniazid, ethambutol and pyrazinamide for pulmonary tuberculosis. Acute renal failure developed 1 month after re-administration of rifampicin following 1 month's interruption of treatment. A renal biopsy showed crescentic lesions characteristic of rapidly progressive glomerulonephritis. This is, to our knowledge, the fourth case of rapidly progressive crescentic glomerulonephritis associated with rifampicin treatment, which responded to methylprednisolone pulse therapy followed by oral steroid therapy.

Antibiotics, Antitubercular↗
PubMed2002

Plasma orexin concentrations in patients on hemodialysis.

BACKGROUND: Orexins A and B are neuropeptides that regulate feeding behavior and are localized exclusively in neurons within and around the lateral hypothalamic area. Intracerebroventricular injection of orexin A stimulates food consumption in rats. Plasma concentrations of orexins may reflect nutritional states and may have clinical significance in patients on hemodialysis. In this study, we investigated the relationship between plasma orexin concentrations and nutritional states in patients on hemodialysis. METHOD: We measured plasma orexin concentrations in patients on hemodialysis (HD group, n = 67), patients with IgA nephropathy (n = 10), patients with diabetes mellitus (n = 11) and healthy controls (n = 10). We examined the relationships between plasma orexin concentrations and nutritional indices. RESULTS: Plasma orexin A concentrations were significantly higher in the HD group than in the control group and showed a significant correlation with serum creatinine. In all subjects, there was a positive correlation between the plasma orexin A concentration and the serum creatinine concentration, but there were no correlations between these concentrations in each group. In the HD group, plasma orexin A concentrations had a significant positive correlation with the serum albumin concentration and percent creatinine generation rate (%CGR). Multiple regression analysis demonstrated that %CGR was the only independent factor associated with plasma orexin A concentrations. CONCLUSION: Plasma orexin A concentrations are increased in patients on hemodialysis. It is possible that the kidney plays a major role in the clearance of orexins. The plasma orexin A concentration is significantly correlated with %CGR, and it may be able to be used as a clinical marker of the nutritional state in patients on hemodialysis.

Adult↗
PubMed2002

High-dose calcium stimulation test in a case of insulinoma masquerading as hysteria.

It is reported that some cases with insulinoma present with neuropsychiatric symptoms and are often misdiagnosed as psychosis. Here we report a case of insulinoma masquerading as hysteria, whose final diagnosis could be made using high-dose calcium stimulation test. A 28-yr-old woman was referred presenting with substupor, mutism, mannerism, restlessness, and incoherence. Laboratory examinations revealed hypoglycemia (33 mg/dL) and detectable insulin levels (9.7 microU/mL), suggesting the diagnosis of insulinoma. However, neither imaging studies nor selective arterial calcium injection (SACI) test with a conventional dose of calcium (0.025 mEq/kg) indicated the tumor. High-dose calcium injection (0.05 mEq/kg) evoked insulin secretion when injected into superior mesenteric artery. A solitary tumor in the head of the pancreas was resected, and her plasma glucose returned to normal. Postoperatively, iv injection of secretin resulted in a normal response of insulin, which was not found preoperatively. This case suggests the usefulness of the SACI test with high-dose of calcium in the case of insulinoma when the standard dose fails to detect such a tumor.

Adult↗
PubMed2002

[A case of minimal change nephrotic syndrome manifesting acute renal failure in the course of systemic lupus erythematosus].

A 51-year-old woman with systematic lupus erythematosus(SLE) associated with minimal change nephrotic syndrome(MCNS) is described. The patient was diagnosed as SLE at 33 years of age. After steroid therapy for two years, the patient's course was uneventful without therapy until June 2000, when facial erythema and facial, pretibial edema developed. On admission, proteinuria and renal dysfunction were detected. Subsequently, oliguric acute renal failure developed and hemodialysis was started. Laboratory examination showed no significant change in complements and anti ds-DNA antibody levels. Renal biopsy revealed minor glomerular abnormalities without the deposition of immune complexes. Electron microscopic examination showed foot process fusion and a vacuolar change in glomerular epithelial cells. The diagnosis of MCNS was made and administration of steroid(40 mg/day) was started. Urine volume and renal function improved after 2 weeks, and nephrotic syndrome remitted completely after 5 weeks. Although the association of SLE and MCNS is rare, the findings suggest that in the course of SLE manifesting acute ranal failure, not only lupus nephritis, but also the complication of MCNS should be considered.

Acute Kidney Injury↗
PubMed2002

[Effect of angiotensin II receptor blocker on insulin signaling in skeletal muscle cells].

Impairment of insulin-dependent glucose uptake in skeletal muscles plays a major role in the pathogenesis of diabetes mellitus. Angiotensin converting-enzyme inhibitor (ACEI) has been demonstrated to improve insulin-sensitivity in diabetic patients, partly through the increase in peripheral blood flow mediated by either suppressed angiotensin II or elevated bradykinin. Recently, angiotensin II type-1 receptor blocker (ARB) has been shown to produce similar effects, postulating the importance of intracellular signaling cross-talk between angiotensin II and insulin. In this brief review, we focused on insulin receptor substrate-1(IRS-1) in skeletal muscle cells, and the significance of its serine(612)-phosphorylation was discussed.

Angiotensin Receptor Antagonists↗