IL-16 promotes leukotriene C(4) and IL-4 release from human eosinophils via CD4- and autocrine CCR3-chemokine-mediated signaling.

Human eosinophils are potential sources of inflammatory and immunomodulatory mediators, including cysteinyl leukotrienes, chemokines, and cytokines, which are pertinent to allergic inflammation. We evaluated the means by which IL-16, a recognized eosinophil chemoattractant, might act on eosinophils to affect their capacity to release leukotriene C(4) (LTC(4)) or their preformed stores of chemokines (eotaxin, RANTES) or Th1 (IL-12) or Th2 (IL-4) cytokines. IL-16 dose dependently (0.

The cellular biology of eosinophil eicosanoid formation and function.

Eosinophils are capable of generating eicosanoid derivatives of arachidonic acid by means of cyclooxygenase and the 5- and 15-lipoxygenase (LO) pathways. Moreover, eosinophils, because of their expression of leukotriene (LT) C(4) synthase, are a major source of 5-LO-derived cysteinyl LTs, which are potent paracrine mediators of bronchial obstruction and inflammation pertinent to asthma. The regulation of eicosanoid formation within eosinophils involves activation of key enzymes at specific intracellular sites.

Gender differences and normal left ventricular anatomy in an adult population free of hypertension. A cardiovascular magnetic resonance study of the Framingham Heart Study Offspring cohort.

Objectives: We sought to derive gender-specific cardiovascular magnetic resonance (CMR) reference values for normative left ventricular (LV) anatomy and function in a healthy adult population of clinically relevant age.

Background: Cardiovascular magnetic resonance imaging is increasingly applied in the clinical setting, but age-relevant, gender-specific normative values are currently unavailable.

Methods: A representative sample of 318 Framingham Heart Study (FHS) Offspring participants free of clinically overt cardiovascular disease underwent CMR examination to determine LV end-diastolic and end-systolic volume (EDV and ESV, respectively), mass, ejection fraction (EF) and linear dimensions (wall thickness, cavity length).

Cocaine enhances myocarditis induced by encephalomyocarditis virus in murine model.

This study was designed to investigate whether cocaine can exacerbate viral myocarditis and increase its incidence. Recent clinical evidence suggests that cocaine abuse increases the incidence of myocarditis. However, it has not been directly demonstrated that cocaine exposure enhances murine myocarditis.

Enhancement of nitric oxide production by methylecgonidine in cultured neonatal rat cardiomyocytes.

1. In the present experiments, we investigated the effects of methylecgonidine (MEG) on nitric oxide (NO) production in cultured neonatal rat cardiomyocytes. Incubation of cultured cardiomyocytes with carbachol or MEG for 48 h significantly enhanced NO production.

Transplantation of embryonic stem cells improves cardiac function in postinfarcted rats.

Massive loss of cardiac myocytes after myocardial infarction (MI) is a common cause of heart failure. The present study was designed to investigate the improvement of cardiac function in MI rats after embryonic stem (ES) cell transplantation. MI in rats was induced by ligation of the left anterior descending coronary artery.

A historic photomicrograph of a parasite (Trichomonas vaginalis).

Knowing that Alfred Donné was the discoverer of an important human parasite, and finding that he was also a pioneer of photomicrography, it occurred to me that his parasite might well have become a subject of his photography. It was a simple matter to confirm that this was indeed the case. The parasite he discovered was Trichomonas vaginalis; and, in collaboration with Foucault, Donné made a photomicrograph showing several protozoan parasites lying among vaginal epithelial cells.

Use of screening and preventive services among women with disabilities.

Roughly 54 million Americans have some disability; at older ages, women are more likely to be disabled than men. Many people with disabilities today live virtually normal life spans, and therefore routine screening and preventive services are essential to their overall quality of care. We used the 1994-1995 National Health Interview Survey (NHIS), with Disability, Family Resources, and Healthy People 2000 supplements, to examine screening and preventive service use for adult women with disabilities living in the community--about 18.

Why do older women discontinue hormone replacement therapy?

Postmenopausal women who choose hormone replacement therapy (HRT) often discontinue this therapy within 1 year. Few studies have considered why older women (aged > or =65 years) discontinue therapy. To investigate this question and its relationship to HRT-related side effects, we analyzed data collected during the 3-month open-label (active HRT and alendronate placebo) run-in phase of a clinical trial for osteoporosis prevention and treatment in older women.

Synchronicity of frequently sampled thyrotropin (TSH) and leptin concentrations in healthy adults and leptin-deficient subjects: evidence for possible partial TSH regulation by leptin in humans.

Leptin signals the status of energy reserves to the brain. Leptin stimulates biosynthesis of TRH in vitro and influences the activity of the hypothalamic-pituitary-thyroid axis in vivo in rodents. Because blood levels of both leptin and TSH display diurnal variation with a distinct nocturnal rise, we sought to determine whether a relationship exists between fluctuations in circulating leptin and TSH.

Metoprolol attenuates postischemic depressed myocardial function in papillary muscles isolated from normal and postinfarction rat hearts.

The present study was designed to test the hypothesis that metoprolol treatment may enhance tolerance to ischemia in normal and postinfarction rat myocardium. Myocardial infarction was induced by permanent ligation of the left coronary artery in adult rats. Animals were divided into sham-operated and infarction groups with or without metoprolol treatment.

Differential patterns of cocaine-induced organ toxicity in murine heart versus liver.

To determine cocaine's toxicity in different organs, BALB/c mice were intraperitoneally injected daily for 15 days with either saline or cocaine: 10 mg/kg, 30 mg/kg, or 60 mg/kg. Cardiac function, hepatic pathophysiology, heart and liver apoptosis, and tumor necrosis factor (TNF-alpha) levels were analyzed. After administration of cocaine, cardiac function decreased.

Patient motion compensation during transthoracic 3-D echocardiography.

Bulk patient motion during transthoracic 3-D echocardiography (3DE) produces image plane misregistration and errors in left ventricular (LV) volume and ejection fraction (EF). To correct for patient motion, we used a magnetic locating system to track both the ultrasound transducer and the chest wall of the patient, so images could be registered in a patient-centered coordinate system ("correction"). Fourteen subjects each underwent 3DE, with deliberate patient motion, to measure LV volume and EF.

Unilateral induced neocortical malformation and the formation of ipsilateral and contralateral barrel fields.

Freezing lesions to the developing cortical plate of rodents results in a focal malformation resembling human 4-layered microgyria, and this malformation has been shown to result in local and widespread disruptions of neuronal architecture, connectivity, and physiology. Because we had previously demonstrated that microgyria caused disruptions in callosal connections, we hypothesized that freeze lesions to the postero-medial barrel sub-field (PMBSF) in one hemisphere would affect the organization of this barrel field contralaterally. We placed freeze lesions in the presumptive PMBSF of neonatal rats and, in adulthood, assessed the architecture of the ipsilateral and contralateral barrel fields.

Cutting edge: eotaxin elicits rapid vesicular transport-mediated release of preformed IL-4 from human eosinophils.

IL-4 release is important in promoting Th2-mediated allergic and parasitic immune responses. Although human eosinophils are potential sources of IL-4, physiologic mechanisms to elicit its release have not been established. By flow cytometry and microscopy, eosinophils from normal donors uniformly contained preformed IL-4.

Can cocaine abuse exacerbate the cardiac toxicity of human immunodeficiency virus?

Both cocaine use and human immunodeficiency virus (HIV) infection alone have been associated with an increased incidence of cardiac dysfunction. Concomitant exposure to cocaine and HIV infection may exacerbate the cardiac toxicity of either agent alone, a hypothesis that is examined in this review article. A possible unifying hypothesis based on enhancement of adrenergic stimulation is proposed.

Extranuclear lipid bodies, elicited by CCR3-mediated signaling pathways, are the sites of chemokine-enhanced leukotriene C4 production in eosinophils and basophils.

Eosinophils and basophils, when activated, become major sources of cysteinyl leukotrienes, eicosanoid mediators pertinent to allergic inflammation. We show that the C-C chemokines, eotaxin and RANTES (regulated upon activation normal T cell expressed and secreted), activate eosinophils and basophils for enhanced leukotriene C(4) (LTC(4)) generation by distinct signaling and compartmentalization mechanisms involving the induced formation of new cytoplasmic lipid body organelles. Chemokine-induced lipid body formation and enhanced LTC(4) release were both mediated by CCR3 receptor G protein-linked downstream signaling involving activation of phosphoinositide 3-kinase, extracellular signal-regulated kinases 1 and 2, and p38 mitogen-activated protein kinases.

Single point mutations affect fatty acid block of human myocardial sodium channel alpha subunit Na+ channels.

Suppression of cardiac voltage-gated Na(+) currents is probably one of the important factors for the cardioprotective effects of the n-3 polyunsaturated fatty acids (PUFAs) against lethal arrhythmias. The alpha subunit of the human cardiac Na(+) channel (hH1(alpha)) and its mutants were expressed in human embryonic kidney (HEK293t) cells. The effects of single amino acid point mutations on fatty acid-induced inhibition of the hH1(alpha) Na(+) current (I(Na)) were assessed.

Three-dimensional echocardiographic measurement of left ventricular mass: comparison with magnetic resonance imaging and two-dimensional echocardiographic determinations in man.

Unlabelled: This study was performed to compare a novel three-dimensional echocardiography (3DE) system to clinical two-dimensional echocardiography (2DE) and magnetic resonance imaging (MRI) for determination of left ventricular mass (LVM) in humans. LVM is an independent predictor of cardiac morbidity and mortality. Echocardiography is the most widely used clinical method for assessment of LVM, as it is non-invasive, portable and relatively inexpensive.

Point mutations in alpha-subunit of human cardiac Na+ channels alter Na+ current kinetics.

Dietary polyunsaturated fatty acids (PUFAs) prevent ischemia-induced fatal cardiac arrhythmias in animals and probably in humans. This action results from inhibition of ion currents for Na+, Ca2+, and possibly other ions. To extend understanding of this protection we are seeking a possible binding site for the PUFAs on the alpha-subunit of the human cardiac Na+ channel, hH1alpha, transiently expressed in HEK293t cells.

Effect of increased body mass index on accuracy of two-dimensional echocardiography for measurement of left ventricular volume, ejection fraction, and mass.

We used 2- and 3-dimensional echocardiography to determine left ventricular volume, mass, and ejection fraction in overweight (body mass index [BMI] > or = 25 kg/m2), obese (BMI > or = 30 kg/m2), and control (BMI < 25 kg/m2) subjects. Compared with corresponding magnetic resonance imaging measurements, 3-dimensional echocardiography is more accurate than 2-dimensional echocardiography in all patients, but particularly in overweight and obese subjects.

Evidence for cocaine and methylecgonidine stimulation of M(2) muscarinic receptors in cultured human embryonic lung cells.

1. Muscarinic cholinoceptor stimulation leads to an increase in guanylyl cyclase activity and to a decrease in adenylyl cyclase activity. This study examined the effects of cocaine and methylecgonidine (MEG) on muscarinic receptors by measurement of cyclic GMP and cyclic AMP content in cultured human embryonic lung (HEL299) cells which specifically express M(2) muscarinic receptors.

Importance of an intact growth hormone/insulin-like growth factor 1 axis for normal post-infarction healing: studies in dwarf rats.

Treatment with GH attenuates remodeling and improves left ventricular function in the setting of experimental heart failure following coronary ligation. This study was designed to test the hypothesis that an intact GH/insulin-like growth factor 1 (IGF-1) axis is required for normal myocardial infarction healing. Myocardial infarction was induced by coronary ligation in GH-deficient dwarf rats and in age-matched controls.