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Biomedical subjects

K Kinugawa

Publications and source records attributed to K Kinugawa.

At least 37 records · Page 2Linked to original sources
PubMed1995

Ca(2+)-growth coupling in angiotensin II-induced hypertrophy in cultured rat cardiac cells.

OBJECTIVES: There remain some controversies about the effect of angiotensin II on intracellular Ca2+ concentration ([Ca2+]i) in cardiac myocytes. The aim of this study was to investigate different roles of intracellular Ca2+ in the responses to angiotensin II between cardiac myocytes and nonmyocytes. METHODS: Primary cultures of neonatal rat cardiac myocytes and nonmyocytes were prepared. [Ca2+]i was measured with indo-1. Cellular growth was assayed by [3H]thymidine uptake, RNA content, [3H]phenylalanine incorporation and protein content. Induction of immediate-early gene was examined by Northern blot analysis. RESULTS: In myocytes, angiotensin II decreased [Ca2+]i transients, induced c-fos mRNA, and accelerated hypertrophy. These effects were completely suppressed by AT1 receptor blockade or protein kinase C inhibition. After chelation of extracellular Ca2+, angiotensin II caused no change in [Ca2+]i or no induction of c-fos in myocytes. Phorbol 12-myristate 13-acetate also decreased [Ca2+]i transients, caused c-fos induction, and provoked hypertrophy in myocytes. In nonmyocytes, angiotensin II increased [Ca2+]i transiently, induced c-fos mRNA and hypertrophy. These effects of angiotensin II were not fully abolished by protein kinase C inhibition. Extracellular Ca2+ chelation did not completely inhibit the effects of angiotensin II on [Ca2+]i or c-fos induction in nonmyocytes. Phorbol 12-myristate 13-acetate did not affect [Ca2+]i or cellular growth in nonmyocytes but did cause c-fos induction. CONCLUSIONS: These results suggest that angiotensin II induces cellular hypertrophy and immediate-early genes through the activation of protein kinase C in myocytes, although angiotensin II decreases [Ca2+]i transients via this signaling pathway. Induction by angiotensin II of hypertrophy and immediate-early genes in nonmyocytes may be in part mediated by a transient increase in [Ca2+]i which acts synergistically with protein kinase C activation.

Angiotensin II↗
PubMed1994

Nitric oxide-mediated effects of interleukin-6 on [Ca2+]i and cell contraction in cultured chick ventricular myocytes.

Cytokines have significant roles in some cardiovascular disorders, but direct myocardial effects of cytokines remain to be elucidated. In the present study, we examined both the early and delayed effects of interleukin-6 (IL-6) on cultured chick embryo ventricular myocytes. Exposure of these cells to human recombinant IL-6 significantly decreased peak systolic [Ca2+]i (71.0 +/- 0.6% of the control value) and the amplitude of cell contraction (66.0 +/- 7.4% of the control value) within a few minutes. Pretreatment with NG-monomethyl-L-arginine (L-NMMA) or methylene blue completely inhibited the IL-6-induced early changes. Subsequent addition of L-arginine reversed the effects of L-NMMA. The levels of cGMP were significantly increased after 30 minutes of exposure to IL-6 (134.4 +/- 9.1% of the control value). Pretreatment with L-NMMA or EGTA significantly inhibited the IL-6-induced early elevation of cGMP. These results suggest that IL-6 acutely decreases intracellular Ca2+ transients and depresses cell contraction by nitric oxide (NO)-cGMP-mediated pathway. Therefore, IL-6 may enhance the Ca(2+)-dependent constitutive NO synthase activity in cardiac myocytes. On the other hand, 24-hour exposure to IL-6 also increased the levels of cGMP (159.0 +/- 22.8% of the control value) regardless of pretreatment with EGTA. These delayed increases in cGMP were also shown to be coupled with decreases in intracellular Ca2+ transients and the amplitude of cell contraction. Thus, IL-6 may induce Ca(2+)-independent NO synthase in cardiac myocytes. Together with the previous reports that have suggested the possible roles of IL-6 in myocardial stunning or endotoxic shock, this negative inotropic effect of IL-6 may contribute to these clinical settings.

Amino Acid Oxidoreductases↗
PubMed1994

Polyclonal human T-cell activation by silicate in vitro.

Silica (SiO2) or related substances such as silicone ([-R2Si-O-]n), which is used in plastic surgery, or asbestos (e.g. chrysotile; 3MgO.2SiO2.H2O) have 'adjuvant effects'. In a study of scleroderma patients in Germany more than 78% had experienced exposure to silicate dust. T-cell receptor (TcR) V beta gene analysis on CD4- CD8- double-negative alpha beta T cells from scleroderma patients, using polymerase chain reaction (PCR), showed that certain V beta genes, V beta 5, V beta 7 and V beta 17, were predominantly expressed in the cells. We found that certain V beta repertoires, V beta 5.3 and V beta 6.7, were predominantly expressed on fractionated T cells with a high Ca2+ level that had been stimulated by chrysotile in vitro. The intracellular Ca2+ level in human peripheral blood mononuclear cells (PBMC) increased after incubation with silica or chrysotile. Interleukin-2 (IL-2) release from PMBC also rose significantly with chrysotile stimulation, but no change was observed when major histocompatibility complex (MHC) class II DP/DR positive cells were depleted. Therefore, our results support the possibility that silicate acts as a superantigen.

Adult↗
PubMed1993

Effects of a nonpeptide angiotensin II receptor antagonist (CV-11974) on [Ca2+]i and cell motion in cultured ventricular myocytes.

We studied the effects of angiotensin II and CV-11974 (a newly synthesized angiotensin II receptor antagonist) on cell contraction and [Ca2+]i in cultured neonatal rat ventricular myocytes. Exposure of these cells to 10 nM angiotensin II significantly decreased peak systolic cell position (60.1 +/- 3.3% of the control, P < 0.01) and peak systolic [Ca2+]i (from 1111 +/- 250 to 572 +/- 143 nM, P < 0.05) within 60 s. Pretreatment of ventricular myocytes with CV-11974 (10-100 nM) completely suppressed the angiotensin II-induced changes in peak systolic cell position and [Ca2+]i. These results suggest that CV-11974 inhibits cardiac angiotensin II receptors.

Angiotensin Receptor Antagonists↗
PubMed1992

Activation of human CD4+CD45RA+ T cells by chrysotile asbestos in vitro.

Chrysotile asbestos stimulates T lymphocyte subsets. Cell surface CD4 or CD45RA expression in peripheral blood mononuclear cells (PBMC) was downregulated after incubation with chrysotile asbestos in vitro temporarily. The percentage of CD4+CD45RA+ cells and mean fluorescence intensity in CD4 or CD45RA decreased after incubation with asbestos and returned to the original level after 24 h of incubation, which suggests that chrysotile asbestos activates CD4+CD45RA+ cells. No change was observed in CD29 expression. An increased percentage of IL-2R positive cells and an elevated intracellular Ca++ level were also indicative of the activation of PBMC by chrysotile asbestos.

Antigens, CD↗
PubMed1992

Crocidolite asbestos suppresses the differentiation of HL-60 cells induced by DMSO.

This study was undertaken to determine if the biological function of inducers for cell differentiation is affected by asbestos fibers, which are sometimes deposited in human tissues. Protein kinase C activity, c-myc protein expression and cell surface CR3 expression were used as the markers of cell differentiation. The function of dimethylsulfoxide (DMSO), an inducer of cell differentiation, was suppressed by the co-culturing of crocidolite asbestos, because DMSO reacted with the hydroxyl radical released after the stimulation with crocidolite and spent itself. Superoxide dismutase (SOD) inhibited the effect of crocidolite, reacting rapidly with .O2- before the secondary release of .OH. Asbestos fibers deposited in tissues may inhibit the function of inducers which stimulate immature cells to differentiate, because such inducers frequently are also radical scavengers.

Asbestos↗
PubMed1992

[Assessment of coronary artery bypass grafts by X-ray computed tomography with and without contrast enhancement].

To assess the patency of coronary artery bypass grafts, we tested the capability of X-ray computed tomography (CT) with and without contrast enhancement. This procedure was used on 63 grafts (30 in the LAD; 20 in the LCX; 13 in the RCA) in 32 patients with a mean age of 56 +/- 8 years, all of whom were referred to our department for postoperative management or evaluation. The CT scanner used was Toshiba TCT-60A with a scan time of 3 sec, 5 mm thick slices, and 512 x 512 pixels. CT scans without contrast enhancement were obtained from the level of the aortic arch to the left ventricle. Eight sec after 30 ml of contrast media was injected at a rate of 3 ml/sec into an antecubital vein, 5 scans were made at the same level of the pulmonary artery truncus. After positioning the regions of interests on the ascending aorta and grafts, we obtained time-density curves (TDCs) and compared the data with those recorded from an intraoperative electromagnetic flow meter (EMF). Fifty grafts were angiographically patent. The appearance time, build-up time, peak time, disappearance time and peak densities obtained from TDCs of grafts did not correlate with the flow volumes measured by EMF. Patent grafts were easily identified visually, without contrast enhancement (sensitivity; 88%, specificity; 100%, accuracy; 91%). Occluded grafts were not imaged on CT, either with or without contrast enhancement. We concluded that the TDCs of grafts obtained by CT are of no value for predicting the graft flow, and that plain CT without contrast enhancement is sufficiently useful for assessing the patency of such grafts.

Aged↗
PubMed1992

[Doppler and echocardiographic study of normal systolic murmurs].

To elucidate the genesis of normal ejection systolic murmurs, we performed phono and Doppler echocardiography in 42 normal subjects. Individuals with hypertension, ST.T changes on ECG, anemia or other cases with definite cardiovascular findings were excluded from the study. Their ages ranged from 22 to 61 years with an average of 48.1 years. They were classified in 2 groups; 9 with Levine 2/6 systolic murmur and 33 without murmur or with 1/6 murmur. Fifteen patients with pure aortic regurgitation or with aortic prosthesis but without significant stenosis, and 7 patients with pulmonic valvular stenosis were served as control. We correlated the intensity and timing of murmur with maximal flow velocity, acceleration time and other parameters. All systolic murmurs were early systolic. Mid-systolic murmur was not noted. Peak of flow velocity increased at the aortic orifice than at the left ventricular outflow tract or pulmonary orifice. Left-sided peak flow velocity occurred earlier than the right-sided peak flow velocity. Early systolic maximal flow velocity of the aorta significantly increased in 9 subjects with murmur than in the remaining 33 without significant murmur. Ejection fraction, hematocrit and body surface area did not differ between the groups with and without significant murmur. Systolic blood pressure and age, however, were higher in subjects with murmur. In aortic valvular disease, systolic murmurs and peak flow signals were early systolic, but in pulmonary stenosis these were mid-systolic in timing. In conclusion, normal ejection systolic murmurs were early systolic and originated at the aortic orifice. Mid-systolic murmurs were unlikely as left-sided murmur in origin. Flow velocity was the most important determinant of the intensity of ejection murmur.

Adult↗
PubMed1991

[Effects of asbestos on the cell cycle of PHA-stimulated human peripheral blood lymphocytes].

It is well known that persons exposed to asbestos display systemic immunological alterations: impaired lymphocyte response to PHA, the appearance of autoantibodies and elevation of the serum immunoglobulin level. The authors intend in this report to determine whether asbestos fibres (crocidolite, chrysotile and amosite) have any effect on the cell cycle of human lymphocytes after PHA stimulation. Peripheral blood mononuclear (PBM) cells were incubated with 10 micrograms/ml PHA for 2 days. After PHA stimulation, a decrease in the percentage of cells in the G0 phase and an increase in that of cells in the G1A, G1B and S phases was observed. When asbestos fibres or titanium dioxide (TiO2) was added to the culture dish at the beginning of the experiment, the progression of the cell cycle was inhibited only by asbestos fibres, in which case the percentage of cells in the G0 phase was significantly increased, while those of cells in the G1B and S phases were significantly decreased. The experiment for determining the critical period for inhibition of blastogenic response revealed that no inhibition was demonstrable when crocidolite fibre was added at 24 hr after PHA stimulation. Although the mechanisms of asbestos-fibre-mediated suppression remain to be clarified, these results showed that asbestos fibres act at an early stage (G0 phase) of the cell cycle and suppress the PHA stimulation of PBM cells.

Asbestos↗
PubMed1991

[The effects of asbestos fibers on the protein kinase C activity in HL-60 cells. The role of free radicals].

It was confirmed that the function of DMSO as an inducer of cell differentiation was suppressed by co-culture of crocidolite asbestos, using the activity of protein kinase C as indicator, because DMSO reacted with .OH radical released by stimulation with crocidolite and wasted itself. SOD inhibited the effect of crocidolite, because SOD reacted with .O2- released by stimulation with crocidolite and inhibited the subsequent development of .OH.

Asbestos↗
PubMed1990

Elevated binding activity of CD8+ cells with phytohaemagglutinin by asbestos fibre in vitro.

Asbestos fibres are known to depress the mitogenic stimuli of phytohaemagglutinin (PHA) to lymphocytes. We examined effects of asbestos (chrysotile) fibre on the proliferation of PHA-stimulated lymphocytes and the PHA binding activity of lymphocytes in vitro. The incorporation of 3H-thymidine and the expression of interleukin-2 receptor were depressed when the cells were exposed to 50 micrograms/ml of chrysotile fibre. The PHA binding activity of lymphocytes was significantly enhanced after chrysotile fibre exposure, as compared with non-exposed group. These results indicate that the depression of PHA stimuli with chrysotile fibre was not due to blocking of PHA binding to lymphocytes. The enhancement of PHA binding activity by chrysotile fibre was observed on CD8+ but not on CD4+ cells. It is possible, therefore, that treatment of peripheral blood mononuclear cells with chrysotile fibre induces increased reactivity of CD8+ cells with PHA, and that intensely activated CD8+ cells suppress proliferation of lymphocytes.

Antigens, CD↗
PubMed1990

[Suppressive effect of crocidolite fibers on the differentiation of HL-60 cells induced with DMSO].

HL-60 cells were derived from a patient with myelocytic leukemia, and are known to be in the promyelocytic stage and to differentiate into myelocytes or granulocytes after induction with several materials, e.g., DMSO, retinoic acid, and interferons. The authors intended in this report to determine whether asbestos fibers have any effect on the differentiation processes of HL-60 cells induced with DMSO. The cells were induced to differentiate by incubation with 1.25% DMSO for 4 days. A decrease in the percentage of c-myc-protein-positive cells and an increase in the number of C3bi receptor (CD11b) positive cells were observed after differentiation. When crocidolite (50 micrograms/ml) was added to the culture dishes at the beginning of the experiments, the differentiation was inhibited. An increase in the percentage of c-myc-protein-positive cells and a decrease in that of C3bi-receptor-positive cells were observed compared with the cells induced with DMSO alone. It has been reported that DMSO activates phospholipid- and Ca2(+)-dependent protein kinase and induces the differentiation of HL-60 cells. The mechanisms of inhibition by crocidolite fibers of the effects of DMSO remain to be clarified, but the strength of activation of phospholipid- and Ca2(+)-dependent protein kinase may play an important role in the following induction of cell differentiation.

Asbestos↗
PubMed1983

[Value of contrast-enhanced CT scan in prediction of development of contusional hemorrhage].

It is often experienced that even if there are no significant findings on the initial plain CT scan in the patient with cerebral contusion, the patient has thereafter a serious clinical course and requires emergency operation for so-called contusional hemorrhage. In order to predict of the development of contusional hemorrhage we performed contrast-enhanced CT scan at the time of patient's arrival within 12 hours after injury, if there was cerebral contusion on 24 hours after the contrast-enhanced CT scan. If enhancement was demonstrated on the contrast-enhanced CT scan, we predicted the development of contusional hemorrhage and if not demonstrated, we predicted no more development of contusional hemorrhage and then we studied the correlation between the prediction and the plain CT 24 hours after the contrast-enhanced CT scan. The results were as follows: 1) The prediction was correct in 13 cases out of 16 cases in which the development of contusional hemorrhage was observed. In 18 cases where no development of contusional hemorrhage was observed, the prediction was correct without exception. 2) Most of the cases in which enhancement was demonstrated were ones examined not before 3 hours after injury. 3) The extent of enhancement shown on contrast-enhanced CT scan was well consistent with that of contusional hemorrhage on the plain CT scan 24 hours after the contrast-enhanced CT scan. From these results, the contrast-enhanced CT scan in acute stage of head injury was considered to by very useful in prediction of the development of contusional hemorrhage.

Adolescent↗
PubMed1982

[Experimental studies of the effect of diltiazem (Ca-antagonist) on cerebral circulation and cerebral arterial spasm].

Polygraphycal studies were carried out in order to evaluate the effects of Diltiazem (Ca-antagonist) on cerebral circulation in cats. In addition to these studies, the inhibitory effect of Diltiazem on incubated blood-, and serotonin-induced vasocontraction of basilar arteries was observed through on operating microscope. Experimental vasospasm were induced by local administration of incubated blood and 10(-5)--10(-6) M serotonin solution. The required dose of Diltiazem, 30-300 micrograms/kg, was injected by one shot intravenously. CBF slightly decreased concomitantly with transiently decreased blood pressure shortly after intravenous injection of Diltiazem. After that, CBF increased for 15-20 minutes and returned to the state similar to that before the administration of Diltiazem. The changes in reactive pattern of CBF depend on the doses of Diltiazem and related to changes of CAR and VAR which were thought to indicate the blood of cardiac output. Vasocontraction induced by incubated blood and serotonin was released 30-35 per cent for 30 minutes after intravenous injection of Diltiazem 100 micrograms/kg. However, by administration of Diltiazem before and after local application of incubated blood and serotonin on basilar arteries, vasocontraction was inhibited completely. These data suggest that administration of Diltiazem (Ca-antagonist) might be useful in the prophylaxis and treatment of vasospasm following rupture of cerebral aneurysm.

Animals↗