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Biomedical subjects

S Shibata

Publications and source records attributed to S Shibata.

At least 361 records · Page 20Linked to original sources
PubMed1995

5-Fluorouracil and high-dose calcium leucovorin for hepatocellular carcinoma: a phase II trial.

A phase II trial of 5-fluorouracil (5-FU) [250-450 mg/m2/day x 5 days as an intravenous (IV) bolus] combined with calcium leucovorin (500 mg/m2/day x 5 1/2 days by continuous IV infusion) administered on a 28-day schedule was performed in 15 patients with advanced hepatocellular carcinoma. The median age was 58 years; performance status ranged from 50 to 100%. Of 15 evaluable patients, 1 (7%) had a partial response lasting 2.4 months; 8 (53%) had stable disease with a median duration of 5.7 months; and 6 (40%) had progressive disease with a median time to progression of 2.7 months. Median survival was 3.8 months. Treatment with 5-FU and calcium leucovorin was moderately well tolerated; 9% of the treatment courses were complicated by grade 3 or 4 hematological toxicity, and 10% of the courses were complicated by grade 3 or 4 gastrointestinal toxicity. Despite the efficacy of the combination of 5-FU and leucovorin in advanced colorectal cancer, our results document the general resistance of hepatocellular carcinoma to modulated 5-FU.

Adult↗
PubMed1995

Involvement of dopamine, N-methyl-D-aspartate and sigma receptor mechanisms in methamphetamine-induced anticipatory activity rhythm in rats.

Daily injection of methamphetamine (MAP) increased the locomotor activity and produced the development of MAP-induced anticipatory activity on the next withdrawal day. Daily restricted feeding also causes a feeding-associated anticipatory activity rhythm. The importance of catecholaminergic neurons has been suggested in the manifestation of a feeding-associated corticosterone rhythm. In our study, we examined the role of dopaminergic neurons in the development of MAP-induced anticipatory activity. The development of MAP-induced anticipatory activity was blocked by coadministration of dopamine D2 receptor antagonists such as YM-09151-2 and sulpiride, the D1 receptor antagonist SCH23390 and haloperidol weak D1/D2 receptor antagonist, but not by clozapine. The anticipatory activity increase was reproduced by daily injection of the D2 receptor agonist quinpirole as well as moderately by the D1 receptor agonist SKF38393. Moreover, MAP-induced anticipation was blocked by coadministration of the N-methyl-D-aspartate receptor antagonist MK-801 or sigma ligands rimcazol and NE-100. Our results suggest that activation of the dopaminergic system, especially via D2 receptors may be required for the development of MAP-associated anticipatory activity increases and that N-methyl-D-aspartate receptors and sigma receptor mechanisms are also involved in the development of this behavior.

Animals↗
PubMed1995

[A case of chronic empyema due to tuberculosis with bronchopleural fistulae treated successfully by extraperiosteal air plombage thoracoplasty and omentoplasty].

A 63-year-old man, who had undergone induction of artificial pneumothorax at 20 years of age as a treatment for right tuberculosis, developed fever and cough. A chest X-ray film showed marked pleural effusion in the right chest. Examination of sputum and the pleural effusion revealed tubercle bacillus, and right tuberculous empyema was diagnosed. At surgery, the right thoracic cavity was occupied by empyema, and multiple bronchopleural fistulae were observed. Because of the presence of tubercle bacilli in the empyema cavity, extraperiosteal air plombage thoracoplasty was insufficient for control of the empyema. Therefore, omentoplasty was added. Two months after the operation, the patient was discharged in good condition. He has been doing well without any sign of recurrence of empyema for the last two years. Although extraperiosteal air plombage thoracoplasty is a considerably effective therapy for empyema, its curability rate is lower in cases like the present one in which bronchopleural fistulae and bacteria are present in empyema cavity, such as our case. We consider that our method, extrapriosteal air plombage thoracoplasty with omentoplasty, is a reliable one for control of empyema, in patient with high risk factors for recurrence, such as bronchopleural fistulae and bacteria in the cavity.

Bronchial Fistula↗
PubMed1995

[Marked dilatation of the bilateral common carotid artery: a case report].

We reported a rare case of marked dilatation of the bilateral common carotid artery (CCA) associated with stenosis of the left middle cerebral artery (MCA). A 64-year-old female was admitted with right hemiparesis and dysarthria. She was hospitalized 2 years ago for cholecystitis. For 5 years, she has been under medical treatment for hypertension, diabetes mellitus, hyperlipidemia, cardiac failure associated with hypertrophic cardiomyopathy, and atrial fibrillation. Brain CT scan showed infarction of the left corona radiata. Angiography revealed marked dilatation of the bilateral CCA and the internal carotid artery (ICA), moderate dilatation of the innominate artery and the right subclavian artery, kinking of the right CCA, diverticular outpouching of the left ICA, and stenosis of the right external carotid artery and the left MCA. Breast CT scan revealed moderate dilatation and marked calcification of the ascending aorta and the aortic arch. Laboratory examination did not show any sign of inflammation, rheumatoid factor (RA), antistreptolysis-O (ASLO) and antinucleotic antibody. Based on the clinical course, radiological findings and laboratory data, possible diagnosis of the dilatation of the bilateral CCA was discussed with particular emphasis on arteriosclerotic aneurysm and aortitis syndrome.

Aortic Arch Syndromes↗
PubMed1995

In vivo regeneration of vestibular hair cells of guinea pig.

Recent studies have shown that inner ear sensory cells may regenerate in mammals as well as in birds. In this in vivo study we investigated the regeneration of vestibular hair cells in guinea pigs after gentamycin intoxication, and found that the vestibular sensory epithelia reproduced new hair cells 30 days after degeneration, due to 30 consecutive days of gentamycin treatment. From the regeneration pattern of sensory epithelia, the supporting cells were identified as the progenitors of hair cells.

Animals↗
PubMed1994

A novel oligosaccharide, GlcA beta 1-4Xyl beta 1-(4-methylumbelliferone), synthesized by human cultured skin fibroblasts.

Human skin fibroblasts were cultured in the presence of 4-methylumbelliferyl-beta-D-xyloside (Xyl-MU) using a mass-culture system with a microcarrier. The structures of Xyl-MU-induced sugars purified from the dialysable fraction of the incubation medium were investigated. In addition to glycosaminoglycans the elongation of which initiated by Xyl-MU has already been reported, and oligosaccharides similarly initiated by Xyl-MU, such as Gal-Gal-Xyl-MU, Gal-Xyl-MU and SA-Gal-Xyl-MU, a novel Xyl-MU-induced oligosaccharide was detected. This oligosaccharide was identified as GlcA beta 1-4Xyl beta 1-(4-methylumbelliferone) using sugar composition analysis, enzyme digestion, mass spectrometry and Smith degradation. Using this culture system, the amount of the new oligosaccharide produced increased with the incubation time, even after the production of glycosaminoglycan initiated by Xyl-MU and Gal-Xyl-MU had reached a plateau. These results suggest that this oligosaccharide may be involved in terminating the elongation of glycosaminoglycan chains that is initiated by Xyl-MU.

Benzoates↗
PubMed1994

Effects of naloxone, morphine and kappa-opioid receptor agonists on hypoxia/hypoglycemia-induced reduction of 2-deoxyglucose uptake in hippocampal slices from U-50,488H-tolerant rats.

The aim of the present study was to determine whether U-50,488H and U-62,066E, kappa-opioid receptor agonists cause a neuroprotective action against hypoxia/hypoglycemia-induced reduction in 2-deoxyglucose (2-DG) uptake of hippocampal slices from U-50,488H-tolerant rats. Both U-50,488H and U-62,066E exhibited an attenuating effect on hypoxia/hypoglycemia-induced reduction in 2-DG uptake of hippocampal slices. Hypoxia/hypoglycemia-induced deficit of 2-DG uptake was prevented by cotreatment with naloxone, an opioid receptor antagonist, but potentiated by cotreatment with morphine, a mu-opioid receptor agonist. Chronic administration of U-50,488H resulted in the development of tolerance to the analgesic effect as well as the neuroprotective effect whereas this treatment affected neither basal- nor hypoxia/hypoglycemia-induced decreases in 2-DG uptake. Chronic administration of U-50,488H did not modify naloxone-induced attenuation of 2-DG uptake deficit but slightly potentiated the morphine-induced exacerbation. These findings suggest that the tolerance to kappa-opioid receptors does not affect the mu-opioid receptor-mediated neuroprotective or neurotoxic action.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1994

Facilitatory effect of olfactory bulbectomy on 2-deoxyglucose uptake in rat amygdala slices.

The aim of the present study was to determine whether the 2-deoxyglucose uptake of amygdala slices was affected by olfactory bulbectomy. At 7, 14 and 21 days post-lesion, bilateral olfactory bulbectomized rats exhibited a significant increase of 2-deoxyglucose uptake in amygdala slices, but not in the cerebral cortex. In addition, unilateral olfactory bulbectomized rats showed a high uptake of 2-deoxyglucose uptake in the ipsilateral amygdala, but not in the contralateral amygdala. These results suggest that the enhancement of 2-deoxyglucose uptake is related to the hyperexcitability of amygdala neurons following bulbectomy, and that this enhancement may be responsible for the behavioral changes in olfactory bulbectomized rats.

Amygdala↗
PubMed1994

Involvement of D1 dopamine receptor mechanism in ischemia-induced impairment of CA1 presynaptic fiber spikes in rat hippocampal slices.

The effect of dopamine (DA) receptor agonists and antagonists on hypoxia/hypoglycemia (ischemia)-induced decrease in CA1 presynaptic fiber spikes elicited by the stimulation of Schaffer collateral were investigated using hippocampal slices. Treatment with D1 dopamine receptor antagonist, SCH23390 produced a concentration-dependent attenuation of the ischemia-induced decrease of presynaptic potentials. The magnitude of recovery of the CA1 presynaptic potential in SCH233390-treated slices at 10 and 100 microM was 28 and 54%, respectively. Whereas, treatment with D1 dopamine receptor agonist, SKF38393 exacerbated the ischemia-induced decrease in the CA1 presynaptic potential. The decrease of CA1 presynaptic potential by ischemia was affected by neither D2 dopamine receptor agonist, bromocriptin and quinpirole nor D2 dopamine receptor antagonist, sulpiride. The neuroprotective effect of SCH23390 was completely blocked by cotreatment with SKF38393. The present results demonstrated that the blockade of D1 dopamine receptor function played a neuroprotective role in ischemic damage, suggesting a facilitatory role of D1 dopamine receptor-operated function in ischemia-induced neuronal deficits.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Facilitatory effects of somatostatin on reduced uptake of 2-deoxyglucose in cerebral cortical and hippocampal slices from aged rats.

The aim of the present study was to determine whether or not the reduction of 2-deoxyglucose uptake by the cerebral cortical slices in aged rats (22-23 months old) was attenuated by somatostatin or carbachol. In 8-week-old rats, somatostatin and carbachol produced concentration-dependent increases in 2-deoxyglucose uptake. 2-Deoxyglucose uptake of the cortical slices in 22-23-month-old rats was significantly facilitated by treatment with 0.1-1 microM somatostatin or 1-100 microM carbachol. Metabolic responses to somatostatin or carbachol were quite similar in young and aged rats. The present results demonstrated that 2-deoxyglucose uptake by the cerebral cortex was facilitated by somatostatin and carbachol in both young and old rats.

Aging↗
PubMed1994

Aging impairs methamphetamine-induced free-running and anticipatory locomotor activity rhythms in rats.

In the present experiment, under drinking of 0.01% methamphetamine (MA), young rats exhibited free-running locomotor rhythm ranging from 24.6 to 30.9 h period under light-dark cycle. In contrast, 24-month-old rats showed a low activity and did not exhibit MA-induced free-running rhythm. When MA was injected at a fixed time of day (14:00), young rats exhibited intense locomotor activity from 1-2 h before drug-injection time. This preinjection activity was still detected on the withdrawal day. In addition, intense locomotor activity was observed for 12:00-17:00, even on the withdrawal day (MA-associated anticipatory activity). Thus, MA-associated activity of the withdrawal day became an another good index for MA anticipatory activity rhythms whereas old rats did not exhibit this anticipatory activity. The present study suggests that aging strongly impairs the manifestation of MA-induced free-running and anticipatory activity rhythms in rats.

Aging↗
PubMed1994

Effects of nitric oxide synthase inhibitors on N-methyl-D-aspartate-induced phase delay of circadian rhythm of neuronal activity in the rat suprachiasmatic nucleus in vitro.

Excitatory amino acid (EAA) receptors such as N-methyl-D-aspartate (NMDA) and non-NMDA receptors have been suggested to play an important role in the regulation of photic information from the retina to the suprachiasmatic nucleus (SCN). Therefore, we investigated the role of glutamate as a retinohypothalamic transmitter by analyzing the phase-resetting effects of NMDA and a non-NMDA agonist, (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), on the circadian rhythm of SCN firing activity. Nitric oxide (NO) production is believed to be an essential intermediate in NMDA-induced cGMP production in the CNS. Thus, we examined the effects of blockers of NO production on NMDA- or AMPA-induced phase delay of SCN activity rhythm. N-nitro-L-arginine methylester (L-NAME) blocked NMDA- but not AMPA-induced phase shift, indicating the involvement of NO synthesis in NMDA-induced phase changes. L-arginine but not D-arginine caused a phase delay, and L-NAME blocked L-arginine-induced phase delay. In addition, cotreatment with NMDA and L-arginine did not have an additive effect. These results suggest that NO production itself is involved in the phase change of SCN neuron activity, and NMDA-induced phase changes are also mediated via activation of NO synthesis in this nucleus.

Amino Acid Oxidoreductases↗
PubMed1994

Facilitatory effect of vasopressin on the ischemic decrease of the CA1 presynaptic fiber spikes in rat hippocampal slices.

We investigated the effects of vasopressin-related neuropeptides on the hypoxia/hypoglycemia (ischemia)-induced decrease of the CA1 presynaptic potential elicited by stimulation of Schaffer collaterals in rat hippocampal slices. Treatment with arginine-vasopressin (AVP) potentiated the ischemic decrease of the CA1 presynaptic potential. In contrast, a V1 receptor antagonist produced a dose-dependent neuroprotective effect, whereas a V2 receptor antagonist had no effect. The AVP-induced decrease of the CA1 presynaptic potential was completely blocked by simultaneous application of the V1 receptor antagonist. Because AVP4-9 is regarded as the major proteolytic product of AVP in the rat brain, we examined its effect on the ischemic decrease of the CA1 presynaptic potential. Treatment with AVP4-9 produced a more marked reduction of the potential than treatment with AVP itself. The present study demonstrates that stimulation of the V1 receptor has a detrimental effect on the development of ischemic damage whereas V1 receptor blockade has a neuroprotective effect, suggesting that AVP may potentiate ischemic neuronal deficits via V1 receptor stimulation.

Animals↗
PubMed1994

Autoantibodies to heparin from patients with antiphospholipid antibody syndrome inhibit formation of antithrombin III-thrombin complexes.

The antiphospholipid antibody syndrome (APS) is characteristically associated with thrombosis. Heparan sulfate (HS) is a physiologic endothelial cell surface modulator of normal anticoagulation, containing a specific oligosaccharide sequence that binds antithrombin III with high affinity and also is present in heparin, a related glycosaminoglycan. We hypothesized that a subset of antiphospholipid antibodies with high affinity for heparan sulfate/heparin epitopes may inhibit the function of HS, promoting a procoagulant state. Purified IgG from all seven patients with APS studied were reactive with heparin by enzyme-linked immunosorbent assay, whereas none of five controls had antiheparin reactivity. IgG antiheparin antibodies were purified from two APS patients by affinity chromatography on heparin-Sepharose. Specificity studies showed that low-affinity electrostatic interactions clearly did not account for the observed reactivity with heparin, and that APS IgG antiheparin antibodies were specifically reactive with a disaccharide present in the heparin pentasaccharide that binds antithrombin III. Furthermore, APS IgG antiheparin antibodies inhibited heparin-accelerated formation of antithrombin III-thrombin complexes. We conclude that antiheparan sulfate/heparin antibodies may be a cause of autoimmune vascular thrombosis in the antiphospholipid antibody syndrome.

Adult↗
PubMed1994

Protein-synthesis inhibitor blocks (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-or substance P-induced phase shift of the circadian rhythm of neuronal activity in the rat suprachiasmatic nucleus in vitro.

The mammalian suprachiasmatic nucleus (SCN) has been identified as a circadian pacemaker. N-methyl-D-aspartate (NMDA), non-NMDA and substance P receptors have been suggested to be involved in handling of photic information in the SCN. In the Aplysia eyes, in which the circadian clocks are involved, serotonin- or cAMP-induced phase changes of the circadian rhythm were reported to be blocked by protein-synthesis inhibitors. Therefore, we investigated whether protein-synthesis inhibitor can block the non- NMDA receptor agonist (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA)- or substance P (SP)-induced phase changes of SCN activity rhythm. Although application of 10 microM cycloheximide alone during the early part of the subjective night did not cause phase change, it blocked both 10 microM AMPA- and 1 microM SP-induced phase delay. The present result suggests that protein synthesis may be required in the manifestation of AMPA- and SP-induced phase change of circadian clock.

Animals↗
PubMed1994

Neuroprotective effect of cholecystokininB receptor antagonist on ischemia-induced decrease in CA1 presynaptic fiber spikes in rat hippocampal slices.

The effects of cholecystokinin (CCK) receptor agonists and antagonists on hypoxia/hypoglycemia (ischemia)-induced decrease in CA1 presynaptic fiber spikes elicited by the stimulation of Schaffer collaterals were investigated using rat hippocampal slices. Treatment with the CCKB receptor agonist CCK tetrapeptide (CCK4, 0.01-10 microM) exacerbated the ischemia-induced decrease in the CA1 presynaptic potential in a concentration-dependent manner. Whereas, treatment with the CCKB receptor antagonist [(3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl)-N1-(3-methylphenyl)-urea] (L365260), and not with CCKA receptor antagonist [(3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl)-1H-indole-2-carboxamide] (L364718), produced a concentration-dependent attenuation of the ischemia-induced decrease. The magnitude of recovery of the CA1 field potentials in L365260-treated groups at 10 and 100 nM was 34% and 45%, respectively. The neuroprotective effect of L365260 (0.01 and 0.1 microM) was completely blocked by co-treatment with CCK4 (0.1 microM), a concentration that did not affect the decreased presynaptic potential induced by ischemia. These results demonstrated that the stimulation of the CCKB receptor played a detrimental role in the development of ischemic damage, whereas the blockade of CCKB receptors played a neuroprotective role in ischemic damage, suggesting a facilitatory role of CCK receptor-operated function in ischemia-induced neuronal deficits.

Animals↗