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Biomedical subjects

H Shima

Publications and source records attributed to H Shima.

At least 235 records · Page 13Linked to original sources

Loss of the MYC gene amplified in human HL-60 cells after treatment with inhibitors of poly(ADP-ribose) polymerase or with dimethyl sulfoxide.

In HL-60 cells, a human promyelocytic leukemia cell line, the human c-myc gene, designated MYC, is amplified about 16-fold. On differentiation of the HL-60 cells into granulocytes induced by several inhibitors of poly(ADP-ribose) polymerase [NAD+ poly(adenosine diphosphate D-ribose)ADP-D-ribosyltransferase, EC 2.4.2.30] including benzamide, nicotinamide, coumarin, and 4-hydroxyquinazoline or dimethyl sulfoxide, some MYC loss was observed. In contrast, benzoic acid, a noninhibitory analogue of benzamide, did not induce either granulocytic differentiation or loss of MYC. Loss of MYC seems to be associated with granulocytic differentiation because the time course of its loss was similar to that of appearance of nitroblue tetrazolium-positive cells, mature granulocytes, and its loss was not observed on differentiation of HL-60 cells into macrophages induced by phorbol 12-myristate 13-acetate or teleocidin. The loss of MYC is not the reason for the down regulation of MYC expression observed within 1 hr after addition of inducers, since the loss of MYC was not detected by 1-day treatment with inducers.

Benzamides↗

Facilitatory effects of ouabain and digitalis-like substance on adrenergic transmission in hypertension.

The purpose of the present study was to examine the role of Na+,K+-ATPase activity in vascular adrenergic transmission of hypertension. In isolated perfused mesenteric vasculatures of spontaneously hypertensive rats (SHR, Okamoto and Aoki strain, seven- to ten-weeks-old) and age-matched Wistar Kyoto rats (WKY), the effects of ouabain, a potent Na+,K+-ATPase inhibitor, or partially purified plasma obtained from salt-induced hypertension on pressor responses and norepinephrine overflow were investigated. Pressor responses and norepinephrine overflow during electrical nerve stimulation were significantly greater in SHR than in WKY. Ouabain increased the stimulation-evoked pressor responses and norepinephrine overflow. This facilitation was more prominent in SHR than in WKY. Partially purified plasma obtained from reduced renal mass-salt hypertensive rats, which had a crossimmunoreactivity with digoxin, also increased the pressor responses and norepinephrine overflow during electrical nerve stimulation, and the effects were greater in SHR than in WKY. These results suggest that Na+,K+-ATPase on vascular adrenergic neurons has an important role in the regulation of neurotransmitter release, and that its activity might be enhanced in SHR.

Animals↗

Polyorchidism: preoperative diagnosis by ultrasonography.

Polyorchidism is an unusual abnormality of the genital tract in which supernumerary testicles are present, usually within the scrotum. We report a recently encountered case with no remarkable symptoms. Preoperative ultrasonographic evaluation differentiates this rare benign entity from more ominous abnormalities such as neoplastic involvement of the scrotal contents.

Child↗

[Treatment of congenital urethral stenosis (urethral ring) in children. Optic internal urethrotomy in the congenital bulbar urethral stenosis in boys].

Congenital urethral stenosis in boys occurs at the junction of the entodermal primary urethra and ectodermal secondary urethra. Endoscopically this lesion is recognized as a ring-form stenosis just distal to the external urethral sphincter. It has been considered as rare congenital anomaly in American literature. But in our experience congenital urethral stenosis is an important cause of recurrent urinary tract infections, enuresis, pollakisuria or hematuria in pediatric urological practice. It also disturbs spontaneous healing of vesicoureteral reflux. The most effective treatment of this lesion is optic internal urethrotomy under direct vision. We would like to report our experience of optic internal urethrotomy for congenital urethral stenosis in boys. From 1974 to 1986, 226 boys with congenital bulbar urethral stenosis were treated in our clinic. Optic internal urethrotomy was performed using a Sachse urethrotome with a 10 or 13 Fr. sheath. Of the 176 ureters with vesicoureteral reflux, spontaneous disappearance of reflux after optic internal urethrotomy was noted in 62.5% of Grade I-II, 65.0% of Grade III, 28.9% of Grade IV and 16.7% of Grade V ureters. These spontaneous disappearance rates were significantly higher than those of primary vesicoureteral reflux in Grade III, IV and V ureters. Of the drug-resistant enuretic boys with a congenital bulbar urethral stenosis, enuresis disappeared or ameliorated in 69.4% after optic internal urethrotomy. Furthermore, urinary tract infections were mostly prevented by optic internal urethrotomy, irrespective of the presence or absence of vesicoureteral reflux. Our results support the view that congenital urethral stenosis (urethral ring) is an important clinical entity in pediatric urology.

Adolescent↗

Role of protein phosphatases in malignant transformation.

Many oncogene products are protein kinases and signals are transduced via phosphorylation of proteins. Similarly, protein-dephosphorylation may play a critical role in malignant cell transformation. We have cloned two catalytic subunits of ser/thr protein phosphatase (PP) type 2A, PP2A alpha, and PP2A beta, from a rat liver cDNA library. Both cDNAs encode peptides of 309 amino acids with a difference of only 8 amino acids between the two. All primary hepatocellular hyperplastic nodules or carcinomas, which were induced by a food carcinogen, 2-amino-3-methylimidazo[4,5-f]quinoline, showed up-regulation of expression of the mRNAs of both PP2A alpha and PP2A beta. NIH3T3 cell transformants obtained by introducing activated c-raf, ret-II or Ki-ras oncogenes also showed high levels of PP2A alpha transcripts. Okadaic acid, a non-TPA type tumor promoter, was found to be a potent inhibitor of PP1 and PP2A. Its IC50 for PP1 was much higher than that for PP2A with phosphorylase a as a substrate. When raf and ret-II transformants were cultured with okadaic acid at 8 ng/ml for 2 days, both transformants became flattened and showed strict contact inhibitions. This flat cell morphology was stable for at least one month in the presence of okadaic acid, but in its absence, the cells reverted to their original transformed shape within 7-10 days. Colony formation by raf and ret-II transformants in soft agar was inhibited dose-dependently by okadaic acid; very few colonies grew in the presence of the acid at 8 ng/ml. Okadaic acid had less effect on a transformant of the Ha-ras gene, causing only 50% inhibition of colony formation at 8 ng/ml. The role of protein phosphatases in cellular transformation by certain oncogenes is suggested.

Animals↗

[Transurethral ureterolithotripsy under hydraulic ureteral dilatation].

Transurethral ureterolithotripsy was performed in 32 patients with ureteral stones. A rigid ureteroscope was used and for the purpose of ureteral dilatation a hydraulic ureteral dilator (Ureteromat) was used. In total 39 stones were treated and of these 30 stones (77%) were successfully extracted or disintegrated. The success rate according to the location of the stone was as follows; 50% for the upper ureteral stone, 55% for middle ureteral stone and 96% for lower ureteral stone. As a complication of the procedure a lower ureteral stricture was noted in one patient. Hydraulic ureteral dilatation is a useful method of ureteral dilatation in transurethral ureterolithotripsy.

Adolescent↗

[Four successfully operated cases of ball thrombus in the left atrium].

The authors report four cases of the left atrial ball thrombus associated with mitral stenosis. Three of four which had floating ball thrombus in the left atrium presented with syncopal attacks and systemic embolism. Echocardiography was the most effective method for preoperative diagnosis of ball thrombus in the left atrium and mitralstenosis. After having accurate diagnosis of ball thrombus in the left atrium by echocardiogram, all of cases were treated urgently with removal of the thrombus and mitral valve replacement or mitral commissurotomy. During operation, the head down position and slight right lateral position had been maintained to prevent the impaction of the ball thrombus into mitral valve orifice and the immediate cardiopulmonary bypass by ascending aortic, superior and inferior venous cannulation were placed through midsternal splitting incision. Because of high frequency of peripheral embolism and sudden death, left atrial ball thrombus should be recommended to be removed urgently.

Aged↗

Destruction of renal parenchyma at percutaneous nephrolithotripsy; experimental study.

The destruction of renal parenchyma caused by excess deflection of the sheath was examined to determine at what level of force the renal parenchyma was ruptured during PNL. The kidney obtained from right nephroureterectomy due to renal pelvic cancer (stage T2N0M0) of a 54-year-old female patient was punctured at the posterolateral portion with a puncture needle. The tract was dilated up to 26 Fr. in size with an Amplatz renal dilation set. The 26 Fr. sheath was left in the tract and fixed to the metal bar attached to Gig Boring Machine (Hydroptic-6) which could sense the change of pressure added to the renal parenchyma in the parallel movement of the metal bar. The critical angle in regard to the deflection of the renal parenchyma in order not to cause the rupture of renal parenchyma on PNL was calculated from both the resultant force and the shape of the wound of renal parenchyma at rupture. The safety angle against horizontal plane of the tract ranged from 18 to 37 degree.

Biomechanical Phenomena↗

[Clinical statistics on outpatients, inpatients and operations in 1987].

Statistical studies were made on 1,859 outpatients, 587 inpatients and 601 operative procedures at our department in 1987. The most frequent diseases among the outpatients were urogenital infections followed by anomalies, tumors and stones. The major diseases among the inpatients were hypospadias, vesicoureteral reflux, congenital urethral stenosis, benign prostatic hypertrophy and bladder tumor. A total of 601 operations were performed. The five major operations were hypospadias repair, optic internal urethrotomy, transurethral resection of prostate, ureterocystoneostomy and transurethral resection of bladder tumor.

Hospital Departments↗

Deletion of transfected oncogenes from NIH 3T3 transformants by inhibitors of poly(ADP-ribose) polymerase.

a1-1 cells, a transformant line obtained by transfection of NIH 3T3 cells with human c-Ha-rasT24 (hc-Ha-rasT24), were converted to morphologically normal flat cells following a 2-week culture in the presence of benzamide (BA), an inhibitor of poly(ADP-ribose) polymerase [ADP-ribosyltransferase (polymerizing); EC 2.4.2.30]. Concomitant with these morphological changes was the loss of the exogenous hc-Ha-rasT24 sequence. When cells were cultured without transfer, multiple clusters of flat revertant cells surrounded by transformed cells within single colonies of a1-1 cells were observed. This, together with the slow growth rate of flat cells in the presence of BA, indicated that flat revertants were induced rather than selected by BA. Flat cells isolated from mixed colonies completely lost the exogenous and amplified hc-Ha-rasT24 gene. In contrast, the endogenous mouse c-Ha-ras in flat revertant cells was not lost during culture with BA. Similarly, the endogenous hc-Ha-rasT24 in human bladder carcinoma T24 cells was not affected by BA. By using various chemicals, it was suggested that inhibition of poly(ADP-ribose) polymerase induces an efficient and specific loss of the exogenous transforming genes including Ki-ras, N-ras, c-raf, and ret-II.

Animals↗

Effects of calcium antagonists on membrane fluidity in hypertension--an electron spin resonance study.

We examined alterations in membrane fluidity of hypertension and the effects of calcium antagonists on these changes by means of an electron spin resonance (ESR) and spin-label technique. Washed erythrocytes from spontaneously hypertensive rats (SHRs; aged 4 and 10-13 weeks) and from patients with essential hypertension, or cultured vascular smooth muscle cells from SHRs were examined and compared with those from normotensive controls. Electron spin resonance spectra for a fatty acid spin label-agent (5-nitroxy stearate) in the membranes were obtained. The values of hyperfine splitting and other parameters of the spectra were significantly higher in erythrocytes from hypertensive rats than in normotensive controls. Similar results were obtained in cultured vascular smooth muscles. These findings indicate that the membrane fluidity might be decreased in hypertension. When calcium was loaded to erythrocytes with Ca-ionophore A23187, the fluidity was decreased. The alternative degrees were greater in hypertensive rats than in controls, and these hypertensive changes were antagonized by diltiazem or verapamil. The results revealed that abnormalities of membrane fluidity in hypertension might be more prominent in the presence of calcium. Further, it is suggested that calcium antagonists could correct these membrane abnormalities in hypertension.

Adult↗

Relationship between the sympathetic nervous system and sodium potassium adenosine triphosphatase inhibitor in salt-sensitive patients with essential hypertension.

In order to evaluate endogenous Na+,K+-ATPase inhibitor on sympathetic nerve endings, endogenous Na+,K+-ATPase inhibitor and plasma noradrenaline were determined in patients with essential hypertension under different sodium conditions. Compared with the plasma from non-salt-sensitive patients, that from salt-sensitive patients showed significantly higher Na+,K+-ATPase inhibitor and plasma noradrenaline levels. Salt-induced changes in endogenous Na+,K+-ATPase inhibitor and those in blood pressure or plasma noradrenaline showed positive correlations. These results suggest that the salt-induced increase in endogenous Na+,K+-ATPase inhibitor might induce blood pressure elevation in essential hypertension, at least partly via increased noradrenaline levels.

Blood Pressure↗

Membrane abnormality of erythrocytes is highly dependent on salt intake and renin profile in essential hypertension: an electron spin resonance study.

The purpose of the present study was to investigate membrane fluidity in essential hypertension using electron spin resonance (ESR) and spin-labelling. Erythrocytes from patients with untreated essential hypertension were examined and compared with age-matched normotensive subjects. The values of outer hyperfine splitting (2T') and order parameter (S) of the ESR spectra for a fatty acid spin label agent (5-nitroxy stearate) were significantly higher in essential hypertension than in the normotensive subjects. However, these values were not changed in secondary hypertension. This finding indicates that the membrane fluidity of erythrocytes was lower in essential hypertension. Further, the abnormality was attenuated with low-salt intake, and, on the contrary, was more prominent with high-salt intake in essential hypertension. Calcium loading to erythrocytes in vitro caused a greater decrease in the membrane fluidity in essential hypertension than in the normotensive controls. This calcium-induced change in the membrane fluidity was significantly inversely correlated with the value of plasma renin activity in essential hypertension. These results suggest that abnormality in the membrane fluidity might be emphasized in the presence of calcium, especially in low-renin essential hypertension, implying enhanced calcium sensitivity in this type of hypertension.

Calcium↗

Endogenous noradrenaline re-uptake blocking factor in rats with reduced renal mass hypertension.

This study was carried out to elucidate the involvement of the peripheral sympathetic nervous system in the pathogenesis of reduced renal mass (RRM)-salt hypertension in rats. Male Wistar rats underwent subtotal nephrectomy (70-80% reduction in renal mass). On the 10th postoperative day, systolic blood pressure was higher in RRM-salt rats than in RRM-water rats. Perfusion of isolated mesenteric vasculature from normotensive rats, with the deproteinized plasma from RRM-salt hypertensive rats induced significantly higher pressor responses and noradrenaline overflow with electrical stimulation than the perfusate from RRM-water normotensive rats; the responses to exogenous noradrenaline showed no significant changes. In the presence of desipramine, noradrenaline overflow did not increase following perfusion with plasma from RRM-salt hypertensive rats. These data indicate that plasma from rats with RRM-salt hypertension might contain some noradrenaline re-uptake blocking factor.

Animals↗

Role of substance P and neurotensin in the regulation of neurosecretion and vascular responsiveness in hypertension.

The purpose of the present study was to investigate the effects of vasoactive neuropeptides, such as substance P or neurotensin, on vascular adrenergic neurotransmission in hypertension. In perfused mesenteric vasculatures prepared from spontaneously hypertensive rats (SHR), we examined the effects of substance P and neurotensin on vascular responsiveness and noradrenaline release from the sympathetic nerve endings. Stimulation-evoked noradrenaline release and pressor responses were inhibited by substance P and neurotensin. In SHR, the noradrenaline release and pressor responses during electrical nerve stimulation were significantly greater than in Wistar-Kyoto rats (WKY). The inhibitory effects of these responses by substance P and neurotensin were attenuated in SHR compared with WKY. These results showed that substance P and neurotensin could affect the presynaptic site of the blood vessels and cause a decrease in electrically stimulated noradrenaline release from the vascular adrenergic neurons. The reduction of noradrenaline release and pressor responses by substance P and neurotensin in SHR might suggest insufficient regulation of the vascular adrenergic transmission by these vasoactive peptides in hypertension.

Animals↗

Protein kinase C-dependent and calmodulin-dependent regulation of neurotransmitter release and vascular responsiveness in spontaneously hypertensive rats.

This study was designed to investigate the role of protein kinase C and calmodulin in adrenergic transmission in hypertension. In isolated mesenteric vasculature prepared from spontaneously hypertensive rats (SHR, Okamoto and Aoki strain) and age-matched Wistar-Kyoto rats (WKY), we examined the effects of protein kinase C inhibitor (H-7) and calmodulin antagonist (W-7) on pressor responses and noradrenaline release from the vascular adrenergic neurons. Endogenous noradrenaline release and vasoconstrictor responses evoked by periarterial nerve stimulation were significantly enhanced in SHR compared to those in age-matched WKY. Protein kinase C inhibitor H-7 and the calmodulin antagonist W-7 inhibited the stimulation-evoked noradrenaline release and pressor responses, respectively, in a dose-dependent manner. Further, these inhibitory effects of H-7 and W-7 were greater in SHR than in WKY. These results demonstrate that noradrenaline release and vascular responsiveness are increased in the mesenteric vasculatures of SHR. The marked reduction in noradrenaline release and pressor responses induced by H-7 and W-7 in SHR suggests the presence of enhanced protein kinase C-dependent and calmodulin-dependent regulation of adrenergic neurotransmission, which may contribute to the calcium abnormalities in this model of hypertension.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Evidence in volume-dependent hypertension for an augmenting factor for norepinephrine overflow from sympathetic nerve endings.

It has been reported that salt loading induces a blood pressure rise in rats whose renal mass has been reduced. We examined the involvement of the peripheral sympathetic nervous system in the pathogenesis of hypertension in subtotally nephrectomized and salt-loaded rats. Male Wistar rats (200-240 g) underwent subtotal nephrectomy (removal of 70-80% of the renal mass). After surgery, 1% saline was given ad libitum as drinking water in the experimental group (E), while tap water was given to the controls (C). On the 10th day after nephrectomy, blood pressure was determined, and plasma samples were collected. Deproteinized plasma samples were diluted with Ringer-Locke solution (1/40 v/v), and were perfused into isolated mesenteric artery-intestinal loop preparations of normotensive male Wistar rats. Pressor responses and norepinephrine overflow induced by electrical nerve stimulation, and the pressor responses to exogenous norepinephrine were assessed before and after the addition of deproteinized plasma to the perfusate. Systolic blood pressure was significantly elevated in the experimental group (E: 150 +/- 5 mmHg, C: 109 +/- 4 mmHg, p less than 0.01). When deproteinized plasma from the experimental group was perfused, pressor responses to electrical nerve stimulation were significantly increased (E: 167.2 +/- 13.7%, C: 91.1 +/- 6.4%; p less than 0.01), as was norepinephrine overflow (E: 117.3 +/- 6.4%, C: 90.7 +/- 5.9%; p less than 0.05), while responses to exogenous norepinephrine were only slightly augmented compared with the control group (E: 120.0 +/- 2.7%, C: 105.5 +/- 9.0%; n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Membrane fluidity of erythrocytes and its relevance to renin profile in essential hypertension.

This study was performed to investigate the membrane fluidity of hypertension by means of an electron spin resonance (E.S.R.) and a spin-labeling technique. Erythrocytes from patients with untreated essential hypertension (WHO I, II) and secondary hypertension were compared with those from normotensive subjects, and E.S.R. spectra for a fatty acid spin label agent (5-nitroxy stearate) incorporated into the erythrocyte membranes were obtained. The values of outer hyperfine splitting (2T'parallel) and order parameter (S) were significantly higher in erythrocytes from patients with essential hypertension than in those from normotensive subjects. However, these values were not significantly changed in patients with secondary hypertension compared with those in the normotensive subjects. This finding may indicate the reduced erythrocyte membrane fluidity in essential hypertension. Calcium-loading to erythrocytes with calcium-ionophore caused a greater decrease in the membrane fluidity of erythrocytes in patients with essential hypertension than in those from the normotensive subjects. This Ca-induced change in membrane fluidity was inversely correlated with plasma renin activity in essential hypertension. In addition, changes in membrane fluidity by Ca-loading in essential hypertension were inhibited by Ca-antagonists (diltiazem, verapamil). These results demonstrate that the membrane fluidity of erythrocytes might be decreased in essential hypertension, and that this abnormality could be accelerated by calcium, especially in low renin essential hypertension. Furthermore, it is suggested that Ca-antagonists might correct this Ca-abnormality at cellular levels of hypertension.

Adult↗