PubMed HealthSearch

Biomedical subjects

K Kamata

Publications and source records attributed to K Kamata.

At least 19 recordsLinked to original sources

Functional changes in vascular smooth muscle and endothelium of arteries during diabetes mellitus.

To investigate the influence of diabetes mellitus on the responsiveness of the vascular smooth muscle, the effects of various vasoactive agents on the reactivity of the vascular smooth muscle from diabetic animals have been undertaken, focusing on the functional changes in the endothelium, alpha-adrenoceptors, beta-adrenoceptors, voltage-dependent Ca(2+)-channels, receptor-operated Ca(2+)-channels, phosphatidylinositol turnover and potassium channels. Among the functional changes, it is a common phenomenon that decreases in acetylcholine-induced production of cyclic GMP are due to the attenuation of release of endothelium-derived relaxing factor through an impairment of endothelium; this observation was found in both rats and rabbits with diabetes mellitus. These functional changes in diabetes may be responsible for the vascular complications such as coronary heart disease, cerebrovascular disease, and an acceleration in atherosclerosis.

Animals

Changes in responsiveness of the aorta to vasorelaxant agents in genetically diabetic rats: a study in WBN/Kob rats.

The effects of various vasorelaxant agents on aortas from control and genetically diabetic rats were examined. The concentration-response curves for the isoproterenol (ISO)-induced relaxation of both aortic strips with and without endothelium are shifted to the right in diabetic rats. The relaxation responses of diabetic aorta to forskolin and vasoactive intestinal peptide did not differ from those of controls. The relaxation responses of diabetic aorta to cromakalim and nicorandil did not differ from those of controls. These results indirectly indicate that ISO-induced relaxation responses of the aortic strips from genetically diabetic rats decreased, and that this decreased relaxation response of the strips to ISO may be due to decreased density or affinity of beta adrenoceptors on the endothelium and vascular smooth muscle.

Animals

Age-related changes in endothelium-dependent relaxation in aorta from genetically diabetic WBN/Kob rats.

Experiments were designed to investigate the effects of aging and hyperglycemia on relaxation of the aorta for both endothelium-dependent and -independent agents in Wistar (control) and WBN/Kob (genetically diabetic) rats. The concentration of glucose in serum was elevated significantly in aged (90-92 wk) but not young (13-15 wk) WBN/Kob rats. Endothelium-dependent relaxations of both control and WBN/Kob rats to acetylcholine were reduced by aging. The relaxations induced by acetylcholine in aortic strips were significantly attenuated in both young (nondiabetic) and aged (diabetic) WBN/Kob rats, compared with those from age-matched control vessels, respectively. The concentration-response curves for sodium nitroprusside in aortic strips from both aged control and aged WBN/Kob rats were shifted to the left when compared with those from young rats, respectively. However, the maximal relaxation responses to sodium nitroprusside showed no difference among all vessels studied. The relaxations induced by sodium nitroprusside in aortic strips from both young and aged WBN/Kob rats were similar to those from age-matched control rats, respectively. The relaxations induced by atrial natriuretic peptide showed no difference among all vessels studied. In genetically diabetic rats, functional changes in endothelium occurred before elevation of the levels of glucose in the serum. Thus impaired endothelium-dependent relaxation may play an important role in the high incidence of vascular complications in diabetes mellitus.

Acetylcholine

Effect of 15-deoxyspergualin on lupus nephropathy in New Zealand black/white F1 mice.

Fourteen-week-old female New Zealand B/W F1 mice were treated subcutaneously with 15-deoxyspergualin (DSP) at 0.3 mg-6.0 mg/kg body weight, 4 times/week. They were sacrificed at 36 weeks of age to determine the minimal effective dose as well as the lowest maximally effective dose without toxicity of DSP required to suppress the development of nephropathy. The life span of the animals was significantly prolonged with 0.6 mg/kg or more DSP. Additionally, glomerular (immuno)histological improvement of the kidney at 36 weeks was observed with 0.6 mg/kg DSP, although a higher dose was required to lower serum anti-DNA activity or to decrease proteinuria. In addition, DSP produced a decrease of L3T4+ splenocytes without affecting the number of Lyt 2+ cells, while the level of IL-2 generated in vitro was somewhat elevated. It may be concluded that DSP has a therapeutic range within an order of ten, but its exact mechanism of immunosuppression remains to be determined.

Animals

Intraocular manifestations of systemic sarcoidosis.

The incidence of intraocular manifestations was studied in 159 patients with systemic sarcoidosis. Eighty-seven patients (54.7%) who presented ocular lesions suggestive of sarcoidosis as an initial manifestation were diagnosed after a systemic survey. Seventy-two patients (45.3%) had chest signs or symptoms and were referred to ophthalmic examination during a diagnostic survey. Of the 159 patients, 126 (79.2%) showed intraocular involvements at diagnosis. In these patients with ocular involvements, iritis was the most frequent lesion, being seen in 74.7%. Gonioscopic examinations revealed trabecular nodules and tent-like peripheral anterior synechia in 61.2 and 54.5% of the patients respectively. Retinal perivasculitis and spotty retinochoroidal exudates were seen in 67.3 and 53.9% of the patients respectively. The data indicated the presence of intraocular lesions in a significant number of patients with sarcoidosis. These findings emphasize that all patients with systemic sarcoidosis need a thorough eye examination. This ocular examination should include gonioscopy.

Adolescent

Changes in muscarinic responsiveness, muscarinic receptor density and Ca2+ mobilization of the urinary bladder in streptozotocin-induced diabetic rats.

Functional changes in the urinary bladder obtained from diabetic rats were investigated by determining the responsiveness to acetylcholine (ACh). Maximal contraction of the detrusor strips in response to ACh was significantly enhanced in the diabetic rats. Ca(2+)-induced contracture of the detrusor strips, which had been incubated with 10(-3) M ACh in the presence of nicardipine in Ca(2+)-free medium, was significantly augmented in diabetic rats. Ca(2+)-contracture in Ca(2+)-free, isotonic high-K+ (60 mM) medium was not changed in diabetic state. The density of muscarinic receptors to 3H-QNB was significantly higher in the bladder from diabetic rats compared to age-matched control rats. These results suggest that tone of the autonomic nervous system in the bladder may be decreased in diabetes and, thus, compensatory increase in density of muscarinic receptors may occur. Furthermore, an increased contractile response of the detrusor strips of the urinary bladder to ACh in diabetic rats also may be due to an increased influx of extracellular Ca2+ through the receptor-operated Ca2+ channels but not the voltage-dependent Ca2+ channels.

Acetylcholine

Abnormalities of the autonomic nervous system of the duodenum in streptozotocin-induced diabetic rats.

The changes in sensitivity of the rat duodenum to ATP were examined in preparations from control rats and from rats with streptozotocin (STZ)-induced diabetes. ATP was able to relax the duodenum of control animals in a concentration-dependent manner and this relaxation was significantly increased in STZ-diabetic rats. In preparations from diabetic rats, relaxation responses to ATP were greater than those of age-matched control groups. These results suggest that functional changes or degeneration of non-adrenergic, non-cholinergic nerves in the myenteric plexus may occur in STZ-diabetic rats, and that these alterations may result in the increased sensitivity of the relaxation of the duodenum to ATP.

Adenosine Triphosphate

A study on peroxidative damage of the porcine intestinal brush-border membranes using a fluorogenic thiol reagent, N-(1-pyrene)maleimide.

To examine the effects of lipid peroxidation on the protein conformation in the porcine intestinal brush-border membranes, a fluorogenic thiol reagent, N-(1-pyrene)maleimide (NPM) was employed. By treatment of NPM-labeled membranes with 100 microM ascorbic acid/10 microM Fe2+ in the presence of various concentrations of tert-butyl hydroperoxide (t-BuOOH), the fluorescence intensity of the complex decreased with the formation of conjugated diene, depending on the hydroperoxide concentration. The temperature dependence profile of the fluorescence intensity of NPM-labeled control membranes showed a thermal transition of the NPM fluorescence at 27-28 degrees C. The transition phenomenon of the NPM fluorescence in the membranes around this temperature disappeared by treatment of the labeled membranes with 100 microM ascorbic acid/10 microM Fe2+/0.6 mM t-BuOOH. The difference in response of the fluorescence characteristics of the bound NPM for temperature variation between the control and peroxidized membranes was also observed in the quenching efficiency with acrylamide. Measurement of the fluorescence polarization revealed that the harmonic mean of the rotational relaxation times of the bound NPM molecules to the membrane proteins increased from 1.96 to 4.93 microseconds by lipid peroxidation of the membranes. This indicates that the movement of the region containing NPM-labeled SH groups in the membrane proteins is restricted by lipid peroxidation. Treatment of NPM-labeled peroxidized membranes with sodium dodecyl sulfate (SDS) resulted in a restoration of the intensity of the NPM fluorescence to the level of the control ones. In addition, the temperature dependence profile of the fluorescence intensity of NPM-labeled peroxidized membranes in the presence of SDS also showed an appearance of a transition phenomenon around 30 degrees C. The result of SDS-polyacrylamide gel electrophoresis of the peroxidized membranes revealed that high-molecular-weight aggregates of the membrane proteins were not formed by lipid peroxidation. On the basis of these results, changes in the environmental properties around NPM-labeled SH groups in the membrane proteins by lipid peroxidation are discussed.

Animals

Changes in responsiveness of the canine basilar artery to endothelin-1 after subarachnoid hemorrhage.

The effect of endothelin-1 (ET-1) on the basilar arteries from control and subarachnoid hemorrhage (SAH) dogs were examined. The maximal contraction of the basilar artery in response to ET-1 was markedly decreased in the SAH group. Treatment with 10(-8)M phorbol 12-myristate 13-acetate (PMA) reduced the contractile responses to ET-1 in the basilar arteries from control dogs. ET-1-induced contractions of the basilar arteries from control dogs were similar to those in strips from SAH dogs by the treatment with 10(-8) M PMA. Ca(2+)-induced contraction of the basilar arteries which were depolarized with isotonic K+ (64 mM) were significantly attenuated in SAH dogs. Treatment with PMA also reduced the contractile responses to Ca2+ in the basilar arteries from control dogs. These results indicate that decreased contractile responses of the basilar arteries to ET-1 and Ca2+ in the SAH group may be related to changes in the activity of the protein kinase C in vascular smooth muscle.

Animals

Reversal of established nephropathy in New Zealand B/W F1 mice by 15-deoxyspergualin.

The therapeutic effect of 15-deoxyspergualin (DSP) in old New Zealand Black/White F1 mice (B/W mice) with clinical nephropathy was studied and compared with cyclophosphamide (CY). The mice were treated with 0.05 ml phosphate-buffered saline, subcutaneously, four times/week, with DSP, 6 mg/kg body weight, s.c., four times/week, or with CY, 15 mg/kg, i.p., once a week, starting at the 28th week of age. They were serially semiquantitated for proteinuria, and serum IgG anti-dsDNA antibody was measured by ELISA. Spleen cell surface markers such as L3T4, Lyt2 and IgG were flow-cytometrically analyzed, and interleukin-2 (IL-2) activity in vitro was measured using CTLL cells. Kidney specimens were studied with light and immunofluorescence microscopy. The mice treated with either CY or DSP survived significantly longer than the control mice. L3T4+ cells in the DSP-treated mice at 40 weeks of age were significantly less than those in the 28-week-old control mice (p less than 0.05). In contrast, IL-2 generation in the three groups of mice showed no significant variations at 32-40 weeks of age. Serum anti-DNA antibody levels in both of the CY and DSP groups remained low and comparable with that in the 28-week-old mice, and the incidence of significant proteinuria decreased. Likewise, glomerular histology in the treated groups was improved compared with the 28-week-old control mice, and the deposition of IgG and C3 in the treated groups remained unchanged or further decreased. Accordingly, the renal (immuno)histological findings in the DSP group were quite comparable with or even better than those in the CY-treated mice. DSP may have suppressed the abnormal antibody production by modulating the T cell function(s), which is in contrast to the direct action against B cells due to CY.

Animals

Attenuation of depressor response induced by platelet activating factor and acetylcholine in streptozotocin-induced diabetic rats.

The in vivo and in vitro effects of platelet-activating factor (PAF, 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphorylcholine) and acetylcholine (ACh) on vascular relaxation responses were examined in streptozotocin-induced diabetic rats. Intravenous injection of PAF and ACh (0.03 to 10 micrograms/kg) decreased the mean blood pressure in both control and diabetic rats in a dose-dependent fashion. Initial blood pressure in diabetic rats did not significantly differ from that in control rats. However, depressor responses induced by PAF and ACh in diabetic rats were attenuated more than those in control rats. In perfused mesenteric arterial bed preconstricted with methoxamine (10(-5) - 10(-4) M), PAF (10(-11) -3 x 10(-10) M) produced a concentration-dependent relaxation. However, this relaxation was significantly attenuated in the diabetic preparation compared with the control preparation. ACh also produced a concentration-dependent vasodilation in perfused mesenteric arterial bed. The concentration-response curve for the relaxation of the mesenteric arterial bed to ACh in diabetic preparation was shifted to the right compared with that in control preparation. A pretreatment with oxyhaemoglobin (10(-6) M) also shifted the concentration-response curves for relaxation to ACh in both control and diabetic preparation to the right. There was no difference in relaxation induced by sodium nitroprusside between the diabetic and the control preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

Hemodynamic mechanism of the elevation in blood pressure following the improvement of anemia with recombinant human erythropoietin.

Following the administration of recombinant human erythropoietin (rHuEPO) to 18 patients undergoing hemodialysis, the hematocrit (Ht) increased from 19.7 +/- 1.8 to 31.0 +/- 2.0%. The incidence of hypertension according to the criteria of WHO was 11.1%. The systolic blood pressure (SBP) increased significantly from 120 +/- 21 to 129 +/- 26 mmHg (p less than 0.01) and diastolic blood pressure (DBP) increased from 67 +/- 14 to 73 +/- 12 mmHg (p less than 0.05). The cardiac index (CI) decreased significantly from 4.07 +/- 1.13 to 3.56 +/- 0.88 L/min/m2 (p less than 0.05). Total peripheral resistance index (TPRI) and blood volume (BV) increased significantly from 1,725 +/- 406 to 2,170 +/- 643 dynes/sec/cm-5/m2 (p less than 0.001) and from 78.9 +/- 11.2 to 87.8 +/- 14.8 ml/kg (p less than 0.005) respectively. Pulse rate (PR) decreased significantly from 73.0 +/- 10.7 to 65.9 +/- 7.8 beats/min (p less than 0.01). Patients who developed a blood pressure (BP) elevation of 10% or more for the mean blood pressure (MBP) showed a slight and insignificant decrease in CI from 3.65 +/- 1.12 to 3.49 +/- 1.06 L/min/m2, which clearly contrasted to that in another group of patients who showed a reduced increase in MBP and a significant reduction in CI from 4.50 +/- 1.03 to 3.63 +/- 0.72 L/min/m2 (p less than 0.05). Stroke volume index (SVI) was unchanged in both groups but PR decrease significantly in the latter group. A significant increase in TPRI or BV was observed equally in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Pharmacological actions of chemically-modified phospholipase A2 from the venom of Trimeresurus flavoviridis on the smooth muscle of the rat stomach fundus.

The pharmacological activities of Trimeresurus flavoviridis phospholipase A2 (PLA2) and their chemically-modified PLA2 were characterized by measuring the contraction of rat stomach fundus strips. The native PLA2 produced a contraction of rat fundus strips. The alpha-amino-modified enzyme induced an almost identical contraction of the fundus with that of the native enzyme, whereas His-modified and Lys-modified enzymes induced a markedly decreased contraction as compared with the native enzyme. These results demonstrate that lysine and histidine residues but not the alpha-amino group in the PLA2 molecule are essential for contractile activity of the stomach fundus.

Animals

Effects of chronic diabetes on vascular responses of basilar artery and aorta from rabbits with alloxan-induced diabetes.

The influences of chronically diabetic states on contraction and relaxation responses of the isolated basilar artery and aorta to various vasoactive agents were examined in alloxan-induced diabetic rabbits with 2 years duration. There were no significant differences in the reactivities of basilar artery to norepinephrine (NE), 5-hydroxytryptamine (5-HT) and KCl between age-matched control and diabetic rabbits. Maximal contractions of aorta with endothelium in response to NE and 5-HT were significantly enhanced in case concentration-response curves for NE and 5-HT-induced contractions in the aorta without endothelium from diabetic rabbits were not different from those from age-matched control rabbits. Acetylcholine-induced relaxations in both the basilar artery and aorta from diabetic rabbits were significantly attenuated compared with those from age-matched control rabbits. However, no differences were observed in concentration-response curves for sodiumnitroprusside-induced relaxations in both the basilar artery and aorta between diabetic rabbits and age-matched control rabbits. These results indicate that chronic diabetes induces an specific enhancement in the contractile responses to NE and 5-HT in aorta and an attenuation in the endothelium-dependent relaxation in both the basilar artery and aorta. These results further demonstrated that the cerebral artery is resistant to diabetes of 2 years duration as compared with the peripheral artery.

Acetylcholine

Effects of CD-349, a dihydropyridine derivative, on contraction induced by vasoactive agents in canine basilar artery after subarachnoid hemorrhage.

We investigated the effects of CD-349, a dihydropyridine derivative, on contraction induced by vasoactive agents in canine basilar artery after subarachnoid hemorrhage (SAH). Ca(2+)-induced contraction of basilar arterial strips preincubated with serotonin (5-HT, 3x10(-6)M) was potentiated in strips from SAH. However, Ca(2+)-induced contraction of arterial strips which were depolarized with isotonic K+ (64mM) was attenuated in strips from SAH. These Ca(2+)-induced contractions of the basilar arteries preincubated with 5-HT and K+ from both control and SAH dogs were significantly inhibited by CD-349 and nicardipine, both dihydropyridine derivatives. 5-HT contracted the basilar arterial strips in a concentration-dependent manner; however, the maximal contraction of the basilar arterial strips to 5-HT was enhanced in SAH. Endothelium-dependent relaxation in response to substance-P was attenuated in SAH when compared to that in control dogs. Early treatment with CD-349 (1 or 2mg/kg/day, i.m.) for 1 week reversed not only the enhanced contraction of the basilar artery in response to 5-HT but also the impairment of endothelium-dependent relaxation in response to substance-P in SAH. It is expected that CD-349 may be a useful agent for the treatment of cerebrovascular diseases such as SAH.

Animals

[Immunogenetic mechanism of Behçet's disease].

In order to investigate the immunogenetic mechanism of Behçet's disease, frequencies of HLA antigens were studied in patients. The subjects consisted of 66 patients and 99 normal controls. A lymphocyte cytotoxicity test was used for typing HLA-A, -B, -C, -DR, -DQ antigens. HLA-DP antigens were analyzed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. A significant increase of HLA-B15 was observed in the patients. In contrast, no significant difference was observed in HLA-Bw52 which possesses only two different amino acids from HLA-B15. On the contrary, frequencies of HLA-A11, HLA-Aw33, HLA-B35, HLA-B44 and HLA-DQw1 were significantly lower in the patients than in the controls. No significant difference was observed in HLA-DP antigens. These results suggest that Behçet's disease involves both disease susceptibility factors and disease resistance factors and that such genetic factors are mapped within or very close to the HLA-B gene in the class I gene region. Additionally class II HLA-DQ antigen is associated with disease resistance factors.

Amino Acid Sequence