Inositol 1,4,5-trisphosphate receptor down-regulation is activated directly by inositol 1,4,5-trisphosphate binding. Studies with binding-defective mutant receptors.

Activation of certain phosphoinositidase C-linked cell surface receptors is known to cause an acceleration of the proteolysis of inositol 1,4,5-trisphosphate (InsP3) receptors and, thus, lead to InsP3 receptor down-regulation. To gain insight into this process, we examined whether or not InsP3 receptor degradation is a direct consequence of InsP3 binding by analyzing the down-regulation of exogenous wild-type and binding-defective mutant InsP3 receptors expressed in SH-SY5Y human neuroblastoma cells. Stimulation of these cells with carbachol showed that wild-type exogenous receptors could be down-regulated but that the binding-defective mutant exogenous receptors were not.

Step-tracking movements of the wrist. IV. Muscle activity associated with movements in different directions.

We examined the patterns of muscle activity associated with multiple directions of step-tracking movements of the wrist in humans and monkeys. Human subjects made wrist movements to 12 different targets that required varying amounts of flexion-extension and radial-ulnar deviation. Wrist muscles displayed two patterns of electromyographic (EMG) modulation as movement direction changed: amplitude graded and temporally shifted.

Ectopic expression of tropomyosin promotes myofibrillogenesis in mutant axolotl hearts.

Expression of tropomyosin protein, an essential component of the thin filament, has been found to be drastically reduced in cardiac mutant hearts of the Mexican axolotl (Ambystoma mexicanum) with no formation of sarcomeric myofibrils. Therefore, this naturally occurring cardiac mutation is an appropriate model to examine the effects of delivering tropomyosin protein or tropomyosin cDNA into the deficient tissue. In this study, we describe the replacement of tropomyosin by using a cationic liposome transfection technique applied to whole hearts in vitro.

Evolution of antiviral activity in the ribonuclease A gene superfamily: evidence for a specific interaction between eosinophil-derived neurotoxin (EDN/RNase 2) and respiratory syncytial virus.

We have demonstrated that the human eosinophil-derived neurotoxin (EDN, RNase 2), a rapidly evolving secretory protein derived from eosinophilic leukocytes, mediates the ribonucleolytic destruction of extracellular virions of the single-stranded RNA virus respiratory syncytial virus (RSV). While RNase activity is crucial to antiviral activity, it is clearly not sufficient, as our results suggest that EDN has unique structural features apart from RNase activity that are necessary to promote antiviral activity. We demonstrate here that the interaction between EDN and extracellular virions of RSV is both saturatable and specific.

Laparoscopic anterior gastroplasty. A preliminary report of a new technique.

Background: The treatment of the morbidly obese patient is difficult because compliance with dietary regimens is poor. As a result, most weight reduction programs fail very quickly. Surgical treatment, on the other hand, provides a reliable method for sustained weight reduction.

Patterns of lateral sensory cortical activation determined using functional magnetic resonance imaging.

Object: Functional magnetic resonance (fMR) imaging was performed in human volunteers to determine the lateral perisylvian cortical areas activated by innocuous cutaneous stimulation.

Methods: Eight volunteers who underwent 53 separate experiments form the basis of this report. Eight contiguous coronal slices were obtained using echoplanar fMR imaging techniques while participants were at rest and while somatosensory activation stimuli consisting of vibration or air puffs were delivered to various body areas.

Fatal adverse event secondary to high osmolality contrast agent.

Adverse drug events secondary to iodinated contrast agents are of particular concern to all clinicians. Despite the availability of newer agents, the mortality rates remain unchanged. We describe a fatal adverse event secondary to use of the high osmolality agent iothalmate meglumine 30%.

AST/ALT ratio > or = 1 is not diagnostic of cirrhosis in patients with chronic hepatitis C.

Medical guidelines for interferon-alpha2a or -alpha2b (IFN-alpha) treatment of chronic hepatitis C virus (HCV) infection depend upon baseline liver histology. A better long-term response to IFN-alpha therapy correlates with less inflammation and absence of cirrhosis. It has been suggested that the presence of cirrhosis in patients with chronic hepatitis C virus infection may be predicted based on an AST/ALT ratio > or = 1.

Periareolar Breast Abscess: Redefining the Disease and Its Treatment.

Periareolar breast abscess has been an elusive condition, with much debate about its etiology over the last several decades. Presenting symptoms include nipple discharge, mastalgia, and recurrent abscesses with draining fistulas. Many experts disagree about whether this condition develops when inflammation of the duct leads to dilation or whether it begins with dilation that leads to inflammation.

Treating histologically mild chronic hepatitis C: monotherapy, combination therapy, or tincture of time?

The recent National Institutes of Health Consensus Conference on hepatitis C solidified the justification for a selective approach to treatment. Nevertheless, the high profile of chronic hepatitis C has led to a sense of urgency about treating "all-comers" and thus has caused the variable natural history of this disease to be overlooked. The debate about whom to treat has failed to focus attention on the alternative approach of waiting for better emerging therapies for the subset of patients with histologically mild chronic hepatitis C.

Serine and threonine phosphorylation of the paxillin LIM domains regulates paxillin focal adhesion localization and cell adhesion to fibronectin.

We have previously shown that the LIM domains of paxillin operate as the focal adhesion (FA)-targeting motif of this protein. In the current study, we have identified the capacity of paxillin LIM2 and LIM3 to serve as binding sites for, and substrates of serine/threonine kinases. The activities of the LIM2- and LIM3-associated kinases were stimulated after adhesion of CHO.

Eosinophil cationic protein/RNase 3 is another RNase A-family ribonuclease with direct antiviral activity.

Eosinophil cationic protein (ECP) is one of two RNase A-superfamily ribonucleases found in secretory granules of human eosinophilic leukocytes. Although the physiologic function of eosinophils [and thus of the two eosinophil ribonucleases, ECP and eosinophil-derived neurotoxin (EDN)] remains controversial, we have recently shown that isolated human eosinophils promote ribonuclease-dependent toxicity toward extracellular virions of the single-stranded RNA virus, respiratory syncytial virus, group B (RSV-B). We have also shown that recombinant human EDN (rhEDN) can act alone as a ribonuclease-dependent antiviral agent.

Expansion of clonotypic T-cell populations in the peripheral blood of asymptomatic Gran Chaco Amerindians infected with HTLV-IIB.

Peripheral blood mononuclear cells from asymptomatic HTLV-II-infected and uninfected Gran Chaco Amerindians were analyzed using polymerase chain reaction (PCR) for expansions of T-cell receptor (TCR) V-beta gene clonotypes. Analyses were performed using primer pairs designed to identify expanded T-cell familial clonotypes based on their unique TCR beta gene rearrangements. Of the 30 HTLV-IIB-positive samples tested, five showed evidence of V-beta clonotypic T-cell expansion.

Double-outlet right ventricle (tetralogy of Fallot type) associated with anomalous origin of the left coronary artery from the right pulmonary artery: report of successful total repair in a 2-month-Old infant.

The case reported herein demonstrates the rare association of double-outlet right ventricle (tetralogy of Fallot type) with anomalous origin of the left coronary artery from the pulmonary artery. It is the first reported successful total surgical repair in an infant.

The effect of cimetidine on the formation of sulfamethoxazole hydroxylamine in patients with human immunodeficiency virus.

Hypersensitivity reactions from trimethoprim/sulfamethoxazole are likely caused by a reactive nitroso intermediate formed from sulfamethoxazole hydroxylamine. This pilot study tested whether cimetidine inhibits the urinary excretion of sulfamethoxazole hydroxylamine. Ten outpatients infected with human immunodeficiency virus (HIV) and currently receiving trimethoprim/sulfamethoxazole prophylaxis were randomly selected from 59 eligible patients.

Differences among type I, II, and III inositol-1,4,5-trisphosphate receptors in ligand-binding affinity influence the sensitivity of calcium stores to inositol-1,4,5-trisphosphate.

Type I, II, and III inositol-1,4,5-trisphosphate (InsP3) receptors are expressed selectively in different cell lines and tissues. We examined whether type I, II, and III InsP3 receptors differ in ligand-binding affinity and whether such differences influence the sensitivity of Ca2+ stores to InsP3. Initially, SH-SY5Y human neuroblastoma cells, AR4-2J rat pancreatoma cells, and RINm5F rat insulinoma cells were studied because these cells express predominantly (>85%) type I, II, and III receptors, respectively.

Bi-site activation occurs with the native and nucleotide-depleted mitochondrial F1-ATPase.

Experiments are reported on the uni-site catalysis and the transition from uni-site to multi-site catalysis with bovine heart mitochondrial F1-ATPase. The very slow uni-site ATP hydrolysis is shown to occur without tightly bound nucleotides present and with or without Pi in the buffer. Measurements of the transition to higher rates and the amount of bound ATP committed to hydrolysis as the ATP concentration is increased at different fixed enzyme concentrations give evidence that the filling of a second site can initiate near maximal turnover rates.

Phosphorylation of inositol 1,4,5-trisphosphate receptors by cAMP-dependent protein kinase. Type I, II, and III receptors are differentially susceptible to phosphorylation and are phosphorylated in intact cells.

The ability of cAMP-dependent protein kinase (PKA) to phosphorylate type I, II, and III inositol 1,4,5-trisphosphate (InsP3) receptors was examined. The receptors either were immunopurified from cell lines and then phosphorylated with purified PKA or were phosphorylated in intact cells after activating intracellular cAMP formation. The former studies showed that the type I receptor was a good substrate for PKA (0.

The use of near-infrared cerebral oximetry in awake carotid endarterectomy.

Study Objective: To determine the utility of cerebral oximetry for monitoring the adequacy of cerebral blood flow (CBF) during carotid cross-clamp.

Design: Prospective study.

Setting: University hospital.

Gender differences in cardiac rehabilitation.

It is now widely recognized that comprehensive cardiac rehabilitation has substantial benefits in patients with cardiovascular disease. Despite the fact that cardiovascular disease is the leading cause of death for women in the United States with more than 250,000 deaths each year, most studies of cardiac rehabilitation have not included a substantial number of women. By making cardiac rehabilitation programs more responsive to the needs and goals of female coronary patients, participation rates and compliance rates should increase with a favorable impact on morbidity, mortality, and quality of life for women with cardiovascular diseases.

Provider practice patterns in nursing home-acquired pneumonia.

Objective: To describe provider practice patterns in the diagnosis and treatment of Nursing Home-Acquired Pneumonia (NHAP) and to document associations with cure, mortality, and transfer.

Design: A retrospective cohort.

Setting: Six nursing homes in Seattle, Washington.

Troponin, where do we go from here?

The development of new techniques brings new challenges of interpretation and changes in previously standard clinical paradigms, but it also provides an opportunity to markedly enhance our understanding of the processes that lead to cardiovascular pathobiology. The troponins offer great promise as a method for us to further our understanding of the pathogenesis of a variety of cardiac syndromes.