Biomedical subjects

M Kambe

Publications and source records attributed to M Kambe.

At least 55 records · Page 3Linked to original sources

PubMed1998

Increased cytosolic free Mg2+ and Ca2+ in platelets of patients with vasospastic angina.

This study was designed to test the hypothesis that the cellular metabolism of Ca2+ and Mg2+, which is important in platelet function, is abnormal in the platelets of patients with vasospastic angina. Cytosolic free Mg2+ concentration ([Mg2+]i) and Ca2+ handling were determined in the platelets of 24 patients with vasospastic angina and 24 control subjects by use of mag-fura 2 and fura 2. Platelet aggregation was also examined. Basal [Mg2+]i and cytosolic free Ca2+ concentration ([Ca2+]i) in platelets were significantly higher in patients with vasospastic angina than in control subjects. The amplitude of the [Ca2+]i transient induced by thrombin (0.03-1.0 U/ml) was significantly increased in the presence, but not in the absence, of extracellular Ca2+ in patients with vasospastic angina, as compared with controls. Therefore, the influx of Ca2+ across the plasma membrane may be accelerated in vasospastic angina. Thrombin (0.1-1.0 U/ml)-induced maximum aggregation response was significantly greater in patients with vasospastic angina than in controls. Results suggest that increased [Mg2+]i and altered Ca2+ handling by platelets may be associated with coronary vasospasm.

Adenosine Diphosphate↗

PubMed1998

Effect of 17beta-estradiol on inhibition of platelet aggregation in vitro is mediated by an increase in NO synthesis.

The low prevalence of coronary heart disease in premenopausal women and its increase after menopause are well established. Although estrogen is thought to play a role in protecting the vasculature, the mechanism has not been fully clarified. The contribution of platelets to atherosclerotic cardiovascular diseases is well recognized. The present study focused on the still-controversial effect of estrogen on platelet function. We investigated the in vitro effects of estrogen on human platelets, including their aggregation, Ca2+ metabolism, the synthesis of cyclic nucleotides, and NO (nitrite/nitrate) synthesis after stimulation with thrombin or ADP. Pretreatment of platelets with 17beta-estradiol reduced the platelet aggregation induced by thrombin or ADP, whereas 17alpha-estradiol had no effect. 17Beta-estradiol accelerated the recovery of [Ca2+]i after the agonist-induced peak and reduced the area under the curve of accumulated platelet [Ca2+]i but did not alter the baseline [Ca2+]i, Ca2+ influx induced by thrombin or ADP, the release of Ca2+ from internal stores, or the size of internal Ca2+ stores. Pretreatment of platelets with 17beta-estradiol had no effect on the intracellular concentration of cAMP but increased that of cGMP in agonist-stimulated platelets. Additionally, 17beta-estradiol increased the platelet concentration of nitrite/nitrate in a dose-dependent manner. These effects of 17beta-estradiol on platelet aggregation, Ca2+ metabolism, and NO synthesis were abolished by exposure to N(G)-monomethyl-L-arginine, an NO synthesis inhibitor. These results suggest that 17beta-estradiol plays an important role in inhibiting platelet aggregation by promoting Ca2+ extrusion or reuptake activity that is dependent on the production of cGMP by increasing NO synthesis.

Adult↗

PubMed1998

Angiotensin-converting enzyme inhibition, but not calcium antagonism, improves a response of the renal vasculature to L-arginine in patients with essential hypertension.

Endothelial function has been shown to be impaired in patients with essential hypertension. The purpose of the present study was to determine whether antihypertensive drug therapy improves impaired endothelium-dependent renal vasorelaxation in essential hypertensive patients without atherosclerosis. We evaluated the effects of intravenous infusion of L-arginine (500 mg/kg given over 30 minutes) on systemic and renal hemodynamics in 27 patients with mild to moderate essential hypertension who were randomly assigned to treatment with either the angiotensin-converting enzyme inhibitor imidapril or the calcium antagonist amlodipine for 12 weeks in a double-blind fashion. After the 12 weeks, the decrease in blood pressure was similar in the imidapril (n=14) and amlodipine (n=13) groups. The increase in renal plasma flow was also similar in both groups. L-Arginine-induced renovascular relaxation was increased by imidapril (renal plasma flow, 9.6+/-5.1% to 14.4+/-7.4%; renal vascular resistance, -10.4+/-8.1% to -16.7+/-9.2%, P<0.05, respectively) but not by amlodipine. Urinary excretion of nitrite/nitrate in response to L-arginine was significantly increased by imidapril (90+/-29% to 134+/-63%, P<0.05) but remained unchanged by amlodipine. These findings suggest that angiotensin-converting enzyme inhibition improves the impaired endothelium-dependent renovascular relaxation in patients with essential hypertension due to the increase in nitric oxide production and that the reduction in blood pressure with a calcium antagonist does not play a major role in the potentiation of L-arginine/nitric oxide-mediated effects.

Adult↗

PubMed1998

Activation of platelets in bronchial asthma.

STUDY OBJECTIVES: To investigate whether platelets are activated in asthmatics with increased release of preformed mediators and to investigate the influence of oral administration of theophylline on them. DESIGN: Comparison of the intracellular free calcium concentration ([Ca2+]i) in platelets as an indicator of platelet activation, CD62P expression on platelets, and the chemokine regulated upon activation in normal T cells expressed and presumably secreted (RANTES) level in platelet-rich buffer supernatants between asthmatics and normal subjects. SETTING: The respiratory outpatient clinics, Hiroshima University, Japan. PARTICIPANTS: Twenty-five normal volunteers, 19 asthmatics taking no oral drugs associated with asthma treatment (group A), and 18 asthmatics taking oral theophylline (group B). MEASUREMENTS AND RESULTS: While the resting [Ca2+]is in platelets were similar among the three groups, the [Ca2+]is in group A were significantly higher than those in normal subjects (p<0.05) and group B (p<0.01) after thrombin or 9,11-epithia-11,12-methano-thromboxane A2 (STA2) stimulation in the absence of external Ca2+. The CD62P expression level and RANTES level in group A after STA2 stimulation were significantly higher than those in normal subjects and group B (p<0.05). CONCLUSIONS: We conclude that agonist-mediated activation of platelets is augmented in asthmatics resulting in enhanced release of chemokine such as RANTES, which could be suppressed by oral administration of theophylline.

Administration, Oral↗

PubMed1998

[A case of cervical-mediastinal lymph node tuberculosis progressed to pulmonary lesion through a bronchial fistula].

The patient was a 25-year-old man who had been admitted to a local hospital due to fever and trachelophyma. Tubercle bacillus was detected in pus culture obtained by biopsy of the trachelophyma, but not in sputum culture. Because combined therapy with 3 antituberculous drugs (RFP, INH and SM) failed to reduce the fever or drainage from the biopsy region, the patient was transferred to our hospital. Chest X-ray films taken on admission revealed dilatation of the superior mediastinal shadow; chest CT images revealed cervical and mediastinal lymphadenopathy and an anterior mediastinal abscess, but no pulmonary lesion. About 2 months after admission, cough developed and Gaffky type 2 was detected in the patients sputum. Bronchoscopy and bronchography revealed a bronchomediastinal fistula. Forty days after the onset of cough, reticulogranular shadows were observed in the right upper lobe on chest X-ray films, and a diffuse centrilobular lesion was observed in the right upper lobe on chest CT images. From these clinical observations, the patient was given a diagnosis of cervical-mediastinal lymph node tuberculosis, which had progressed to pulmonary lesion through a bronchial fistula due to lymphadenitis.

Adult↗

PubMed1998

[Measurement of expired nitric oxide concentration].

UNLABELLED: Much interest has been focused on standardization of measurement of expired nitric oxide (NO) concentration. The aim of this study was establish a simple measurement of expired NO concentration. SUBJECTS AND METHODS: This study included 5 healthy male adults. To clarify whether NO is excreted in expired air constantly, its concentrations were measured while changing the flow rate. To examine the influence of NO derived from the nasal cavity, we compared expired No concentrations sampled from the month with those sampled from the endotracheal tube inserted to the trachea at a constant flow rate serially. RESULTS: Expired NO concentrations decreased in inverse with the flow rate. No may be serially excreted in expired air. When serial changes of expired No concentrations sampled from the mouth were examined, its NO concentration initially reached a peak, then showed a plateau. Serial changes of those sampled from the endotracheal tube showed only a plateau. Plateau levels were not different between the two kinds. Therefore the peak values may have been influenced by NO derived from the nose that fell in the trachea by inspiration. Plateau values appeared to represent airway and lung-derived NO. CONCLUSIONS: A simple measurement of expired NO concentration should be sampled from the mouth at a constant flow rate serially. Evaluating plateau values is appropriate for expired NO concentration.

Adult↗

PubMed1998

[A mild case of acute eosinophilic pneumonia].

We encountered a mild case of acute eosinophilic pneumonia in a 24-year-old man who developed symptoms once he started smoking. Bronchoalveolar lavage revealed eosinophilia. Chest computed tomography revealed a small amount of bilateral pleural effusion and multicentric panacinar shadows with peripheral ground-glass opacities. During the clinical course, the patient suffered only cough and fever, which subsided in 13 days without the administration of steroids. Although the clinical course in this case resembled that of simple pulmonary eosinophilia, we diagnosed it as a mild case of acute eosinophilic pneumonia because pleural effusion rarely accompanies simple pulmonary eosinophilia, symptoms developed when the patient began smoking, and interstitial involvement was suggested by bilateral effusion and ground-glass opacity. We look forward to the establishment of the disease concept of acute eosinophilic pneumonia, including mild cases, and a classification system for eosinophilic lung diseases, including acute eosinophilic pneumonia.

Acute Disease↗

PubMed1997

Lack of effect of transmembrane gradient of magnesium and sodium on regulation of cytosolic free magnesium concentration in rat lymphocytes.

The regulation of the intracellular concentration of Mg2+ ([Mg2+]i) is not fully understood. The level of Mg in lymphocytes is a good predictor of total body Mg status. We measured [Mg2+]i and total Mg in rat lymphocytes by using, respectively, the fluorescent Mg2+ indicator mag-fura-2 and atomic absorption spectrophotometry. The basal [Mg2+]i in rat lymphocytes was 328 +/- 23 micromol/l. An elevation to 5 mmol/l or the removal of extracellular Mg2+ did not affect [Mg2+]i. A reduction in extracellular Na+ did not influence [Mg2+]i for 60 min. The total Mg concentration in lymphocytes also remained stable. Results suggest that the permeability of the plasma membrane to Mg2+ is very low, and that Na+/Mg2+ exchange is not involved in the regulation of [Mg2+]i in rat lymphocytes.

Animals↗

PubMed1997

Extracellular Mg2+ inhibits capacitative Ca2+ entry in vascular smooth muscle cells.

BACKGROUND: Agonist-induced Ca2+ entry is thought to be mediated by capacitative Ca2+ entry other than L-type Ca2+ channels in vascular smooth muscle cells (VSMCs). The mechanism for capacitative Ca2+ entry has not been fully elucidated. Our objective was to examine the effect of external Mg2+ on capacitative Ca2+ entry in cultured rat aortic VSMCs. METHODS AND RESULTS: Three doses of external Mg2+ concentration (nominally 0, 1, and 5 mmol/L) were used. After exposure to 1 mumol/L, angiotensin II (Ang II) in Ca(2+)-free medium, addition of Ca2+ to the medium caused an increase in cytosolic free Ca2+ concentration ([Ca2+]i), indicating Ang II-induced Ca2+ influx. This Ca2+ influx was attenuated in cells preincubated with high external Mg2+ concentrations or with 1 mumol/L nifedipine. After VSMCs in Ca(2+)-free medium were exposed to 1 mumol/L thapsigargin, which inhibits the sarcoplasmic reticulum Ca(2+)-ATPase and depletes Ca2+ stores, addition of Ca2+ to the medium induced an increase in [Ca2+]i, indicating capacitative Ca2+ entry. This entry pathway was found to be independent of dihydropyridine-sensitive Ca2+ channels and inhibited by increased external Mg2+ concentration. External Mg2+ concentration did not influence Ca2+ efflux across the plasma membrane after stimulation with Ang II plus thapsigargin. CONCLUSIONS: Results suggest that in VSMCs, capacitative Ca2+ entry is reduced by external Mg2+. This mechanism may explain in part the inhibitory effect of external Mg2+ on Ca2+ handling.

Angiotensin II↗

PubMed1997

Whole-blood incubation method to study neutrophil cytoskeletal dynamics.

To reduce artifactual effects in the study of filamentous (F)-actin dynamics in neutrophils, we have developed a whole-blood incubation method. Neutrophils in whole blood contained significantly less basal F-actin than did separated neutrophils. Although the peak relative F-actin content of neutrophils in whole blood after formyl-methionyl-leucyl-phenylalanine (fMLP) stimulation was significantly higher than that of separated neutrophils at 10(-9) to 10(-6) M fMLP concentrations (p < 0.05), there was no significant difference in increase in mean fluorescence intensity and the EC50 (concentration of stimulant giving a half-maximum response). On the other hand, the EC50 of platelet-activating factor (PAF) between separated neutrophils and whole-blood-incubated neutrophils differed significantly (1.6 +/- 1.1 x 10(-9) M in separated neutrophils and 2.0 +/- 0.7 x 10(-8) M in whole-blood-incubated neutrophils, p < 0.05). The whole-blood incubation method described presently reduces the sample volume, cost and time needed to separate neutrophils, prevents neutrophil activation during separation, and reserves all blood components that may affect neutrophil function. For these reasons, the conditions adopted in the present method are thought to simulate well neutrophils circulating in vivo and the method would be preferable to other neutrophil function tests performed to study actin dynamics.

Actins↗

PubMed1997

Pentaerythritol tetranicotinate (niceritrol) decreases plasma lipoprotein(a) levels.

We determined the most effective dosage of pentaerythritol tetranicotinate (niceritrol) to reduce plasma lipoprotein(a) [Lp(a)] levels in 44 Japanese patients (16 men and 28 women; mean age, 59.2 +/- 10.8 years) with hyperlipidemia types IIa, IIb, and IV. Patients received oral niceritrol at a dosage of 750 mg (3 tablets)/d for 8 weeks, followed by 1,500 mg (6 tablets)/d for 8 weeks. Administration of niceritrol 750 mg/d for 8 weeks decreased total and low-density lipoprotein (LDL) cholesterol in patients with type IIa hyperlipidemia and decreased triglycerides in patients with type IV hyperlipidemia, but did not affect Lp(a). However, niceritrol 1,500 mg/d for 8 weeks decreased Lp(a) in patients with initial Lp(a) levels greater than 30 mg/dL in addition to decreasing total and LDL cholesterol and triglycerides. These results suggest that the effective dosage of niceritrol to reduce the serum Lp(a) concentration in Japanese hyperlipidemic patients with a high Lp(a) level (> or = 30 mg/dL) is greater than 1,500 mg/d.

Aged↗

PubMed1997

Nonadrenergic, noncholinergic inhibitory innervation in the longitudinal muscle of the rabbit portal vein.

1. We examined whether nitric oxide (NO) and ATP take part in inhibitory nonadrenergic, noncholinergic (NANC) neurotransmission in the portal vein of Japanese White rabbits. Longitudinal strips of the vein were suspended in organ baths containing Krebs bicarbonate solution. Preparations relaxed in response to electrical field stimulation (EFS) (25 V, 0.5 msec in duration, 1-50 Hz) and exogenous ATP (1-300 microM) after contraction was induced with 10 microM ergotamine in the presence of 3 microM guanethidine and 0.1 microM atropine. 2. The relaxation response to EFS was abolished by addition of 100 microM NG-nitro-L-arginine, an NO synthase inhibitor. This abolition was partly reversed by 10 mM L-arginine, a substrate for NO synthase. 3. The relaxation response to exogenous ATP was significantly inhibited by 1 mM suramin, a P2X- and P2Y-purinoceptor antagonist, whereas relaxation response to EFS was not inhibited by 1 mM suramin. 4. From the results of this study, we conclude that the inhibitory NANC neurotransmission is mediated by NO alone and does not involve ATP in the portal vein of Japanese White rabbits under our experimental conditions.

Adenosine Triphosphate↗

PubMed1997

Angiotensin I-converting enzyme gene polymorphism and acute response to captopril in essential hypertension.

Insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene has been shown to be a determinant for serum ACE level and a marker for several cardiovascular diseases. We investigated whether the ACE gene can predict the therapeutic efficacy of ACE inhibitors in essential hypertensive patients. The response of blood pressure and plasma renin activity (PRA) 1 h after 50 mg captopril administration were evaluated in 82 inpatients with untreated essential hypertension (42 men, 40 women; mean age +/- SD: 52 +/- 13 years; range: 27 to 79 years) in relation to ACE genotypes. There were no differences in age, gender, blood pressure, and PRA in the basal conditions, among essential hypertensive patients with the II, ID, and DD genotypes (n = 36, 34, and 12, respectively). The acute responses of PRA and blood pressure to an ACE inhibitor were similar in the three groups. The blood pressure response was negatively correlated with baseline PRA (r = 0.497). These data suggest that PRA but not the I/D polymorphism of the ACE gene is a useful predictor of the short-term antihypertensive effects of ACE inhibitors.

Adult↗

PubMed1997

Change in blood pressure during altered sodium intake is not associated with calciotropic hormone level.

1. We evaluated the effects of the dietary restriction of sodium chloride on blood pressure and systemic calcium metabolism in 19 in-patients with essential hypertension (11 men and 8 women, mean age 49.9 +/- 12.1 years). 2. All patients received a high-sodium diet (250 mmol/day) for 1 week, followed by a low-sodium diet (10 mmol/day) for another week. Intake of potassium (100 mmol/day) and of calcium (15 mmol/day) were kept constant throughout the study. 3. Sodium restriction significantly reduced the mean blood pressure (from 114.0 +/- 1.9 to 105.0 +/- 13.7 mmHg, P < 0.01). Urinary calcium excretion was significantly reduced (from 5.1 +/- 2.4 to 2.2 +/- 1.0 mmol/day, P < 0.01). 4. The change in mean blood pressure after sodium restriction was not correlated with a change in any parameter of calcium metabolism [whole blood ionized calcium, plasma intact parathyroid hormone, or 1,25-(OH)2 vitamin D3]. 5. Plasma renin activity during a regular sodium diet, an index of renin status, was significantly and inversely correlated with the change in blood pressure during sodium restriction, but not with any change in the parameters of calcium metabolism. 6. We conclude that sodium restriction reduces blood pressure and decreases urinary calcium excretion. However, we observed no significant role of extracellular calcium concentration or of calciotropic hormone concentration in the mechanism of sodium sensitivity.

Adult↗

PubMed1997

Induction of p53-independent apoptosis associated with G2M arrest following DNA damage in human colon cancer cell lines.

The tumor suppressor p53 protein induces apoptosis in response to various kinds of DNA damage in normal cells, but it is still unclear whether or not apoptosis induced by DNA damage correlates with the p53 status in tumor cells. We determined the status of p53 by functional analysis of separated alleles in yeast in five human colon cancer cell lines, SW-480, SW-620, DLD-1, COLO320 and LS174T and investigated whether p53 is necessary for apoptosis and cell cycle arrest after treatment of the cells with a DNA-damaging agent, etoposide (VP-16), or gamma-irradiation. Of these cell lines, only LS174T expresses a functional p53. Apoptosis was detected in SW-480 and COLO320 cell lines, but not in the other cell lines, including LS174T cell line with a normal p53 function. Furthermore, cell cycle analysis revealed accumulation in the G2M phase preceding induction of apoptosis in SW-480 and COLO320 cells, but not in the other cells. These results suggest that apoptotic induction by DNA damage is not necessarily related to p53 status and that induction of p53-independent apoptosis following DNA damage may correlate with G2M arrest in the cell cycle, at least in the colon cancer cell lines used in this study.

Apoptosis↗

PubMed1997

Differential effects of extracellular Mg2+ on thrombin-induced and capacitative Ca2+ entry in human coronary arterial endothelial cells.

Receptor-mediated and capacitative Ca2+ entry are the primary Ca2+ entry pathways in endothelial cells (ECs). The mechanisms for Ca2+ entry via these pathways have not been fully elucidated. In this study, the effect of low and high external Mg2+ concentrations on these Ca2+ entry pathways was examined in human coronary arterial ECs. External Mg2+ concentration did not affect cytosolic free Mg2+ concentration. After exposure to thrombin in Ca(2+)-free medium, addition of Ca2+ to the medium caused a rise in cytosolic free Ca2+ concentration ([Ca2+]i), indicating thrombin-induced Ca2+ influx. Thrombin-induced Ca2+ influx was inhibited by not only low but also high external Mg2+ concentrations. After depletion of endoplasmic Ca2+ stores by thapsigargin, addition of Ca2+ to the medium induced an increase in [Ca2+]i, indicating capacitative Ca2+ entry. Capacitative entry was found to be accelerated by low external Mg2+ and inhibited by high external Mg2+ concentration. Results suggest that receptor-mediated Ca2+ influx requires external Mg2+ but is inhibited by increased external Mg2+ concentrations and that capacitative Ca2+ entry is reduced by external Mg2+ in human coronary arterial ECs.

Calcium↗

PubMed1997

Nocturnal decline in blood pressure is attenuated by NaCl loading in salt-sensitive patients with essential hypertension: noninvasive 24-hour ambulatory blood pressure monitoring.

We investigated the effect of NaCl on the circadian blood pressure rhythm in patients with essential hypertension classified according to the presence or absence of salt sensitivity. We obtained 24-hour noninvasive ambulatory blood pressure measurements in 64 Japanese patients with mild to moderate essential hypertension who ate a low NaCl diet (50 mmol/d) for 1 week, followed by a high NaCl diet (340 mmol/d) for 1 week. Twenty-six patients whose mean blood pressure was increased more than 10% by NaCl loading were classified as salt sensitive. The remaining 38 patients were classified as salt resistant. The nocturnal decline in mean blood pressure was significantly smaller in salt-sensitive patients (8.3+/-1.0%) than in salt-resistant patients (11.5+/-0.9%) (P<.05) during a high NaCl diet but was similar in both groups during a low NaCl diet. There was no significant difference in the prevalence of the non-dipper pattern between groups on a low NaCl diet, but the prevalence of the non-dipper pattern was significantly higher in salt-sensitive patients than in salt-resistant patients on a high NaCl diet (0.57 versus 0.26, chi2=6.4; P=.02; odds ratio, 3.82). These findings suggest that the NaCl loading blunted the nocturnal decline in blood pressure in salt-sensitive patients but not in salt-resistant patients.

Blood Pressure↗

PubMed1997

[Evaluation of angiotensin I converting enzyme gene polymorphism in patients with essential hypertension and coronary artery disease].

We investigated the role of the insertion (I)/deletion(D) polymorphism in the angiotensin I converting enzyme (ACE) gene in the cardiovascular diseases. First, we studied 520 patients who had undergone coronary angiography: including 220 patients with acute myocardial infarction, 98 patients with effort angina pectoris (> 75% stenosis), 83 patients with vasospastic angina and 119 controls with normal coronary artery. There was no difference in the frequency of ACE gene I/D allele or genotype II, ID and DD among the four groups. Second, we studied the correlation between ACE gene I/D polymorphism and the clinical characteristics in patients with essential hypertension. The distribution of I/D allele and genotype were similar in 140 essential hypertensives and 83 normal controls. In patients with DD genotype, age at onset of hypertension was lower and left ventricular mass index was greater than those in patients with ID and II, although blood pressure levels and the severity of damage to other organs-were similar in the three groups. Further, 66 patients with essential hypertension were classified into 35 salt-sensitive and 31 salt-resistant patients according to changes in mean blood pressure during a week of low salt diet followed by a week of high salt diet. The frequency of I allele was significantly higher in the salt-sensitive group than in the salt-resistant group. In conclusion, ACE gene I/D polymorphism is not associated with coronary artery diseases. In patients with essential hypertension, the D allele was associated with early onset and left ventricular hypertrophy, while I allele was associated with salt sensitivity.

Age of Onset↗