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Biomedical subjects

H Koike

Publications and source records attributed to H Koike.

At least 289 records · Page 16Linked to original sources

Low level of superoxide dismutase activity in pheochromocytoma.

A copper-zinc superoxide dismutase found in the cytosol and intermembrane space of mitochondria, and a manganese superoxide dismutase detected in the mitochondria were determined in pheochromocytomas and normal adrenal tissues. Manganese superoxide dismutase activity in pheochromocytomas was lower than that in the normal adrenal tissues but copper-zinc superoxide dismutase activity was almost identical. The total catecholamine content in pheochromocytomas was greater than that in the normal adrenal tissues, and negative relationships were noted between superoxide dismutase activities and total catecholamine content in pheochromocytomas alone. The low level of manganese superoxide dismutase activity might be a characteristic of pheochromocytomas and the decrease in manganese superoxide dismutase activity may not be attributed solely to a decrease in the amount of mitochondria but to a nonspecific abnormality in mitochondrial enzymes.

Adrenal Gland Neoplasms↗

Liddle's syndrome, an uncommon form of hyporeninemic hypoaldosteronism: functional and histopathological studies.

Liddle's syndrome was diagnosed in a 72-year-old man who presented clinically with hypertension and muscle weakness. This disorder has been characterized by hyporeninemic hypoaldosteronism, hypertension, hypokalemia and enhanced erythrocyte sodium influx. Administration of spironolactone failed to correct the hypertension and electrolyte abnormality, which subsequently improved with triamterene therapy and a low salt diet. However, suppression of the renin-angiotensin-aldosterone system remained unchanged after this treatment. In addition, an atrophic juxtaglomerular apparatus and hypertensive lesions in the arterioles were confirmed by kidney biopsy after triamterene therapy. Therefore, a process of intrinsic hyperactive distal sodium reabsorption, probably affected by aldosterone-independent sodium transport into erythrocytes, appears to be important in the pathogenesis of this syndrome. Triamterene therapy, which usually is performed in patients with this disease, might not be the ultimate therapy in the future even if electrolyte abnormalities were to be improved temporarily.

Aged↗

Angiotensin-converting enzyme inhibitors: perhydro-1,4-thiazepin-5-one derivatives.

alpha-[6-[[(S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-5-oxoperhydro -1,4-thiazepin-4-yl]acetic acids (monoester monoacids) and their dicarboxylic acids having the hydrophobic substituents at the 2- or 3-position of the thiazepinone ring were prepared and assayed for angiotensin-converting enzyme (ACE) inhibitory activity. The dicarboxylic acids having the pseudoequatorial amino groups at the 6-position and the pseudoequatorial hydrophobic substituents at the 2- or 3-position of the chair conformation of the thiazepinone ring had potent in vitro inhibitory activity. The monoester monoacids having the hydrophobic substituents at the 2-position suppressed pressor response to angiotensin I for a longer duration than those having the substituents at the 3-position when administered orally. The structure-activity relationship was studied by conformational energy calculations of the thiazepinone ring.

Angiotensin-Converting Enzyme Inhibitors↗

In vitro inhibition of human renin by statine-containing tripeptide renin inhibitor (ES-1005).

Dipeptide and tripeptide derivatives containing a statine residue were synthesized as human renin inhibitors. ES-305, bis[(1-naphthyl)methyl]acetyl-histidyl-statine-2(S)-methylbutylami de, was found to be a highly potent human renin inhibitor that is species-specific and enzyme-specific. The replacement of the methylbutylamide of ES-305 with the leucyl-lysinol (ES-1005) showed similar high potency against human renin (Ki value of 2.4 x 10(-9) M) and monkey renin (Ki value of 7.9 x 10(-9) M) as ES-305. ES-1005 competitively inhibited human renin. The compound was about one order of magnitude less potent against pig, dog, and rabbit renins. It had moderate inhibitory potencies against cathepsin D and pepsin (IC50 of cathepsin D and pepsin of 1.6 x 10(-5) and 8.0 x 10(-6) M, respectively). ES-1005, a newly synthesized tripeptide derivative containing statine, is a highly potent inhibitor of not only primate renin but also a wide variety of nonprimate renins.

Animals↗

The extensibility of Aplysia nerve and the determination of true axon length.

1. Characteristics of Aplysia nerves in response to extension were examined in comparison with nerves of the cat, frog and lobster. 2. Only the Aplysia nerve was easily elongated up to about 5 times its resting or relaxing length without impairing propagation of the action potential along the axon in the nerve. 3. The conduction velocity along the elongated nerve increased linearly in proportion to the nerve length in the range from the relaxing length to about 1.2-1.5 times extension (the first phase). However, upon further extension it stayed constant regardless of the nerve length (the second phase). 4. In the relaxed nerve bundle the course of the axons was zigzagging and the axon membrane had numerous foldings or wrinklings. 5. The true length of the zigzagging axon was measured by analysing the length of intra-axonal diffusion following intracellular injection of radioactive acetylcholine ([3H]ACh) whose diffusion kinetics in the axoplasm have been studied in detail (Koike & Nagata, 1979). The length of the axon coincided with the nerve length at which the first phase shifted to the second phase. 6. Cat and frog nerves shrank after dissecting out from the body. When extended, they showed the first phase from the shortened length to their original length in the body. These nerves lacked the second phase. The lobster nerve did not shrink and lacked both phases. 7. Thus the zigzagging course of the axon is suggested to be responsible for the first phase during which the axon length did not change but took a straight course upon nerve extension. 8. On the other hand, the second phase appears to be caused by actual extension of the axon itself and could be explained by reduction of the wrinklings of the membrane.

Action Potentials↗

The disturbance of the fast axonal transport of protein by passive stretching of an axon in Aplysia.

1. Radioactive amino acid, either [3H]leucine or [3H]proline, was injected into neurone R2 in the abdominal ganglion of Aplysia kurodai to investigate the intra-axonal transport of protein in a single axon. 2. Some of the injected amino acid which was not utilized for protein synthesis diffused intra-axonally with a diffusion constant of 6.0 X 10(-6) cm2/s (25 degrees C), which is the value expected from the known diffusion constants of acetylcholine and gamma-aminobutyric acid in the axoplasm (Koike & Nagata, 1979). The true length of the zigzagging axon in the nerve bundle was measured by the diffusion distances. 3. The radioactive proteins newly synthesized in the cell body from either of the injected amino acid were transported axonally in a single axon of R2. 4. Elongation of the axon resulted in a suppression of the fast axonal transport of the proteins and the amount of protein transported. This contrasts with the observation that action potential propagation along the elongated axon never failed. 5. A possible site for the suppression of the axonal transport would be axonal microtubules whose structure is not likely to be resistant to the distortion caused by the elongation.

Animals↗

Active contraction of nerve bundle and identification of a nerve-contractor motoneuron in Aplysia.

1. The active contraction or shortening of the nerves of Aplysia kurodai and Aplysia juliana was examined. 2. A particular neuron in the abdominal ganglion controlled the contractions of the nerves, and the neuron was identified as a gill- and siphon-contractor motoneuron previously identified as L7. This was based on the following observations, which agreed closely with those reported for L7: the position, shape, and color of the cell body of the neuron; the synaptic and antidromic activation of the neuron by stimulation of various nerves; and the configurations of the major axons as revealed by dye injection into the soma of the neuron. Finally, the activation of the neuron contracted the gill, and the characteristics of the contraction were those reported for L7. 3. L7 was the only neuron we could find in the abdominal ganglion that directly controlled the contractions of the nerves. This was supported by the following observations: 1) direct or synaptic activation of L7 made the nerves shorter in a firing frequency-dependent manner. 2) Even single action potentials of L7 contracted the nerves. 3) When L7 was destroyed, no contractions of the nerves were observed however strongly a stimulation was applied. 4) When every synaptic connection in the abdominal ganglion was blocked by bathing the ganglion in Cafree artificial seawater, direct or spontaneous activation of L7 still made the nerves shorter. 4. A sensitive marker, cobaltic-lysine complex solution, was injected into the cell body of L7, and many fine axonal branches were newly found in the epineurium of the nerves. With the use of spike-triggered averaging, small potentials were recorded from the contracting nerves. This suggested that the action potentials were conducted along the newly found fine branches of the axon to innervate the epineurial muscles. 5. We found that L7 is a multifunctional motoneuron that contracts nerves.

Animals↗

Evidence for a defect in urinary concentrating ability in primary aldosteronism and its reversal by adrenal surgery.

Of 15 patients with primary aldosteronism, 7 had idiopathic adrenal hyperplasia (IHA) and 8 had aldosterone-producing adenoma (APA). In order to determine any renal problems involved in the treatment, the renal clearance of these patients was analyzed and the results compared with those obtained from 12 patients with essential hypertension. With water diuresis or under antidiuresis status, levels of urine volume, Cosm and CH2O in patients with APA were greater (p less than 0.05-p less than 0.001) than those of patients with essential hypertension, while the fractional tubular sodium delivery of the former patients was lower than that of the latter patients (p less than 0.001 or less than 0.05). A similar tendency was observed in clearance studies in patients with IHA, although to a lesser extent. Adrenal surgery for patients with APA normalized these values, but administration of trilostane (3 beta-hydrosteroid dehydrogenase inhibitor) to patients with IHA failed to improve these values. These results indicate that impaired urinary concentrating ability as well as reduced urinary diluting capability is a common feature of primary aldosteronism. Such impaired renal function was improved only in patients with APA after adrenal surgery.

Adenoma↗

Significance of staging pelvic lymphadenectomy for prostatic cancer.

Staging pelvic lymphadenectomy in 31 cases in stages A2-C prostatic cancer was performed. In 15 of the cases (48%) lymph node invasion was found. Metastatic tendency strengthened with an increase in Gleason scores, although no metastases were found in 38% of the cases with Gleason scores of 8-10. Percutaneous fine-needle aspiration biopsy guided by lymphography was conducted in 14 cases and 17% were false-negative. Lymph node metastases were found in the common iliac lymph nodes in 47%, external iliac lymph nodes in 67% and internal iliac obturator lymph nodes in 100%. Prolonged lymph drainage in 4 cases (13%) and wound infection in 2 cases (3%) were found as postoperative complications, but they were all treated conservatively. So it was concluded that pelvic lymphadenectomy was a reasonable adjunct to total prostatectomy since it provided an accurate assessment of the anatomic distribution of disease, which could be of help in selecting treatment. Dissection of the lymph nodes of the internal iliac obturator was considered quite sufficient to establish the presence of any lymph node metastases.

Adenocarcinoma↗

Antihypertensive action of melatonin in the spontaneously hypertensive rat.

The effects of melatonin on blood pressure and heart rate were studied in 23-week-old male spontaneously hypertensive rats. Melatonin infused i.p. at a dose of 6 mg/rat per day for 5 days using an osmotic minipump produced a significant reduction of blood pressure and a slight but significant decrease of heart rate in the conscious and unrestrained state. These cardiovascular effects of melatonin developed gradually. Plasma renin concentration tended to decrease after melatonin treatment. These results demonstrate that melatonin has an antihypertensive action. The mechanism of the antihypertensive action of melatonin requires further study.

Animals↗

[Renal cell carcinoma incidentally found by computed tomography: report of 4 cases].

A clinical study was made on 26 patients with renal cell carcinoma, who visited our department between October, 1979 and April, 1984. There were 21 men and 5 women. As the major initial symptoms, hematuria and flank pain were observed in 14 cases (53.8%), followed by symptoms of metastatic tumors in 7 cases (26.9%). Four cases of malignant renal masses which showed no abnormality on the excretory urogram were diagnosed by chance at the time of examination of the abdominal computed tomography (CT). CT was especially useful in diagnosing the renal cell carcinomas.

Adult↗

[Effect of selective intra-arterial infusion of OK-432 against renal cell cancers].

In 8 cases of operable renal cancer, selective intraarterial infusion of the streptococcal preparation, OK-432 was performed and its cytocidal effects on the surgical specimens, which were removed on the 8th day after infusion, were investigated histopathologically with immunological parameters of the peripheral blood. The histopathological study revealed a high grade of sinus histiocytosis of the renal pedicle lymph nodes, but the anti-tumor effect on renal tumors was not so marked in any of the 8 cases. OK-Ia-positive lymphoid cells of peripheral blood were increased significantly and Con-A stimulation index of blastogenesis was lowered without any change in the PHA stimulation index after the OK-432 infusion. No serious complications of the selective intraarterial infusion were experienced except for high fever (less than 38 degrees C). In conclusion, OK-432 selective intraarterial infusion was an effective method for improving regional and systemic immunoactivity, but the cytocidal effect against tumor cells could not be confirmed histopathologically.

Aged↗

Participation of central norepinephrine in the development of two-kidney, one clip Goldblatt hypertension.

Two series of experiments were conducted to ascertain whether the central catecholamines would participate in the elevation of blood pressure in two-kidney, one clip (2K-1C) Goldblatt hypertensive rats. The effect of 6-hydroxydopamine (6-OHDA) injected intraventricularly (250 micrograms/kg.) before the induction of hypertension (acute phase) or after the establishment of hypertension (chronic phase) was examined in 2K-1C rats and sham rats. The evidence has been presented: 1) that the hypothalamic norepinephrine content of 2K-1C rats in acute phase is 50 per cent lower (p less than 0.001) than that of sham rats, but norepinephrine content in the pons is similar in these animals, 2) that the content of dopamine in hypothalamus or pons is similar in 2K-1C rats and normotensive age-matched sham rats in acute phase, 3) that the content of these monoamines either in hypothalamus or pons in 2K-1C rats in chronic phase is almost identical with that in sham rats, 4) that administration of 6-OHDA markedly reduced the development of hypertension in 2K-1C rats in the acute phase, but did not affect their sustained hypertension in the chronic phase. These findings suggest that hypothalamic norepinephrine participates in the development of hypertension in 2K-1C rats in the acute phase but is not connected with the maintenance of their established hypertension in the chronic phase.

Animals↗

Statine-containing dipeptide and tripeptide inhibitors of human renin.

Dipeptide and tripeptide derivatives containing a statine residue were synthesized as inhibitors of human renin. ES-305, bis[(1-naphthyl)methyl]acetyl(BNMA)-histidyl-statine 2(S)-methylbutylamide was found to be a highly potent inhibitor of human renin with a Ki value of 1.7 X 10(-9) M. Dipeptide derivatives with the BNMA group at the N-terminal (BNMA-Val-Sta-isoleucinol [ES-313], BNMA-Leu-Sta-isoleucinol [ES-316], and BNMA-Nle-Sta-isoleucinol [ES-317]) had potencies against human renin that were similar to the potency of ES-305. All these dipeptide derivatives competitively inhibited human renin. The inhibitors were also potent against monkey renin but were less effective against renins from pig, goat, dog, rabbit, and rat. ES-305 had little effect on cathepsin D and pepsin at the concentration of 10(-5) M. The other derivatives showed detectable inhibition of cathepsin D (IC50, 10(-6) - 10(-7) M) and pepsin (10(-5) - 10(-6) M). All the compounds had little or no effect on trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at the concentration of 10(-5) M. Our results indicate that ES-305 is a highly potent and specific inhibitor of human renin. This compound is superior to other, previously described statine-containing renin inhibitors with respect to molecular size and enzyme specificity.

Amino Acids↗