Search PubMed⌕ Search

Biomedical subjects

S Shibata

Publications and source records attributed to S Shibata.

At least 145 records · Page 8Linked to original sources
PubMed1999

Inhibition of light- or glutamate-induced mPer1 expression represses the phase shifts into the mouse circadian locomotor and suprachiasmatic firing rhythms.

mPer1, a mouse gene, is a homolog of the Drosophila clock gene period and has been shown to be closely associated with the light-induced resetting of a mammalian circadian clock. To investigate whether the rapid induction of mPer1 after light exposure is necessary for light-induced phase shifting, we injected an antisense phosphotioate oligonucleotide (ODN) to mPer1 mRNA into the cerebral ventricle. Light-induced phase delay of locomotor activity at CT16 was significantly inhibited when the mice were pretreated with mPer1 antisense ODN 1 hr before light exposure. mPer1 sense ODN or random ODN treatment had little effect on phase delay induced by light pulses. In addition, glutamate-induced phase delay of suprachiasmatic nucleus (SCN) firing rhythm was attenuated by pretreatment with mPer1 antisense ODN, but not by random ODN. The present results demonstrate that induction of mPer1 mRNA is required for light- or glutamate-induced phase shifting, suggesting that the acute induction of mPer1 mRNA in the SCN after light exposure is involved in light-induced phase shifting of the overt rhythm.

Animals↗
PubMed1999

Ischemia-induced neuronal cell loss is associated with loss of atypical angiotensin type-1 receptor expression in the gerbil hippocampal formation.

The hippocampal formation of Mongolian gerbils expresses high amounts of atypical angiotensin II type-1 receptors. We studied the expression of these receptors by in situ hybridization using specific [35S]-labeled riboprobes and by receptor autoradiography using [125I]Sarcosine1-angiotensin II. Angiotensin II receptor mRNA was found in the pyramidal cell layer of the CA1, CA2 and CA3 subfields, with the highest expression in the CA2 subfield, and in the granular cell layer of the dentate gyrus. Angiotensin II binding was detected in the stratum oriens and stratum radiatum of the CA1 and CA2 subfields, in the stratum oriens of the CA3 subfield, and in the molecular layer of the dentate gyrus. We then studied the effect of ischemia on hippocampal angiotensin II receptor expression, 1, 4 and 15 days after bilateral occlusion of the common carotid arteries for 5 min. No changes in angiotensin II receptor mRNA or binding were detected 1 day after ischemia. Delayed, progressive loss of angiotensin II mRNA and binding occurred 4 and 15 days after ischemia, in the CA1, CA2 and CA3 subfields. The decline was faster in the CA1 subfield, and paralleled the loss of neurons after ischemia. In the dentate gyrus, angiotensin II receptor mRNA and angiotensin II binding were not changed when compared to sham operated controls. The decrease of angiotensin II receptor expression may reflect the loss of angiotensin II receptor-producing neurons rather than a down-regulation of receptor expression.

Animals↗
PubMed1999

Effect of interleukin 10 on the hematopoietic progenitor cells from patients with aplastic anemia.

The overproduction of cytokines with inhibitory effects on hematopoiesis is considered to play a role in the pathogenesis of aplastic anemia. While interleukin 10 (IL-10) is a cytokine production inhibitory factor, the possibility of immunosuppressive therapy using IL-10 for aplastic anemia has not been explored. In this study, therefore, we examined the effect of IL-10 on progenitor cells obtained from seven patients with severe aplastic anemia. Our study indicated that IL-10 dramatically enhanced the erythroid colony formation in a dose-dependent manner in two of the seven cases examined. When we examined the concentration of cytokines in the culture supernatants of unstimulated bone marrow cells, the spontaneous production of interferon-gamma (IFN-gamma) was observed in one of these two cases, and this production was completely inhibited by addition of IL-10. These findings suggested that IL-10 enhanced the erythroid colony formation by inhibiting the pathological production of IFN-gamma in this case. This study provides an experimental support for the clinical application of IL-10 in some patients with aplastic anemia.

Adult↗
PubMed1999

Phase II trial of intraperitoneal cisplatin with intravenous doxorubicin and cyclophosphamide in previously untreated patients with advanced ovarian cancer-long-term follow-up.

Forty-three patients with ovarian cancer were entered on this trial and treated with intravenous (iv) cyclophosphamide (C) and doxorubicin (A), and intraperitoneal (ip) cisplatin (DDP), every 21 days for eight cycles. Following iv hydration, the cisplatin was administered through an intraperitoneal catheter in 2 L of 0.9% normal saline with a 4-h dwell. All patients are evaluable for overall and progression-free survival with a median follow-up of 70 months (range: 3-162 months); 39 patients are evaluable for response. All complete responses were surgically confirmed. The median age was 59 (range 28-82 years); 3 patients were stage IC, 5 were IIC, 14 patients were stage III (optimally debulked), 14 patients were stage III (suboptimally debulked), and 7 patients were stage IV. Two patients had received prior alkylator therapy. Six of 8 patients with Stage IC or II remain without evidence of disease at a mean of 12 years following chemotherapy. Of 14 optimally debulked stage III patients, there were 7 complete responses, 3 partial responses, 1 patient with stable disease, and 3 inevaluable patients. Of 14 suboptimally debulked stage III patients there were 4 complete responses, 4 partial responses, 3 with stable disease, 2 progressions on treatment, and 1 inevaluable patient. Five-year progression-free and overall survivals for stage III optimally debulked patients are 21 and 64%, respectively. At 10 years, progression-free and overall survivals for this group are 21 and 29%, respectively. Toxicity included neutropenia (complicated by sepsis in 2 patients), infrequent thrombocytopenia, and mild anemia. Three patients developed transient serum creatinine elevations >2.0 mg/dl; however, decreased creatinine clearance was noted in 93/258 (36%) of evaluable courses which required a cisplatin dose reduction per protocol. Controllable hypomagnesemia, nausea, and emesis were also observed. We conclude that the combination of iv CA and ip DDP is an effective regimen with long-term progression-free and overall survivals that compare favorably with those of other published studies of intravenous or intraperitoneal chemotherapy. This report is unusual in terms of the prolonged follow-up for all patients enrolled. These long-term results lend further support to recently published trials documenting the efficacy of intraperitoneal chemotherapy for patients with this disease.

Adult↗
PubMed1999

The application of immobilized polymyxin B fiber in the treatment of septic shock associated with severe acute pancreatitis: report of two cases.

The elimination of endotoxin by direct hemoperfusion over immobilized polymyxin B fiber (PMX-F) was carried out in two patients who developed septic shock associated with severe acute pancreatitis. Parameters such as blood pressure, body temperature, and plasma endotoxin level improved after PMX-F treatment, and the infected lesions were successfully and safely removed by surgery. Although an aggressive operative strategy of debridement with ultimate closure over drains is generally associated with low mortality in patients with this devastating disease, we often hesitate to perform this operation due to the poor condition of the patient in the acute period, with multiple organ failure and/or septic shock status, and also because of the difficulty in diagnosing the pancreatic infection. In this situation, endotoxin elimination using PMX-F is a useful tool for treating secondary pancreatic infections to help the patient recover in preparation for surgery, or for treating perioperative endotoxemia.

Acute Disease↗
PubMed1999

Characteristics of symptomatic chronic subdural haematomas on high-field MRI.

We studied the frequency of various features of the appearances on high-field MRI in symptomatic patients with chronic subdural haematomas (CSDH). The ability to predict recurrence after treatment with one burr-hole procedure using MRI was evaluated. A total of 40 patients with symptomatic CSDH underwent MRI at 1.5 T. All haematomas were evacuated within a few days of the MRI examination. Symptomatic CSDH were divided into five groups according to the MRI findings: group A (11 cases), isointense or low signal on T1- and low signal on T2-weighted images; group B (18 cases), high signal on T1- and low signal on T2-weighted images; group C (5 cases), high signal on both T1- and T2-weighting; group D (1 case), low signal on T1- and high signal on T2-weighted images; group E (5 cases), heterogeneous intensity on T1- and T2-weighting throughout the haematoma cavity. The mean interval between onset of symptoms and MRI for group A was 5.0 +/- 4.1 days, which was significantly shorter than that for group B (9.4 +/- 4.4 days, P < 0.02), group C (27.8 +/- 20 days, P < 0.005) or group E (17.8 +/- 12.2 days, P < 0.01). Recurrence was seen in three haematomas of group A and one of group B. Reoperation was most closely correlated with diffuse low signal on T2-weighted images but not with a multiloculated appearance. Low signal on T2 weighting was surprisingly high (72.5%) and the age of the haematomas as estimated on the MRI correlated well with the interval between the onset of symptoms and MRI. Our findings support the causative role of recurrent bleeding in the enlargement of CSDH.

Adult↗
PubMed1999

Prune-belly syndrome diagnosed at 14 weeks' gestation with severe urethral obstruction but normal kidneys.

A fetus was diagnosed with prune-belly syndrome (PBS) found by ultrasound demonstration of cystomegaly at 12 weeks' gestation. Fetal urinary electrolyte and beta2-microglobulin concentrations at 14 weeks' gestation indicated a poor renal prognosis. The pregnancy was therefore terminated. An autopsy showed defects of the abdominal wall muscles and megalocystis caused by severe urethral obstruction. However, the kidneys were histologically normal. Together with previous reports, the present case suggests that renal dysplasia in PBS with severe uretheral obstruction may develop after 14 weeks' gestation. We discuss the possibility of preventing the development of renal dysplasia in PBS by early prenatal decompression of the obstructed fetal urinary tract.

Abortion, Induced↗
PubMed1999

Effects of intracisternal methylprednisolone on lipid peroxidation in experimental subarachnoid haemorrhage.

The efficacy of intracisternal methylprednisolone was examined on lipid peroxidation in a canine subarachnoid haemorrhage (SAH) model. The concentration of lipid peroxides increased significantly in the cerebrospinal fluid (CSF) supernatant on Day 4, and also in the arterial wall on Day 7. Intracisternal administration of methylprednisolone reduced markedly the products of lipid peroxidation both in CSF and in the arterial wall. The findings suggest that lipid peroxidation might play a significant role in the genesis of vasospasm after SAH, and that direct administration of methylprednisolone into the subarachnoid space might reduce lipid peroxides in the arterial wall and so influence the prevention of vasospasm.

Animals↗
PubMed1999

Histochemical localization of hyaluronan and versican in the rat molar dental pulp.

The distribution of hyaluronan and versican in the dental pulp of the young rat was mapped histochemically. The pattern of staining showed considerable variation between different teeth and different specimens. The most common pattern was a strong reaction for hyaluronan and a weak reaction for versican in the subodontoblastic region, with the reverse deeper in the pulp. This was not an entirely consistent pattern and there was considerable regional variation in the staining intensity for both molecules. The localization of these molecules at similar sites could thus indicate related roles in the connective tissue matrix rather than any chemical bonding between them.

Animals↗
PubMed1999

The potentiating effect of genistein on the relaxation induced by isoproterenol in rat aortic rings.

In rat aortic rings, the mechanism of potentiating effect of genistein, a tyrosine kinase inhibitor, on the relaxation induced by isoproterenol was examined. Pretreatment of the aortic rings by genistein, but not by daidzein, an inactive analogue of genistein, potentiated the relaxation induced by isoproterenol. Genistein also potentiated the relaxation induced by forskolin, an activator of guanylyl cyclase, and dibutyryl cyclic AMP. In addition, theophylline, an inhibitor of phosphodiesterase, potentiated the relaxation induced by isoproterenol and forskolin. Theophylline partly inhibited the potentiation of isoproterenol-induced relaxation by genistein while it completely inhibited the potentiation of forskolin-induced relaxation by genistein. Iberiotoxin, an inhibitor of Ca-activated K (KCa) channels, partly inhibited the isoproterenol-induced relaxation and the potentiating effect of genistein on the relaxation induced by isoproterenol. Quinacrine (an inhibitor of phospholipase A2), alpha-naphthoflavone (an inhibitor of cytochrome P-450 enzymes), and 8-methoxypsoralen (an inhibitor of cytochrome P-450 enzymes), partly inhibited the potentiating effect of genistein on the isoproterenol-induced relaxation, but metyrapone (an inhibitor of cytochrome P-450 enzymes), indomethacin (an inhibitor of cyclooxygenase), and AA861 (an inhibitor of 5-lipoxygenase) did not. These results suggest that the potentiation of isoproterenol-induced relaxation by genistein may be related to the activities of phosphodiesterase, KCa channels, and cytochrome P-450 enzymes.

Adrenergic beta-Agonists↗
PubMed1999

Inhibition by genistein of the hyperpolarization-activated cation current in porcine sino-atrial node cells.

1 The hyperpolarization-activated cation current (If) was recorded in single pacemaker cells of the porcine sino-atrial node, and the effects of genistein, an isoflavone inhibitor of tyrosine-specific protein kinases was investigated by the whole-cell patch clamp technique. 2 Genistein (20-500 microM) decreased If in a dose-dependent manner with an IC50 value of 62.3 microM and a maximum inhibition of 45.3%. 3 The effect on If appeared without altering the half-activation potential (control, -88.3+/-2.8 mV; genistein, -87.0+/-1.8 mV) and the slope factor (control, 8.0+/-0.3 mV; genistein, 8.6+/-0.7 mV) of the steady-state activation curve. No significant voltage-dependency was detected in the fully-activated current-voltage relation measured by the double-pulse protocols. 4 The inactive form of genistein analogue, daidzein (500 microM) or genistin (200 microM), were without effect. If was not affected by another tyrosine kinase inhibitor, tryphostin-47 (100 microM), but tyrphostin-25 (100-200 microM) suppressed If in an irreversible manner. 5 Neither bath nor intracellular application of the tyrosine phosphatase inhibitor, orthovanadate, affected If, and subsequent application of genistein inhibited If significantly. 6 These data indicate that the inhibition of If by genistein is not mediated through tyrosine kinase inhibition but through nonselective block of the If channels.

Animals↗
PubMed1999

Modulation of mPer1 gene expression by anxiolytic drugs in mouse cerebellum.

1. The mPer1 and mPer2 genes are putative mouse clock genes that regulate circadian oscillator present in the suprachiasmatic nucleus (SCN) neuron. While they are also expressed in the granular cell layer in the cerebellum, their function is unknown. In a first step to verify the physiological roles of mPer1 and mPer2 genes in the cerebellum, we examined the effects of benzodiazepines on the expression of the mPer1 and mPer2 genes. 2. mPer2 mRNA expression was higher at ZT16 than ZT4 in the mouse cerebellum. 3. High-dose administration of diazepam (10 mg kg-1) or triazolam (1 mg kg-1) reduced mPer1 mRNA level 1 h after treatment in the cerebellum. 4. Reduced expression of mPer1 by diazepam treatment was transient. No difference of mPer1 mRNA level between diazepam (10 mg kg-1)- and vehicle-treated group was observed 6 h after treatment. 5. Administration of high doses of tandospirone (30 mg kg-1), a non-benzodiazepine anxiolytic also reduced mPer1 mRNA expression 1 h after treatment. 6. Administration of high doses of clozapine (5 mg kg-1) or haloperidol (1 mg kg-1) impaired the rota-rod performance without affecting on mPer1 mRNA level. 7. Diazepam and tandospirone inhibited the expression of mPer1 mRNA in the primary cultured cerebellum granule cells. 8. Transient reductions of mPer1 mRNA levels by various benzodiazepines and tandospirone is associated with impairment of coordinated movement, such as rota-rod performance and equilibrium.

Animals↗
PubMed1999

In situ hybridisation study of type I, II, X collagens and aggrecan mRNas in the developing condylar cartilage of fetal mouse mandible.

The aim of this study was to investigate the developmental characteristics of the mandibular condyle in sequential phases at the gene level using in situ hybridisation. At d 14.5 of gestation, although no expression of type II collagen mRNA was observed, aggrecan mRNA was detected with type I collagen mRNA in the posterior region of the mesenchymal cell aggregation continuous with the ossifying mandibular bone anlage prior to chondrogenesis. At d 15.0 of gestation, the first cartilaginous tissue appeared at the posterior edge of the ossifying mandibular bone anlage. The primarily formed chondrocytes in the cartilage matrix had already shown the appearance of hypertrophy and expressed types I, II and X collagens and aggrecan mRNAs simultaneously. At d 16.0 of gestation, the condylar cartilage increased in size due to accumulation of hypertrophic chondrocytes characterised by the expression of type X collagen mRNA, whereas the expression of type I collagen mRNA had been reduced in the hypertrophic chondrocytes and was confined to the periosteal osteogenic cells surrounding the cartilaginous tissue. At d 18.0 of gestation before birth, cartilage-characteristic gene expression had been reduced in the chondrocytes of the lower half of the hypertrophic cell layer. The present findings demonstrate that the initial chondrogenesis for the mandibular condyle starts continuous with the posterior edge of the mandibular periosteum and that chondroprogenitor cells for the condylar cartilage rapidly differentiate into hypertrophic chondrocytes. Further, it is indicated that sequential rapid changes and reductions of each mRNA might be closely related to the construction of the temporal mandibular ramus in the fetal stage.

Aggrecans↗
PubMed1999

Mild hypothermia on anoxic depolarization and subsequent cortical injury following transient ischemia.

Anoxic depolarization (AD) is one of the major physiological characteristics in the ischemic core. The effect of mild hypothermia on the appearance of AD and subsequent brain injury following profound ischemia is studied to evaluate the protective mechanism of hypothermia against severe ischemia. Sprague-Dawley rats were subjected to transient ischemia by hypotension (50-20 mmHg) and bilateral carotid artery occlusion (BCA-O) for 20 min in normothermia and 30 min in hypothermia. The temperature of body and temporal muscles was maintained at 37.5 degrees C and 36.5 degrees C in normothermia and 33.0 degrees C and 31.0 degrees C in hypothermia, respectively. Recording of the DC potential shift and electrocorticogram and monitoring of the cortical blood flow (CoBF) with a laser Doppler flowmeter were done epidurally on the right parietal cortex. The right parietal cortex pathology was examined 24 h after ischemia in normothermia and after 30 days in hypothermia. AD appeared in all seven normothermic rats with a fall in the CoBF to 9%-10% of the control flow. However, in spite of CoBF reduction to 8%-9% of the control flow, it did not appear in five hypothermic rats. Intra-ischemic CoBF was not statistically different between these two groups. AD appeared with the CoBF decreasing to 4%-5% of the control flow in seven hypothermic rats. Intra-ischemic CoBF in hypothermic rats exhibiting AD was significantly lower than the other two groups. The interval between BCA-O and the appearance of AD in hypothermic rats was 5.1 +/- 0.3 min (mean +/- SE), which was significantly longer than the 2.2 +/- 0.5 min observed in normothermia (p < 0.0005). Of seven normothermic rats exhibiting AD, two died within 24 h and four revealed massive neuronal injury. Of seven hypothermic rats with AD, four died between day 2 and day 13, and one revealed diffuse cerebral infarction. However, no severe ischemic injury or ischemic death was observed in all five hypothermic rats without AD. The incidence of severe neuronal injury or ischemic death was significantly lower in hypothermic rats without AD compared with normothermic rats with AD (p < 0.02) or hypothermic rats with AD (p < 0.05). Although mild hypothermia delays AD, it is suggested that raising the cerebral blood flow threshold for AD appearance has a key role in the hypothermic protection of a severely ischemic area such as the ischemic core.

Animals↗