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At least 523 records · Page 29Linked to original sources
PubMed2005

A study of glutathione S-transferase pi expression in central nervous system of subjects with amyotrophic lateral sclerosis using RNA extraction from formalin-fixed, paraffin-embedded material.

The expression of glutathione S-transferase pi (GST pi), an enzyme responsible for inactivation of a large variety of toxic compounds was studied in spinal cord, motor and sensory brain cortex obtained from patients who died in the course of amyotrophic lateral sclerosis (ALS). The studies were performed on formalin-fixed, paraffin-embedded (FFPE) and freshly frozen tissues. The method of RNA isolation from FFPE was modified. A significant decrease of GST pi-mRNA expression was found in cervical spinal cord and motor brain cortex of ALS subjects comparing to analogue control tissues (P<0.01), as well as in motor cortex of ALS subjects comparing to their sensory cortex (P<0.05). In spinal cords the decrease in GST pi-mRNA expression was accompanied by a decrease of GST pi protein level. Results indicated lowered GST pi expression on both mRNA and protein levels in the regions of nervous system affected by ALS. The non-properly inactivated by GST toxic electrophiles and organic peroxides may thus contribute to motor neurons damage.

Adult↗
PubMed2006

Tau isoforms expression in transgenic mouse model of amyotrophic lateral sclerosis.

Tau is a protein involved in regulation of microtubule stability, axonal differentiation and transport. Alteration of retrograde transport may lead to motor neuron degeneration. Thus alternative mRNA splicing and expression of tau isoforms were studied in a transgenic mouse model harboring the human SOD1 G93A mutation. The studies were performed on cortex, hippocampus and spinal cord of 64- and 120-day-old animals (presymptomatic and symptomatic stage) and wild type controls. Exon 10 was found in all studied tissues. The 2N isoform containing exons 2 and 3 (+2+3) and the 1N (+2-3) predominated over the 0N (-2-3) in brain regions of the studied mice. The 2N expression was significantly lower in cortex and hippocampus of symptomatic animals compared to analogue control tissues. The decrease in 2N expression resulted in lower levels of total tau mRNA and tau protein. No changes in tau expression were observed in spinal cord of studied animals.

Alternative Splicing↗
PubMed2006

Conversion of MapMan to allow the analysis of transcript data from Solanaceous species: effects of genetic and environmental alterations in energy metabolism in the leaf.

The tomato microarray TOM1 offers the possibility to monitor the levels of several thousand transcripts in parallel. The microelements represented on this tomato microarray have been putatively assigned to unigenes, and organised in functional classes using the MapMan ontology (Thimm et al., 2004. Plant J. 37: 914-939). This ontology was initially developed for use with the Arabidopsis ATH1 array, has a low level of redundancy, and can be combined with the MapMan software to provide a biologically structured overview of changes of transcripts, metabolites and enzyme activities. Use of this application is illustrated using three case studies with published or novel TOM1 array data sets for Solanaceous species. Comparison of previously reported data on transcript levels in potato leaves in the middle of the day and the middle of the night identified coordinated changes in the levels of transcripts of genes involved in various metabolic pathways and cellular events. Comparison with diurnal changes of gene expression in Arabidopsis revealed common features, illustrating how MapMan can be used to compare responses in different organisms. Comparison of transcript levels in new experiments performed on the leaves of the cultivated tomato S. lycopersicum and the wild relative S. pennellii revealed a general decrease of levels of transcripts of genes involved in terpene and, phenylpropanoid metabolism as well as chorismate biosynthesis in the crop compared to the wild relative. This matches the recently reported decrease of the levels of secondary metabolites in the latter. In the third case study, new expression array data for two genotypes deficient in TCA cycle enzymes is analysed to show that these genotypes have elevated levels of transcripts associated with photosynthesis. This in part explains the previously documented enhanced rates of photosynthesis in these genotypes. Since the Solanaceous MapMan is intended to be a community resource it will be regularly updated on improvements in tomato gene annotation and transcript profiling resources.

Arabidopsis↗
PubMed2006

Dietary onion intake as part of a typical high fat diet improves indices of cardiovascular health using the mixed sex pig model.

The aim of this study was to evaluate the potential health benefits of onions consumed at two levels of intake, using the pig model. The dietary fat content was set at a level typical of a "western" diet (25% w/w). Fifteen female and fifteen male pigs (Large White x Landrace) were allocated to one of three dietary treatments in a randomised block design. Treatments consisted of control diet (no onion) and onion supplementation at either 8.6 or 21.4 g of onion/MJ DE fed for six weeks. Onion consumption reduced plasma triglyceride levels by 15% (P=0.030) regardless of sex and onion dose. Total plasma cholesterol and cholesterol fractions were unaffected by onion supplementation (P>0.050). The bioactivity of onion was evident in haematocrit measures, where red blood cell and haemoglobin were significantly reduced in a dose dependant manner (P<0.001 and P=0.011, respectively), while other cell counts, with exception of segmented neutrophils (-18%, P=0.012), were largely unaffected. Serum oxidative status was improved (P=0.007) in pigs consuming onions. These data demonstrate that consumption of onions can have positive health effects in both male and female pigs consuming a high fat diet.

Animals↗
PubMed2006

Influence of chronic cardiovascular disease and hospitalisation due to this disease on quality of life of community-dwelling elderly.

The aim of this study was to describe the impact of chronic cardiovascular disease (CVD) and hospitalisation due to this disease on quality-of-life (QOL) in community-dwelling elderly. The study was carried out in the three age- and gender-matched groups of older subjects: 100 elderly without CVD, 100 elderly with CVD and 100 patients actually hospitalised for the cardiologic reasons. The assessment included demographic and social variables, health status, nutritional state, physical activity (PA), physical and cognitive function. QOL was assessed with the Euroqol 5D questionnaire. Presence of CVD per se detracted from QOL only moderately, increasing the subjective perception of pain/discomfort. Hospitalisation was connected with the reduction of the majority of QOL dimensions and the decrease of rating on visual analogue scale (VAS). When taking into account all confounders the presence of CVD did not significantly contribute to overall QOL, while hospitalisation decreased the usual activity dimension of QOL and VAS, but interestingly, improved the perception of well-being in relation to anxiety/depression. Variables that most powerfully detracted from QOL were lower functional status, higher number of medications used, poor nutritional state, low habitual PA and above all, depression. These findings suggest that physical and cognitive function as well as regular PA may affect QOL more in community-dwelling elderly than the presence of CVD or even need of hospitalisation.

Aged↗
PubMed2003

Divergent pattern of polyisoprenoid alcohols in the tissues of Coluria geoides: a new electrospray ionization MS approach.

Polyisoprenoid alcohols of the plant Coluria geoides were isolated and analyzed by HPLC with UV detection to determine the nature of the polyprenol and dolichol mixture in the organs studied. In roots, a family of dolichols (Dol-15 to Dol-23, with Dol-16 dominating, where Dol-n is dolichol composed of n isoprene units) was accompanied by traces of polyprenols of similar chain lengths, whereas in hairy roots grown in vitro, identical patterns with a slightly broader chain-length range were found. Conversely, in leaves and seeds polyprenols were the dominant form, and their pattern was shifted toward longer chains (maximal content of Pren-19, where Pren-n is polyprenol composed of n isoprene units). Interestingly, the pattern of dolichols in seeds and leaves (in which Dol-17 dominated) was similar to that found in roots. Structures of the dolichols and polyprenols isolated were confirmed by the application of a new HPLC/electrospray ionization-MS method, which also offers a much higher sensitivity in detection of these compounds compared to a UV detector. The highest sensitivity was obtained when the [M + Na]+ ions of polyprenols and dolichols were recorded in the selected ion monitoring mode and a small amount of sodium acetate solution was added post-column to enhance the formation of these ions in an electrospray ion source.

Alcohols↗
PubMed2002

Neurogenic factors in renal hypertension.

Hypertension is very common in patients with chronic renal failure and contributes to cardiovascular morbidity and mortality. Several mechanisms may contribute to hypertension in these patients, but recently a large body of evidence supports the notion that activation of the sympathetic nervous system (SNS) may play a very important role. In rats with 5/6 nephrectomy, the turnover rate of norepinephrine was increased in brain nuclei involved in the noradrenergic control of blood pressure, and dorsal rhizotomy prevented hypertension. Studies in human subjects with chronic renal failure and hypertension have also shown increased peripheral SNS activity measured my microneurography in the peroneal nerve and normalization with nephrectomy. In all, these studies indicate that renal injuries may activate renal afferent pathways that connect with integrative brain structures in SNS activity and blood pressure. We have also shown that central SNS activity is modulated by local expression of nitric oxide, which, in turn, is regulated by interleukin-1b.

Animals↗
PubMed2006

The prevalence and clinical significance of antiphospholipid antibodies in rheumatoid arthritis.

Published data were reviewed to evaluate the occurrence of antiphospholipid antibodies (aPL) in rheumatoid arthritis (RA) patients and to investigate their clinical relevance in this population. The mean prevalence was calculated at 28% and the median was 22%. Few studies have found a relationship between aPL antibodies and thrombosis, particularly in combination with other risk factors. Conflicting results have been reported on the association of anticardiolipin (aCL) antibody positivity and neurologic symptoms, Reynaud's phenomenon, disease activity, radiographic erosions, extra-articular RA manifestations, rheumatoid factor, and atherosclerosis. Some studies, however, suggest that there is a correlation present between those antibodies and C-reactive protein levels, rheumatoid nodules, and antinuclear antibodies. TNF-alpha blocking agents may cause an induction of aCL antibodies, but it seems like they do not cause any clinical features related to the antiphospholipid syndrome. Higher 17beta-estradiol levels were observed in aCL antibody-positive RA patients than in aCL antibody-negative patients and especially in premenopausal women, which may predispose to a more efficient immune response.

Antibodies, Antiphospholipid↗
PubMed2005

Ethics in an operations management course.

Graduates of the management major at the University of Pittsburgh at Greensburg find employment in a variety of organizations. As future managers with employees from different professions, students expressed an interest in discussing ethics cases in the operations management class. The semester starts with students familiarizing themselves with various professional and corporate codes of ethics. Throughout the semester a number of short ethics' cases in operations' areas such as inventory management, scheduling, facility location, and product design are introduced to illustrate ethical issues that a manager and his/her employees might face. Students prepare individual responses before the in-class discussions. The semester ends with a long group ethics case discussion and formal case presentations. In the end-of-semester survey, students responded very favorably to an ethics component in the operations management class.

Ethics, Professional↗
PubMed2003

Sorting functional classes of evoked potentials by wavelets.

Evoked potentials (EPs) recorded within the primary sensory cortex of non-anesthetized rats vary considerably with each peripheral stimulation. We have previously shown that most of this variance reflects the shift of cortical activation between habituated and aroused states. Here we show that a method of matching the potential's course by wavelet functions can reliably differentiate single EPs and may therefore, be used as a probe for indicating the current activation state of the cortex.

Animals↗
PubMed2005

The application of nuclear magnetic resonance-based metabonomics to the dominant-submissive rat behavioral model.

Nuclear magnetic resonance (NMR) methods were used to study whether there are differences in the urine content between behaviorally distinct groups of rats: dominant and submissive. The dominant-submissive relationships (DSRs) were established in rat pairs competing for access to the feeder filled with sweetened milk. Dominant rats spend significantly longer amounts of time at the feeder than do their submissive partners. During a 2-week period, rats were tested for the DSR. At the end of the second week, behavioral groups of rats were selected and urine was collected during a 3.5-h time period. Principal component analysis revealed a metabolite from milk sugar, galactose, as a discriminating factor between rats classified as dominant and those classified as submissive. Measurements of galactose showed that the amount present in the urine correlated with the time spent in the feeder zone, thereby supporting the time criterion established for the DSR model.

Animals↗
PubMed2005

Analyzing a kinetic titration series using affinity biosensors.

The classical method of measuring binding constants with affinity-based biosensors involves testing several analyte concentrations over the same ligand surface and regenerating the surface between binding cycles. Here we describe an alternative approach to collecting kinetic binding data, which we call "kinetic titration." This method involves sequentially injecting an analyte concentration series without any regeneration steps. Through a combination of simulation and experimentation, we show that this method can be as robust as the classical method of analysis. In addition, kinetic titrations can be more efficient than the conventional data collection method and allow us to fully characterize analyte binding to ligand surfaces that are difficult to regenerate.

Antibodies, Monoclonal↗
PubMed2004

Function of several critical amino acids in human pyruvate dehydrogenase revealed by its structure.

Pyruvate dehydrogenase (E1), an alpha(2)beta(2) tetramer, catalyzes the oxidative decarboxylation of pyruvate and reductive acetylation of lipoyl moieties of the dihydrolipoamide acetyltransferase. The roles of betaW135, alphaP188, alphaM181, alphaH15, and alphaR349 of E1 determined by kinetic analysis were reassessed by analyzing the three-dimensional structure of human E1. The residues identified above are found to play a structural role rather than being directly involved in catalysis: betaW135 is in the center of the hydrophobic interaction between beta and beta' subunits; alphaP188 and alphaM181 are critical for the conformation of the TPP-binding motif and interaction between alpha and beta subunits; alphaH15 is necessary for the organization of the N-terminus of alpha and alpha' subunits; and alphaR349 supports the interaction of the C-terminus of the alpha subunits with the beta subunits. Analysis of several critical E1 residues confirms the importance of residues distant from the active site for subunit interactions and enzyme function.

Amino Acids↗
PubMed2006

Serpin crystal structure and serpin polymer structure.

Serpins are a family of structurally homologous proteins having metastable native structures. As a result, a serpin variant destabilized by mutation(s) has a tendency to undergo conformational changes leading to inactive forms, e.g., the latent form and polymer. Serpin polymers are involved in a number of conformational diseases. Although several models for polymer structure have been proposed, the actual structure remains unknown. Here, we provide a comprehensive list of serpins, both free and in complexes, deposited in the Protein Data Bank. Our discussion focuses on structures that potentially can contribute to a better understanding of polymer structure.

Amino Acid Sequence↗
PubMed2006

Proposed program guidelines for pregnant radiology residents: a project supported by the American Association for Women Radiologists and the Association of Program Directors in Radiology.

RATIONALE AND OBJECTIVES: Written institutional policies governing radiation exposure and work responsibilities for pregnant radiology residents are not uniform and often are nonexistent. Standardized program guidelines would allow residents and program directors alike to prepare for a resident pregnancy with objectivity and consistency. MATERIALS AND METHODS: The American Association for Women Radiologists (AAWR) launched a task force to revisit guidelines for the protection of pregnant residents from radiation exposure during training. We conducted two surveys of the Association of Program Directors in Radiology (APDR) membership. Survey 1 was designed to learn about existing program and institutional policies and to assess the need for and interest in standardized guidelines that would address radiation exposure and work responsibilities for pregnant radiology residents. Based on those responses, we drafted a set of program guidelines incorporating policies contributed by responding program directors. Our follow-up APDR survey, survey 2, was conducted to determine opinions and acceptance of the drafted program guidelines. Each survey was analyzed by using a proportion of means test. RESULTS: Fifty-five of 156 program director APDR members (35%) responded to survey 1. Only half the respondents had formal written policies at their respective institutions. Review of submitted policies showed widely divergent opinions about appropriate policies for pregnant radiology residents. Most (34/52; 75%) supported the development of standardized guidelines. In survey 2, 38/73 responding APDR members (53%) offered their opinions and comments on our drafted guidelines. Approximately 90% agreement was catalogued on 13 of 18 items (72%); a majority (>60%) agreed on all points, even the most controversial points concerning fluoroscopy. CONCLUSION: A minority of radiology residency programs have written policies addressing pregnancy during training. With expressed support from a majority of responding program directors, we have developed and present here proposed program guidelines for pregnant radiology residents to serve as a framework for radiology residents and program directors alike.

Data Collection↗
PubMed2005

Pregranulomatous phase of sarcoidosis: immunohistochemical diagnosis.

Histopathological confirmation of clinical suspicion of sarcoidosis is based on the finding of non-caseating granulomas in biopsy material, usually in prescalene lymph nodes or in transbronchial lung biopsies. Lymph node reactive sinus histiocytosis (RSH) seen in relation to various inflammatory and non-inflammatory diseases can mimic the pregranulomatous phase of sarcoidosis (PSH). Differentiation of sinus histiocytosis based on histopathological features alone is limited. The purpose of this study is immunohistochemical determination of lymph node cellular response in granulomatous sarcoidosis, the PSH and RSH using a immunohistochemistry employing a panel of antibodies. Patient groups under study each contained 25 patients and included: those with clinical picture of sarcoidosis and non-caseating granulomatous lymphadenitis; those with confirmed sarcoidosis and with sinus histiocytosis without granuloma formation in lymph nodes; and finally, those without sarcoidosis and with "reactive" sinus histiocytosis in lymph nodes. Lymph node biopsy tissue was fixed in buffered formaldehyde, routinely processed to paraffin wax blocks, cut into 4-microm-thick sections, stained with hematoxylin and eosin and immunohistochemically labelled using a triple-layer APAAP protocol with purified polyclonal antibodies directed against SP 70 and SP90 from Mycobacterium tuberculosis and monoclonal antibodies against CD22, CD4, CD8, CD56, and CD68. Intensity of immunolabelling was assessed semiquantitatively by two independent observers. An increased CD4:CD8 ratio, moderate increase of immunolabelling for CD68 and slight decrease in immunolabelling for CD20, CD56, and SP90 was indicative of PSH when compared with RSH. The most notable difference between the studied groups was a difference in immunoreactivity to SP70 and CD4 antibodies. Lymph nodes with pregranulomatous sinus histiocytosis labelled with both antibodies. This profile of immunolabelling can be used in the differentiation of this condition from reactive sinusoidal lesions.

Adolescent↗
PubMed2006

Evaluation of a novel anti-ischemic agent in acute coronary syndromes: design and rationale for the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-elevation acute coronary syndromes (MERLIN)-TIMI 36 trial.

BACKGROUND: Despite advances in antithrombotic therapies and invasive technology, the risk of recurrent ischemic complications in patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs) remains substantial. Ranolazine is a novel agent that inhibits the late sodium current thereby reducing cellular sodium and calcium overload and has been shown to reduce ischemia in patients with chronic stable angina. STUDY DESIGN: MERLIN-TIMI 36 is a phase III, randomized, double-blind, parallel-group, placebo-controlled, multinational clinical trial to evaluate the efficacy and safety of ranolazine during long-term treatment of patients with NSTE-ACS receiving standard therapy (N = 6500). Eligible patients are randomized 1:1 to ranolazine or matched placebo, initiated as 200 mg intravenously over 1 hour, followed by an 80-mg/h infusion (40 mg/h for patients with severe renal insufficiency) for up to 96 hours and oral ranolazine ER 1000 mg BID or matched placebo until the end of study. The primary end point is the time to first occurrence of any element of the composite of cardiovascular death, myocardial infarction, or recurrent ischemia. Secondary end points include ischemia on Holter monitoring, hospitalization for new or worsening heart failure, quality of life measures, and exercise performance. The evaluation of long-term safety will include death from any cause and symptomatic documented arrhythmia. Recruitment began in October 2004. The trial will continue until 730 major cardiovascular events and 310 deaths are recorded with expected completion in 24 to 28 months. CONCLUSIONS: MERLIN-TIMI 36 will evaluate the role of ranolazine in the acute and chronic management of patients presenting with NSTE-ACS.

Acetanilides↗
PubMed2006

Adjunctive therapy with low-molecular-weight heparin in patients with chronic heart failure secondary to dilated cardiomyopathy: one-year follow-up results of the randomized trial.

BACKGROUND: Defective endothelial function has been shown in dilated cardiomyopathy. Therefore, improvement in endothelial function after low-molecular-weight heparin (LMWH) therapy may be clinically beneficial. Consequently, the effect of adjunct enoxaparin, a LMWH, on standard treatment of dilated cardiomyopathy was investigated. METHODS: This was a randomized, standard treatment-controlled, 2-center pilot trial of 102 patients (52 receiving adjunctive therapy with enoxaparin at a dosage of 1.5 mg/kg daily for 3 months and 50 receiving standard therapy with angiotensin-converting enzyme inhibitors, beta-blockers, and diuretics alone) with stable chronic heart failure secondary to dilated cardiomyopathy (New York Heart Association [NYHA] class II and III; left ventricular [LV] ejection fraction, < or = 40%). All patients underwent coronary angiography and endomyocardial biopsy and were clinically stable for at least 6 months before enrollment. The combined primary end point included mortality, urgent heart transplantation, and readmission to hospital due to heart failure progression. The secondary end point was to determine the severity of heart failure (serum level of N-terminal brain natriuretic peptide), cardiac function (LV ejection fraction by radionuclide ventriculography), LV diameters by echocardiography, exercise capacity (changes in NYHA class, changes in peak oxygen consumption), and changes in quality of life (Minnesota Living with Heart Failure questionnaire). The clinical outcome was assessed after 6 and 12 months of therapy. RESULTS: Baseline characteristics were comparable in both groups. Five patients dropped out during 12 months of the study. Twelve patients achieved primary end point (8 in the control group and 4 in the LMWH group). The free survival rate was 94% for the LMWH group and 90% for the controls (not statistically significant). After the 12-month period, in the LMWH group, N-terminal brain natriuretic peptide level and LV diameters decreased significantly (P < .001 and P = .006, respectively), whereas LV systolic function increased (P < .001). Changes in exercise capacity and subjective improvement did not differentiate the groups (nonsignificant). Adverse reactions to the enoxaparin therapy were minor and transient. CONCLUSIONS: In patients with chronic heart failure due to dilated cardiomyopathy, adjunct long-term enoxaparin therapy may offer additional clinical benefit without deleterious effects on major cardiac events.

Adult↗