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PubMedDate not supplied

A comparison of DSM-IV brief psychotic disorder with "positive" schizophrenia and healthy controls.

To determine the psychosocial features, course, and outcome of DSM-IV brief psychotic disorder (BPD) in a comparative study, we recruited a cohort of 26 consecutive inpatients fulfilling DSM-IV criteria of BPD as well as a control group with "positive" schizophrenia (PS) and psychiatrically healthy controls matched for age and sex. Demographic and clinical features were systematically evaluated and follow-up investigations were performed at an average of 2.1 years after the index episode or 7.8 years after onset of the disorder using standardized instruments. The index group of 26 cases represented 2.5% of 1,036 patients treated as inpatients for psychotic disorders or major affective episode during the 5-year inclusion period. Eighty-one percent of the BPD patients were female. Indicators of premorbid functioning slightly favored BPD patients. Age at first episode and episode frequency did not differentiate between BPD and PS patients. Relapse was frequent in both groups. At follow-up BPD patients had a significantly more favorable outcome than patients with PS as evidenced by employment, independent living, social role functioning, psychological impairment, and global functioning. As a group, in many respects BPD patients approached the status of psychiatrically healthy controls. DSM-IV BPD is a psychotic disorder of favorable prognosis despite frequent relapse.

Achievement↗
PubMed1996

Carboxy-terminal vesicular stomatitis virus G protein-tagged intestinal Na+-dependent glucose cotransporter (SGLT1): maintenance of surface expression and global transport function with selective perturbation of transport kinetics and polarized expression.

The Na+-dependent glucose transporter (SGLT1) mediates absorption of luminal glucose by the intestine. However, available intestinal cell lines that recapitulate a monolayer phenotype only express SGLT1 at low levels. Thus, to facilitate studies of the biology of SGLT1 function in epithelial monolayers, we engineered an epitope-tagged construct containing the YTDIEMNRLGK sequence (from the vesicular stomatitis virus G protein). The tag was placed at the carboxyl terminus since this is the least conserved portion of SGLT1. Transiently transfected COS-1 cells demonstrated surface expression of the immunoreactive protein and enhanced Na+-dependent glucose uptake that was phloridzin-sensitive (a specific competitive inhibitor of SGLT1). However, subsequent detailed analyses of epitope-tagged SGLT1 using stably transfected clones derived from the Caco-2 human intestinal epithelial cell line revealed substantial effects of the epitope on critical functions of SGLT1. When compared with native SGLT1 transfectants, the apparent Km for sugar transport was increased 23-fold (313 microM to 7.37 mM for native versus epitope-tagged SGLT1). In contrast, the apparent KNa for epitope-tagged SGLT1 was similar to that for native SGLT1. Permeabilization studies indicated that the C-terminal epitope tag was intracellular and thus could not directly disrupt extracellular ligand-binding sites. Immunolocalization and functional assays designed to detect polarized surface expression indicated that epitope tagging resulted in loss of apical targeting and enrichment of basolateral expression. Functional isolation of the small apical pool of epitope-tagged SGLT1 (by selective inhibition of basolateral epitope-tagged SGLT1) revealed that, despite the documented kinetic alterations in sugar transport, epitope-tagged SGLT1 could promote absorptive Na+ currents. These data show that 1) the C terminus of SGLT1 is intracellular; 2) disruption of protein structure by addition of a C-terminal tag leads to selective modifications of SGLT1 function; 3) the kinetics of sugar transport can be altered independently of influences on the Na+-binding site of SGLT1; and 4) the weak basolateral targeting sequence present within the epitope tag is dominant over endogenous SGLT1 apical targeting information and can direct polytopic membrane protein localization. The data also caution that subtle effects of foreign sequences must be considered when epitope tagging polytopic membrane proteins.

Amino Acid Sequence↗
PubMed2004

Global protein function annotation through mining genome-scale data in yeast Saccharomyces cerevisiae.

As we are moving into the post genome-sequencing era, various high-throughput experimental techniques have been developed to characterize biological systems on the genomic scale. Discovering new biological knowledge from the high-throughput biological data is a major challenge to bioinformatics today. To address this challenge, we developed a Bayesian statistical method together with Boltzmann machine and simulated annealing for protein functional annotation in the yeast Saccharomyces cerevisiae through integrating various high-throughput biological data, including yeast two-hybrid data, protein complexes and microarray gene expression profiles. In our approach, we quantified the relationship between functional similarity and high-throughput data, and coded the relationship into 'functional linkage graph', where each node represents one protein and the weight of each edge is characterized by the Bayesian probability of function similarity between two proteins. We also integrated the evolution information and protein subcellular localization information into the prediction. Based on our method, 1802 out of 2280 unannotated proteins in yeast were assigned functions systematically.

Bayes Theorem↗
PubMed2001

Ischemic preconditioning preserves mitochondrial function after global cerebral ischemia in rat hippocampus.

Ischemic tolerance in brain develops when sublethal ischemic insults occur before "lethal" cerebral ischemia. Two windows for the induction of tolerance by ischemic preconditioning (IPC) have been proposed: one that occurs within 1 hour after IPC, and another that occurs 1 or 2 days after IPC. The authors tested the hypotheses that IPC would reduce or prevent ischemia-induced mitochondrial dysfunction. IPC and ischemia were produced by bilateral carotid occlusions and systemic hypotension (50 mm Hg) for 2 and 10 minutes, respectively. Nonsynaptosomal mitochondria were harvested 24 hours after the 10-minute "test" ischemic insult. No significant changes were observed in the oxygen consumption rates and activities for hippocampal mitochondrial complexes I to IV between the IPC and sham groups. Twenty-four hours of reperfusion after 10 minutes of global ischemia (without IPC) promoted significant decreases in the oxygen consumption rates in presence of substrates for complexes I and II compared with the IPC and sham groups. These data suggest that IPC protects the integrity of mitochondrial oxidative phosphorylation after cerebral ischemia.

Animals↗
PubMedDate not supplied

Cementless hip arthroplasty in juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. The hip is usually affected later, and its involvement is the most common cause of disability in JIA. Failure of medical and preventive treatment, significant joint destruction, or multiarticular involvement may necessitate total hip arthroplasty (THA) to restore good function. Related clinical trials show initially good THA results in most of the series, but long-term outcomes are uncertain due to a significant arthroplasty loosening rate in the initial years, particularly with cemented stems. The authors report the results of 62 noncemented THAs in 34 children with JIA after an average follow-up of 6 years (range 3-13). Mean age at surgery was 18.3 years (range 11.8-31) and 14 of the 34 children had active disease. Clinical results were good for hip function but less for global function. There were no infections. Two acetabular cups early in the series failed due to poor primary fixation and had to be revised. Survivorship analysis was performed with the Kaplan-Meier method. At 13 years, the survival rate was 100% for the femoral component and 90.1% for the acetabular component.

Adolescent↗
PubMed2004

Echocardiographic assessment of global ventricular function using the myocardial performance index in rats with hypertrophy.

Myocardial hypertrophy is the hallmark of chronic pressure overload and the myocardial performance index (MPI) is an easily recordable measurement of Doppler time intervals. In this study, the utility of using MPI to assess the progression of hypertrophy in the aortic-banded rat model was evaluated. Male Wistar rats (70-90 g) underwent ascending aorta constriction (n = 4) or a sham operation (n = 5). High-resolution echocardiography was performed 4, 7, 10, and 12 weeks after the surgery. Over this follow-up interval, animals in the aortic-banded group demonstrated an increase in their mean left ventricular (LV) mass and MPI compared with controls. MPI reflects ventricular performance in small animals with LV hypertrophy, showing alterations early after aorta constriction.

Animals↗
PubMed1998

Global regulatory functions of Oaf1p and Pip2p (Oaf2p), transcription factors that regulate genes encoding peroxisomal proteins in Saccharomyces cerevisiae.

Two transcription factors, Oaf1p and Pip2p (Oaf2p), are key components in the pathway by which several Saccharomyces cerevisiae genes encoding peroxisomal proteins are activated in the presence of a fatty acid such as oleate. By searching the S. cerevisiae genomic database for the consensus sequence that acts as a target for these transcription factors, we identified 40 genes that contain a putative Oaf1p-Pip2p binding site in their promoter region. Quantitative Northern analysis confirmed that the expression of 22 of the genes identified is induced by oleate and that either one or both of these transcription factors are required for the activation. In addition to known peroxisomal proteins, the regulated genes encode novel peroxisomal proteins, a mitochondrial protein, and proteins of unknown location and function. We demonstrate that Oaf1p regulates certain genes in the absence of Pip2p and that both of these transcription factors play a role in maintaining the glucose-repressed state of one gene. Furthermore, we provide evidence that the defined consensus binding site is not required for the regulation of certain oleate-responsive genes.

ATP-Binding Cassette Transporters↗
PubMed1993

Differences in cardioprotective efficacy of adrenergic receptor antagonists and Ca2+ channel antagonists in an animal model of dilated cardiomyopathy. Effects on gross morphology, global cardiac function, and twitch force.

Turkey poults fed furazolidone (Fz) in high concentrations (700 ppm) develop dilated cardiomyopathy (Fz-DCM). We tested whether five cardioactive agents were cardioprotective in this model of heart failure, ie, whether they prevented dilatation and wall thinning and improved contractile performance. We compared the effects of chronic administration of a beta 1-selective and a nonselective beta-receptor antagonist, an alpha-receptor antagonist, and two Ca2+ channel antagonists in the presence of Fz administration. The greatest cardioprotection was found with treatment with either propranolol or nifedipine. At the gross morphological level, the effect of propranolol (a nonselective beta-adrenergic antagonist) was greater than the effect of atenolol (a selective beta 1-adrenergic antagonist), and the effect of nifedipine was greater than that of verapamil (Ca2+ channel antagonists), with all agents more cardioprotective than phenoxybenzamine (an alpha 1-adrenergic > alpha 2-adrenergic antagonist). Differences in cardioprotective efficacy of each agent increased with increased concentration. These data indicate that the dose and choice of a specific type of Ca2+ channel antagonist or beta-receptor antagonist might be important in the treatment of dilated cardiomyopathy. All agents that were cardioprotective caused similar functional improvements at both the whole heart and isolated muscle levels. Compared with control animals, Fz-DCM animals showed a significant reduction in peak left ventricular (LV) developed pressure (92 +/- 17 versus 143 +/- 24 mm Hg, P < .05), +dP/dt (1151 +/- 219 versus 2454 +/- 549 mm Hg/s), and -dP/dt (1128 +/- 291 versus 1875 +/- 396 mm Hg/s), with a significant increase in LV end-diastolic volumes (2.8 +/- 0.7 versus 0.16 +/- 0.1 mL for control animals, P < .05). In contradistinction, LV + dP/dt and -dP/dt values for animals receiving Fz plus a cardioactive agent that demonstrated cardioprotection were not significantly different from control values. Peak LV developed pressures were also similar for Fz animals receiving an agent that demonstrated cardioprotection and control animals not receiving any pharmacologic agent. Isolated muscles from Fz-DCM animals as well as animals receiving Fz plus cardioprotective pharmacologic agents responded normally with regard to increasing extracellular Ca2+ concentrations. Peak twitch forces were greater for animals receiving cardioprotective agents plus Fz than control animals not receiving any pharmacologic agents or Fz alone. At higher stimulation rates, Fz-DCM muscles demonstrated a significantly reduced peak twitch force (4 +/- 0.5 versus 1.5 +/- 0.4 g/mm2 for control muscles versus Fz-DCM muscles, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Effect of mild hyperthermia on recovery of metabolic function after global cerebral ischemia in cats.

We investigated the effect of mild whole-body hyperthermia before and after 16 minutes of global cerebral ischemia on metabolic recovery during recirculation in cats using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy. Hyperthermia (temperature 40.6 +/- 0.2 degrees C) was induced greater than or equal to 1 hour before ischemia and was maintained during 1.5-2 hours of recirculation in nine cats; four cats were subjected to hyperthermia without cerebral ischemia, six to hyperthermia during recirculation (after return of intracellular pH to preischemic values), and 14 to normothermic ischemia and recirculation. Our data indicate that preischemic hyperthermia results in an intracellular cerebral pH during recirculation significantly lower than that in normothermic cats. In hyperthermic cats beta-ATP and phosphocreatine (PCr) concentrations and the ratio of PCr to inorganic phosphate failed to return to preischemic levels during recirculation in contrast to normothermic cats. Hyperthermia without ischemia and hyperthermia during recirculation had no significant effect on intracellular pH. Thus, preischemic hyperthermia has a detrimental effect on metabolic recovery after transient global cerebral ischemia.

Acidosis↗
PubMed2002

Efficacy and safety of rivastigmine in patients with Alzheimer's disease who failed to benefit from treatment with donepezil.

BACKGROUND: Selective acetylcholinesterase (AChE) and dual acetyl- and butyrylcholinesterase inhibitors constitute the only approved agents for the symptomatic treatment of Alzheimer's disease (AD). Donepezil is a specific, reversible inhibitor of AChE, while rivastigmine is a slowly reversible (pseudoirreversible) dual cholinesterase (ChE) inhibitor, with brain-regional specificity for the cerebral cortex and hippocampus. According to the European Marketing Authorisations, the clinical benefit of ChE inhibitors should be reassessed on a regular basis and discontinuation should be considered when evidence of a therapeutic effect is no longer present. However, substantial differences in the pharmacological and pharmacokinetic profiles of the available ChE inhibitors suggest that it may be desirable to switch between ChE inhibitors if patients fail to show efficacy, deteriorate or are unable to tolerate their initially prescribed medication. DESIGN: This open-label, six-month study evaluated the efficacy and safety of rivastigmine in 382 AD patients who had previously failed to benefit from treatment with donepezil (80% due to lack of efficacy, 11% due to tolerability problems, 9% both reasons). RESULTS: At the end of the study, 56.2% of patients were responders to rivastigmine, as assessed using a global function scale (the Clinicians' Global Impression of Change). Cognitive performance (measured by the Mini-Mental State Examination) and the ability to perform activities of daily living (measured by the Instrumental Activities of Daily Living scale) were improved/stabilised in 48.9% and 57.0% of patients, respectively. Rivastigmine was generally well tolerated, the most common adverse events being nausea and vomiting, consistent with reports from previous clinical studies. The occurrence of side-effects or lack of efficacy with donepezil treatment was not a predictor of similar problems when treated with rivastigmine. CONCLUSION: Rivastigmine treatment appears to be beneficial in AD patients who have previously failed to benefit from, or were unable to tolerate treatment with, donepezil.

Aged↗
PubMed2005

Assessment of atrial regional and global electromechanical function by tissue velocity echocardiography: a feasibility study on healthy individuals.

BACKGROUND: The appropriate evaluation of atrial electrical function is only possible by means of invasive electrophysiology techniques, which are expensive and therefore not suitable for widespread use. Mechanical atrial function is mainly determined from atrial volumes and volume-derived indices that are load-dependent, time-consuming and difficult to reproduce because they are observer-dependent. AIMS: To assess the feasibility of tissue velocity echocardiography (TVE) to evaluate atrial electromechanical function in young, healthy volunteers. SUBJECTS AND METHODS: We studied 37 healthy individuals: 28 men and nine women with a mean age of 29 years (range 20-47). Standard two-dimensional (2-D) and Doppler echocardiograms with superimposed TVE images were performed. Standard echocardiographic images were digitized during three consecutive cardiac cycles in cine-loop format for off-line analysis. Several indices of regional atrial electrical and mechanical function were derived from both 2-D and TVE modalities. RESULTS: Some TVE-derived variables indirectly reflected the atrial electrical activation that follows the known activation process as revealed by invasive electrophysiology. Regionally, the atrium shows an upward movement of its walls at the region near the atrio-ventricular ring with a reduction of this movement towards the upper levels of the atrial walls. The atrial mechanical function as assessed by several TVE-derived indices was quite similar in all left atrium (LA) walls. However, all such indices were higher in the right (RA) than the LA. There were no correlations between the 2-D- and TVE-derived variables expressing atrial mechanical function. Values of measurement error and repeatability were good for atrial mechanical function, but only acceptable for atrial electrical function. CONCLUSION: TVE may provide a simple, easy to obtain, reproducible, repeatable and potentially clinically useful tool for quantifying atrial electromechanical function.

Atrial Function↗
PubMed2004

Effect of smoking on global cognitive function in nondemented elderly.

BACKGROUND: Contrary to early case-control studies that suggested smoking protects against Alzheimer disease (AD), recent prospective studies have shown that elderly who smoke may be at increased risk for dementia. OBJECTIVE: To examine prospectively the effect of smoking on cognition in nondemented elderly. METHOD: In a multicenter cohort, the European Community Concerted Action Epidemiology of Dementia (EURODEM), including the Odense, Personnes Agées Quid (Paquid), Rotterdam, and Medical Research Council: Ageing in Liverpool Project-Health Aspects (MRC ALPHA) Studies, 17,610 persons aged 65 and over were screened and examined for dementia. After an average 2.3 years of follow-up, 11,003 nondemented participants were retested. Excluding incident dementia cases and those without baseline information on smoking gave an analytical sample of 9,209 persons. Average yearly decline in Mini-Mental State Examination (MMSE) score was compared among groups, adjusting for age, sex, baseline MMSE, education, type of residence, and history of myocardial infarction or stroke. RESULTS: MMSE score of persons who never smoked on average declined 0.03 point/year. The adjusted decline of former smokers was 0.03 point greater and of current smokers 0.13 point greater than never smokers (p < 0.001). Higher rates of decline by smoking were found in men and women, persons with and without family history of dementia, and in three of four participating studies. Higher cigarette pack-year exposure was correlated with a significantly higher rate of decline. CONCLUSION: Smoking may accelerate cognitive decline in nondemented elderly.

Age Distribution↗
PubMed2004

Active orthostatic stress and respiratory sinus arrhythmia in patients with Chagas' disease with preserved left ventricular global systolic function.

OBJECTIVE: To assess the use of the active orthostatic stress test for detecting vagal dysfunction in patients with Chagas' disease with preserved overall systolic function, and to compare it with the respiratory sinus arrhythmia test. METHODS: Sixty-one chagasic patients (Ch) and 38 nonchagasic (NCh) patients with no significant evidence of heart disease or systemic diseases underwent Doppler echocardiography and autonomic function tests. The respiratory sinus arrhythmia test was performed through electrocardiographic recording during deep breathing, at 6 ripm, calculating the E:I ratio (mean ratio between the longest expiratory RR interval and the shortest inspiratory RR interval at each cycle). The electrocardiogram was recorded during the act of standing and during the following 30 seconds (active orthostatic stress test), and the max RR/min RR ratio (the longest and shortest RR intervals right after change in posture) was calculated. The indices were adjusted for significant covariables. RESULTS: The max RR/min RR ratio (NCh: 1.52 [1.44-1.74] x Ch: 1.43 [1.33-1.51], P < 0.001) and the E:I ratio (NCh: 1.38 +/- 0.02 x Ch: 1.25 +/- 0.02, P<0.001) were lower among chagasic patients. A high correlation was observed between the adjusted max RR/min RR ratio and E:I ratio (r = 0.628, P < 0.001), but neither significantly correlated with left ventricular ejection fraction. CONCLUSION: Chagasic patients with preserved left ventricular overall systolic function showed a significant reduction in the vagal indices obtained on short-lasting tests, as compared with normal controls. The active orthostatic stress test that, showed a good correlation with the respiratory sinus arrhythmia maneuver, constituted a valid option for the outpatient care assessment of vagal control.

Adolescent↗
PubMed2006

The effect of derotational humeral osteotomy on global shoulder function in brachial plexus birth palsy.

BACKGROUND: Derotational humeral osteotomies have been used in older children with brachial plexus birth palsy and glenohumeral joint deformity to place the upper extremity in a more functional position. The purpose of this study was to determine the effects of these procedures on shoulder function and joint morphology. METHODS: Forty-three patients underwent a derotational humeral osteotomy for functional impairment in the setting of internal rotation contracture and/or glenohumeral joint deformity at our institution from 1996 to 2004. Osteotomies were performed proximal to the deltoid insertion and were stabilized with plate-and-screw fixation. The average age of the patients at the time of surgery was 7.6 years (range, 2.3 to 17.0 years). Shoulder function was graded according to the modified Mallet classification system. Glenohumeral deformity was graded according to the classification scheme of Waters et al. The results for twenty-seven patients who were followed for a minimum of two years (average, 3.7 years) are reported. RESULTS: The average amount of external rotation achieved with osteotomy was 64 degrees (range, 35 degrees to 90 degrees). The mean aggregate Mallet classification score improved from 13 to 18 points (p < 0.01). The mean Mallet classification scores for the individual elements similarly demonstrated improvement following osteotomy, with the greatest gains in hand-to-mouth, hand-to-neck, and external rotation motions. The mean classification of the glenohumeral deformity was type IV preoperatively and postoperatively, signifying the persistence of glenohumeral dysplasia. There were no nonunions. One patient required a revision osteotomy for inadequate initial correction. One patient sustained a humeral fracture distal to the plate fixation because of sports-related trauma. CONCLUSIONS: Derotational humeral osteotomy improves shoulder function in patients with brachial plexus birth palsy, internal rotation contracture, and/or advanced glenohumeral joint deformity. This osteotomy provides an attractive treatment option for patients with brachial plexus birth palsy who have advanced glenohumeral dysplasia precluding soft-tissue releases and tendon transfers.

Adolescent↗