Nuclear multicatalytic proteinase subunit RRC3 is important for growth regulation in hepatocytes.

Multicatalytic proteinases (MCPs) are macromolecular structures involved in the intracellular degradation of many types of proteins. MCPs are composed of a 20S "core" of both structural (alpha) and presumed catalytic (beta) subunits, in association with regulatory proteins. They are characteristically found in both the nucleus and cytoplasm of cells, although mechanisms governing the subcellular distribution of MCPs are not known.

Improved left ventricular function after chronic left ventricular unloading.

Background: This study assessed the effect of prolonged left ventricular unloading on native ventricular function.

Methods: We reviewed data from 31 patients (30 men, 1 woman) supported more than 30 days (mean, 137 days; range, 31 to 505 days) with the HeartMate left ventricular assist system. The patients' mean age was 46 years (range, 22 to 64 years); 17 had idiopathic and 14 had ischemic cardiomyopathy.

Prognostic significance of plasma norepinephrine in patients with asymptomatic left ventricular dysfunction. SOLVD Investigators.

Background: Elevated plasma neurohormonal levels are associated with increased mortality rates in patients with symptomatic heart failure. A previous Studies of Left Ventricular Dysfunction (SOLVD) trial suggested that neurohumoral activation precedes the development of symptoms as demonstrated by increased neurohormonal levels in patients with asymptomatic left ventricular dysfunction. However, the significance of this early neurohumoral activation is unclear.

Double-blind, randomized comparison of the antiemetic efficacy of intravenous dolasetron mesylate and intravenous ondansetron in the prevention of acute cisplatin-induced emesis in patients with cancer. Dolasetron Comparative Chemotherapy-induced Emesis Prevention Group.

Purpose: To assess the comparative antiemetic efficacy of single-dose intravenous (IV) dolasetron mesylate and ondansetron in preventing cisplatin-induced nausea and vomiting.

Patients And Methods: Cancer patients (n = 609) receiving first-course cisplatin chemotherapy were randomized to one of three treatments: 1.8 or 2.

Single-blind study of the effects of intravenous dolasetron mesylate versus ondansetron on electrocardiographic parameters in normal volunteers.

A single-blind, randomized, five-way cross-over, safety and tolerability trial was conducted to determine whether intravenous (i.v.) dolasetron mesylate at varying single doses induces changes in ECG intervals in healthy volunteers and to compare these changes with a single intravenous dose of ondansetron or placebo.

Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD).

Objectives: This study sought to assess proinflammatory cytokine levels in patients in the studies of left ventricular dysfunction trial (SOLVD) in relation to both their New York Heart Association functional classification and their neurohormonal status before randomization.

Background: Elevated levels of tumor necrosis factor-alpha have been identified in 30% to 40% of patients with heart failure. However, it is unclear which subsets of patients with heart failure elaborate tumor necrosis factor-alpha.

Relation of ventricular size and function to heart failure status and ventricular dysrhythmia in patients with severe left ventricular dysfunction.

Patients with severe left ventricular (LV) dysfunction may or may not have overt heart failure and ventricular dysrhythmia. To study factors behind this variability, we examined a subset of 311 patients from the Studies of Left Ventricular Dysfunction-95 with a history of moderate heart failure (treatment trial) and 216 with no failure (prevention trial), all with ejection fractions <0.35.

Multiple-dose, placebo-controlled, phase I study of oral dolasetron.

Study Objectives: To evaluate the safety, tolerability, and pharmacokinetics of increasing dose levels of oral dolasetron mesylate, a new 5-HT3 antagonist.

Design: Double-blind, placebo-controlled, dose-ranging phase I study.

Setting: A clinical research center.

Single-dose, placebo-controlled, phase I study of oral dolasetron.

Study Objectives: To evaluate the safety, tolerability, and pharmacokinetics of single, escalating doses of oral dolasetron mesylate, a new 5-HT3 receptor antagonist.

Design: Double-blind, placebo-controlled, dose-escalating phase I study.

Setting: A clinical research center.

New variant of human tissue plasminogen activator (TPA) with enhanced efficacy and lower incidence of bleeding compared with recombinant human TPA.

Background: The thrombolytic properties of a new variant of tissue plasminogen activator (TPA) (T103N, N117Q, KHRR 296-299 AAAA, or TNK-TPA) with longer plasma half-life, greater fibrin specificity, and increased resistance to inhibition by plasminogen activator inhibitor (PAI-1) were investigated in a rabbit thrombosed carotid artery model.

Methods And Results: After 60 minutes of arterial occlusion, TPA (1.5, 3.

Differential induction of 3-hydroxy-3-methylglutaryl CoA reductase in two cotton species following inoculation with Verticillium.

Gossypium barbadense cottons are typically more resistant to wilt pathogens than are Gossypium hirsutum cultivars. Both species make terpenoid phytoalexins in response to infection, implicating isoprenoid biosynthesis as a factor in resistance. Conserved regions in plant 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), the first enzyme in the terpene biosynthesis pathway, were used to design polymerase chain reaction primers for cloning a fragment of a cotton HMGR gene.

Nuclear multicatalytic proteinase alpha subunit RRC3: differential size, tyrosine phosphorylation, and susceptibility to antisense oligonucleotide treatment.

Multicatalytic proteinases (MCPs) are macromolecular structures involved in intracellular degradation of many types of proteins. MCPs are composed of a 20S "core" which consists of both structural (alpha) and presumed catalytic (beta) subunits in association with complexes of accessory proteins. Immunohistochemical studies have shown MCP subunits to be largely cytoplasmic, although nuclear localization is also observed.

A double-blind, placebo-controlled, dose-ranging safety evaluation of single-dose intravenous dolasetron in healthy male volunteers.

The safety and tolerability of dolasetron mesylate, a potent and selective 5-HT3 receptor antagonist, were evaluated after single intravenous doses in healthy male volunteers. In this double-blind, placebo-controlled, randomized, phase I study, 80 subjects received either placebo or dolasetron in escalating doses (0.6 to 5.

Effect of long-term enalapril therapy on neurohormones in patients with left ventricular dysfunction. SOLVD Investigators.

The aim of this study was to compare the long-term effects of treatment with enalapril or placebo on plasma neurohormones in patients with left ventricular (LV) dysfunction. Elevated neurohormonal levels are associated with increased mortality in patients with congestive heart failure. Multiple studies have shown that angiotensin-converting enzyme inhibitors decrease mortality and morbidity in these patients.

Novel 21-aminosteroidlike compounds prevent iron-induced free radical-mediated injury to vascular endothelial cells.

Free radicals appear to play a major role in the reperfusion injury of the myocardium. Iron chelators and antioxidants can prevent the reperfusion injury. The cellular source of free radicals during reperfusion is not clearly established.

Effects of long-term enalapril therapy on cardiac structure and function in patients with left ventricular dysfunction. Results of the SOLVD echocardiography substudy.

Background: Studies of Left Ventricular Dysfunction (SOLVD) demonstrated that enalapril therapy significantly improved the clinical course of patients with left ventricular (LV) dysfunction. The goals of this substudy were to evaluate changes in LV structure and function in SOLVD patients and to test the hypothesis that enalapril inhibits remodeling in patients with LV dysfunction.

Methods And Results: Patients entering both the prevention and treatment arms of SOLVD from 5 of the 23 clinical centers were recruited for this substudy.

Calreticulin, an antithrombotic agent which binds to vitamin K-dependent coagulation factors, stimulates endothelial nitric oxide production, and limits thrombosis in canine coronary arteries.

Coagulation Factor IX/IXa has been shown to bind to cellular surfaces, and Factor IXa expresses its procoagulant activity by assembling into the intrinsic Factor X activating complex (Factors IXa/VIIIa/X), which also forms on membrane surfaces. This led us to identify cellular proteins which bind Factor IX/IXa; an approximately 55-kDa polypeptide was purified to homogeneity from bovine lung extracts based on its capacity to bind 125I-Factor IX in a dose-dependent and saturable manner. From protein sequence data of the amino terminus and internal peptides, the approximately 55-kDa polypeptide was identified as calreticulin, a previously identified intracellular calcium-binding protein.

Neurohumoral variability in left ventricular dysfunction. SOLVD Investigators. Studies of Left Ventricular Dysfunction.

The immediate and longer term variability of selected vasoactive- and volume-regulating neurohormones were measured in patients entering a substudy of the Studies of Left Ventricular Dysfunction--a randomized clinical trial in patients with left ventricular ejection fraction < or = 35%. The variability of these hormones has not been determined in a large cohort of patients. Immediate (short-term) variability was assessed by systematically comparing levels after 15 and 30 minutes of supine rest at the initial visit, and longer term variability was assessed by comparing 30-minute supine rest values at the initial visit with corresponding values taken at 30 minutes after 16 to 24 days of stable therapy.

Intracardiac angiotensin-converting enzyme inhibition improves diastolic function in patients with left ventricular hypertrophy due to aortic stenosis.

Background: Cardiac hypertrophy is associated with elevated intracardiac angiotensin-converting enzyme activity, which may contribute to diastolic dysfunction.

Methods And Results: We infused enalaprilat (0.05 mg/min) for 15 minutes into the left coronary arteries of 20 adult patients with left ventricular (LV) hypertrophy due to aortic stenosis (mean aortic valve area, 0.

Increasing coordination of the dementia service delivery network: planning for the Community Outreach Education Program.

Dementia is an emerging public health concern because of its prevalence and the cost and extent of care typically needed for people with cognitive disorders. When family members seek assistance in providing care, they frequently encounter a fragmented service delivery network. To increase the coordination of services for people with dementia, the Community Outreach Education Program (COEP) has been designed to provide educational interventions to disseminate information about the diagnosis, assessment, management, and treatment of dementia to health care professionals, service providers, staff of volunteer and community organizations, and family members.

Peri-operative anticoagulant effects of heparinization for carotid endarterectomy.

The question of whether or not to reverse heparin following carotid endarterectomy is a topic of debate. The potential reduction of the risk of thrombosis at the endarterectomy site with non-reversal has to be measured against a potential increase in the risk of wound haematoma. This study prospectively followed activated clotting time (ACT) of 42 consecutive patients undergoing carotid endarterectomy.

Mitogenic effect of serotonin on vascular endothelial cells.

Background: Recent studies indicate that serotonin (5-HT) has a growth-promoting effect on several different cell types, including smooth muscle cells. After percutaneous transluminal coronary angioplasty, there is damage and denudation of vascular endothelial cells, which promotes platelet aggregation at the site of injury. Aggregating platelets release 5-HT; thus, a high concentration of the amine may be present at sites of endothelial damage, which may act as a mitogen to endothelial cells.

Angiotensin-converting enzyme inhibition prolongs survival and modifies the transition to heart failure in rats with pressure overload hypertrophy due to ascending aortic stenosis.

Background: We tested the hypotheses that long-term administration of the angiotensin-converting enzyme (ACE) inhibitor fosinopril will regress hypertrophy, modify the transition to heart failure, and prolong survival in rats with chronic left ventricular (LV) pressure overload due to ascending aortic stenosis.

Methods And Results: Aortic stenosis was created in weanling male Wistar rats by a stainless steel clip placed on the ascending aorta. Age-matched control animals underwent a sham operation (Sham group, n = 57).