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Biomedical subjects

S Sakamoto

Publications and source records attributed to S Sakamoto.

At least 181 records · Page 10Linked to original sources

Hopelessness in a community population: factorial structure and psychosocial correlates.

The factorial structure of the Beck Hopelessness Scale (BHS; A. T. Beck, A. Weissman, D. Lester, & L. Trexler, 1974) was examined in a nonclinical sample (N = 154) in Japan, and the relationships between dimensions of hopelessness and psychosocial variables were analyzed. A semistructured interview was used, as well as a questionnaire consisting of the BHS, the Eysenck Personality Questionnaire (EPQ; H. J. Eysenck & S. B. Eysenck, 1975), and the Parental Bonding Instrument (PBI; G. Parker, H. Tupling, & L. B. Brown, 1979). A factor analysis with principal components solution after oblimin rotation yielded 2 factors--Doubt About a Hopeful Future (Factor 1) and Belief About a Hopeless Future (Factor 2). Significant, positive correlations were found between Factor 2 and (a) the number of emotional symptoms of depression in a 4-day depressive episode and (b) scores on the Neuroticism subscale of the EPQ. The Factor 1 score was significantly and negatively correlated with the Extraversion subscale of the EPQ and the Paternal Care subscale of the PBI.

Adolescent↗

Clinical evaluation of a portable digital hearing aid with narrow-band loudness compensation.

A new portable digital hearing aid referred to as CLAIDHA (Compensate for Loudness by Analyzing Input-signal Digital Hearing Aid), which employs frequency-dependent amplitude compression based on narrow-band loudness compensation, was clinically evaluated in 159 subjects with hearing loss. The results of speech tests revealed better intelligibility compared with the subject's own hearing aids; the advantage of using CLAIDHA in daily life was also indicated by the results of a questionnaire completed by the subjects. In about 64% of the subjects with a flat, gradually sloping type of hearing loss, CLAIDHA was satisfactorily adopted for daily use. However, in the subjects with a steeply sloping type of hearing loss and subjects with losses mainly at high and low frequencies, with near-normal mid-frequency hearing. this loudness compensation scheme seems to be slightly less effective.

Aged↗

Dynamics of hepatitis C viremia following interferon-alpha administration.

Knowledge of the dynamics of hepatitis C virus (HCV) in vivo is important for elucidation of its pathogenesis and the establishment of therapeutic guidelines. The aim of this study was to obtain kinetic information about virus load following interferon-alpha (IFN-alpha) administration. Serial serum HCV core protein and HCV RNA levels were measured. IFN-alpha exponentially reduced serum HCV levels. The mean (+/-SD) viral half-life was 7.0 +/- 2.6 h in HCV core protein assay and 7.2 +/- 3.1 h in HCV RNA assay on the first day of therapy. This initial rapid decrease was followed by a slower decrease in serum HCV levels thereafter. Thus, the biphasic reduction in virus load during IFN-alpha therapy was demonstrated.

Adult↗

Additive effects of medroxyprogesterone acetate and 5-fluorouracil derivative on 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors.

Chronic oral administration of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil suppressed thymidylate synthetase (TS) gene expression followed by reduction of TS activity in rat mammary tumors induced with 7,12-dimethylbenz[a]anthracene. Addition of medroxyprogesterone acetate (MPA) to the anticancer drug caused an additional decrease in TS and thymidine kinase activities in the tumor growth and restoration of bone loss. These results suggest that the simultaneous administration of MPA and anticancer drugs causes increased inhibition of mammary tumor growth and also diminishes the bone loss.

9,10-Dimethyl-1,2-benzanthracene↗

In-vitro characterization of YM872, a selective, potent and highly water-soluble alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonist.

The in-vitro pharmacological properties of (2,3-dioxo-7-(1H-imidazol-1-yl)-6-nitro-1,2,3,4-tetrahydro-1-quinoxal inyl)-acetic acid monohydrate, YM872, a novel and highly water-soluble alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-receptor antagonist were investigated. YM872 is highly water soluble (83 mg mL(-1) in Britton-Robinson buffer) compared with 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX), 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione hydrochloride (YM90K) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). YM872 potently inhibits [3H]AMPA binding with a Ki (apparent equilibrium dissociation constant) value of 0.096 +/- 0.0024 microM. However, YM872 had very low affinity for other ionotropic glutamate receptors, as measured by competition with [3H]kainate (high-affinity kainate binding site, concentration resulting in half the maximum inhibition (IC50) = 4.6 +/- 0.14 microM), [3H]glutamate (N-methyl-D-aspartate (NMDA) receptor glutamate binding site, IC50 > 100 microM) and [3H]glycine (NMDA receptor glycine-binding site, IC50 > 100 microM). YM872 competitively antagonized kainate-induced currents in Xenopus laevis oocytes which express rat AMPA receptors, with a pA2 value of 6.97 +/- 0.01. In rat hippocampal primary cultures, YM872 blocked a 20-microM AMPA-induced increase of intracellular Ca2+ concentration with an IC50 value of 0.82 +/- 0.031 microM, and blocked 300-microM kainate-induced neurotoxicity with an IC50 value of 1.02 microM. These results show that YM872 is a potent and highly water-soluble AMPA antagonist with great potential for treatment of neurodegenerative disorders such as stroke.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Does prolonged exercise alter diet-induced thermogenesis?

Diet-induced thermogenesis (DIT) is mainly an insulin-mediated response and the result of fat and glycogen synthesis. We investigated DIT at rest and after exercise to clarify the mechanism of exercise-induced changes in DIT in 6 healthy men (mean age 36 +/- 16 years). Subjects exercised for 1 h at 58% of maximal O2 consumption on a bicycle ergometer and then rested for 8 h sitting in a comfortable chair (exercise experiment). On a different day, subjects rested for 8 h without preceding exercising (non-exercise experiment). At 12.30 h, the subjects were given their second meal. DIT to individual meal did not differ significantly between the exercise and non-exercise days. Increased insulin sensitivity and increased free fatty acid oxidation by exercise may facilitate the conversion of glucose to glycogen in muscle. On the other hand, insulin secretion expressed as the ratio of plasma levels of insulin to glucose after the meal was significantly decreased in the exercise experiment (p < 0.05). Study of heart rate variability showed that sympathetic tone, a primary hormonal determinant of glucose metabolism during exercise, was increased and parasympathetic tone was decreased during the recovery period in the exercise experiment (p < 0.05). These findings suggest that changes in DIT are affected by many factors and may be related to the balance between these counteracting factors.

Adult↗

Respiratory quotient in patients with non-insulin-dependent diabetes mellitus treated with insulin and oral hypoglycemic agents.

The respiratory quotient (RQ) reflects the amount of energy derived from carbohydrate as apposed to fat metabolism. To assess the metabolic state of patients with non-insulin-dependent diabetes mellitus, the RQ was measured five times a day (at 09.00, 11.00, 13. 00, 14.00, and 17.00 h) in 20 healthy subjects and 60 diabetic patients. Diabetic patients treated with insulin or sulfonylurea showed significantly higher RQ values than normal subjects and nontreated diabetic patients. Diabetic patients without treatment showed higher glucose levels, and their RQ values were significantly lower than those of treated patients. There was a significant inverse correlation between RQ and blood glucose levels at 11.00 h (r = -0.361, p < 0.01) in diabetic patients, but no significant relation with HbA1c. Treated diabetic patients with a higher body mass index tended to show a higher RQ than those with a lower one (r = -0.269, p = 0.083). Within 1 year, 7 of 13 patients, who had RQ > 1.0, gained more than 3 kg, while only 5 of the remaining 32 treated diabetic patients gained more than 3 kg (p < 0.05). This demonstrates that diabetic patients with a higher RQ tended to gain weight despite the use of insulin or oral hypoglycemia agents. The RQ increased by infusing both insulin and glucose in normal subjects. These results suggest that a high RQ results from excess insulin and excess food. The RQ is a good predictor of weight gain in diabetic patients treated with either insulin or oral hypoglycemic agents.

Calorimetry, Indirect↗

Interleukin-1beta induces tissue- and cell type-specific expression of adhesion molecules in vivo.

We examined the tissue distribution of adhesion molecule gene expression in mice treated intravenously with interleukin (IL)-1 beta. E-selectin mRNA expression was selectively induced in the heart by IL-1 beta, but only slight or no induction was observed in other organs. On the other hand, intercellular adhesion molecule-1 mRNA expression was inducible in all organs examined, although it showed the strongest induction in the lung and the weakest responses in the brain and skin. Vascular cell adhesion molecule-1 mRNA was also inducible in all organs with the exception of the skin, but it was induced most markedly in the lung and the heart. The accessibility of IL-1 beta to the heart was less than that to other organs except the brain. Similar tissue-specific induction of these mRNAs was also seen when tumor necrosis factor (TNF)-alpha or lipopolysaccharide was substituted for IL-1 beta. Analysis of E-selectin mRNA expression in the heart by in situ hybridization indicated that expression was most prominent in microvascular endothelial cells and some other stromal cells, but this transcript was not seen in the lung. Although intercellular adhesion molecule-1 mRNA expression was restricted to the endothelium lining the capillaries and small arteries in the heart, its distribution in the lung covered not only the endothelium but also the cells composing the alveolar septa. In contrast, vascular cell adhesion molecule-1 mRNA expression was most prominent in endothelial cells of larger vessels in both the heart and the lung. Our results demonstrate that expression of adhesion molecules is tissue- and cell type-specific and that endothelial cells differentially express adhesion molecules depending on the size of the blood vessels.

Animals↗

Regional cerebral glucose metabolism in dementia with Lewy bodies and Alzheimer's disease.

OBJECTIVE: To delineate the features of regional cerebral metabolic rate of glucose (CMRglc) in dementia with Lewy bodies (DLB). METHODS: We compared absolute CMRglc in 12 patients with a clinical diagnosis of DLB, 12 patients with a clinical diagnosis of Alzheimer's disease (AD), and 12 normal volunteers (NC), using 18F-fluorodeoxyglucose (FDG) and PET. The three groups were matched for age and sex, and there were no differences in disease duration or severity of cognitive disturbances between the DLB and AD groups. RESULTS: CMRglc was significantly lower in patients with DLB than in that of NC in most parts of the brain, except the sensorimotor cortices, basal ganglia, thalamus, and pons. Between the DLB and AD groups, there were significant regional CMRglc differences in the medial and lateral occipital lobes. In DLB and AD, the CMRglc reduction patterns were similar, though the global metabolic reduction was larger in DLB, and the occipital CMRglc reduction in DLB could differentiate DLB from AD. The relative occipital CMRglc (normalized to the sensorimotor CMRglc) was a useful measure for the differential diagnosis of DLB from AD. The sensitivity and the specificity were 92% when using the minimal value of the normalized occipital CMRglc in the NC group as the cut-off point. CONCLUSION: These different regional CMRglc reductions substantiate the pathologic, neurochemical, and clinical differences between DLB and AD.

Aged↗

Studies on novel bone resorption inhibitors. II. Synthesis and pharmacological activities of fused aza-heteroarylbisphosphonate derivatives.

Two new series of fused aza-heteroarylbisphosphonates (5, 8), which are structurally quite different from incadronate (YM175), and related compounds were synthesized and evaluated for antiresorptive activity using a parathyroid hormone(PTH)-induced hypercalcemia model in rats (PIH model). Among these compounds, several exhibited more potent antiresorptive activity than pamidronate. In particular, [1-hydroxy-2-(imidazo[1,2-a]pyridin-3-yl)ethylidene]bisphosphonic acid (5b, minodronate) was 100-fold more potent than pamidronate in not only the PIH model, but also in an immobilization bone atrophy model in rats (DA model), and was selected for clinical development. The structure-activity relationships in these new series of bisphosphonates are discussed.

Animals↗

The AMPA-receptor antagonist YM90K reduces AMPA receptor-mediated excitotoxicity in rat hippocampal cultures.

The effects of YM90K on alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated excitotoxicity were investigated using kainate, AMPA and cyclothiazide in rat hippocampal cultures. YM90K had neuroprotective actions against both kainate toxicity and cyclothiazide-enhanced AMPA toxicity. YM90K induced a parallel and rightward shift of both kainate and AMPA dose-response curves. The application of YM90K even 3 hr after the start of kainate exposure significantly reduced kainate toxicity. These results indicate that YM90K protects neurons against AMPA receptor-mediated toxicity at an agonist site on the AMPA receptor and that YM90K protects against AMPA receptor-mediated toxicity even if applied after neurotoxic insult.

Animals↗

Intramedullary hemangioblastoma of the medulla oblongata--two case reports and review of the literature.

We determined the treatment modality of hemangioblastoma of the brain stem on the bases of our two cases and 31 cases searching from the literature since 1960 which were treated surgically. Hemangioblastomas of the brain stem were categorized according to one of three locations: hemangioblastoma of the fourth ventricle attached to the floor of the ventricle (Type A), hemangioblastoma of the fourth ventricle partially embedded in the floor of the ventricle (Type E), and intramedullary hemangioblastoma of the medulla oblongata (Type I); and were evaluated their clinical features including the operative mortality and morbidity of each location. In our two cases of Type I hemangioblastoma, Case 1, removed partially, died due to sleep apnea and Case 2 lead to normal school life after hemangioblastomas were removed radically. In our review of the 33 surgically-treated cases, radical excision was carried out in 29 cases (87.9%). The mortality was 24.2% overall; that of Type A was 25%, Type E was 28.6%, and Type I was 14.3%. In terms of postoperative mortality, the location of the hemangioblastoma was irrelevant and radical excision was much better than partial removal. Hemangioblastomas of the brain stem could be removed radically by meticulous dissection of the tumor on distinct cleavage, even in cases of intramedullary location. Microsurgical dissection of medullary hemangioblastomas with low morbidity is feasible and prudent postoperative care is mandatory to reduce the operative mortality and morbidity.

Adolescent↗

Effect of exercise training and food restriction on endothelium-dependent relaxation in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous NIDDM.

We investigated whether endothelial function may be impaired in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous NIDDM. The effect of exercise training and food restriction on endothelial function was also studied. OLETF rats were divided into three groups at age 16 weeks: sedentary, exercise trained, and food restricted (70% of the food intake of sedentary rats). Otsuka Long-Evans Tokushima rats were used as the age-matched nondiabetic controls. Endothelium-dependent relaxation of the thoracic aorta induced by histamine was significantly attenuated in the sedentary or food-restricted rats, and exercise training improved endothelial function. Relaxation induced by sodium nitroprusside, a donor of nitric oxide, did not differ significantly among groups. Both exercise training and food restriction significantly suppressed plasma levels of glucose and insulin and serum levels of triacylglycerol and cholesterol and reduced the accumulation of abdominal fat. Insulin sensitivity, as measured by the hyperinsulinemic-euglycemic clamp technique, was significantly decreased in sedentary rats but was enhanced in exercise-trained and food-restricted rats. The urinary excretion of nitrite was significantly decreased in sedentary and food-restricted rats compared with nondiabetic rats and was significantly increased in exercise-trained rats. These results indicate that exercise training, but not food restriction, prevents endothelial dysfunction in NIDDM rats, presumably due to the exercise-induced increase in the production of nitric oxide.

Abdomen↗

Japanese psychology students as psychiatric diagnosticians: application of criteria of mood and anxiety disorders to written case vignettes using the RDC and DSM-IV.

It is commonly believed in Japan that only psychiatrists are capable of providing reliable psychiatric diagnosis. The present study, therefore, examined using a case vignette design, how well Japanese psychology students agreed with a psychiatrist on the diagnoses of mood disorders (major depressive disorder and bipolar disorder) and anxiety disorders (pain disorder, obsessive-compulsive disorder, phobic disorder, and generalized anxiety disorder). The results suggest that appropriately trained Japanese psychology students can apply reliably the diagnostic criteria for these disorders, except for generalized anxiety disorder. It appeared that the students did not identify symptoms of restlessness and nervous tension, which may explain the relatively low reliability of the diagnosis for generalized anxiety disorder. The cross-cultural variation in the experience of anxiety is suggested as an explanation. The present study argues that it is feasible that Japanese nonmedical mental health professionals become familiar with the psychiatric diagnoses.

Adult↗

YM872, a novel selective alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, reduces brain damage after permanent focal cerebral ischemia in cats.

YM872 ([2,3-dioxo-7-(1H-imidazol-1-yl)-6-nitro-1,2,3, 4-tetrahydro-1-quinoxalinyl]-acetic acid monohydrate), a selective, potent and highly water-soluble competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, was investigated for its neuroprotective effect against focal cerebral ischemia in halothane-anesthetized cats. Cats were subjected to permanent occlusion of the left middle cerebral artery for 6 h, then sacrificed and examined histologically. The electroencephalogram and cerebral blood flow were monitored. Intravenous infusion of YM872 starting 10 min after the onset of ischemia at a rate of 2 mg/kg/h for 6 h markedly reduced the volume of ischemic damage by 61% (from 2604 +/- 202 mm3 of the cerebral hemisphere in saline-treated cats to 1025 +/- 277 mm3 in YM872-treated cats; P < .01), as assessed in 12 stereotaxically determined coronal sections. No significant differences were observed between YM872- and saline-treated cats concerning physiological variables including brain temperature. No precipitation of YM872 in the kidney was seen in any YM872-treated animal. The present data further support the notion that the AMPA receptor plays an important role in the progression of focal ischemic damage in a gyrencephalic model. This evidence for the neuroprotective efficacy of YM872 suggests its therapeutic potential in the treatment of acute stroke in humans.

Animals↗

Paradoxical hippocampus perfusion in mild-to-moderate Alzheimer's disease.

UNLABELLED: The purpose of this study was to clarify the changes in hippocampal perfusion in mild-to-moderate Alzheimer's disease using PET and (15)O-labeled water. METHODS: Sixteen patients with probable mild-to-moderate Alzheimer's disease (age: 68.1+/-11.3 yr; MMSE: 21.1+/-4.5) and 10 normal volunteers (age: 65.1+/-8.2 yr) were studied. Regional cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured using (15)O-labeled water autoradiographic method, C(15)O-gas inhalation technique and PET. RESULTS: Although the mean CBF in the parietotemporal region was significantly lower in the patient group than in the control group, the mean CBF in the hippocampus did not show significant reduction between the two groups, both in absolute and relative values. There was no significant regional CBV difference between the two groups. Parietotemporal perfusion correlated well with cognitive scores, both in absolute and relative values, in Alzheimer's disease, but hippocampal perfusion did not correlate well. CONCLUSION: Hippocampal perfusion was preserved in mild-to-moderate Alzheimer's disease.

Aged↗