Biomedical subjects

F Yatsu

Publications and source records attributed to F Yatsu.

10 recordsLinked to original sources

PubMed1996

Inhibition of vascular smooth muscle cell proliferation by the calcium antagonist clentiazem: role of protein kinase C.

The proliferation of vascular smooth muscle cells has been implicated as a causative factor in atherogenesis. Calcium channel blockers have been shown to retard the progression of atherosclerosis. To elucidate the mechanism by which these drugs mediate such actions, we studied the effects of a new calcium antagonist, clentiazem, on the in vitro proliferation of vascular smooth muscle cells. PDGF-induced prolifertion of these cells is markedly inhibited by clentiazem. The probable involvement of protein kinase C (PKC) in this cellular response is suggested. Clentiazem appear to cause inhibition of PKC translocation that is induced by phorbol esters and PDGF-BB and the phosphorylation of the 80 kDa protein substrate of PKC in vascular smooth muscle cells. Moreover, treatment with clentiazem leads to a marked decrease in the number of specific phorbol ester binding sites. Analysis of the membrane bound isoenzymes of protein kinase C revealed that the inhibition was specific to delta enzymes. Arterial cholesterol ester hydrolysis is not significantly altered by clentiazem. Our results suggest that clentiazem may inhibit cell proliferation by regulating cytosolic PKC and preventing its membrane translocation and activation.

Adenosine Monophosphate↗

PubMed1993

Crescendo transient ischemic attacks: a surgical imperative. Veterans Affairs trialists.

PURPOSE: In a randomized, prospective, multicenter trial at 16 medical centers, 189 of 5000 patients screened with cerebrovascular disease were identified as having angiographic internal carotid artery stenosis (> 50%) corresponding to presenting symptoms of transient ischemic attacks (TIAs), transient monocular blindness, or recent, minor completed stroke. METHODS: Patients were randomly assigned to carotid endarterectomy plus the best medical care (n = 91) versus the best medical care alone (n = 98). RESULTS: After 1 year there was a significant reduction in stroke or crescendo attacks in the 91 patients who received carotid endarterectomy (7.7%) compared with 98 patients who did not undergo operation (19.4%) (p = 0.011). Twelve (12%) of the 98 patients with symptomatic carotid stenosis treated medically had crescendo TIAs, four had minor strokes, and three had major strokes. Crescendo TIAs were defined as disabling, recurrent transient cerebral or retinal ischemia characterized by an increased frequency, duration, or severity of events. The average time from randomization until the onset of crescendo TIAs was 2 months. Seven of the 12 patients in whom crescendo TIAs developed had stenosis greater than 90%, one had greater than 80% stenosis, and four had between 70% and 80% stenosis, with one of these four having contralateral occlusion. Another three patients had 50% or greater contralateral occlusion. Patients with crescendo TIAs were offered carotid endarterectomy, and all 12 had an uncomplicated, urgent procedure. On follow-up the 12 patients were symptom free at the study conclusion. CONCLUSIONS: Crescendo TIAs are disabling symptoms that occur in patients with high-grade carotid stenoses often within 3 months of the initial symptoms of ischemic cerebrovascular disease. The 12% of medically treated patients in whom crescendo TIAs developed had carotid endarterectomy, which abolished symptoms on follow-up.

Blindness↗

PubMed1991

Carotid endarterectomy and prevention of cerebral ischemia in symptomatic carotid stenosis. Veterans Affairs Cooperative Studies Program 309 Trialist Group.

OBJECTIVE: To determine whether carotid endarterectomy provides protection against subsequent cerebral ischemia in men with ischemic symptoms in the distribution of significant (greater than 50%) ipsilateral internal carotid artery stenosis. DESIGN: Prospective, randomized, multicenter trial. SETTING: Sixteen university-affiliated Veterans Affairs medical centers. PATIENTS: Men who presented within 120 days of onset of symptoms that were consistent with transient ischemic attacks, transient monocular blindness, or recent small completed strokes between July 1988 and February 1991. Among 5000 patients screened, 189 individuals were randomized with angiographic internal carotid artery stenosis greater than 50% ipsilateral to the presenting symptoms. Forty-eight eligible patients who refused entry were followed up outside of the trial. OUTCOME MEASURES: Cerebral infarction or crescendo transient ischemic attacks in the vascular distribution of the original symptoms or death within 30 days of randomization. INTERVENTION: Carotid endarterectomy plus the best medical care (n = 91) vs the best medical care alone (n = 98). RESULTS: At a mean follow-up of 11.9 months, there was a significant reduction in stroke or crescendo transient ischemic attacks in patients who received carotid endarterectomy (7.7%) compared with nonsurgical patients (19.4%), or an absolute risk reduction of 11.7% (P = .011). The benefit of surgery was more profound in patients with internal carotid artery stenosis greater than 70% (absolute risk reduction, 17.7%; P = .004). The benefit of surgery was apparent within 2 months after randomization, and only one stroke was noted in the surgical group beyond the 30-day perioperative period. CONCLUSIONS: For a selected cohort of men with symptoms of cerebral or retinal ischemia in the distribution of a high-grade internal carotid artery stenosis, carotid endarterectomy can effectively reduce the risk of subsequent ipsilateral cerebral ischemia. The risk of cerebral ischemia in this subgroup of patients is considerably higher than previously estimated.

Aged↗

PubMed1991

Early treatment of ischemic stroke with a calcium antagonist.

We performed a feasibility and safety study (phase II) of nicardipine, a calcium antagonist, in 57 patients. The objectives of the study were to begin therapy as early as possible (less than or equal to 12 hours) after the onset of ischemic stroke and to administer as high a dose as possible. All patients received an intravenous infusion of nicardipine for 72 hours, starting with a dose of 3 mg/hr and increasing to a maximum dose of 7 mg/hr. Upward titration of the dose was limited by a 10% decrease in blood pressure or a 20 beats/min increase in pulse. Intravenous therapy was followed by 30 days of oral therapy. The mean +/- SD interval from onset of stroke to commencement of therapy was 9.1 +/- 5.4 hours. Adverse reactions consisted primarily of hypotension requiring discontinuation of therapy in four patients. Score on a graded neurologic examination increased from 41/100 at baseline to 64/100 at 3 months for the 41 patients completing follow-up. There was no correlation between the dose of nicardipine administered and outcome, but the 11 patients starting therapy less than or equal to 6 hours after onset did better than those starting therapy 6-12 hours after onset. Further study of very early therapy with nicardipine is justified.

Blood Pressure↗

PubMed1980