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Biomedical subjects

T Ide

Publications and source records attributed to T Ide.

At least 91 records · Page 5Linked to original sources

Role of Ca2+ availability to myofilaments and their sensitivity to Ca2+ in myocyte contractile dysfunction in heart failure.

OBJECTIVE: Contractile function is depressed at the isolated myocyte level in heart failure (HF), which could result from the decreased availability of intracellular calcium ([Ca2+]i) to the myofibrils and/or the depressed sensitivity of myofilaments to [Ca2+]i. However, the cellular basis of contractile dysfunction remains unestablished. METHODS: We isolated left ventricular myocytes from dogs with rapid pacing-induced HF. Cell shortening and [Ca2+]i transients were measured by indo-1 fluorescence and the myofilament Ca2+ sensitivity was analyzed by the shortening-[Ca2+]i relation in intact myocytes as well as by the pCa tension relation in skinned cells. RESULTS: Peak cell shortening magnitude was depressed in HF, associated with a parallel decrease of [Ca2+]i transient amplitude. There was a significant positive correlation between these two variables (r = 0.71, P < 0.01). In contrast, myofibrillar sensitivity to Ca2+, determined by both intact and skinned myocytes, was comparable between control and HF. Further, there was no significant difference in Ca2+ sensitivity between control and HF even at shorter (1.8 microns) or longer (2.2 microns) sarcomere length. CONCLUSIONS: Using both intact and skinned cellular preparations, a potential defect in myocyte contractile function in HF was a reduction in Ca2+ availability to the myofilaments, rather than the inherent defects in myofilament sensitivity to Ca2+.

Actin Cytoskeleton↗

Amelioration by KRP-297, a new thiazolidinedione, of impaired glucose uptake in skeletal muscle from obese insulin-resistant animals.

We examined the effect of KRP-297, a new thiazolidinedione derivative, on glucose uptake in the soleus muscle of two animal models of insulin resistance that show moderate (ob/ob mice) and severe (db/db mice) hyperglycemia. Insulin-stimulated 2-deoxyglucose (2DG) uptake in soleus muscle was 53.8% lower in ob/ob mice versus lean mice (P < .05). When administered to ob/ob mice, KRP-297 (0.3 to 10 mg/kg) decreased plasma glucose and insulin levels and improved the impaired insulin-stimulated 2DG uptake in soleus muscle in a dose-dependent manner. Soleus muscle from db/db mice exhibited defects in both basal (35.0% decrease, P < .01) and insulin-stimulated (50.5% decrease, P < .01) 2DG uptake. These defects were improved by treatment with KRP-297 (0.3 to 10 mg/kg). Moreover, KRP-297 prevented severe hyperglycemia and the marked decrease in pancreatic insulin content in db/db mice. These results suggest that KRP-297 treatment is useful to prevent the development of diabetic syndromes in addition to ameliorating the impaired glucose transport in skeletal muscle.

Animals↗

Sesamin, a sesame lignan, is a potent inducer of hepatic fatty acid oxidation in the rat.

The effects of sesamin, one of the most abundant lignans in sesame seed, on hepatic fatty acid oxidation were examined in rats that were fed experimental diets containing various amounts (0%, 0.1%, 0.2%, and 0.5%) of sesamin (a 1:1 mixture of sesamin and episesamin) for 15 days. Dietary sesamin dose-dependently increased both mitochondrial and peroxisomal palmitoyl-coenzyme A (CoA) oxidation rates. Mitochondrial activity almost doubled in rats on the 0.5% sesamin diet. Peroxisomal activity increased more than 10-fold in rats fed a 0.5% sesamin diet in relation to rats on the sesamin-free diet. Dietary sesamin greatly increased the hepatic activity of fatty acid oxidation enzymes, including carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase, and 3-ketoacyl-CoA thiolase. Dietary sesamin also increased the activity of 2,4-dienoyl-CoA reductase and delta3,delta2-enoyl-CoA isomerase, enzymes involved in the auxiliary pathway for beta-oxidation of unsaturated fatty acids dose-dependently. Examination of hepatic mRNA levels using specific cDNA probes showed a sesamin-induced increase in the gene expression of mitochondrial and peroxisomal fatty acid oxidation enzymes. Among these various enzymes, peroxisomal acyl-CoA oxidase and bifunctional enzyme gene expression were affected most by dietary sesamin (15- and 50-fold increase by the 0.5% dietary level). Sesamin-induced alterations in the activity and gene expression of carnitine palmitoyltransferase I and acyl-CoA oxidase were in parallel with changes in the mitochondrial and peroxisomal palmitoyl-CoA oxidation rate, respectively. In contrast, dietary sesamin decreased the hepatic activity and mRNA abundance of fatty acid synthase and pyruvate kinase, the lipogenic enzymes. However, this lignan increased the activity and gene expression of malic enzyme, another lipogenic enzyme. An alteration in hepatic fatty acid metabolism may therefore account for the serum lipid-lowering effect of sesamin in the rat.

Administration, Oral↗

Methylprednisolone and vitamin E therapy in perinatal hypoxic-ischemic brain damage in rats.

To study the efficacy of methylprednisolone/vitamin E in reducing cerebral edema and improving the ultimate neuropathological outcome in perinatal cerebral hypoxia-ischemia, 40 seven-day postnatal rats were subjected to right common carotid artery ligation followed by exposure to 8% oxygen at 37 degrees C for 3 h. The animals were divided into groups. Twenty rat pups received an intraperitoneal injection of 30 mg/kg body weight methylprednisolone and vitamin E (100 U/kg) immediately following cerebral hypoxia-ischemia. Control animals received either no therapy (n = 10) or an equivalent volume of normal saline (n = 10). After 72 h of recovery from hypoxia-ischemia, the animals were killed and their brains were examined to measure the water contents in the right and left hemispheres (29 rat pups), whereas the others were killed at 21 days for neuropathological examination. Methylprednisolone/vitamin E-treated rats had significantly less water content in the right hemisphere (87.08 +/- 0.28%, mean +/- S.E.M.) than saline-treated animals (89.07 +/- 0.37%, mean +/- S.E.M., P < 0.0001). Methylprednisolone/vitamin E significantly reduced water content in the right hemisphere of the brain. Neuropathological study was performed on nine rat pups. The brains of four methylprednisolone/vitamin E- and five saline-treated pups were examined at the end of the 21-day recovery period. Two groups of the right cerebral cortex included thinning of the cortex. Significantly less damage was seen in the methylprednisolone/vitamin E-treated pups. Our study suggests that trials of methylprednisolone/vitamin E might be effective if they are given to the mother at risk of fetal hypoxia during labor or to the hypoxic infant right after delivery in preventing hypoxic brain damage.

Animals↗

Noninvasive evaluation of in vivo free radical reactions catalyzed by iron using in vivo ESR spectroscopy.

The noninvasive, real time technique of in vivo electron spin resonance (ESR) spectroscopy was used to evaluate free radical reactions catalyzed by iron in living mice. The spectra and signal decay of a nitroxyl probe, carbamoyl-PROXYL, were observed in the upper abdomen of mice. The signal decay was significantly enhanced in mice subcutaneously loaded with ferric citrate (0.2 micromol/g body wt) and the enhancement was suppressed by pre-treatment with either desferrioxamine (DF) or the chain breaking antioxidant Trolox, but only slightly suppressed by the hydroxyl radical scavenger DMSO. To determine the catalytic form of iron, DF was administered at different times with respect to iron loading: before, simultaneously, and after 20 and 50 min. The effect of DF on signal decay, liver iron content, iron excretion, and lipid peroxidation (TBARs) depended on the time of the treatment. There was a good correlation between the signal decay, iron content, and lipid peroxidation, indicating that "chelatable iron" contributed to the enhanced signal decay. The nitroxyl probe also exhibited in vivo antioxidant activity, implying that the process responsible for the signal decay of the nitroxyl probe is involved in free radical oxidative stress reactions catalyzed by iron.

Animals↗

Platanionosides A-C, megastigmane diglycosides from the leaves of Alangium platanifolium.

From the leaves of Alangium platanifolium var. platanifolium collected in Fukuoka Prefecture, Japan, three megastigmane diglycosides (1-3) were isolated, along with two known compounds, benzyl alcohol 7-O-beta-D-(6'-O-beta-D-xylopyranosyl)glucopyranoside and Z-hex-3-en-1-ol 1-O-beta-D-glucopyranoside. The structures of the new compounds, named platanionosides A (1), B (2), and C (3) were elucidated by spectroscopic evidence to be 3S,5R,6R,9R, 7E-megastigma-3,9-diol 3,9-di-O-beta-D-glucopyranoside, 3R,9R, 7E-megastigma-5,7-diene-3,9-diol 3,9-di-O-beta-D-glucopyranoside, and 5R,6S,7E-megastigma-3-on-7-en-9-ol 9-O-beta-D-(6'-O-beta-D-xylopyranosyl)glucopyranoside, respectively.

Chromatography, High Pressure Liquid↗

IgE reactivity and cross-reactivity of Japanese monkeys (Macaca fuscata) to Japanese cedar (Cryptomeria japonica) and cypress (Chamaecyparis obtusa) pollen allergens.

BACKGROUND: The natural occurrence of Japanese cedar (Cryptomeria japonica, CJ) pollinosis has been reported in Japanese monkeys (Macaca fuscata). However, the reactivity to Japanese cypress (Chamaecyparis obtusa, CO) pollen allergens in these monkeys has not yet been reported. OBJECTIVES: The present study was designed to investigate the reactivity to CO pollen allergens in monkeys sensitized to CJ pollen allergens. METHODS: Serum samples from 40 monkeys naturally sensitized to CJ pollen allergens were collected from four troops. We measured the specific IgE to CO pollen allergens and examined the reactivity to the allergens by intradermal test. Cross-reactivity between CJ and CO pollen allergens was examined by ELISA inhibition method. Furthermore, we examined the sensitivity to the allergens by histamine release assay from leucocytes. RESULTS: All 40 monkeys had specific IgE to crude and purified major allergens (Cha o 1) of CO pollen. The monkeys showed a positive reaction to CO pollen allergens in the intradermal test. Allergenic cross-reactivity between Cha o 1 and Cry j 1 (a major allergen in CJ pollen) was also observed. Specific histamine release to both the major allergens was noted in two monkeys with CJ pollinosis. CONCLUSION: Japanese monkeys sensitized to Japanese cedar pollen allergens also demonstrate reactivity to Japanese cypress pollen allergens.

Allergens↗

Advantage of the uncemented total hip system with three spiked socket.

Atotal hip arthroplasty was performed on 112 joints of 110 patients from November 1983 to January 1998 using three different types of uncemented total hip systems with a three spiked socket. The clinical results of 87 joints of 85 patients, followed up 5 years or more after operation, were evaluated with the comparison among the three different types (original type [JIAT] in 6, type Y in 24, and type Y2 in 57). In 73 of the 87 patients, the age at the time of the operation was more than 60. The preoperative diagnosis was osteoarthritis with acetabular hypoplasia in 61, rapidly destructive coxarthrosis in 17, and so on. We have been receiving excellent clinical results of patients who were implanted with type Y2 compared with the other types. There was no different clinical results between patients who were less than 60 and patients who were over 60. Injuries of neurovascular bundle relating to the penetration of the tip of the spike, which was a concern in this type of socket, were not encountered. The type Y2 uncemented total hip system shows an indication of being successful even if the patients have poor bone stock in acetabulum or are elderly.

Acetabulum↗

Mutations in the NS5A gene predict response to interferon therapy in Japanese patients with chronic hepatitis C and cirrhosis.

The virus genotype, serum HCV-RNA level and liver histology are reported to be important factors in the response to interferon therapy. Recent studies have revealed that HCV NS5A 2209-2248 amino acid changes affect the response to interferon therapy of genotype 1b chronic hepatitis C. In contrast, some studies done in western countries have reported no such correlation. In the present study, interferon therapy was given to 58 Japanese patients, including 15 liver cirrhosis patients. NS5A 2209-2248 changes, the serum HCV level, ALT level, age and histology were examined in relation to the interferon effect. Twenty-four of the 58 patients (41%) showed a sustained virological response to the therapy. The responses to interferon therapy were significantly correlated with NS5A 2209-2248 changes (p < 0.0001), the HCV-RNA level (p < 0.0001) and histology (p < 0.0060). Among 15 liver cirrhosis patients, 3 of 6 mutant type patients showed a sustained virological response; 5 intermediate and 4 with wild type virus infected patients showed no responses. In conclusion, NS5A 2209-2248 changes may be a useful predictive marker of response to interferon therapy in addition to the serum HCV RNA level even in histologically advanced patients.

Adult↗

A low concentration of nitrous oxide reduces dyspnoea produced by a combination of hypercapnia and severe elastic load.

We have measured how a low concentration of nitrous oxide affected respiratory sensation and ventilation. Severe dyspnoea was induced in nine normal subjects by a combination of hypercapnia and inspiratory elastic load (50 cm H2O litre-1). Subjects were asked to rate their sensation of respiratory discomfort using a visual analogue scale (VAS) while breathing either 20% nitrous oxide or 20% nitrogen gas mixture. We compared the effects of each gas mixture on respiratory sensation and ventilation using steady-state values of ventilatory variables and VAS scores obtained before, during and after inhalation of each gas mixture. Inhalation of 20% nitrous oxide reduced the sensation of respiratory discomfort from a median VAS score of 6.5 (range 5.0-8.1) before inhalation to 3.6 (2.4-5.9) during inhalation (P < 0.05). There was no significant change in minute ventilation but tidal volume increased during inhalation of 20% nitrogen did not alter VAS scores or ventilatory variables. We found that a low concentration of nitrous oxide greatly alleviated the intensity of dyspnoea without changing respiratory load compensation.

Adult↗

Contribution of peripheral chemoreception to the depression of the hypoxic ventilatory response during halothane anesthesia in cats.

BACKGROUND: The effects of inhalational anesthetics on the hypoxic ventilatory response are complex. This study was designed to determine the contribution of peripheral chemoreception to the depression of hypoxic ventilatory response seen with halothane anesthesia. METHODS: Cats were anesthetized with pentobarbital sodium and alpha-chloralose and artificially ventilated. Respiratory output was evaluated by phasic inspiratory activity of the phrenic nerve. In 12 cats, this activity was measured during inhalation of an hypoxic gas mixture with halothane, 0, 0.1, and 0.8%, with intact or denervated carotid bodies. In 10 cats, a carotid body was isolated from the systemic circulation and perfused with hypoxic Krebs-Ringer solution equilibrated with halothane, 0, 0.1, and 0.8%. RESULTS: The hypoxic ventilatory response was depressed in a dose-dependent manner during halothane anesthesia. In carotid body perfusion studies, the response was significantly depressed only with halothane, 0.80%. CONCLUSION: The hypoxic ventilatory response is depressed by a high dose of halothane through a peripheral effect at the carotid body.

Anesthetics, Inhalation↗

Experimental pain augments experimental dyspnea, but not vice versa in human volunteers.

BACKGROUND: Pain and dyspnea frequently coexist in many clinical situations. However, whether the two different symptoms interact with each other has not been elucidated. To elucidate the interaction between pain and dyspneic sensations, the authors investigated separately the effects of pain on dyspnea and the effects of dyspnea on pain in 15 healthy subjects. METHODS: Subjects were asked to rate their sensation of pain or dyspnea using a visual analog scale (VAS) during pain stimulation produced by tourniquet inflation (inflation cuff pressure: 350 mmHg) around the calf, and/or the respiratory loading consisted of a combination of resistive load (77 cm H2O x l(-1) x s(-1)) and hypercapnia induced by extra mechanical dead space (255 ml). In addition to changes in VAS scores, changes in ventilatory airflow and airway pressure were continuously measured. RESULTS: Pain stimulation and loaded breathing increased VAS scores, ventilation, and occlusion pressure (P0.1). The addition of a pain stimulus during loaded breathing increased the dyspneic VAS score (median 56 [interquartile range 50-62] vs. 64 [55-77]: before vs. after addition of pain stimulus, P < 0.05) with concomitant increases in minute ventilation (10.8 [10.1-13.3] vs. 12.4 [11.0-14.8] l/min, P < 0.05) and P0.1 (5.5 [4.9-7.2] vs. 6.8 [5.8-9.0] cm H2O, P < 0.05). The addition of respiratory loading during pain stimulation did not cause a significant change in pain VAS score (40 [33-55] vs. 31 [30-44]: before vs. after addition of respiratory loading), although both additional burdens increased further minute ventilation (10.0 [8.8-10.9] vs. 12.0 [10.6-13.2] l/min, P < 0.05) and P0.1 (2.5 [2.0-3.0] vs. 6.2 [4.9-7.0] cm H2O, P < 0.05). CONCLUSION: The authors' findings suggest that pain intensifies the dyspneic sensation, presumably by increasing the respiratory drive, whereas dyspnea may not intensify the pain sensation.

Adult↗

Ubiquitin stress response in postischemic hippocampal neurons under nontolerant and tolerant conditions.

Ubiquitin, an essential protein in nonlysosomal proteolytic system, is expressed after metabolic stress to the cell. The authors investigated stress response of ubiquitin in the hippocampus of the Mongolian gerbil after forebrain ischemia. The level of hippocampal ubiquitin was compared with that under ischemic tolerance induced by ischemic preconditioning. The authors also studied ubiquitin gene expression using in situ hybridization method. Transient ischemia resulted in consumption of free ubiquitin and an increase of multiubiquitin chains. These changes were transient in the hippocampus outside of the CA1 region where neurons survived, whereas it was persistent in the CA1 region where neurons were destined to die after ischemia. Under tolerant condition, subsequent ischemia provoked rapid recovery and further increase of free ubiquitin. The signal of ubiquitin messenger ribonucleic acid was continuously detected after ischemia, not only under tolerant conditions, but without tolerance induced by preconditioning. Thus, ubiquitin stress response takes place, at least at a transcriptional level, in dying CA1 neurons. Under tolerant conditions, however, subsequent ischemia in the CA1 region induces the stress response of ubiquitin up to the translational level, leading to the rapid restoration of protein synthesis and to eventual neuronal survival.

Animals↗

Immunohistochemical detection of human telomerase reverse transcriptase in normal mucosa and precancerous lesions of the stomach.

Telomerase activity confers cell immortality through stabilization of the chromosome, participating in the development of a majority of human cancers. Human telomerase reverse transcriptase (TERT) has been identified as a catalytic subunit of telomerase, and is overexpressed in most gastric carcinomas. We immunohistochemically examined the expression of TERT in normal gastric mucosa and candidate precancerous lesions such as intestinal metaplasia and adenoma. In non-neoplastic gastric mucosa including intestinal metaplasia and normal fundic mucosa, weak but significant expression of TERT was detected in nuclei of epithelial cells located in the lower two-thirds of the glands (wider than the proliferative zone). The telomerase activity was found in a half of gastric adenomas, whose levels of the activity were about 10% of those in gastric carcinomas. TERT protein was expressed in the nuclei of the adenoma cells at moderate levels, that were not necessarily comparable with the telomerase activities. These findings overall suggest that TERT expression may be one of the prerequisites for telomerase activation in an early stage of stomach carcinogenesis.

Adenoma↗

Intraspousal transmission of GB virus C/hepatitis G virus in an hepatitis C virus hyperendemic area in Japan.

OBJECTIVE: An immunoassay for antibodies against an hepatitis G virus (HGV) protein (anti-E2) was recently developed that might serve as a useful marker for diagnosing recovery from HGV infection. METHODS: We investigated the intraspousal transmission of GB virus C/hepatitis G virus (GBV-C/HGV) using both reverse transcription hemipolymerase chain reaction (RT-hemi-PCR for the 5' untranslated region) and a recently developed anti-E2. RESULTS: Thirty-two GBV-C/HGV-infected index subjects were selected from an hepatitis C virus hyperendemic area in Japan. Of the 32 subjects, seven (6.4%) were GBV-C/HGV RNA-positive, 24 (21.8%) were anti-E2-positive, and one (0.9%) was both GBV-C/HGV RNA- and anti-E2-positive. Among the 32 spouses of these subjects, GBV-C/HGV RNA, anti-E2, and both GBV-C/HGV RNA and anti-E2 positivity were detected in 0, 6, (18.8%), and one (3.1%) spouses, respectively (the total prevalence of GBV-C/HGV was 7 spouses [21.9%]). Thus, the intraspousal transmission of GBV-C/HGV was undeniable in these seven couples. The respective positive rates of 175 sex- and age-matched controls were 7 (4.0%), 26 (14.9%), and 0 (the total prevalence of GBV-C/HGV was 34 [19.4%]). No significant difference in positive rates was observed between the subjects/spouses and the controls. Five spouses among the seven couples who were positive for any of GBV-C/HGV markers had parenteral risk factors such as blood transfusion, acupuncture, and major surgery. CONCLUSION: Based on these observations, we cannot draw a definitive conclusion that intraspousal transmission of GBV-C/HGV had occurred among these seven couples.

Aged↗

Energy conservation by the H2:heterodisulfide oxidoreductase from Methanosarcina mazei Gö1: identification of two proton-translocating segments.

The membrane-bound H2:heterodisulfide oxidoreductase system of the methanogenic archaeon Methanosarcina mazei Gö1 catalyzed the H2-dependent reduction of 2-hydroxyphenazine and the dihydro-2-hydroxyphenazine-dependent reduction of the heterodisulfide of HS-CoM and HS-CoB (CoM-S-S-CoB). Washed inverted vesicles of this organism were found to couple both processes with the transfer of protons across the cytoplasmic membrane. The maximal H+/2e- ratio was 0.9 for each reaction. The electrochemical proton gradient (DeltamicroH+) thereby generated was shown to drive ATP synthesis from ADP plus Pi, exhibiting stoichiometries of 0.25 ATP synthesized per two electrons transported for both partial reactions. ATP synthesis and the generation of DeltamicroH+ were abolished by the uncoupler 3,5-di-tert-butyl-4-hydroxybenzylidenemalononitrile (SF 6847). The ATP synthase inhibitor N,N'-dicyclohexylcarbodiimide did not affect H+ translocation but led to an almost complete inhibition of ATP synthesis and decreased the electron transport rates. The latter effect was relieved by the addition of SF 6847. Thus, the energy-conserving systems showed a stringent coupling which resembles the phenomenon of respiratory control. The results indicate that two different proton-translocating segments are present in the H2:heterodisulfide oxidoreductase system; the first involves the 2-hydroxyphenazine-dependent hydrogenase, and the second involves the heterodisulfide reductase.

Adenosine Triphosphate↗