Bone marrow mobilized with granulocyte colony-stimulating factor in related allogeneic transplant recipients: a study of 29 patients.

We studied whether a short course of granulocyte colony-stimulating factor (G-CSF) administered to normal donors immediately before bone marrow (BM) harvest would shorten time to neutrophil and platelet engraftment in matched related allogeneic BM recipients. Twenty-nine normal donors received 4 consecutive daily subcutaneous injections of G-CSF (median dose, 12.1 microg/kg per day; range, 9.

Vascular compression of the rostral ventrolateral medulla in sympathetic mediated essential hypertension.

The pathophysiological factors of neurogenic or sympathetically mediated essential hypertension are unknown. Neurons close to the surface of the ventrolateral medulla (specifically, in the retro-olivary sulcus [ROS]) are integrally involved in the control of blood pressure by means of efferent connections to presympathetic neurons in the spinal cord. It is hypothesized that vascular contact with the ROS is pathogenically involved in neurogenically mediated hypertension.

Low birth weights contribute to high rates of early-onset chronic renal failure in the Southeastern United States.

Background: The southeastern United States is a region in which rates of cardiovascular and renal diseases are excessive. Within the Southeast, South Carolina has unusually high rates of end-stage renal disease (ESRD) in young people, with more than 70% of cases attributed to hypertension and diabetes.

Objective: To determine whether the increased vulnerability to early-onset ESRD might originate through impaired renal development in utero as measured by low birth weight.

Short-term impact of a church-based approach to lifestyle change on cardiovascular risk in African Americans.

While lifestyle modification decreases cardiovascular risk, there are barriers to lifestyle education in usual clinical practice, especially among the medically underserved. To address this gap, "Lighten Up," a church-based lifestyle program was developed in collaboration with the local African-American Christian community. Lighten Up includes a baseline health assessment (week 1), eight educational sessions (weeks 2-9) combining study of scripture and a health message, a short-term health check (week 10) and a long-term health check (week 52).

The dominant role of systolic hypertension as a vascular risk factor: evidence from the southeastern United States.

A high burden of hypertension-related cardiovascular disease remains an unfortunate hallmark in the southeastern United States (also known as the Stroke Belt). A convergence of factors related to aging, systolic blood pressure (BP), and hypertension control rates indicate that the Southeast burden will remain and probably increase well into the next century unless strategic initiatives are undertaken soon. More specifically, systolic BP, which is a major independent risk factor, increases as a function of age, whereas diastolic BP reaches a plateau.

Managing hypertension in the southeastern United States: applying the guidelines from the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI).

The southeastern United States has the highest occurrence of heart disease and stroke and among the highest rates of congestive heart failure and renal failure in the country. The Consortium for Southeastern Hypertension Control (COSEHC) is cooperating with other organizations in implementing initiatives to reduce morbidity and mortality from hypertension-related conditions in the southeastern United States. This article outlines for clinicians special consideration for implementation of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) in the southeastern United States.

Vascular effects of non-esterified fatty acids: implications for the cardiovascular risk factor cluster.

Insulin resistance emerges as a central component of the risk factor cluster and is a likely contributor to vascular disease independently of traditional risk factors such as hypertension and diabetes mellitus. However, the intermediary mechanisms by which atherosclerosis is accelerated among patients with the insulin resistance syndrome remain inadequately defined. Most of the attention has centered on hyperinsulinemia and defects of insulin-mediated glucose disposal.

Plasma aldosterone, plasma lipoproteins, obesity and insulin resistance in humans.

Aldosterone production in vitro can be affected by many hormones, autacoids, ions, and lipids, but regulation in humans is incompletely understood. We measured plasma aldosterone in adult subjects with a wide range of obesity and insulin resistance. Aldosterone levels correlated with measures of visceral obesity in one predominantly male cohort and in the women of a second cohort.

Impact of nativity and race on "Stroke Belt" mortality.

The southeastern region of the United States has been recognized for 6 decades as an area of excess cerebrovascular mortality rates. While the reasons for the disease variation remain an enigma, South Carolina has consistently been the forerunner of the "Stroke Belt." To determine the effects of nativity (birthplace) on stroke mortality rates in South Carolina, proportional mortality ratios (PMRs) were calculated for stroke deaths in South Carolina during 1980-1996 according to birthplace and stratified by gender, race, age, and educational status.

Targeting of tail-anchored proteins to yeast mitochondria in vivo.

Tail-anchored proteins are inserted into intracellular membranes via a C-terminal transmembrane domain. The topology of the protein is such that insertion must occur post-translationally, since the insertion sequence is not available for membrane insertion until after translation of the tail-anchored polypeptide is completed. Here, we show that the targeting information in one such tail-anchored protein, translocase in the outer mitochondrial membrane 22, is contained in a short region flanking the transmembrane domain.

PU.1 and USF are required for macrophage-specific mannose receptor promoter activity.

In the current study we report the isolation of 854 base pairs of the rat mannose receptor promoter. Analysis of the sequence revealed one Sp1 site, three PU.1 sites, and a potential TATA box (TTTAAA) 33 base pairs 5' of the transcriptional start site.

Management and outcome of acute myocardial infarction in older patients in the thrombolytic era.

Objective: Acute myocardial infarction (AMI) is an important cause of mortality and morbidity in older patients. The aim of this study was to determine the proportion of unselected admissions with AMI that is older than 75 years and to examine management and outcomes in this group.

Design: An historical cohort study of consecutive unselected admissions with AMI identified using the Hospital In Patient Enquiry (HIPE) database and validated according to MONICA criteria for definite or probable AMI.

Aldosterone in obesity.

Plasma aldosterone levels were measured in adults whose body mass index ranged from lean to obese. Blood was drawn while subjects rested supine for 30-90 minutes. Aldosterone was higher in obese subjects, but could not be explained by renin or K+.

Reactive oxygen species are critical in the oleic acid-mediated mitogenic signaling pathway in vascular smooth muscle cells.

Obese hypertensive patients with cardiovascular risk factor clustering have increased plasma nonesterified fatty acid levels and are at high risk for atherosclerotic events. Our previous studies demonstrated that oleic acid induces a mitogenic response in rat aortic smooth muscle cells (RASMCs) through protein kinase C (PKC)- and extracellular signal-regulated kinase (ERK)-dependent pathways. In the present study we investigated the possibility that the generation of reactive oxygen species (ROS) constitutes a critical component of the oleic acid-induced mitogenic signaling pathway in RASMCs.

Intralipid enhances alpha1-adrenergic receptor mediated pressor sensitivity.

The dyslipidemia in obese hypertensive persons may contribute to their increased vascular alpha-adrenergic receptor reactivity and tone. To further examine this notion, we conducted 2 studies of pressor sensitivity to phenylephrine, an alpha1-adrenergic receptor agonist, in lean normotensive subjects. In the first study (n=6), pressor responses to phenylephrine were obtained before and during a saline and heparin infusion.

Characterization of a rat alveolar macrophage cell line that expresses a functional mannose receptor.

The mannose receptor is a single polypeptide transmembrane glycoprotein expressed on the surface of macrophages that binds and internalizes soluble and particulate ligands. Physiological ligands for this receptor are pathogens, such as mycobacteria, and extracellular acid hydrolases and peroxidases. Expression of the mannose receptor is tightly linked to the functional state of the macrophage: the receptor appears during differentiation, is increased by macrophage deactivating agents, and is reduced in the presence of macrophage activating agents.

Commun-I-Care: experience in the first four years.

The medically uninsured ("working poor") comprise roughly 10 percent of the citizens in South Carolina. These individuals are more likely than the insured to have chronic health conditions including hypertension, diabetes, and respiratory diseases. They appear to have poorer outcomes as as result of misallocation of health care resources from prevention to acute intervention.

Strategies for cardiovascular disease prevention: importance of public and community health programs.

Cardiovascular diseases (CVD), principally coronary heart disease (CHD), stroke, and congestive heart failure, continue to be the leading cause of death claiming nearly 1,000,000 lives annually and accounting for more than 40% of the deaths in the United States (American Heart Association). While cardiovascular disease is often viewed as a problem of the elderly, 45% of heart attacks occur among individuals less than 65 years old. Moreover, CVD is the second leading cause of death for those 45 to 64 years of age and the third leading cause of death for those 25 to 44 years old.

Oleic acid and angiotensin II induce a synergistic mitogenic response in vascular smooth muscle cells.

Oleic acid and angiotensin II (Ang II) are elevated and may interact to accelerate vascular disease in obese hypertensive patients. We studied the effects of oleic acid and Ang II on growth responses of rat aortic smooth muscle cells (VSMCs). Oleic acid (50 micromol/L) raised thymidine incorporation by 50% at 24 hours and cell number by 55% at 6 days (P<.

Fatty acids augment endothelium-dependent dilation in hand veins by a cyclooxygenase-dependent mechanism.

Evidence supports the hypothesis that elevated nonesterified fatty acids (NEFAs) in patients with insulin resistance, eg, obese hypertensive subjects, contribute to increased vascular alpha-adrenergic reactivity and tone by impairing endothelium-dependent vasodilation. To generate further support for this notion, we studied responses to endothelium-dependent and independent dilators under control (0.9% NaCl/heparin) conditions in one hand and with elevated NEFAs in the contralateral hand (10% intralipid/heparin).

Fatty acids, not insulin, modulate alpha1-adrenergic reactivity in dorsal hand veins.

Resistance to the vasodilator action of insulin and its capacity to antagonize vascular alpha-adrenergic reactivity may contribute to the increased neurovascular tone and blood pressure in obese hypertensive subjects. We showed that nonesterified fatty acids (NEFAs) were elevated in obese hypertensive subjects and that raising NEFAs locally in dorsal hand veins of healthy normotensive subjects enhances alpha1adrenoceptor reactivity. Research by others suggests that insulin antagonizes alpha1-adrenoceptor tone in dorsal hand veins.

Nonesterified fatty acids in the pathogenesis of hypertension: theory and evidence.

This paper approaches the hypothesis that fatty acids contribute to hypertension by examining possible interactions of nonesterified fatty acids with renal pressure-natriuresis, peripheral vascular resistance, and the central nervous barostat, three loci where long-term regulation of blood pressure is probably controlled. By inhibiting aldosterone secretion, nonesterified fatty acids may lower blood pressure by facilitating pressure-natriuresis. Oxygenated metabolites of fatty acids appear to stimulate aldosterone secretion.

Hypertension-related morbidity and mortality in the southeastern United States.

Stroke mortality is higher in the Southeast compared with other regions of the United States. The prevalence of hypertension is also higher (black men = 35%, black women = 37.7%, white men = 26.

Adverse effects of short-term, very-low-salt diets in subjects with risk-factor clustering.

Obesity is associated with risk-factor clustering, including risk factors for hypertension, hyperinsulinemia, resistance to insulin's lowering of glucose and fatty acid concentrations, and a complex dyslipidemia. Obese hypertensive subjects are presumed to be salt sensitive because of the antinatriuretic actions of insulin. However, in our studies obese hypertensive subjects aged < 45 y were not more salt sensitive than were lean individuals.

Differences in macronutrient selections in users and nonusers of an oral contraceptive.

One of the problems inherent in using women in clinical research is the effect that oral contraceptive (OC) use might have on physical indexes. Although weight gain is frequently reported as a side effect of OC use, there is little empirical evidence that such weight gain actually occurs. The current study investigated differences in energy balance [ie, dietary intake, resting energy expenditure (REE), and physical activity] between groups of users and nonusers of OCs.