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Biomedical subjects

K Hirata

Publications and source records attributed to K Hirata.

At least 379 records · Page 21Linked to original sources
PubMed1998

Regulatory roles of complexins in neurotransmitter release from mature presynaptic nerve terminals.

Complexins are presynaptic proteins whose functional roles in synaptic transmission are still unclear. In cultured rat hippocampal neurons, complexins are distributed throughout the cell bodies, dendrites and axons, whereas synaptotagmin I and synaptobrevin/VAMP-2, essential proteins for neurotransmitter release, accumulated in the synaptic-releasing sites as early as 1 week in culture. With a maturation of synapses in vitro, complexins also accumulated in the synaptic release sites and co-localized with synaptotagmin I and synaptobrevin/VAMP-2 after 3-4 weeks in culture. Complexins I and II were expressed in more than 90 and 70% of the cultured neurons, respectively; however, they were largely distributed in different populations of synaptic terminals. In the developing rat brain, complexins were distributed in neuronal cell bodies in the early stage of postnatal development, but gradually accumulated in the synapse-enriched regions with development. In mature presynaptic neurons of Aplysia buccal ganglia, injection of anticomplexin II antibody caused a stimulation of neurotransmitter release. Injection of recombinant complexin II and alphaSNAP caused depression and facilitation of neurotransmitter release from nerve terminals, respectively. The effect of complexin was reversed by a subsequent injection of recombinant alphaSNAP, and vice versa. These results suggest that complexins are not essential but have some regulatory roles in neurotransmitter release from presynaptic terminals of mature neurons.

Adaptor Proteins, Vesicular Transport↗
PubMed1998

Evaluation of 9-cis retinoic acid for a new remedy of human retinoblastoma.

We investigated the effect of two isomers of retinoic acid (RA), all-trans RA and 9-cis RA, on the proliferation of Y79 human retinoblastoma cells. The two isomers inhibited the cell proliferation in a concentration-dependent manner. The IC50 for this inhibition by all-trans RA and 9-cis RA was 1.50 and 0.15 microM, respectively. The inhibitory effect of 9-cis RA on Y79 cell growth was observed within 24 hr, thereafter the cell number was gradually decreased. In contrast, no inhibition by all-trans RA of Y79 cell growth was observed within 24 hr, thereafter the cell number was slightly increased. In these cases, the cell viability at 4 days after the addition of 9-cis RA and all-trans RA was more than 90% and 95%, respectively. These results indicate that the two RA inhibit the proliferation of Y79 human retinoblastoma cells without inducing the cell death and that the effect of 9-cis RA on the inhibition of Y79 cell growth is much greater than that of all-trans RA.

Alitretinoin↗
PubMed1998

Cyclophosphamide, adriamycin, 5-fluorouracil and high-dose toremifene for patients with advanced/recurrent breast cancer. The Japan Toremifene Cooperative Study Group.

BACKGROUND: Multi-combination chemotherapy consisting of anthracyclines has been effective but has not invariably prolonged the survival period in advanced/recurrent breast cancer. The possibility has been discussed that chemoendocrine therapy combined with endocrine agents is more effective. METHODS: In order to evaluate the toxicity and efficacy of a new endocrine therapy for advanced/recurrent breast cancer, we ran a pilot study during the period from July 1994 to July 1996. RESULTS: Twenty-two patients with advanced/recurrent breast cancer were treated with chemoendocrine therapy consisting of cyclophosphamide (100 mg/body) p.o. daily for 14 days, with adriamycin (40 mg/m2) i.v. and 5-fluorouracil (500 mg/body) i.v. on day 1 (repeated every 3 weeks for 9 weeks) (CAF therapy), and high-dose toremifene (120 mg/body) p.o. daily. Of 20 evaluable patients, two showed complete response (10%), eight partial response (40%), six no change (30%) and four progressive disease (20%). The overall response rate was 50%, and the median duration of response was 69.5 days (28-133+ days). The major toxicities were drug-induced alopecia, gastrointestinal toxicity and hematological toxicity, but these were clinically well tolerated. No serious cardiac, liver or renal symptom was seen. CONCLUSIONS: Based on these results, we consider the addition of high-dose toremifene to the CAF therapy to be useful in the treatment of advanced and recurrent breast cancer.

Adult↗
PubMed1998

Inhibition of liver metastasis of human pancreatic carcinoma by angiogenesis inhibitor TNP-470 in combination with cisplatin.

The anti-tumor and anti-metastatic effects of O-(chloroacetyl-carbamoyl) fumagillol (TNP-470), an angiogenesis inhibitor, and cisplatin (CDDP), an anti-neoplastic agent, were investigated using our established liver-metastasizing pancreatic carcinoma line, HPC-3H4. HPC-3H4 was injected into the spleens of nude mice. Mice were randomly divided into 5 groups; a control group given saline solution, a group receiving 45 mg/kg TNP-470, a group receiving 90 mg/kg TNP-470, a group receiving 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP, and a group receiving 0.25 mg/kg CDDP. In the control group, liver metastasis developed in 14 of 15 mice (93.3%). Liver metastasis developed in 9 of 11 mice (81.8%) receiving 0.25 mg/kg CDDP. It developed in 11 of 15 mice (73.3%) receiving 45 mg/kg TNP-470, in 17 of 18 mice (94.4%) receiving 90 mg/kg TNP-470, and in 4 of 10 mice (40%) receiving 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP. TNP-470 in combination with CDDP displayed a significant inhibitory effect on liver metastasis compared to the control. Although TNP-470 alone and CDDP alone had no effect on the tumor growth in vivo, 90 mg/kg TNP-470 in combination with 0.25 mg/kg CDDP had a significant effect. In vitro examinations demonstrated that the growth of HPC-3H4 cells was only mildly inhibited by TNP-470, but the production of vascular endothelial growth factor (VEGF) by HPC-3H4 was clearly inhibited by TNP-470. The inhibitory effect on the production of VEGF was not strong with CDDP treatment. These results indicate that the angiogenesis inhibitor TNP-470 in combination with low-dose CDDP has inhibitory activity against liver metastasis of human pancreatic carcinoma.

Animals↗
PubMed1998

A case of Arnold-Chiari Type I malformation presenting with dysrhythmic breathing during sleep.

A 43-year-old woman presented with dull headache, left tinnitus and dizziness. Neurological examination revealed down-beat gaze nystagmus, left tinnitus, positive Romberg sign, poor standing on the left foot, poor tandem gait, left spastic gait and positive pathological reflexes in the bilateral upper and lower extremities. Plain X-ray of the skull and cervical vertebrae demonstrated basilar impression and atlantoaxial fusion. Magnetic resonance imaging of the brain and cervical spine showed cerebellar tonsil descent and syringomyelia located in the left side of the spine at the II-III vertebral level which communicated with the fourth ventricle. The patient was diagnosed as having cervical syringomyelia. Arnold-Chiari type I malformation and basilar impression. Preoperative polysomnography showed dysrhythmic breathing and bradypnea during sleep. Abnormal breathing improved after suboccipital decompression craniotomy and upper cervical laminectomy. It was suggested that dysrhythmic breathing was caused by a disorder of the medullary respiratory center. Herniation of the cerebellar tonsil and syringomyelia might have compressed the medulla.

Adult↗
PubMed1998

Enhancement of albumin production by hepatocyte growth factor in rat hepatocytes: distinction in mode of action from stimulation of DNA synthesis.

Hepatocyte growth factor (HGF) has been shown to enhance albumin production as well as stimulate DNA synthesis in hepatocytes. The mode of action of HGF in exerting both effects is to be elucidated. We previously observed that hepatocyte proliferation occurred in normal rats given recombinant human HGF (rhHGF) intravenously. When rats received rhHGF similarly, serum albumin levels were significantly increased compared to controls. In primary culture of rat hepatocytes, albumin concentration in culture medium was significantly increased by rhHGF added at 24 h of culture compared to controls, increasing with time of culture. This effect of rhHGF was dose-related. When actinomycin D was added to the medium, the albumin concentration was reduced in a dose-related manner, but its enhancement by rhHGF was maintained. Albumin mRNA levels were not increased by rhHGF. When rhHGF was added similarly to the medium, immunocytochemically positive hepatocytes for 5-bromo-2'-deoxyuridine (BrdU) incorporation appeared 30 h later. Of these labeled hepatocytes, 12.5% were concomitantly stained for albumin. In contrast, albumin-positive hepatocytes were seen in 77% of BrdU-non-labeled hepatocytes (p<0.01). We conclude that HGF may enhance albumin production through post-transcriptional regulation in non-proliferating hepatocytes, but not in proliferating hepatocytes.

Animals↗
PubMed1998

Stimulatory interaction between vascular endothelial growth factor and endothelin-1 on each gene expression.

The precise regulation of cell growth in the vascular wall maintains vascular integrity, and its disruption leads to cardiovascular disorders including atherosclerosis and restenosis. Vascular endothelial growth factor (VEGF) is a specific mitogen for endothelial cells, and endothelin-1 (ET-1) is known to stimulate the proliferation of smooth muscle cells. The aim of this study was to explore a potential interaction between VEGF and ET-1 on each expression in vascular cells. VEGF enhanced preproET-1 mRNA expression and ET-1 secretion in bovine aortic endothelial cells (BAECs). Similarly, in rat vascular smooth muscle cells (VSMCs), ET-1 enhanced VEGF mRNA expression and stimulated VEGF secretion. ET-1-induced VEGF mRNA expression was abolished by a selective ET(A) receptor antagonist, BQ-485, but not by an ET(B)-selective blocker, BQ-788. It was also inhibited by pretreatment with actinomycin D but not by pretreatment with cycloheximide. Furthermore, the actinomycin D chase experiment revealed that ET-1 did not alter VEGF mRNA stability. Coculture of BAECs and VSMCs enhanced both ET-1 and VEGF gene expression in these cells, and the conditioned media from BAECs and VSMCs reproduced the augmentation of each gene expression, which was partially inhibited by BQ-485 or an antibody specific to VEGF. Our results indicate that VEGF and ET-1 have stimulatory interactions on each expression, which may play an important role in concomitant proliferation of endothelial and smooth muscle cells in the vascular wall.

Animals↗
PubMed1998

Beat-to-beat variation of the ST segment in a patient with right bundle branch block, persistent ST segment elevation, and ventricular fibrillation: a case report.

The authors describe a patient with ventricular fibrillation associated with right bundle branch block-like QRS morphology and persisting ST segment elevation in the precordial leads, in whom the morphology of the ST segment changed from the coved type to the saddle-back type or vice versa on a beat-to-beat basis. Such an observation has never been reported in the previous literature.

Adult↗
PubMed1998

Severity of exercise-induced bronchoconstriction is related to airway eosinophilic inflammation in patients with asthma.

Exercise-induced bronchoconstriction (EIB) is widely prevalent in asthmatic patients. Eosinophilic airway inflammation is considered to be a major factor in the pathogenesis of asthma. However, the effects of eosinophilic airway inflammation on EIB have been elucidated insufficiently. To examine the relationship between the severity of EIB and eosinophilic inflammation, sputum induction and exercise challenge were performed in 21 asthmatic patients. Significantly higher percentages of eosinophils and levels of eosinophil cationic protein (ECP) were found in induced sputum in EIB-positive asthmatics (median (range), eosinophils: 23.5 (11.0-61.0)%; ECP: 1,475 (74.8-17,701) ng x mL(-1)) than in EIB-negative asthmatics (eosinophils: 6.0 (1.0-41.5)% (p=0.006); ECP: 270.6 (10.8-7,700) ng x mL(-1) (p=0.049)). There was a significant correlation between the severity of EIB and the sputum eosinophil percentage (r=0.59, p=0.009) and the level of ECP (r=0.47, p=0.037). The area under the curve of the forced expiratory volume in one second for 30 min after exercise correlated with the percentage of eosinophils (r=0.60, p=0.008) and the level of ECP (r=0.45, p=0.04). There was no correlation between airway responsiveness to methacholine on the one hand and EIB, sputum eosinophils or ECP on the other. In conclusion, these results provide evidence that the severity of bronchoconstriction evoked by exercise is more closely related to eosinophilic airway inflammation than airway hyperresponsiveness to methacholine in asthmatic patients.

Adolescent↗
PubMed1998

Subthreshold concentration of endothelin-1-enhanced, capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs.

An increasing number of studies have been performed to address a possible role for endothelin-1 (ET-1) as a significant mediator in asthma. However, the effects of subthreshold concentrations of ET-1, which cannot elicit bronchial smooth muscle contraction itself, in asthma has yet to be determined. This study determined these effects of ET-1 on capsaicin-induced bronchoconstriction in anaesthetized guinea-pigs. Aerosolized ET-1 administered at doses of 10(-9) M and higher induced a dose-dependent increase in pulmonary resistance, but ET-1 at 10(-10) M did not have any bronchoconstrictive effect. However, this subthreshold concentration of ET-1 potentiated capsaicin-induced bronchoconstriction. In addition, the potentiation of capsaicin-induced bronchoconstriction by this subthreshold concentration of ET-1 was completely abolished by BQ788 (ET(B) receptor antagonist), but not BQ123 (ET(A) receptor antagonists). Immunoreactive substance P (SP) levels in bronchoalveolar lavage fluid after capsaicin administration were significantly higher than those after solvent administration. However, ET-1 alone did not significantly stimulate immunoreactive SP release and ET-1 (10(-10) M) did not potentiate capsaicin-induced immunoreactive SP release. In contrast, ET-1 (10(-10) M) potentiated exogenous neurokinin A- and SP-induced bronchoconstriction. These findings suggest that a subthreshold concentration of endothelin-1 does not potentiate the tachykinin release induced by capsaicin but the airway smooth muscle contraction through endothelin-B receptors.

Aerosols↗
PubMed1998

Minimal number of plasma exchanges needed to reduce immunoglobulin in Guillain-Barré syndrome.

Plasma exchange (PE) in Guillain-Barré syndrome (GBS) probably removes pathogenic antibodies. Results of a recent clinical study by the French Cooperative Group suggest that at least two sessions of PE are required. As an alternative procedure, we examined the effect of the number of PEs on the reduction of immunoglobulins in 11 patients. A significant immunoglobulin decrease was obtained in the first two sessions but not in subsequent ones. Based on the French trial results and our findings, we conclude that at least two PEs are needed for treating GBS.

Gangliosides↗
PubMed1998

Properties of alpha-mannosidase partially purified from the apple snail, Pomacea canaliculata.

Pomacea canaliculata alpha-mannosidase (260 kDa), composed of at least two isoforms with different pI, was partially purified. The activity was maximum at pH 4 and unaltered after incubation at 60 degrees C for 60 min. ZnCl2, CaCl2, NaCl, and SH-reagents increased the activity, while MnCl2 and EDTA inhibited it. The enzyme catalyzed the hydrolysis of alpha 1-2, alpha 1-3, and alpha 1-6 mannosidic linkages.

Animals↗
PubMed1998

5-HT1Dbeta receptor mediates the supersensitivity of isolated coronary artery to serotonin in variant angina.

Although serotonin (5-hydroxytryptamine; 5-HT) is used for provocation of coronary spasm, 5-HT receptor subtypes in spastic coronary arteries remain undetermined. We demonstrated the supersensitivity of isolated coronary artery to ergonovine, 5-HT, and sumatriptan, a 5-HT1D receptor agonist, in a patient with variant angina. Furthermore, we detected gene expression of 5-HT1Dbeta and 5-HT2A receptors in spastic coronary artery using RNase protection assay. These findings suggest that the leftward shift of the dose-response curve for 5-HT, which plays an important role in the pathogenesis of coronary spasm, is mediated by activation of 5-HT1Dbeta receptor.

Angina Pectoris, Variant↗
PubMed1998

Analytical histopathological diagnosis of small hepatocellular nodules in chronic liver disease.

Due to the recent progress in radiology and increased clinical and pathological interest, small hepatocellular nodules about 1 cm in size are frequently being detected in patients with chronic liver disease, particularly liver cirrhosis. Two new types of small hepatocellular nodules are now known: low-grade hepatocellular carcinomas (HCC) and dysplastic nodules, in addition to the previously known HCC (classical) and regenerative nodules. Ultrasound-guided needle biopsies from these nodules are routinely used for the differential diagnosis. For comparison, a simultaneous needle biopsy from the liver remote from the nodule is strongly recommended. Low-grade HCC, which are different from classical HCC in their morphological atypia and also biological behaviors, show local invasion into the portal tracts and surrounding hepatic parenchyma, but not intrahepatic or extrahepatic metastasis. Dysplastic nodules show mild cellular and structural atypia, a finding which is not sufficient for making a diagnosis of malignancy. An increased nuclear/cytoplasmic (N/C) ratio and nuclear crowding, small cell-dysplasia, increased cytoplasmic staining, clear cell change, pseudogland formation, and fatty change of hepatocytes are variably seen in these nodules. Nuclear changes, local invasion to the portal tract and surrounding liver, and loss of the reticulum fibers along the hepatocytes are useful markers favoring low-grade HCC rather than dysplastic nodules. These low-grade HCC and dysplastic nodules should also be distinguished from classical HCC as well as large-sized regenerative nodules. A comparative analysis of the histological findings observed in individual nodules is a reasonable approach to differential diagnosis at present. The recognition and analysis of these two new hepatocellular nodules may augur a new horizon in the study of hepatocellular neoplasm.

Adenoma↗
PubMed1998

Frequency of chromosome 7 gain in human breast cancer cells: correlation with the number of metastatic lymph nodes and prognosis.

Trisomy 7 has been reported in various malignant neoplasms, but there are no reports in breast cancer. In order to evaluate the contribution of chromosome 7 gain to breast cancer, we investigated the relationship of numerical abberation of chromosome 7 with clinicopathological variables and prognosis in seventy-nine breast cancer cases (invasive carcinomas) using the technique of fluorescence in situ hybridization (FISH) on paraffin-embedded sections. A significant correlation of the frequency of cells with extra copies of chromosome 7 (percent polysomy 7 cell score) was found with tumor size, regional lymph node status, tnm stage, histological extension, estrogen receptor (ER), and DNA ploidy. The number of metastatic lymph nodes was positively correlated with percent polysomy 7 cell score (correlation coefficient=0.623, p < 0.01). Furthermore, cases with a high percent polysomy 7 cell score had a shorter disease-free survival and overall survival times, especially in the lymph node-positive group. It was demonstrated that percent polysomy 7 cell value was closely associated with lymph node metastasis and prognosis and might be a useful prognostic predictor of breast cancer patients.

Adenocarcinoma↗