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Biomedical subjects

H Koike

Publications and source records attributed to H Koike.

At least 271 records · Page 15Linked to original sources
PubMed1988

Effect of arylidene-cyclopentenedione radiosensitizers on ATP synthesis in mitochondria: action as potent inhibitors of phosphate transport.

The effects of the arylidene-cyclopentenedione radiosensitizers, KIH-200, 201 and 202 on ATP synthesis in mitochondria were examined. In spite of the close similarity of their chemical structure to that of the most potent known weakly acidic uncoupler, SF 6847, they did not show any uncoupling activity at concentrations of up to 50 microM. However, these three compounds were found to have very potent inhibitory effects on Pi-transport into mitochondria, all causing 50% inhibition (I50%) at about 7 microM. Thus they are much more potent than the commonly used Pi-transport inhibitors N-ethylmaleimide (I50% = about 40 microM), and mersalyl (I50% = about 30 microM). They may act as SH-reagents, and inhibit Pi-transport by modifying an SH-group(s) in the Pi-transporter.

Adenosine Triphosphate↗
PubMed1988

Effects of chronic treatment with a novel angiotensin converting enzyme inhibitor, CS622, and a vasodilator, hydralazine, on atrial natriuretic factor (ANF) in spontaneously hypertensive rats (SHR).

We studied the effects of chronic treatment with a novel angiotensin converting enzyme inhibitor, alpha-[(2S,6R)-6-[(1S)-1-ethoxycarbonyl-3-phenylpropyl]amino-5-oxo-2- (2-thienyl)perhydro-1,4-thiazepin-4-yl]acetic acid.HCl (CS622), and a vasodilator, hydralazine, on plasma atrial natriuretic factor (ANF) levels and kidney ANF receptors in spontaneously hypertensive rats (SHR). Plasma ANF level was decreased and cardiac hypertrophy reduced in CS622 treated SHR, but not in hydralazine treated SHR, although blood pressure was lowered similarly in both SHR groups. The binding capacity of kidney ANF receptors increased and the affinity decreased in CS622 treated SHR compared to untreated SHR. These results suggest that decrease of plasma ANF results from decreased cardiac load but not from lowered blood pressure, and that changes in ANF receptors result from increased plasma ANF.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Changes of vasoactive substances following embolization for renal cell carcinoma.

Renal arterial embolization and subsequent nephrectomy or nephrectomy alone were performed in 34 patients with renal cell carcinoma. Renal arterial embolization caused a blood pressure elevation concomitant with an increase in plasma renin activity (PRA), urinary aldosterone excretion or urinary prostaglandin (PGE2) excretion. Subsequent nephrectomy normalized hypertension and reduced the levels of these vasoactive substances. There were significant relationships between the increase in mean blood pressure and the increase in PRA, the increment in mean blood pressure and the increment in urinary aldosterone excretion, and the increase in PRA and increase in log urinary PGE2 excretion following embolization. These evidences suggest that enhancement of the renin-angiotensin-aldosterone system participates in the development of hypertension following embolization, and increased PRA may play an important role in the release of urinary PGE2.

Aged↗
PubMed1988

Central noradrenergic neurons and vascular non-collagen protein in the initial phase of two-kidney, one-clip renovascular hypertension.

Rats had been given intraventricular injection of 6-hydroxydopamine (6-OHDA) before clipping the unilateral renal artery (2K-1C) that caused selective ablation of the central noradrenergic neurons. Central catecholamines and the in vivo incorporation of 3H-proline into vascular non-collagen protein were determined in 2K-1C rats in the acute hypertensive stage. It is suggested that increased non-collagen protein synthesis in the mesenteric artery and the low level of hypothalamic norepinephrine concentration may participate in the development of 2K-1C hypertension in rats.

Animals↗
PubMed1988

Therapeutic results of primary aldosteronism with special reference to renal or renovascular lesions.

A study was made of 9 patients with primary aldosteronism due to aldosterone-producing adenoma (APA) and 8 subjects with idiopathic adrenal hyperplasia (IHA) to clarify the pathogenesis of sustained hypertension after surgical or non-surgical treatment. Following each treatment, a complete improvement of hypertension was obtained in 12 patients (6 APA, 6 IHA), while 5 (3 APA, 2 IHA) showed still hypertensive status. Renal or renovascular lesions were prominent only in the hypertension-unchanged group. Under regular sodium diet, the ratio of urinary excretion of sodium to creatinine of this hypertensive group was significantly lower than that of the hypertension-improved group. However, the results of other renal function tests were similar in both groups. After respective treatments, suppressed plasma renin activity and elevated plasma aldosterone concentration were improved in all patients. In addition, patients of both groups showed normal response of the renin-aldosterone system following diuretic and dietary induced sodium and volume depletion. Based on these findings, renal or renovascular lesions appear to play an important role in the pathogenesis of maintenance of hypertension in this disorder after respective treatments.

Adenoma↗
PubMed1988

Angiotensin-converting enzyme inhibitors. 2. Perhydroazepin-2-one derivatives.

alpha-[(3S)-3-[[(S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-2-oxo-6 or 7-phenylperhydroazepin-1-yl]acetic acids (monoester monoacids) and their dicarboxylic acids were synthesized, and their angiotensin-converting enzyme (ACE) inhibitory activities were evaluated. The dicarboxylic acids having phenyl substituents at the 6R, 6S, and 7S positions on the azepinone ring showed potent inhibition in vitro. The corresponding monoester monoacids, when administered orally, suppressed the pressor response to angiotensin I administered intravenously. The monoester monoacids having the phenyl substituent at the 6-position showed a longer duration of action than one having the substituent at the 7-position. The structure-activity relationship was studied on the basis of the conformational energy calculation.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

DNA ploidy of colorectal carcinoma. Correlation with conventional prognostic variables.

The DNA content of tumor cells was determined in 51 cases of colorectal carcinoma and correlated with conventional clinicopathologic features. Normal diploid content of DNA was found in cells from 19 tumors, and aneuploidy was found in cells from 32 tumors. An aneuploid stemline of tumor cells appeared to be associated with advanced disease. However, a statistical analysis using Pearson's chi-square test disclosed no significant correlation between DNA ploidy of tumor cells and conventional clinicopathologic characteristics of colorectal carcinoma, such as differentiation, staging, lymph node status, and depth of invasion.

Adenocarcinoma↗
PubMed1988

Superoxide dismutase activity in renal cell carcinoma.

Both Cu-Zn- and Mn-superoxide dismutase (SOD) activities were determined in renal cell carcinoma and tumor-uninvolved renal tissues in 25 patients with renal cancer. These enzymatic activities were similar in tumor and tumor-uninvolved renal tissues. The age of the patients, grade or stage of tumors had no apparent effect on SOD activities. Renal arterial embolization caused a slight decrease (p less than 0.05) in Cu-Zn-SOD activity in tumor tissues, but none in other enzymes in the same tissues, while renal arterial embolization reduced each SOD activity in tumor-uninvolved renal tissues (p less than 0.01 - p less than 0.001). Therefore the development of renal cell carcinoma is probably not related to the abnormality of renal SOD, but renal ischemic changes appear to lower each SOD activity in normal renal tissues.

Aged↗
PubMed1988

A highly potent and long-acting oral inhibitor of human renin.

An orally active renin inhibitor, ES 6864 (N-[(2R)-3-morpholinocarbonyl-2-(1-naphthylmethyl)propionyl]-(4- thiazolyl)-L-alanyl-cyclostatine-(2-morpholinoethyl)amide), was synthesized. ES 6864 was found to be a highly potent inhibitor of human renin with a Ki value of 7.3 x 10(-9) M. The compound competitively inhibited human renin. The inhibitor was also potent against monkey renin but was less effective against renins from pig, goat, dog, rabbit, and rat. ES 6864 did not inhibit cathepsin D, pepsin, trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at a concentration of 10(-5) M. ES 6864 was resistant to proteolytic actions of the enzymes in rat tissue homogenates (liver, kidney, pancreas, and small intestine). Oral administration of ES 6864 at 30 mg/kg to conscious, sodium-depleted marmosets produced a significant blood pressure reduction and almost complete inhibition of plasma renin activity, which persisted for 5 hours. Oral administration of ES 6864 also produced dose-related decreases of blood pressure in hog renin-infused rats, but the duration of action was much shorter than that in conscious marmosets. The parent compound in the blood following oral administration of ES 6864 to marmosets was confirmed directly by measuring the plasma concentration of ES 6864. These results enhance the possibility of developing renin inhibitors that can be used clinically.

Administration, Oral↗
PubMed1988

Cardiovascular pharmacology of RS-1893, an orally active cardiotonic agent with arterial and venous vasodilator actions.

RS-1893, 2-[2-chloro-4-(2,3,4,5-tetrahydro-3-oxo-6-pyridazinyl)]-phenoxy-N- (2-(2-morpholinoethyl)-acetamide, is a newly synthesized compound whose structure is different from that of cardiac glycosides and beta-stimulants. The in vitro cardiotonic action of RS-1893 was about 3 times more potent than that of milrinone. This action is most likely due to inhibition of phosphodiesterase-III, as has been suggested for many other cardiotonic agents. In pentobarbital anesthetized dogs, RS-1893 (1-30 micrograms/kg, i.v.) produced dose dependent increases in left ventricular dP/dtmax and cardiac output and caused decreases in blood pressure and total peripheral resistance with a relatively small increase in heart rate. Central venous pressure decreased markedly, suggesting venous vasodilation. The in vivo cardiotonic action of RS-1893 was 3 times more potent than that of milrinone and was not affected in the presence of a large dose of propranolol. Oral administration of RS-1893 (0.03 and 0.1 mg/kg) also produced a dose-related increase in cardiac contractility in conscious beagles. The increase in LVdP/dtmax reached a maximum in 1-3 hr after administration and lasted for more than 8 hr. Thus, RS-1893 appeared to be an orally active cardiotonic agent with vasodilator properties, probably acting on both arterioles and veins.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1988

Pharmacological profiles of CS-622, a novel angiotensin converting enzyme inhibitor.

CS-622 is a prodrug type ACE inhibitor with a thiazepin ring. Its active form, CS-622 diacid, was slightly more potent than enalaprilat in inhibiting ACE isolated from rabbit lung. The inhibitory potency of CS-622 diacid on isolated rat aorta was 3 times that of enalaprilat. The inhibitory action of enalaprilat was abolished quickly by washing the aortic strip with drug-free solution, whereas that of CS-622 diacid was abolished only slowly. This difference suggests that CS-622 diacid binds to vascular ACE more firmly than enalaprilat. By oral administration, CS-622 was 3 times more potent than enalapril, and its onset of action was faster than that of enalapril, suggesting that the conversion of CS-622 to its active diacid occurs faster than the conversion of enalapril. Although CS-622 diacid was only slightly more potent than enalaprilat by intravenous administration, it had a longer duration than enalaprilat. Elimination of renal excretory function potentiated the action of captopril but not that of CS-622, suggesting that unlike captopril, only a small portion of CS-622 is excreted through the kidney.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Hyperplasia of juxtaglomerular cells and renomedullary interstitial cells after renal arterial embolization in patients with renal cell carcinoma.

Renal tissue was obtained from 36 patients with renal cell carcinoma, some of whom received renal arterial embolization. The removed specimens was examined histopathologically and the concentration of some vasoactive substances in these patients was measured. Nephrectomy alone produced no discernible changes in blood pressure, vasoactive substances determined or histopathological findings of the kidney. Renal arterial embolization raised the blood pressure in association with the elevation of plasma renin activity (PRA) and urinary prostaglandin (PG) E2 excretion. A linear relationship was found to exist between PRA and mean blood pressure (r = 0.70, p less than 0.001). Hyperplasia of the juxtaglomerular (JG) apparatus, and high granularity of sudan black B granules in renomedullary interstitial cells were confirmed in removed kidneys of patients who had received embolization alone. Subsequently high renin production would be anticipated to influence overproduction of renal PG E2 in acute ischemic kidney in patients with renal cell carcinoma, and hypertension following renal arterial embolization appears to be caused by the hyperplasia of the JG apparatus.

Aged↗
PubMed1988

[The efficacy of recombinant interleukin 2 in local treatment of superficial bladder tumors].

The present study was undertaken to assess the efficacy of recombinant Interleukin 2 (rIL-2: S-6820) in treatment of superficial bladder tumors. Three intratumor injections at a dose of 5 x 10(5) units/day via urethra, were performed every other day under endoscopic control in 12 patients with superficial bladder cancer. On the 15th day after completion of the series of injections, the tumor had disappeared in one patient and 50% regression over was observed in two other patients. Therefore, the response rate to the rIL-2 treatment in our study was 25.0%. Each tumor which responded to the therapy, was single, small and low grade. In the peripheral blood of the 12 patients, an increase in IL-2 receptor-positive lymphocytes and augmentation of natural killer activity were detected after the rIL-2 intratumor injection. There were no serious side effects except for moderate fever in our study.

Aged↗
PubMed1987

Clinical analysis of ureteral tumours with or without renal pelvic neoplasms.

Twelve patients with ureteral tumours with or without ipsilateral renal pelvic neoplasms were retrospectively analysed. Haematuria was the most common symptom. Location of all tumours was preoperatively detected by conventional diagnostic methods, such as intravenous or retrograde pyelography, washing cytology of the upper urinary tract, computed tomography, echogram and abdominal aortography. Cumulative proportion survivals of 1, 3 and 5 years were 81.9%, 68.2% and 45.5%, respectively. Patients with high Karnovsky rating survived longer (p less than 0.05) than those with low rating. Patients with low-stage tumours (T1, T2) showed longer survival rate (p less than 0.001) than those with high-stage tumours (T3, T4). Vascular invasion of tumour cells was present in removed specimens in 4 out of 7 patients who died or are alive with cancer, but none in those who survived without disease. Good therapeutic response could not be achieved unless surgery was performed.

Aged↗