Structural determinants underlying constitutive dimerization of unoccupied human follitropin receptors.

The human follitropin receptor (hFSHR) is a G protein-coupled receptor (GPCR) central to reproductive physiology that is composed of an extracellular domain (ECD) fused to a serpentine region. Using bioluminescence resonance energy transfer (BRET) in living cells, we show that hFSHR dimers form constitutively during their biosynthesis. Mutations in TM1 and TM4 had no effect on hFSHR dimerization, alone or when combined with mutation of Tyr(110) in the ECD, a residue predicted to mediate dimerization of the soluble hormone-binding portion of the ECD complexed with FSH (Q.

Cellular factor YY1 downregulates the human papillomavirus 16 E6/E7 promoter, P97, in vivo and in vitro from a negative element overlapping the transcription-initiation site.

Cellular factors that bind to cis sequences in the human papillomavirus 16 (HPV-16) upstream regulatory region (URR) positively and negatively regulate the viral E6 and E7 oncogene promoter, P97. DNase I footprinting has revealed the binding of cellular proteins to two previously undetected cis elements overlapping and 3' of the transcription-initiation site of the P97 promoter. Mutations within homologous motifs found in both of these cis elements abolished their negative function in vivo and the binding of the same cellular complex in vitro.

Reliability and validity of the Borderline Evaluation of Severity Over Time (BEST): a self-rated scale to measure severity and change in persons with borderline personality disorder.

A new self-rated scale to measure severity and change in persons with borderline personality disorder (BPD) is described. The Borderline Evaluation of Severity Over Time (BEST) was developed to rate the thoughts, emotions, and behaviors typical of BPD. Data were collected in the course of a randomized controlled trial (RCT) of Systems Training for Emotional Predictability and Problem Solving (STEPPS) for subjects with BPD.

Sarcoglycan complex: implications for metabolic defects in muscular dystrophies.

The sarcoglycans are known as an integral subcomplex of the dystrophin glycoprotein complex, the function of which is best characterized in skeletal muscle in relation to muscular dystrophies. Here we demonstrate that the white adipocytes, which share a common precursor with the myocytes, express a cell-specific sarcoglycan complex containing beta-, delta-, and epsilon-sarcoglycan. In addition, the adipose sarcoglycan complex associates with sarcospan and laminin binding dystroglycan.

Musculoskeletal CT: recent advances and current clinical applications.

This article discusses the indications for CT in the management of acute fractures and postoperative complications related to orthopedic procedures. The current clinical use of CT in spine injuries, pelvic/acetabular fractures, and major fractures in the extremities is discussed. Multidetector CT techniques to minimize metal artifacts and common hardware complications are reviewed.

Predictors of response to Systems Training for Emotional Predictability and Problem Solving (STEPPS) for borderline personality disorder: an exploratory study.

Objective: Few predictors of treatment outcome or early discontinuation have been identified in persons with borderline personality disorder (BPD).

Aim: The aim of the study was to examine the relationship between baseline clinical variables and treatment response and early discontinuation in a randomized controlled trial of System Training for Emotional Predictability and Problem Solving, a new cognitive group treatment.

Method: Improvement was rated using the Zanarini Rating Scale for BPD, the Clinical Global Impression Scale, the Global Assessment Scale and the Beck Depression Inventory.

Lactobacillus delbrueckii as the cause of urinary tract infection.

Lactobacilli are part of the normal bacterial flora of the vagina and are typically considered contaminants when cultured from urine specimens of female patients. Here we describe the case of a female patient with chronic pyuria and urinary tract symptoms in which Lactobacillus delbrueckii was determined to be the causative microorganism.

Scavenging superoxide selectively in mouse forebrain is associated with improved cardiac function and survival following myocardial infarction.

Dysregulation in central nervous system (CNS) signaling that results in chronic sympathetic hyperactivity is now recognized to play a critical role in the pathogenesis of heart failure (HF) following myocardial infarction (MI). We recently demonstrated that adenovirus-mediated gene transfer of cytoplasmic superoxide dismutase (Ad-Cu/ZnSOD) to forebrain circumventricular organs, unique sensory structures that lack a blood-brain barrier and link peripheral blood-borne signals to central nervous system cardiovascular circuits, inhibits both the MI-induced activation of these central signaling pathways and the accompanying sympathoexcitation. Here, we tested the hypothesis that this forebrain-targeted reduction in oxidative stress translates into amelioration of the post-MI decline in myocardial function and increase in mortality.

Subclinical obsessive-compulsive disorder in children and adolescents: additional results from a "high-risk" study.

Introduction: The concept of subclinical obsessive-compulsive disorder is explored using data from a "high-risk" study of offspring of persons with (OCD) and offspring of controls. Offspring with OCD were compared to those with subclinical OCD, and those without either condition. Subclinical OCD is defined as the presence of obsessions and/or compulsions without functional impairment.

Recognition without awareness in a patient with simultanagnosia.

We report a psychophysiological study of "recognition without awareness" in patient 2354, who had severe but circumscribed atrophy in the occipitoparietal region bilaterally (caused by visual-variant Alzheimer's disease, documented by structural and functional neuroimaging) and an accompanying Balint syndrome that prevented her from recognizing the emotional valence of many highly charged negative visual scenes (e.g., a burned body).

ES-cell derived hematopoietic cells induce transplantation tolerance.

Background: Bone marrow cells induce stable mixed chimerism under appropriate conditioning of the host, mediating the induction of transplantation tolerance. However, their strong immunogenicity precludes routine use in clinical transplantation due to the need for harsh preconditioning and the requirement for toxic immunosuppression to prevent rejection and graft-versus-host disease. Alternatively, embryonic stem (ES) cells have emerged as a potential source of less immunogenic hematopoietic progenitor cells (HPCs).

Murine pancreatic duct ligation induces stress kinase activation, acute pancreatitis, and acute lung injury.

Background: Acute lung injury is a major determinant of outcomes in acute pancreatitis. We evaluated acute lung injury and stress kinase activation in ligation-induced acute pancreatitis in mice.

Methods: Mice with duct ligation or sham operation were killed after 24 or 48 hours.

The E8--E2 gene product of human papillomavirus type 16 represses early transcription and replication but is dispensable for viral plasmid persistence in keratinocytes.

A conserved E8(wedge)E2 spliced mRNA is detected in keratinocytes transfected with human papillomavirus type 16 (HPV-16) plasmid DNA. Expression of HPV-16 E8--E2 (16-E8--E2) is independent of the major early promoter, P97, and is modulated by both specific splicing events and conserved cis elements in the upstream regulatory region in a manner that differs from transcriptional regulation of other early viral genes. Mutations that disrupt the predicted 16-E8--E2 message also increase initial HPV-16 plasmid amplification 8- to 15-fold and major early gene (P97) transcription 4- to 5-fold over those of the wild type (wt).

Application of lean manufacturing techniques in the Emergency Department.

Background: "Lean" is a set of principles and techniques that drive organizations to continually add value to the product they deliver by enhancing process steps that are necessary, relevant, and valuable while eliminating those that fail to add value. Lean has been used in manufacturing for decades and has been associated with enhanced product quality and overall corporate success.

Objectives: To evaluate whether the adoption of Lean principles by an Emergency Department (ED) improves the value of emergency care delivered.

Inhibition of apoptotic signaling and neointimal hyperplasia by tempol and nitric oxide synthase following vascular injury.

Objectives: We hypothesized that redox-mediated apoptosis of medial smooth muscle cells (SMC) during the acute phase of vascular injury contributes to the pathophysiology of vascular disease.

Methods: Apoptosis of medial SMC (1-14 days following balloon injury) was identified in rat carotid arteries by in situ DNA labeling. NADPH-derived superoxide and expression of Bcl-xL, Bax, caspase-3 and caspase-9 were assessed.

Insulin-like growth factor-1 improves survival in sepsis via enhanced hepatic bacterial clearance.

Rationale: Both insulin-like growth factor (IGF)-1 and bacterial clearance by Kupffer cells are significantly reduced in severe sepsis. Kupffer cell apoptosis is triggered by tumor necrosis factor (TNF)-alpha and activation of the PI-3 kinase pathway prevents TNF-induced Kupffer cell death.

Objectives: We evaluated if the marked decline in IGF-1 is related to bacterial clearance in sepsis.

Extended release carbamazepine in the treatment of pathological gambling: an open-label study.

Background: The efficacy and tolerability of extended release carbamazepine was tested in the treatment of pathological gambling (PG).

Method: Non-depressed outpatients with DSM-IV PG received flexibly dosed extended release carbamazepine in a prospective 10-week open-label trial following a two-week observation period. Subjects were evaluated at baseline and at one week intervals during a four week titration period, and every two weeks thereafter for assessment of gambling behavior, mood, and adverse experiences.

Internet addiction: definition, assessment, epidemiology and clinical management.

Internet addiction is characterized by excessive or poorly controlled preoccupations, urges or behaviours regarding computer use and internet access that lead to impairment or distress. The condition has attracted increasing attention in the popular media and among researchers, and this attention has paralleled the growth in computer (and Internet) access. Prevalence estimates vary widely, although a recent random telephone survey of the general US population reported an estimate of 0.

Bile and pancreatic juice exclusion activates acinar stress kinases and exacerbates gallstone pancreatitis.

Bile and pancreatic juice exclusion from gut activates acinar stress kinases and exacerbates gallstone pancreatitis as evidenced by the ameliorating effects of replacement therapy in an experimental model of duct ligation-induced acute pancreatitis. In the early stages of gallstone pancreatitis, bile-pancreatic juice cannot enter the gut. Enteral exclusion worsens pancreatitis by causing feedback hyperstimulation of the exocrine pancreas that activates acinar cell stress kinases.

A common disease-associated missense mutation in alpha-sarcoglycan fails to cause muscular dystrophy in mice.

Limb-girdle muscular dystrophy type 2D (LGMD2D) is caused by autosomal recessive mutations in the alpha-sarcoglycan gene. An R77C substitution is the most prevalent cause of the disease, leading to disruption of the sarcoglycan-sarcospan complex. To model this common mutation, we generated knock-in mice with an H77C substitution in alpha-sarcoglycan.

Risk of depression and other mental health disorders in women with polycystic ovary syndrome: a longitudinal study.

Objective: To determine the conversion risk and predictors for depression in women with polycystic ovary syndrome.

Design: Prospective longitudinal study.

Setting: University practice.

Enteral exclusion increases MAP kinase activation and cytokine production in a model of gallstone pancreatitis.

Background: We have previously demonstrated that enteral exclusion augments pancreatic p38 mitogen-activated protein (MAP) kinase activation and tumor necrosis factor-alpha (TNF-alpha) production after bile-pancreatic duct ligation in rats.

Methods: In the present study, we evaluated c-Jun NH(2)-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) activation, and cytokine production, in pancreata of duct-ligated rats with and without duodenal bile-pancreatic juice replacement from a donor rat. We hypothesized that enteral exclusion of bile-pancreatic juice activates stress kinases and induces cytokine production in ligation-induced acute pancreatitis.

RDP58 inhibits T cell-mediated bladder inflammation in an autoimmune cystitis model.

Interstitial cystitis (IC) is a chronic inflammatory condition of the urinary bladder with a strong autoimmune component. Currently, the major challenge in IC treatment is the development of effective therapies. RDP58 is a novel d-amino acid decapeptide with potent immunosuppressive activity.