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K Segawa

Publications and source records attributed to K Segawa.

At least 55 records · Page 3Linked to original sources
PubMed1996

Inhibition of GABAA ligand-gated Cl- channels by zinc in adult rat brain: a regional study.

Zinc (Zn2+) was shown to invariably inhibit muscimol-stimulated 36Cl- uptake by synaptoneurosomes in the cerebral cortex, hippocampus and cerebellum. The Zn2+ sensitivity of the GABAA receptor-gated 36Cl- uptake in the cerebral cortex was comparable to that in the hippocampus, whereas the uptake in the cerebellum was less sensitive to Zn2+. Although diazepam-potentiation of muscimol-stimulated 36Cl- uptake was unaltered by 100 microM Zn2+ in the cerebral cortex and hippocampus, diazepam caused no enhancement in the presence of Zn2+ in the cerebellum. Zn2+ inhibited [3H]diazepam binding significantly at 1 mM in the cerebral cortex and cerebellum, whereas Ni2+ increased the binding in a concentration-dependent manner in both regions. Although lower concentrations of Zn2+ did not affect [3H]Ro 15-4513 binding to diazepam-sensitive sites, higher concentrations of ZN2+ increased the binding in both regions. Unlike the diazepam-sensitive sites, the diazepam-insensitive [3H]Ro 15-4513 binding was not affected by Zn2+ or Ni2+ at any of the tested concentrations. These results suggest that the GABAA ligand-gated Cl- flux and its diazepam-potentiation are heterogeneously modulated in various brain regions. It is also suggested that cerebellar diazepam-insensitive [3H]Ro 15-4513 binding sites are insensitive to Zn2+ and Ni2+.

Animals↗
PubMed1996

Inhibitory effect of adrenomedullin on rat mesangial cell mitogenesis.

We investigated the effects of adrenomedullin on rat mesangial cell proliferation. Adrenomedullin (10(-10)-10(-7) M inhibited both [3H]thymidine incorporation into cultured rat mesangial cells and cell proliferation in a concentration-dependent manner. Adrenomedullin (10(-10)-10(-6) M) stimulated cyclic adenosine monophosphate accumulation in rat mesangial cells in a concentration-dependent manner. These findings suggest that adrenomedullin inhibits proliferation of rat mesangial cells probably through a cyclic adenosine monophosphate-dependent mechanism.

Adrenomedullin↗
PubMed1996

Evaluation of 6.5-mm BENT incision to reduce postoperative astigmatism.

We examined surgically induced astigmatism following 6.5-mm incisions between 9 and 12 o'clock (BENT incision) in 50 cases with cataracts who underwent phacoemulsification-aspiration and 6-mm intraocular lens implantation. The surgically induced astigmatism (n = 50) shifted to against-the-rule astigmatism (ATR; -0.03 +/- 0.95 dpt) 1 day after the operation and then tended to shift to with-the-rule astigmatism (WTR). The results of a group with preexisting ATR (> 2 dpt; n = 4) were similar to the results of the aforementioned group, whereas the results of a group (n = 7) with preexisting WTR (> 2 dpt) were different. Astigmatism in this group shifted to ATR of about 1.0 dpt. This study suggests that the BENT incision procedure can reduce both preexisting WTR > 2.0 dpt and preexisting ATR > 2 dpt.

Aged↗
PubMed1996

The relationship between refractory period and conduction time of the AV node under various cycle lengths in the canine heart. The significance of wavelength and excitable gap in reentrant tachycardia.

To evaluate the significance of the refractory period and conduction time of the AV node for reentrant tachycardias incorporating the AV node, the effective refractory period of the AV node (ERP) and AH interval (AH) during atrial pacing at various cycle lengths were measured in 12 anesthetized dogs after verapamil administration. ERP-AH tended to be constant in each dog at different cycle lengths and increased as the AV node was suppressed. In reentrant tachycardia incorporating the AV node, assuming that the conduction time outside of the AV node is constant, the excitable gap decreases as ERP-AH increases and disappears if ERP-AH is prolonged up to the conduction time outside of the AV node. ERP-AH was calculated as an index of the excitable gap. On the other hand, ERP/AHs were significantly correlated with cycle lengths and tended to be similar at the same cycle length among the different dogs. ERP/AH is considered to be an index of the wavelength which is expressed as the product of refractory period and conduction velocity. However, because ERP was always longer than AH, ERP/AH was not applicable as an index of the wavelength in the AV node. The length through which the wavefront ran during the refractory period of the AV node was also dependent on ERP-AH. In conclusion, prolonging ERP-AH played an important role in suppressing reentrant tachycardias incorporating the AV node.

Animals↗
PubMed1996

Apoptosis-related fas antigen on memory T cells in aqueous humor of uveitis patients.

To investigate the role of lymphocytes in the pathogenesis of uveitis, we analyzed the expression of memory markers, CD29 and CD45RO antigens, and apoptosis-related Fas antigen on T lymphocytes in the aqueous humor (AH) and peripheral blood (PB) from patients with uveitis. Using three-color flow cytometry, we assessed the number of T lymphocyte subsets that stained with fluorescence-conjugated anti-CD3, CD4, CD8, CD29, CD45RA, CD45RO, HLA-DR, and Fas monoclonal antibodies in the AH and PB from 19 patients with active uveitis who were diagnosed as having sarcoidosis, Vogt-Koyanagi-Harada disease, HLA-B27+ uveitis, or idiopathic uveitis. Cells from AH and PB were evaluated by light and electron microscopy before and after 6 h of incubation. The majority of lymphocytes in AH but not in PB, were CD3+HLA-DR+ (activated) T cells. The percentage of CD4+ lymphocytes was significantly higher in uveitic AH than in PBL (P < 0.01). While the percentage of CD4+ CD45RA+ (naive) cells within T cells was much lower in uveitic AH than in PB, the percentage of CD4+CD29+ or CD4+CD45RO+ (memory) cells was significantly higher in uveitic AH than in PBL (P < 0.01). Fas antigen was expressed preferentially on memory cells in uveitic AH. Apoptosis of cells in the AH was observed by microscopically following after incubation with no stimulation. Lymphocytes from the AH of patients with uveitis were more activated than those from PB. The majority of T lymphocytes from uveitic AH expressed memory markers and Fas antigen. Results suggest that an increase in the number of Fas+ memory T lymphocytes in AH is involved in the pathogenesis of uveitis.

Adolescent↗
PubMed1996

[Arrhythmias with normal heart rate].

Arrhythmias with ventricular rate between 60-100/min are discussed. Premature ventricular complex is considered to be a risk factor for sudden cardiac death and sustained ventricular tachycardia under some particular conditions, especially after myocardial infarction. To improve the prognosis of patients with ventricular arrhythmias, many trial were performed. Ventricular arrhythmia hypothesis was based on the thought that the patients' prognosis would be improved by suppression of ventricular arrhythmias with antiarrhythmic agents. However, CAST study showed unexpected results. Recently, some investigators suggest that antiectopic action and antifibrillatory action are different and empiric therapy with amiodarone is reported. Other arrhythmias with normal heart rate are considered to have little risk for survival. Then antiarrhythmic therapy should be based on quality of life.

Amiodarone↗
PubMed1996

[Renovascular hypertension associated with antiphospholipid antibodies in a woman with systemic lupus erythematosus].

Systemic lupus erythematosus (SLE) patients, especially those with antiphospholipid antibodies, have a high incidence of arterial and venous thrombotic manifestations. However, renovascular hypertension (RVH) has been rarely reported in these patients. We describe here a 49-year-old female with antiphospholipid antibodies, complicated with RVH and presenting with sudden onset of severe hypertension, headache and nausea. She had experienced phlebitis and arterial thrombosis of the right leg. At the age of 38 years, she was diagnosed as SLE and steroid therapy was started, but she had poor drug compliance and irregularly visited our clinic. On admission, hypertension was recognized and abdominal bruit was audible on physical examination. Serological findings were compatible with SLE. She was also found to have IgG anti-cardiolipin antibody and lupus anticoagulant. Peripheral plasma renin activity (PRA) was elevated, and captopril test showed hyper-response of PRA with lowering of blood pressure. Renal echography and scintigram showed a small and poorly perfused right kidney. Selective angiography demonstrated a severe stenosis of the right renal artery at origin. A stenosis at the origin of both the superior mesenteric artery (SMA) and celiac trunk was also detected. Percutaneous transluminal angioplasty was performed, achieving successful dilatation of the right renal artery and SMA, whereas the attempt to insert the catheter into the celiac trunk was unsuccessful. After this procedure, abdominal bruit has not been audible. Following the initiation of steroid pulse therapy combined with heparin and dipyridamole, her blood pressure was gradually depressed and the test for lupus anticoagulant became negative. Therefore, RVH of this patient is thought to be associated with antiphospholipid antibodies.

Antibodies, Antiphospholipid↗
PubMed1996

Inhibition by protamine of catecholamine secretion and ion influxes in bovine adrenal medullary cells in culture.

To elucidate the mechanism of protamine-induced hypotension, we examined the effects of protamine on catecholamine secretion in bovine adrenal medullary cells and on the serum norepinephrine in the rat. 1) in bovine adrenal medullary cells in culture, protamine at concentrations of 10 to 100 micrograms/ml inhibited catecholamine secretion stimulated by carbachol. The inhibitory effect of protamine was diminished by heparin at concentrations of 3.5 to 14 U/ml. Protamine suppressed carbachol-stimulated 22Na+ influx and 45Ca++2 influx at a concentration similar to that which inhibited catecholamine secretion. Protamine (10-100 micrograms/ml) also inhibited veratridine-induced 22Na+ influx and 45Ca++ influx and 56 mM K(+)-evoked 45Ca++ influx. The inhibition of these ion influxes by protamine was closely correlated with that of catecholamine secretion. 2) In rats, i.v. administration of protamine (10 mg/kg) attenuated the arterial blood pressure and the serum norepinephrine. There was a high correlation (r = 0.96) between the serum norepinephrine and the arterial blood pressure in protaminetreated rats. Furthermore, pretreatment with heparin (1000 U/kg) abolished the protamine-induced decreases in arterial blood pressure and serum norepinephrine. Because protamine seems to inhibit catecholamine secretion by interfering with Na+ influx and Ca++ influx to adrenal medullary cells, the protamine-induced hypotension may be, at least in part, due to inhibition of norepinephrine release and ion channel activities of sympathetic nerve terminals in rats.

Adrenal Medulla↗
PubMed1995

Differences in substrate specificity between Cdk2-cyclin A and Cdk2-cyclin E in vitro.

Cyclin-dependent kinase 2 (Cdk2), when bound to either cyclin A or cyclin E, recognizes the Ser/Thr-Pro-X-basic amino acid (motif A) as a phosphorylation site. In this study, we designed several peptides based on motif A and examined the substrate specificity of Cdk2-cyclin A and Cdk2-cyclin E using these peptides. Peptides containing a proline residue in the sequence Pro-X-Thr-Pro-X-basic amino acid (motif B) had higher affinity for both Cdk2 complexes than peptides containing motif A. Furthermore, differences in substrate affinity between the two Cdk2 complexes were caused by a proline residue adjacent to or three positions before the threonine residue. Similarly, the presence of different basic amino acids in motif B also had different effects on affinity for each complex. We demonstrate the possibility that the substrate specificity of Cdk2 bound to cyclin might be regulated by the species of cyclin.

Amino Acid Sequence↗
PubMed1995

Phosphorylation of E2F-1 by cyclin A-cdk2.

Transcription factor E2F-1 has a putative consensus sequence for phosphorylation by cyclin dependent kinase (Ser-Pro-X-Lys/Arg). Therefore, we studied the phosphorylation of E2F-1 in vivo and in vitro and its biological functions. E2F-1 was prepared by immunoprecipitation with anti-E2F-1 antibody from IMR32 lysates and was effectively phosphorylated by human cyclin A-cdk2 which was expressed in insect cells using baculovirus system. GST-E2F-1 was phosphorylated by cyclin A-cdk2 more efficiently than by cyclin E-cdk2. Cyclin D1-cdk4 phosphorylated pRB but scarcely phosphorylated GST-E2F-1 or H1 histone. The 60 kd protein precipitated with anti-E2F-1 antibody was phosphorylated in vivo. Phospho-peptide mapping indicated that its cleavage profile was identical with that of E2F-1 phosphorylated by cyclin A-cdk2 in vitro. This 60 kd protein, which is likely to be E2F-1, was not phosphorylated during the G0 and early G1 phase. Phosphorylation of E2F-1 began from the S phase while phosphorylation of pRB started nearly at G1/S. The in vivo phosphorylation of E2F-1 was inhibited by butyrolactone I, a cyclin-dependent kinase inhibitor (Kitagawa et al., 1993, Oncogene, 8, 2425-2432). The binding of E2F-1 to E2 promoter was found to be reduced by phosphorylation of E2F-1 by cyclin A-cdk2, suggesting that phosphorylation of E2F-1 may induce shut off of gene expression at the transcriptional level. These results suggest that E2F-1 is phosphorylated by cyclin A-cdk2 in the S phase in vivo as well as in vitro and that its phosphorylation by cyclin A-cdk2 may modulate its activity.

Baculoviridae↗
PubMed1995

Functional diversity of GABAA receptor ligand-gated chloride channels in rat synaptoneurosomes.

Experiments were performed to examine neurochemically the functional diversity of GABAA receptors as measured by muscimol-, 5 alpha-pregnane-3 alpha,21-diol-20-one (THDOC)-, and pentobarbital-stimulated 36Cl- uptake, and region-specific changes in muscimol-, THDOC- and THDOC-induced potentiation of muscimol-stimulated 36Cl- uptake in rats treated acutely or subacutely with a subconvulsive dose of bicuculline. The data for stimulation of 36Cl- uptake by muscimol showed a single binding site interaction in the cerebral cortex, hippocampus and cerebellum. The concentration-response curves for muscimol in the cerebral cortex and hippocampus were steep and indicated an increase of approximately 130% at the maximum concentration. In contrast, the curve for the cerebellum was shallow and exhibited a smaller maximal response (approximately 60%). Apparent affinity for muscimol also differed among these brain regions. The regional differences in 36Cl- uptake induced by THDOC and pentobarbital were not as apparent as those induced by muscimol; however, the maximal modulatory effect of pentobarbital in the hippocampus was significantly higher than that in the cerebellum. In rats treated subacutely with a subconvulsive dose of bicuculline, a significant increase in muscimol-stimulated 36Cl- uptake was observed in the cerebellum but not in the frontal cortex or hippocampus. Analysis of the concentration-response curves for muscimol-stimulated 36Cl- uptake in the cerebellum revealed that the Vmax for muscimol in the subacutely treated group was significantly higher than those for muscimol in the control and acutely treated groups without any differences in the KD value.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Auditory stimuli as a major cause of syncope in a patient with idiopathic long QT syndrome.

A 35-year-old woman was hospitalized due to frequent attacks of syncope immediately after the ringing of a bell or alarm clock. Her standard electrocardiograms showed a long QT interval (QTc = 0.56 s) with a bizarre T-wave inversion in precordial leads. After admission, a total of 9 events of syncope were observed. Malignant ventricular tachyarrhythmia (torsade de pointes, ventricular flutter or fibrillation) was recorded during each episode, and DC shock was required to abolish such tachyarrhythmias on 3 occasions. On monitored electrocardiograms, an additional 8 events of ventricular tachycardia without syncope were also detected. Auditory stimuli appeared to be involved in the initiation of malignant ventricular arrhythmia. Immediately after auditory stimuli, changes in the QT interval and T-wave morphology resulted in ventricular premature beats, leading to ventricular tachycardia. The episodes of syncope or malignant ventricular arrhythmia were frequently observed early in the morning and near midnight. She had been treated with various types of antiarrhythmic agents, and propranolol was the most effective in preventing ventricular arrhythmia. These findings indicate that auditory stimuli may cause ventricular arrhythmia and subsequent cardiac syncope, or even sudden cardiac death, in some patients with long QT syndrome.

Acoustic Stimulation↗
PubMed1995

Two-color flow cytometric analysis of activated T lymphocytes in aqueous humor of patients with endogenous vs. exogenous uveitis.

To investigate the immunopathologic role of lymphocytes in aqueous humor of patients with uveitis, we assessed activated T lymphocyte subsets stained with fluorescein isothiocyanate-labeled and phycoerythrin-labeled monoclonal antibodies in aqueous humor and in peripheral blood, using two-color flow cytometry. We divided our 25 patients into those with endogenous or exogenous uveitis. The percentages of activated T lymphocytes in uveitic aqueous humor significantly exceeded those in peripheral blood lymphocytes from patients with either disease form. CD4+HLA-DR+ lymphocytes were predominant in endogenous uveitic aqueous humor, whereas CD8+HLA-DR+ lymphocytes predominated in exogenous uveitic aqueous humor in the early stage of the disease. The percentages of CD4+HLA-DR+ lymphocytes tended to increase while those of CD8+HLA-DR+ cells tended to decrease in aqueous humor from patients in the late phase of exogenous uveitis. Our results may contribute to increasing diagnostic accuracy in patients with uveitis and to developing more rational methods of treatment.

Adult↗
PubMed1995

Electron microscopic lectin histochemistry of the trabecular meshworks in human eyes.

Ten normal human trabecular meshworks were examined by electron microscopy using avidin-biotin complex in order to investigate the localization of binding sites of eight lectins. The tissue specimens were fixed in paraformaldehyde and glutaraldehyde mixture and embedded in Lowicryl K4M at low temperature. The ultrathin sections were stained with biotin labelled lectins and colloidal gold labelled streptoavidin and were observed with the conventional transmission electron microscope. Some lectins such as ABA, ConA and DSA were localized on fine fibrils underneath the endothelium of the trabecular wall of the Schlemm's canal, electron-dense cores of elastic fibers, fine granular like materials, basement membranes, collagen fibers and the long-spacing fibers. However, the other lectins such as DBA, SBA, Lotus, UEA-I and RCA60 were not specifically localized in these tissues. From the results it was demonstrated that the differential ultrastructural localization of glycoconjugate residues in the human trabecular meshworks can be revealed using this lectin staining.

Adult↗
PubMed1995

Incidence of peptic ulcer in men is inversely correlated with blood pressure: study in an apparently healthy Japanese population.

OBJECTIVE: To study the role of autonomic nervous innervation in the etiology of peptic ulcer, we investigated the blood pressure in patients with peptic ulcer. METHODS: In 100,085 Japanese adults who were undergoing health screening examinations, including barium meal study, there were endoscopic evaluation-confirmed diagnoses of gastric ulcer in 769 cases and of duodenal ulcer in 344 cases. The blood pressure in those patients was compared with that in 57,208 normal Japanese controls with no gastrointestinal abnormalities, as confirmed by barium meal study. RESULTS: The blood pressure of younger and middle-aged men with gastric and duodenal ulcer were lower than those of normal control men. In women, except for the diastolic pressure of those in their 50s, the blood pressure in patients with peptic ulcer and normal controls did not differ significantly. The incidence of duodenal ulcer or of gastric ulcer in men was inversely related to the systolic and diastolic pressure. No definite relationship in this respect was seen in women. CONCLUSIONS: An inverse relationship was observed between the occurrence of peptic ulcer and the blood pressure level in Japanese men, but not in women. The relationship may be mediated by an inhibitory effect of the sympathetic nervous system on ulcer formation in hypertensive subjects. The reason for the sex difference in this respect is unknown.

Adult↗
PubMed1995

[Trabecular meshwork and elastin].

Evidence that elastic fibers with elastin exists in the trabecular meshwork (TM) and play an important role in aqueous outflow resistance is presented. The elastic fibers consist of abundant microfibrillar components containing glycoproteins and amorphous components containing elastin. If TM tissues are digested with elastase, the cells composing trabecular sheets and Schlemm's canal are separated with a decrease of elastin and come in contact with each other with reproduction of elastin. When the anterior segments of eyes are perfused with elastase, the intraocular pressure drops with a decrease of outflow resistance. A large quantity of elastin exists in fine fibrils lying underneath the trabecular wall of Schlemm's canal in primary open angle glaucoma (POAG) eyes, in pseudoexfoliation (PE) materials of PE glaucoma eyes and in basement membrane and fine fibril-like materials of steroid glaucoma eyes. In congenital and juvenile glaucoma eyes, however, instead of elastin, fibronectin localizes in basement membrane and fine fibril-like materials. When TM tissues respond to steroid hormone, the tissues synthesize and secret microfibrils and elastin, components of the elastic fibers. Elastin gene expresses in human TM. Orally administered elastase is transferred in aqueous humor and digests elastin in TM. Therefore it is possible that such a drug decreases the outflow resistance of glaucoma eyes.

Animals↗