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Biomedical subjects

H Yamaura

Publications and source records attributed to H Yamaura.

At least 19 recordsLinked to original sources

Decreased contractile effect of endothelin-1 on hyperplastic prostate.

1. The contractile activity, binding activity and localization of endothelin (ET)-1 were evaluated in human nonhyperplastic (control) and hyperplastic prostates. 2. ET-1 caused contraction of both prostates in a dose-dependent manner. However, this contraction was markedly decreased in hyperplastic prostates. 3. Bmax and Kd values of hyperplastic prostates were greater than those of the control. 4. The muscle and proliferative epithelium of hyperplastic prostates showed strong staining for the anti-ET-1 antibody. However, the glandular epithelium of control prostates was weakly stained. 5. These findings indicate that responsiveness to ET-1 is decreased, though the ET-1 and ET-1 receptors increase in the hyperplastic prostate. Namely, the increase in ET-1 receptors is not effective in regulating the contractile response of the prostate, because its expression is rather dominant in proliferated gland. 6. These suggest that ET-1 may not have an important role in the release of the obstructive symptoms of benign prostatic hypertrophy.

Aged

Effects of CD-832, a dihydropyridine derivative with a nitrate ester moiety on rabbit femoral artery and vein.

We investigated the effects of CD-832 ((4R)-(-)-2-(nicotinoyl-amino)ethyl 3-nitroxypropyl 1,4-dihydro-2,6-dimethyl-4,3-nitrophenyl, 3,5-pyridine dicarboxylate), a dihydropyridine derivative with a nitrate ester moiety, on contractile responses in rabbit femoral arteries and veins. CD-832 (10(-8) to 10(-6) M and nifedipine inhibited the 64 mM KCl-induced and 10(-6) M norepinephrine-induced contractions of rabbit femoral arteries, while nitro compounds had no effect on the contractions. CD-832 (10(-8) to 10(-6) M) and nitro compounds inhibited the 10(-6) M norepinephrine-induced contractions in rabbit femoral veins, while other Ca2+ channel antagonists had little effect. The inhibitory effects of CD-832 (10(-7) M) on norepinephrine-induced contractions were antagonized by treatment with methylene blue (10(-5) M). These results indicate that CD-832 potently relaxes venous smooth muscle, and that it may be a useful agent for the treatment of angina pectoris.

Animals

Role of cyclic GMP in inhibitory effects of CD-349 in isolated blood vessels.

1. We investigated the effects of CD-349, a dihydropyridine derivative with nitrate ester, on contractile responses induced by high K+, norepinephrine (NE) and Ca2+ in isolated rabbit aorta. 2. CD-349 (10(-9)-10(-5) M) and nifedipine (10(-9)-10(-5) M) equally inhibited the 64 mM KCl-induced contraction of the aortic strips in a concentration-dependent manner. 8-Br-cyclic GMP (10(-3) M) did not inhibit the KCl-induced contraction of the aortic strips. 3. CD-349 (10(-8)-10(-5) M) and 8-Br-cyclic GMP (10(-6)-10(-3) M) inhibited the 10(-6) M NE-induced contraction of the aortic strips in a concentration-dependent manner. However, nifedipine had no effect on the NE-induced contraction in rabbit aorta. 4. The inhibitory effects of CD-349 on NE-induced contraction were antagonized by treatment with methylene blue and oxyhemoglobin, while they were augmented by treatment with zaprinast. 5. CD-349 (10(-8)-10(-5) M) and 8-Br-cyclic GMP (10(-5)-10(-4) M) inhibited the NE-induced phasic contraction and Ca(2+)-induced contraction of the aortic strips preincubated with NE in Ca(2+)-free medium. However, nifedipine (10(-5) M) had little or no effect on both NE-induced phasic contraction and Ca(2+)-induced contraction of the aortic strips preincubated with NE in Ca(2+)-free medium. 6. CD-349 (10(-7)-10(-5) M) increased the levels of cyclic GMP in rabbit aorta. 7. These results indicate that CD-349 has a hybrid property deriving from Ca(2+)-antagonist and cyclic GMP increasing agents.

8-Bromo Cyclic Adenosine Monophosphate

Multidirectional contraction of human hypertrophied prostate.

1. The purpose of the present investigation is to evaluate muscle contraction in two directions (longitudinal and circumferential to urethra) physiologically and morphologically for alpha-adrenoceptor agonists. 2. Norepinephrine (10(-7)-10(-4) M), phenylephrine (10(-7)-10(-4) M) and clonidine (10(-7)-10(-4) M) induced contractions in a dose-dependent manner on human prostate from patients with benign prostatic hypertrophy (BPH). 3. No significant differences were observed between longitudinal and circumferential directions of human prostate in 50% of the maximal muscle contraction (EC50 values) and the maximal muscle contractions caused by any agents used. 4. Morphometric analysis for muscle in prostates was performed using formalin-fixed, paraffin-embedded sections stained by the Mallory-Azan method. 5. There was no significant difference in the density of the muscle area between longitudinal and circumferential directions of prostatic strips. 6. These results suggest that there are no significant differences in responsiveness of alpha-adrenoceptor agonists and the smooth muscle contents in longitudinal and circumferential directions to urethra, for human hypertrophied prostate.

Adrenergic alpha-Agonists

CD-832, a new dihydropyridine derivative with both nitrate-like and Ca2+ channel antagonist vasodilator activities.

We investigated the effects of CD-832 ((4R)-(-)-2-(nicotinoylamino)ethyl 3-nitroxypropyl 1,4-dihydro-2,6-dimethyl-4,3-nitrophenyl, 3,5-pyridine dicarboxylate), a new dihydropyridine derivative with nitrate ester, on contraction and relaxation responses induced by various vasoactive agents in rabbit aorta. CD-832 potently inhibited the specific binding of [3H](+)-PN200-110 to rat brain membranes. The IC50 values for [3](+)-PN200-110 binding were 2.8 nM and 4.9 nM in CD-832 and nifedipine, respectively. CD-832 (10(-8) to 10(-5) M), diltiazem (10(-8) to 10(-5) M) and benidipine (10(-8) to 10(-5) M) inhibited the 64 mM KCl-induced contraction of the aortic strips in a concentration-dependent manner. Neither nitroglycerin (10(-8) to 10(-5) M) nor nicorandil (10(-8) to 10(-5) M) affected the 64 mM KCl-induced contraction in rabbit aorta. CD-832 (10(-8) to 10(-5) M), nitroglycerin (10(-8) to 10(-5) M) and nicorandil (10(-5) M) had no effect on norepinephrine-induced contraction in rabbit aorta. Nitroglycerin (10(-5) M), atrial natriuretic peptide (10(-8) M), nicorandil (10(-5) M) and CD-832 (10(-7) to 10(-5) M) augmented the isoproterenol-induced relaxation responses of rabbit aorta precontracted with endothelin-1 (1 x 10(-7) to 2 x 10(-7) M). The effects of nitroglycerin (10(-5) M), nicorandil (10(-5) M) and CD-832 (10(-5) M) on isoproterenol-induced relaxation responses were antagonized by treatment with methylene blue (10(-5) M) and oxyhemoglobin (10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effects of VA-045, a novel apovincaminic acid derivative, on isolated blood vessels: cerebroarterial selectivity.

We investigated the effects of VA-045, an apovincaminic acid derivative, on isolated blood vessels. VA-045 (10(-7)-10(-5) M) and vinpocetine (10(-7)-10(-5) M) inhibited the 64 mM KCl-induced and 10(-6)M norepinephrine (NE)-induced contraction of rat aortic strips. VA-045 (10(-7)-10(-4) M) and vinpocetine (10(-7)-10(-4) M) inhibited the activity of cyclic AMP and cyclic GMP phosphodiesterase in porcine coronary artery. VA-045 (3 x 10(-9-3 x 10(-6) M) relaxed the 64 mM KCl-induced contraction of the canine basilar artery without affecting the peripheral arteries. These results indicate that VA-045 selectively dilates canine cerebral artery, and that it may be a useful agent for the treatment of cerebrovascular diseases such as stroke.

3',5'-Cyclic-GMP Phosphodiesterases

[Two cases of early Acanthamoeba keratitis].

Early Acanthamoeba keratitis was diagnosed in two soft contact lens wearers. Both patients had initially been diagnosed as having herpes simplex keratitis and treated with antiherpes drugs. In one patient, slit-lamp examination disclosed dendritiform epithelial keratitis, subepithelial opacities, linear stromal infiltrate along the corneal nerve (radial keratoneuritis), and marked swelling and hyperemia of the limbal conjunctiva. Acanthamoeba castellanii was cultured from the corneal scrapings and contact lens case. The second patient also showed dendritiform keratitis and subepithelial opacities, with swelling of the limbal conjunctiva. Cultures were positive for A. polyphaga from the contact lens case, but negative from the corneal scrapings. The patients were cured of Acanthamoeba keratitis with medical therapy consisting of topical fluconazole and miconazole, systemic fluconazole, and topical corticosteroids. Recognition of distinctive characteristics of the clinical findings in early Acanthamoeba keratitis can lead to the early diagnosis of the disease.

Acanthamoeba

Changes in responsiveness of the aorta to vasorelaxant agents in genetically diabetic rats: a study in WBN/Kob rats.

The effects of various vasorelaxant agents on aortas from control and genetically diabetic rats were examined. The concentration-response curves for the isoproterenol (ISO)-induced relaxation of both aortic strips with and without endothelium are shifted to the right in diabetic rats. The relaxation responses of diabetic aorta to forskolin and vasoactive intestinal peptide did not differ from those of controls. The relaxation responses of diabetic aorta to cromakalim and nicorandil did not differ from those of controls. These results indirectly indicate that ISO-induced relaxation responses of the aortic strips from genetically diabetic rats decreased, and that this decreased relaxation response of the strips to ISO may be due to decreased density or affinity of beta adrenoceptors on the endothelium and vascular smooth muscle.

Animals

Effects of CD-349 and 8-BrcGMP on isoproterenol-induced relaxation in rabbit aorta precontracted with endothelin-1.

We investigated the effects of CD-349, a dihydropyridine derivative, on isoproterenol (Iso)-induced relaxation in rabbit aorta precontracted with endothelin-1 (ET-1). The Iso (10(-8)-10(-5) M)-induced relaxation responses in rabbit aorta precontracted with 1-2 x 10(-7) M ET-1 were augmented by pretreatment with CD-349 (10(-9)-10(-5) M) in a concentration-dependent manner. The effects of CD-349 on Iso-induced relaxation of the aortic strips precontracted with ET-1 were inhibited by treatment with methylene blue (10(-5) M) and oxyhemoglobin (10(-5) M), whereas they were augmented by treatment with N omega-nitro-L-arginine (10(-4) M). The Iso-induced relaxation responses were also augmented by pretreatment with 8-Br-guanosine 3',5'-cyclic monophosphate (cGMP) (3 x 10(-6)-3 x 10(-4) M) in a concentration-dependent manner. However, nifedipine (10(-5) M) and nicardipine (10(-5) M) had no effect on Iso-induced relaxation responses of the aortic strips precontracted with 10(-7) M ET-1. CD-349 also augmented forskolin (10(-8)-10(-5) M)-induced relaxation responses of rabbit aorta in a concentration-dependent manner. CD-349 (10(-7)-10(-5) M) increased the levels of cGMP but not of adenosine 3',5'-cyclic monophosphate (cAMP) in a concentration-dependent manner in rabbit aorta without endothelium. Both CD-349 (10(-5) M) and 8-BrcGMP (3 x 10(-5) M) augmented the Iso-induced elevations of cAMP in rabbit aorta without endothelium. These results indicate that CD-349 and 8-BrcGMP can augment Iso-induced relaxation responses by enhancing the accumulation of cAMP.

Animals

Biological nature of Cryptosporidium sp. isolated from a cat.

A small type of Cryptosporidium oocysts was isolated from a naturally infected cat and its biological nature was investigated. In cats experimentally inoculated with Cryptosporidium oocysts, long-lasting shedding of the oocysts occurred after a prepatent period of 8-10 days, and a number of peaks of oocyst count appeared at intervals of several days to a few weeks, earlier in the infection course. Cryptosporidium infection in cats is likely to pass from an acute to a chronic stage. During the chronic stage, prednisolone injection into the cats gave rise to a recurrence of proliferation of the parasite along with a marked increase in the number of oocysts shed. None of the infected cats showed clinical symptoms. Infection experiments using Cryptosporidium oocysts were unsuccessful in several species of animals such as mice, rats, guinea pigs, dogs, suckling mice and mice previously injected with prednisolone or hydrocortisone.

Acute Disease

Stage-specific response of preimplantation mouse embryos to W-7, a calmodulin antagonist.

Involvement of calmodulin-dependent processes in preimplantation development of mouse embryos was studied with the use of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a specific antagonist of calmodulin. At 25 microM, W-7 interfered with compaction of eight-cell embryos, caused decompaction of compacted eight-cell embryos, inhibited cavitation of late morulae, and caused collapse and degeneration of blastocysts. These effects of W-7 appear to be due to specific inhibition of calmodulin-dependent processes, because W-5, a less active analogue of W-7, was less effective in interfering with development; at 25 microM, W-5 had only a slight effect on compaction and had no effect on blastocyst formation, maintenance of blastocoels, or post-blastocyst development. In addition to the developmental effects just described, W-7 inhibited cell proliferation in four-cell embryos and reduced cell numbers of morulae after treatment at the two- to eight-cell stages. There was a marked increase in embryos' sensitivity to W-7 at the late morula stage, and the sensitivity increased further as embryos developed into blastocysts; the effects of W-7 were largely reversible after treatment at the two-cell through the compacted eight-cell stages, but not after treatment at the late morula or blastocyst stage. At the blastocyst stage, inner cell mass cells appeared to be slightly more resistant to W-7 than trophectoderm cells. This differential sensitivity became more pronounced at the late blastocyst stage: after 3.5-4-h exposure of late blastocysts to 25 microM W-7, all trophectoderm cells degenerated but most of the inner cell masses survived. From these results it appears that calmodulin-dependent processes are involved in development of mouse embryos at all of the preimplantation stages examined.

Animals

Association of hypertension with increased atrophy of brain matter in the elderly.

Atrophy of brain matter in hypertensive and normotensive subjects was studied by quantitative measurements of brain volume and cranial cavity volume using x-ray computed tomography. The 123 normotensive subjects ranged in age from 20 to 79 years and were divided into six ten-year age groups. The 67 hypertensive subjects ranged in age from 40 to 83 years and were divided into four age groups. Values of the brain volume index ( BVI ), the ratio of brain matter volume to cranial cavity volume, for hypertensives and normotensives in the same age groups were compared. Mean BVI values were significantly lower in hypertensives in the fifth (P less than 0.01), sixth (P less than 0.01), seventh (P less than 0.05) and eighth and ninth decades of life (P less than 0.001). Systemic hypertension, which may induce various diseases in the elderly, had a striking effect on atrophic changes of brain matter in elderly subjects.

Adult

Brain atrophy and cerebral infarction.

The subjects of the study (109 males, 48 females) were all diagnosed to have cerebral infarction by computerized tomography (CT). The cerebrospinal fluid (CSF) space volume and cranial cavity volume in the normal hemisphere of the patients were estimated using CT at the time from 1 to 3 weeks after the attack of cerebral infarction. The percentage of the CSF space volume to the cranial cavity volume was calculated as an indicator for brain atrophy and called brain atrophy index (BAI): BAI (%) = 100(%) X (CSF space volume/cranial cavity volume). The BAI immediately after the attack of infarction (6.6 +/- 2.2, n = 15), during which no detectable change occurred on CT examination, was the same as the BAI at the time from 1 to 332 days after the attack (6.6 +/- 2.4, n = 20). Therefore we compared the BAI in patients without infarction with the BAI in patients with infarction irrespective of secondary atrophy of the brain after the attack. The BAIs in males with infarction were significantly greater than the BAIs in males without infarction in the age of fifties, sixties and seventies. The BAIs in females with infarction were significantly greater than in females without infarction in the age of fifties, sixties and eighties.

Adult

[Comparative studies on 99mTc-pyrophosphate and 85Sr-chloride for skeletal imaging].

In order to know the potential merits of 99mTc-pyrophosphate (99mTc-PYP) skeletal imaging, a comparative study was carried out by administering to the rabbit 85Sr-chloride (85Sr), classical bone-seeking agent, and 99mTc-PY simultaneously. Radioisotopic distribution was investigated as regards their deposition in the pelvic bones, and sharpness of the skeletal scintigrams, too. Both agents were remarkably affinitive to the skeletal system and there were remarkably differences in their temporal deposition pattern. Marked deposition was observed of either agent in the metaphyses. With 99mTc-PYP, the vertebral and costal systems were delineated symmetrically and each vertebral body was distinctly depicted as such 99mTc-PYP many possess the following merits over 85Sr; (1) owing to its physical properties, sufficiently large radioactivity of 99mTc-can be administered; (2) body burden of radiation absorption is reduced; (3) skeletal scintigrams of high quality are obtainable in a short period of time.

Animals