Overexpression of nPKC theta is inhibitory for agrin-induced nicotinic acetylcholine receptor clustering in C2C12 myotubes.

Protein kinase C (PKC) activity has been implicated in nicotinic acetylcholine receptor (nAChR) cluster disruption but the specific PKC isoforms involved have not been identified. We first tested whether phorbol esters, which activate PKCs, regulate agrin-induced nAChR clustering in C(2)C(12) cells. We found that extended phorbol ester treatment (6 hr) increased nAChR clustering by two-fold.

Crystallization and preliminary crystallographic analysis of T7 RNA polymerase elongation complex.

Stable transcription-elongation complexes consisting of T7 RNA polymerase (molecular mass 99 kDa) in association with a nucleic acid scaffold consisting of an 8 bp RNA-DNA hybrid and 10 bp of downstream DNA were assembled and crystallized by the sitting-drop vapour-diffusion technique under near-physiological conditions. The crystals diffract beyond 2.6 A resolution and belong to space group P1, with unit-cell parameters a = 79.

Detrimental effect of protracted hyperglycaemia on beta-cell neogenesis in a mouse murine model of diabetes.

Aims/hypothesis: Previous studies have shown that new beta cells differentiate from intra-islet precursors in pancreatic islets of mice in which diabetes is induced by injecting a high dose of the beta-cell toxin streptozotocin. Moreover, the re-establishment of euglycaemia by insulin therapy 1 day after streptozotocin treatment improved the process of regeneration. We sought to assess whether a 1-week delay in the restoration of euglycaemia would affect beta-cell regeneration.

What do the statins tell us?

Until the recent introduction of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), the potential effect of cholesterol lowering on the prevention of clinical manifestations of coronary disease was a matter of debate. In trials conducted before the introduction of statins, cholesterol levels were lowered, on average, by only approximately 10%, resulting in prevention of coronary events but with no effect on total mortality rates. However, statins have been able to reduce low-density lipoprotein cholesterol levels by a mean of roughly 28%, significantly decreasing both relative and absolute risk levels of coronary events and total mortality.

Purine nucleoside phosphorylase deficiency: a new case report and identification of two novel mutations (Gly156A1a and Val217Ile), only one of which (Gly156A1a) is deleterious.

Purine nucleoside phosphorylase (PNP) deficiency results in an autosomal recessive immunodeficiency disease characterized by initial involvement of cellular immunity and neurological manifestations with subsequent abnormalities of humoral immunity. The initial presentation and clinical course has varied widely in the relatively few published cases. The molecular basis has been reported in only 10 patients, precluding evaluation of phenotype-genotype relationships.

Dendritic BC1 RNA: functional role in regulation of translation initiation.

In neurons, local protein synthesis in synaptodendritic microdomains has been implicated in the growth and plasticity of synapses. Prerequisites for local translation are the targeted transport of RNAs to distal sites of synthesis in dendrites and translational control mechanisms to limit synthesis to times of demand. Here we identify dendritic BC1 RNA as a specific repressor of translation.

Preoperative sedation in pediatric patients with sleep-disordered breathing.

Objective: Based on a few reports that describe obstructive sleep apnea (OSA) patients as having an increased risk of acute upper airway obstruction (UAO) after pharmacological sedation, this population is less likely to receive sedation prior to surgery. Our objective was to evaluate pediatric patients with sleep-disordered breathing who received preoperative sedation to determine if there was an increase in preoperative airway obstruction.

Design: Retrospective chart review from 1995 to 2000.

MRI findings of vestibulocochlear hemorrhage in a leukemic patient with sensorineural hearing loss.

This case report presents a patient with M4 leukemia with signs and symptoms of acute sensorineural hearing loss. The patient's MRI demonstrated high signal on unenhanced T1-weighted images within the left vestibulocochlear complex that was consistent with subacute hemorrhage. Follow-up MRI showed clearing of the previously seen high T1-weighted signal from the left vestibulocochlear complex.

Clinical implications of aldosterone blockade.

Background: Aldosterone contributes to hypertension, cardiac and vascular remodeling, and heart failure. The significant risk reduction provided by the addition of spironolactone to standard therapy in patients with severe heart failure has renewed interest in aldosterone blockade.

Methods: This review describes recent clinical studies of eplerenone, a selective aldosterone blocker, in patients with hypertension.

Atrial pacing stress echocardiography: an alternative diagnostic test for chest pain in the elderly.

The authors utilized rapid right atrial pacing and handgrip exercise to provoke myocardial ischemia in 20 participants (age >65 years) who, for reasons of disability, were not candidates for exercise and pharmacologic stress testing. Echocardiographic left ventricular ejection fraction and left ventricular wall motions were obtained during pacing at baseline and at maximal pacing rates and were compared with coronary angiography. Using the failure of left ventricular ejection fraction to increase with pacing as an indicator of myocardial ischemia, the test yielded a sensitivity of 75%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 71%.

Holocaust survivors in a primary care setting: fifty years later.

Past studies have not assessed the prevalence of emotional disturbances in Holocaust survivors seeking medical treatment in a family practice environment. The present study examined the prevalence of lifetime (the presence of symptomatology at any time) and current posttraumatic stress disorder (PTSD) symptoms, general anxiety, and depression in Holocaust survivors seeking medical treatment in a primary care setting. 20 of the 27 Holocaust survivors in our sample received a current diagnosis of PTSD and reported significant symptoms of depression and general anxiety.

Intra-familial transmission of life-threatening group A streptococcal infection.

Invasive group A streptococcal (GAS) infections have been of increasing concern worldwide during the past 15 years. Spread of group A streptococci to contacts with resulting invasive infection has been reported in families, in residential nursing homes, and even from patients to health care workers. We report an instance of temporally related life-threatening group A streptococcal infection in a husband and 2 weeks later in his wife.

Basic rules of parenteral fluid therapy.

The following basic rules of parenteral fluid therapy are formulated with the aim of alleviating concern and confusion about i.v. fluid orders that are experienced by most physicians: Don't be generous with fluid; in determining the water intake, one must know the usual water output through the kidney, skin and lung; one must know the quantities of the electrolytes and nutrients that are being given, and know the initial volume of distribution (usually the ECF); one must know the aim of fluid therapy; one must not give and remove the same substance at the same time; one must be aware that hypertonic saline contains less water for a given amount of Na than isotonic saline; one must be familiar with different i.

Pathogenesis and diagnosis of hyponatremia.

This discussion emphasizes two aspects of hyponatremia: classification according to effective osmolality of the body fluid, and distinction between appropriate and inappropriate ADH secretion. Assessment of the effective osmolality is important because the main deleterious effect of hyponatremia is cell overhydration, which occurs only when the effective osmolality is reduced. Since most cases of hyponatremia are associated with low effective osmolality, cell overhydration is a hallmark of acute hyponatremia.

Linkage and linkage disequilibrium mapping of ERP and EEG phenotypes.

Linkage analyses of highly heritable electrophysiological phenotypes (EEG, ERP) that can potentially identify individuals at risk for alcoholism were performed on a large sample of families with a high density of alcohol dependence as part of the Collaborative Study on the Genetics of Alcoholism (COGA); these genetic findings are summarized. Quantitative trait loci (QTLs) were identified for several ERP characteristics (P300, N100, N400) and for the beta frequencies of the EEG where we report linkage and linkage disequilibrium at a GABA(A) receptor gene on chromosome 4. Genetic analyses of ERPs suggest that several regions of the human genome contain genetic loci related to the generation of N100, N400 and P300, which are possible candidate loci underlying the functional organization of human neuroelectric activity.

Roles of tyrosine kinase-, 1-phosphatidylinositol 3-kinase-, and mitogen-activated protein kinase-signaling pathways in ethanol-induced contractions of rat aortic smooth muscle: possible relation to alcohol-induced hypertension.

Insights into the relations between and among ethanol-induced contractions in rat aorta, tyrosine kinases (including src family of cytoplasmic tyrosine kinases), 1-phosphatidylinositol 3-kinases (PI-3Ks), mitogen-activated protein kinases (MAPKs), and regulation of intracellular free Ca(2+) ([Ca(2+)](i)) were investigated in the present study. Ethanol-induced concentration-dependent contractions in isolated rat aortic rings were attenuated greatly by pretreatment of the arteries with low concentrations of an antagonist of protein tyrosine kinases (genistein), an src homology domain 2 (SH2) inhibitor peptide, a highly specific antagonist of p38 MAPK (SB-203580), a potent, selective antagonist of two specific MAPK kinases-MEK1/MEK2 (U0126)-and a selective antagonist of mitogen-activated protein kinase kinase (MAPKK) (PD-98059), as well as by treatment with wortmannin or LY-294002 (both are selective antagonists of PI-3Ks). Inhibitory concentration 50 (IC(50)) levels obtained for these seven antagonists were consistent with reported inhibition constant (Ki) values for these tyrosine kinase, MAPK, and MAPKK antagonists.

Role of synaptic metabotropic glutamate receptors in epileptiform discharges in hippocampal slices.

Application of group I metabotropic glutamate receptor (mGluR) agonists elicits seizure discharges in vivo and prolonged ictal-like activity in in vitro brain slices. In this study we examined 1) if group I mGluRs are activated by synaptically released glutamate during epileptiform discharges induced by convulsants in hippocampal slices and, if so, 2) whether the synaptically activated mGluRs contribute to the pattern of the epileptiform discharges. The GABA(A) receptor antagonist bicuculline (50 microM) was applied to induce short synchronized bursts of approximately 250 ms in mouse hippocampal slices.

Characterization of T7 RNA polymerase transcription complexes assembled on nucleic acid scaffolds.

We have used synthetic oligomers of DNA and RNA to assemble nucleic acid scaffolds that, when mixed with T7 RNA polymerase, allow the formation of functional transcription complexes. Manipulation of the scaffold structure allows the contribution of each element in the scaffold to transcription activity to be independently determined. The minimal scaffold that allows efficient extension after challenge with 200 mm NaCl consists of an 8-nt RNA primer hybridized to a DNA template (T strand) that extends 5-10 nt downstream.

Isotretinoin made S.M.A.R.T. and simple.

With the introduction of oral isotretinoin 20 years ago, an incredible triumph was achieved in the treatment of acne vulgaris. Much has been learned of the pathogenesis of acne and the mechanism by which isotretinoin affects acne. The teratogenicity of isotretinoin has cast a shadow on this effective drug with recent concern about the regulation of its use.

Prevalence and determinants of burnout among physical and occupational therapists.

It is generally speculated that the ongoing changes in the health care system may increase the incidence of burnout among health care providers. The purposes of this cross-sectional study were to determine (1) the prevalence of burnout among physical therapists (PTs) and occupational therapists (OTs), (2) sociodemographic and work-related factors associated with emotional exhaustion (EE), depersonalization (DP), and personal achievement (PA) traits of PTs and OTs. In fall 1998, 169 PTs and 138 OTs employed in various clinical settings in New York City completed the survey.

The incidence and influence of early traumatic life events in patients with panic disorder: a comparison with other psychiatric outpatients.

Early traumatic life events, including childhood physical and sexual abuse, has been associated with increased risk for panic disorder in adulthood. We examined the incidence and influence of early traumatic life events in outpatients with panic disorder (n = 101), compared to outpatients with other anxiety disorders (n = 58), major depression (n = 19), or chronic schizophrenia (n = 22). Data were obtained by means of Structured Clinical Interviews and self-report questionnaires.

Outcomes of lipid-lowering treatment in postmenopausal women.

Elevated triglycerides and low high-density lipoprotein (HDL) levels are more important coronary risk factors in women, and elevated low-density lipoprotein (LDL) levels less important in women, than men. There is clear-cut evidence in clinical trials that the benefit of cholesterol lowering in women and men is virtually identical. Modifiers of lipids and lipoproteins in women include diabetes mellitus, bodyweight and its distribution, and menopausal status.

Adenotonsillectomy as a treatment option for poststreptococcal uveitis.

Objectives: To report recurrent uveitis as a manifestation of poststreptococcal syndrome and discuss a role of adenotonsillectomy as a treatment option.

Study Design: Case study.

Methods: A case report of a 6-year-old, otherwise healthy girl with group A streptococcal uveitis managed successfully with adenotonsillectomy.

Complexity measures of event related potential surface Laplacian data calculated using the wavelet packet transform.

We describe a method to obtain estimates of EEG signal complexity using the well-established wavelet packet transform with best basis selection. In particular, we use the two-dimensional wavelet packet transform to obtain estimates of the complexity of two-dimensional images. This allows us to calculate complexity estimates of high-resolution brain potential maps generated from 61 scalp electrode Visual Oddball paradigm, grand-mean data.