Biomedical subjects

S Yasuhara

Publications and source records attributed to S Yasuhara.

At least 19 recordsLinked to original sources

PubMed2003

Longitudinal study of auditory brainstem response in leigh syndrome.

To assess the utility of auditory brainstem response (ABR) in diagnosing brainstem changes in patients with Leigh syndrome (LS), we performed a longitudinal study of five patients with LS using both ABR and neuroimaging techniques (CT and MRI). The brainstem components of the initial ABRs we performed on the patients were abnormal in all five patients. In four of the patients, these abnormal findings preceded any clinical signs of brainstem impairment. Improvements in clinical findings were reflected in improvements in ABR findings in three patients. In one of these three patients, improvements in clinical findings were also reflected in improvements in MRI findings. In the other two patients, MRI findings showed no improvements, despite the improvements in clinical findings. In two of our patients, ABR clearly revealed functional improvements in the brainstem which were not revealed by MRI. Therefore, we conclude that ABR is an essential diagnostic technique for patients with LS.

Adolescent↗

PubMed2001

Long-term denervation impairs insulin receptor substrate-1-mediated insulin signaling in skeletal muscle.

Long-term denervation is associated with insulin resistance. To investigate the molecular bases of insulin resistance, the downstream signaling molecules of insulin receptor including insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI 3-K) were examined in skeletal muscle of rats after 7 days of denervation. Long-term denervation attenuated insulin-stimulated activation of the initial steps of the intracellular signaling pathway. Insulin-stimulated tyrosine phosphorylation of insulin receptor was reduced to 36% (P < .005), as was the phosphorylation of IRS-1 to 34% (P < .0001) of control. While insulin receptor protein level was unchanged, the protein expression of IRS-1 was significantly decreased in denervated muscles. Insulin-stimulated percent tyrosine phosphorylation of IRS-1, normalized to the IRS-1 protein expression, was also reduced to 55% (P < .01) of control in denervated muscle. Denervation caused a decline in the insulin-induced binding of p85 regulatory subunit of PI 3-K to IRS-1 to 61% (P < .001) and IRS-1-associated PI 3-K activity to 57% (P < .01). These results provide evidence that long-term denervation results in insulin resistance because of derangements at multiple points, including tyrosine phosphorylation of insulin receptor and its downstream signaling molecule, IRS-1, protein expression of IRS-1, and activation of PI 3-K.

Animals↗

PubMed2001

[A survey on occupational health nursing activities and evaluation in TOHOKU area].

We did a mail survey in 1998 in Tohoku district. We sent questionnaires to approximately 300 Occupational Health (OH) nurses and got 132 replies. Occupations of respondents were 66 public health nurses and 57 nurses. More than 70% did not have a managerial position. About 40% were respondents without colleagues in nursing occupations. Full time occupational physicians were in 40% of companies, and semi-full time occupational physicians were in 60%. Respondents citing good coordination in the former were 60%, and in the latter were 80%. Of all business activities occupying OH nursing employees, persons who performed more than 90% of the tasks numbered more than 30%. Persons not satisfied with present employment positions were 80%. Reasons for dissatisfaction in declining order of incidence were work duties, contract conditions for employment, and personal relations. Planning and summary of OH nursing activities were carefully done highly. For the OH nursing activity evaluation, we examined guidelines for business locations by observing them from the OH nursing aspect and the OH nursing job itself. Guidelines considered for business locales from the OH nursing vantage point show numerically, for example, rates of examinees with abnormal findings, work absenteeism, etc, and expectations as to whether or not health conditions are conspicuously reflected in productivity. Conversely, from the OH nursing vantage point for guidelines on business locales, while receiving affirmative economic evaluation of occupational health and safety measures, progress (process) should also be included in the object of evaluation. Furthermore, guidelines should be mindful of the need to have qualitative and quantitative changes in health behavior of workers and perspectives on health.

Adult↗

PubMed2000

Skeletal muscle apoptosis after burns is associated with activation of proapoptotic signals.

Critical illness is associated with muscle wasting and muscle weakness. Using burn injury as a model of local and systemic inflammatory response, we tested the hypothesis that thermal injury causes apoptosis in muscle. After a 40% body surface area burn to rats, abdominal muscles beneath the burn and limb muscles distant from the burn were examined for apoptosis at varying times after burn. Ladder assay, ELISA, and histological methods showed evidence of apoptosis in the abdominal muscles within 4-12 h with peak changes occurring at 3-7 days. Maximal apoptosis was also evident at distant limb muscles at 3-7 days. Investigation of proapoptotic pathways indicated mitochondrial membrane potential to be altered by 1 h after burn. Starting at 15 min after burn, cytochrome c was released from the mitochondria into the cytosol, followed by increased activity of caspase-3, starting at 6 h after burn. These studies suggest that mitochondria and caspase-mediated apoptotic pathways may be an additional mechanism of muscle weight loss in burns and may be potential therapeutic targets for prevention of muscle wasting.

Abdominal Muscles↗

PubMed2000

Immobilization depresses insulin signaling in skeletal muscle.

Prolonged immobilization depresses insulin-induced glucose transport in skeletal muscle and leads to a catabolic state in the affected areas, with resultant muscle wasting. To elucidate the altered intracellular mechanisms involved in the insulin resistance, we examined insulin-stimulated tyrosine phosphorylation of the insulin receptor beta-subunit (IR-beta) and insulin receptor substrate (IRS)-1 and activation of its further downstream molecule, phosphatidylinositol 3-kinase (PI 3-K), after unilateral hindlimb immobilization in the rat. The contralateral hindlimb served as control. After 7 days of immobilization of the rat, insulin was injected into the portal vein, and tibialis anterior muscles on both sides were extracted. Immobilization reduced insulin-stimulated tyrosine phosphorylation of IR-beta and IRS-1. Insulin-stimulated binding of IRS-1 to p85, the regulatory subunit of PI 3-K, and IRS-1-associated PI 3-K activity were also decreased in the immobilized hindlimb. Although IR-beta and p85 protein levels were unchanged, IRS-1 protein expression was downregulated by immobilization. Thus prolonged immobilization may cause depression of insulin-stimulated glucose transport in skeletal muscle by altering insulin action at multiple points, including the tyrosine phosphorylation, protein expression, and activation of essential components of insulin signaling pathways.

Animals↗

PubMed1999

A unique mechanism of desensitization to lipolysis mediated by beta(3)-adrenoceptor in rats with thermal injury.

Thermal injury causes a hypermetabolic state associated with increased levels of catabolic hormones, but the molecular bases for the metabolic abnormalities are poorly understood. We investigated the lipolytic responses after beta(3)-adrenoceptor (beta(3)-AR) agonists and evaluated the associated changes in beta-AR and its downstream signaling molecules in adipocytes isolated from rats with thermal injury. Maximal lipolytic responses to a specific beta(3)-AR agonist, BRL-37344, were significantly attenuated at post burn days (PBD) 3 and 7. Despite significant reduction of the cell surface beta(3)-AR number and its mRNA at PBD 3 and 7, BRL-37344 and forskolin-stimulated cAMP levels were not decreased. Glycerol production in response to dibutyryl cAMP, a direct stimulant of hormone-sensitive lipase (HSL) via protein kinase A (PKA), was significantly attenuated. Although immunoblot analysis indicated no differences in the expression and activity of PKA or in the expression of HSL, HSL activity showed significant reductions. Finally, beta(3)-AR-induced insulin secretion was indeed attenuated in vivo. These studies indicate that the beta(3)-AR system is desensitized after burns, both in the adipocytes and in beta(3)-AR-induced secretion of insulin. Furthermore, these data suggest a complex and unique mechanism underlying the altered signaling of lipolysis at the level of HSL in animals after burns.

Adipocytes↗

PubMed1998

Regulation of brain G-protein go by Alzheimer's disease gene presenilin-1.

To investigate a possible association between G-proteins and presenilin-1 (PS-1), a series of glutathione S-transferase-fusion proteins containing portions of PS-1 were prepared and used in vitro in binding experiments with tissue and recombinant G-proteins. The results demonstrate that the 39 C-terminal amino acids of PS-1 selectively bind the brain G-protein, Go. Addition of guanosine 5'-3-O-(thio)triphosphate promoted Go dissociation from PS-1, indicating that this domain mimics the function of G-protein-coupling domains found in receptors. The 39-amino acid synthetic polypeptide activated Go in a magnesium ion-dependent manner. Physical interaction of full-length PS-1 and Go was also demonstrated. Following transfection of Goalpha and N-terminally FLAG-tagged PS-1 in COS-7 cells, Go was immunoprecipitated by FLAG antibodies. In addition, endogenous PS-1 and Goalpha were colocalized immunocytochemically in human glioma cell lines. The results indicate that PS-1 regulates Go activities in living cells.

Alzheimer Disease↗

PubMed1998

Value of iodine-123 metaiodobenzylguanidine scintigraphy in patients with vasospastic angina.

To assess the presence and location of presynaptic myocardial sympathetic abnormality in patients with vasospastic angina, iodine-123 labelled metaiodobenzylguanidine (MIBG) single-photon emission tomography (SPET) was performed. Fifty patients suspected of having vasospastic angina pectoris were enrolled in the study. All patients underwent a provocative test with intracoronary ergonovine infusion during coronary angiography, in which 99%-100% obstructive spasm was defined as a positive result. Twenty-five patients were diagnosed as having vasospastic angina based on a positive provocative test. MIBG SPET was performed at 20 min and 3 h after administration of 111 MBq or MIBG. On early images, only 5 of 25 patients with vasospastic angina showed a mild reduction in MIBG uptake, whereas 3-h delayed images demonstrated MIBG abnormality in 20 patients (80%). The location of the MIBG abnormality was completely or partially consistent with the spastic coronary territory in 18 patients. On the other hand, only 4 of 25 patients (16%) with negative provocative test demonstrated reduced MIBG uptake. Accordingly, positive and negative predictive values of MIBG SPET for the provocative test were 83% (20/24) and 81% (21/26) respectively. In conclusion, MIBG scintigraphy with SPET can permit the non-invasive detection and evaluation of suspected vasospastic angina.

3-Iodobenzylguanidine↗

PubMed1998

Infective endocarditis-induced crescentic glomerulonephritis dramatically improved by plasmapheresis.

A 50-year-old woman was referred to our hospital because of skin purpura, anemia, high fever, and acute renal insufficiency. Five years ago, she had been diagnosed as having ventricular septal defect without any complications. A blood culture drawn during the hospitalization grew Streptococcus viridans. She was diagnosed as having infective endocarditis-induced crescentic glomerulonephritis (GN) according to echocardiography and renal biopsy results. Although antibiotic treatment alone showed no apparent efficacy, after the initiation of plasmapheresis, the high fever and acute renal insufficiency were dramatically improved. After clinical stability was achieved, closure of the ventricular septal defect was performed. This result suggests that plasmapheresis may be beneficial in the treatment of infective endocarditis-induced crescentic GN. The possible mechanisms of this therapy are discussed.

Acute Kidney Injury↗

PubMed1998

Efficacy of extracorporeal ultrafiltration of ascitic fluid as a treatment of refractory ascites.

BACKGROUND: Refractory ascites is recognized in patients with various conditions. Although intravenous reinjection of ascitic fluid after its filtration and concentration (IRA) is an effective method of treating this condition, many associated side-effects have been reported. We performed extracorporeal ultrafiltration of ascitic fluid (EUA) to demonstrate the efficacy and advantages of this method of treating refractory ascites. METHODS: EUA was performed in seven patients with hepatic cirrhosis (3 cases), lupus nephritis, diabetic nephropathy, and carcinomatous peritonitis (2 cases) for a total of 122 sessions. IRA was performed in three of these seven patients for a total of 12 sessions. RESULTS: The average volumes of ascitic fluid removed by EUA and IRA were 3.94+/-1.45 litres and 2.87+/-0.69 litres (mean+/-SD) respectively. Although chills and acute renal failure were recognized as complications of IRA in five and one sessions respectively, the only complication of EUA was severe intra-abdominal haemorrhage, which resolved spontaneously. In spite of rapid and massive removal of ascitic fluid (maximum 2.0 litres per 15 min), significant changes in blood pressure were not noted during EUA. In three patients (hepatic cirrhosis, lupus nephritis, and diabetic nephropathy), de novo production of ascitic fluid disappeared. In one patient with hepatic cirrhosis and chronic renal failure on haemodialysis, 67 sessions of EUA have been performed under stable conditions. Three patients (one case of hepatic cirrhosis and two cases of carcinomatous peritonitis) died of their primary diseases. CONCLUSIONS: We conclude that EUA is a useful method for the treatment of massive refractory ascites.

Adult↗

PubMed1997

Recombinant expression of caveolin-1 in oncogenically transformed cells abrogates anchorage-independent growth.

Caveolae are plasma membrane-attached vesicular organelles. Caveolin-1, a 21-24-kDa integral membrane protein, is a principal component of caveolae membranes in vivo. Both caveolae and caveolin are most abundantly expressed in terminally differentiated cells: adipocytes, endothelial cells, and muscle cells. Conversely, caveolin-1 mRNA and protein expression are lost or reduced during cell transformation by activated oncogenes such as v-abl and H-ras (G12V); caveolae are absent from these cell lines. However, its remains unknown whether down-regulation of caveolin-1 protein and caveolae organelles contributes to their transformed phenotype. Here, we have expressed caveolin-1 in oncogenically transformed cells under the control of an inducible-expression system. Regulated induction of caveolin-1 expression was monitored by Western blot analysis and immunofluorescence microscopy. Our results indicate that caveolin-1 protein is expressed well using this system and correctly localizes to the plasma membrane. Induction of caveolin-1 expression in v-Abl-transformed and H-Ras (G12V)-transformed NIH 3T3 cells abrogated the anchorage-independent growth of these cells in soft agar and resulted in the de novo formation of caveolae as seen by transmission electron microscopy. Consistent with its antagonism of Ras-mediated cell transformation, caveolin-1 expression dramatically inhibited both Ras/MAPK-mediated and basal transcriptional activation of a mitogen-sensitive promoter. Using an established system to detect apoptotic cell death, it appears that the effects of caveolin-1 may, in part, be attributed to its ability to initiate apoptosis in rapidly dividing cells. In addition, we find that caveolin-1 expression levels are reversibly down-regulated by two distinct oncogenic stimuli. Taken together, our results indicate that down-regulation of caveolin-1 expression and caveolae organelles may be critical to maintaining the transformed phenotype in certain cell populations.

3T3 Cells↗

PubMed1997

Evolution of coronary vascular tone in vasospastic angina.

In general, anginal symptoms diminish with time in patients with vasospastic angina. We assessed changes in coronary vascular tone (CVT) in patients with vasospastic angina over a 4-year period to evaluate the time course of spastic activity. Vasospastic angina was evaluated in 39 patients in whom occlusive spasm was evoked by selective intracoronary injection of ergonovine maleate (ERG-S) 48 h after stopping all coronary vasodilator drugs. These patients had no organic coronary stenosis and developed no stenosis during follow-up. ERG-S was repeated 3 times at 2-year intervals. CVT was determined at each ERG-S study using the equation: CVT = 1-(coronary artery diameter before ERG-S/coronary artery diameter after intracoronary injection of isosorbide dinitrate). Thirty-four patients (87%) had no angina pectoris at the second ERG-S study and 28 (72%) had none at the third. Coronary spasm was induced in 25 patients at the second ERG-S study and in 20 at the third. The overall CVT was shown to decrease at each successive ERG-S study (p < 0.01). There was no correlation between changes in CVT and anginal symptoms or the coronary spasm induction rate. These results demonstrate that CVT decreases over time in patients with vasospastic angina, suggesting that myocardial ischemia may improve spontaneously.

Aged↗

PubMed1997

[Perforation of the intestine by a peritoneal tube 10 years after a ventriculo-peritoneal shunt].

A case is reported of intestinal perforation by a ventriculoperitoneal shunt (V-P shunt) tube 10 years after V-P shunt. A 49-year-old male received V-P shunt for normal pressure hydrocephalus following subarachnoid hemorrhage. Ten years later he was admitted to our department with an abscess on the anterior chest and on the abdominal wall along the shunt tube. When CT scan revealed that the peritoneal tube had perforated the bowel, the shunt was removed. During the operation it was found that the peritoneal tube was wrapped with fibrous tissue and that it had perforated the intestine. The subcutaneous abscess healed after the patient received systemic antibiotics. He was discharged and returned to work. We discussed the mechanism of bowel perforation in this case. It is assumed that bowel perforation occurred because of continuous friction at the same site of the bowel wall after the peritoneal tube received fibrous encasement in the abdominal cavity. Bowel perforation was diagnosed ten years after the V-P shunt in this case. To our knowledge, this is the longest period amongst reported cases.

Equipment Failure↗

PubMed1996

Clonal involvement of eosinophils in therapy-related myelodysplastic syndrome with eosinophilia, translocation t(1;7) and lung cancer.

We report a therapy-related MDS (RAEB) patient with eosinophilia, unbalanced translocation der(7)t(1;7) (q12;q22) and lung cancer. We observed no increase in cytokine levels in serum or in the conditioned medium (CM) of peripheral T cells cultured with or without IL-2. When bone marrow (BM) cells were cultured with GM-CSF, IL-3 and SCF in a semisolid system, the colonies were exclusively eosinophilic. Cytogenetic analysis of the colony cells identified the same chromosome abnormality in all metaphases to that of BM cells. Suspension and clonogenic colony assay of BM cells cultured with various cytokines showed predominant eosinophilic growth and differentiation with GM-CSF, but not with the other cytokines examined. These findings, together with mild morphological abnormalities of eosinophils, indicate clonal involvement of eosinophils in the myelodysplastic syndrome (MDS) clone, and that the eosinophilia was derived from the neoplastic clone with the translocation and was not associated with the patient's lung cancer.

Aged↗

PubMed1996

Regression of moyamoya vessels and hemodynamic changes after successful revascularization in childhood moyamoya disease.

Successful revascularization improves ischemic symptoms in the pediatric patients with moyamoya disease. However, it is not clear whether the revascularization prevents future intracranial hemorrhage from the residual moyamoya vessels. The purpose of this study is to investigate perioperative morphological and hemodynamic changes in the moyamoya vessels. Four pediatric patients (age < 15 years old) with bilateral moyamoya disease were selected for this study. To quantify the number of moyamoya vessels, T1-weighted transverse images at the level of the basal ganglia and the thalamus were selected and characteristic flow voids in the lentiform nucleus were counted. Resting CBF and cerebrovascular reserve capacity (CRC) were measured pre- and 1 year after surgery using Xenon-CT CBF method with acetazolamide test. The ratio of deep CBF/cortical CBF was calculated as an index of hemodynamic stress distribution. The one-year follow-up studies showed that 1) the number of moyamoya vessels decreased on the operative side, but did not change on the non-operative sides in all cases; 2) the ratio of deep CBF/cortical CBF decreased on the operative sides, but did not change in the non-operative sides; and 3) the CRC increased on both sides. This observation suggests the possibility that revascularization surgery may be effective for preventing the future risk intracranial hemorrhage.

Adolescent↗

PubMed1996

Myocardial VO2 of mechanically unloaded contraction of rat ventricular slices measured by a new approach.

We instituted a new approach of measuring mechanically unloaded myocardial oxygen consumption (VO2) by using rat left ventricular (LV) slices in an air-tight chamber filled with oxygenated Tyrode solution. Myocardial slices (300 microns in thickness) freely shortened without external load by electrical field stimulation (St). VO2 without St (n = 6) was 1.69 +/- 0.41 ml O2.min-1.100 g LV-1. VO2 with St (n = 6) increased to 2.28 +/- 0.36 ml O2.min-1.100 g LV-1. VO2 in Ca(2+)-free Tyrode solution irrespective of St was nearly equal to VO2 without St in normal Tyrode solution, indicating that all these VO2 correspond to basal metabolic VO2. The increment in VO2 by St (delta VO2) increased up to twice normal with the extracellular Ca2+ concentration up to 4 times normal. Inhibition of cross-bridge cycling by 2,3-butanedione monoxime (5 and 10 mM) did not decrease delta VO2. These results suggest that delta VO2 consists of VO2 primarily for excitation-contraction coupling but not for cross-bridge cycling.

Animals↗

PubMed1996

Constancy and variability of contractile efficiency as a function of calcium and cross-bridge kinetics: simulation.

We simulated myocardial Ca2+ (Ca) and cross-bridge (CB) kinetics to get insight into the experimentally observed constancy and variability of cardiac contractile efficiency in generating total mechanical energy under various inotropic and pathological conditions. The simulation consisted of a Ca transient, Ca association and dissociation rate constants of troponin C, and CB on and off rate constants. We evaluated sarcomere isometric twitch contractions at a constant muscle length. We assumed that each CB cycle hydrolyzes one ATP and that the force-length area (FLA) quantifies the total mechanical energy generated by CB cycles in a twitch contraction. FLA is a linear version of pressure-volume area, which quantifies the total mechanical energy of cardiac twitch contraction and correlates linearly with cardiac oxygen consumption (H. Suga, Physiol. Rev. 70: 247-277, 1990). The simulation shows that the contractile efficiency varies with changes in the Ca transient and Ca and CB kinetics except when they simultaneously speed up or slow down proportionally. These results point to possible mechanisms underlying the constancy and variability of cardiac contractile efficiency.

Animals↗

PubMed1996

Use of a split dura for revascularization of ischemic hemispheres in moyamoya disease.

A new technique of indirect revascularization using the dural arterial supply to provide donor vessels is presented together with the results of an assay performed to determine the angiogenic activity of the dura. At surgery, a portion of the dura near the branches of the middle meningeal artery was split into outer and inner layers, and the split surface of the outer layer was attached to the cortical surface. This procedure, combined a with standard encephaloduroarteriosynangiosis, was applied to 25 hemispheres in 18 patients with pediatric moyamoya disease (mean age 6 years). All of the patients were symptom free by 1.5 years after surgery. The follow-up period ranged from 1 to 12 years (mean 6.5 years). Thirteen (81%) of 16 patients were able to lead normal lives and three were mildly handicapped due to mental retardation that existed preoperatively. Postoperative superselective angiograms demonstrated effective cortical revascularization through the dural arteries as well as from the scalp arteries. A histological study of the dura in cases of moyamoya disease showed an increased number of blood vessels in the outer layer. Angiogenic activity determined by chorioallantoic membrane assay was higher in the split surface of the dura than in the internal surface of the dura (the natural interface between the dura and cortex). The split duroencephalosynangiosis described in this report is a useful addition to indirect revascularization techniques, allowing extension of the area of revascularization in the ischemic hemispheres of patients with moyamoya disease.

Brain Ischemia↗