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PubMed1996

Reduced Left Ventricular Contractile Reserve Identified by Low Dose Dobutamine Echocardiography as an Early Marker of Cardiac Involvement in Asymptomatic Patients with Thalassemia Major.

Patients with beta thalassemia major present with severe anemia and need continuous transfusion therapy. The consequent iron overload leads to hemochromatosis. Initial cardiac involvement can be present in thalassemic patients without clinical manifestations of heart failure. The purpose of this study was to assess the contractile reserve of the left ventricle in patients with normal baseline two-dimensional (2-D) echocardiographic findings using low dose dobutamine echocardiography. The underlying hypothesis was that, at an early stage, structural impairment of the myocardial wall due to myocardial iron deposits and/or secondary fibrotic changes could be so subtle so as not to impair resting systolic function, but is severe enough to blunt or even exhaust the contractile response to inotropic stimulation. Twenty-four consecutive patients (13 men and 11 women; ages 18 +/- 3.8 years) with beta thalassemia major undergoing evaluation for bone marrow transplantation entered the study. By selection, all were asymptomatic, without clinical signs of cardiac failure, and had normal regional and global systolic function at baseline echocardiographic study. A control group of 16 age and sex matched subjects was also studied. All underwent baseline, 2-D, and Doppler study, as well as dobutamine stress (up to 5 &mgr;g/kg per min) 2-D echocardiographic study. Patients and controls showed comparable values of indexes of global (ejection fraction: 0.64 +/- 0.06 vs 0.65 +/- 0.05, P = NS) and regional (systolic thickening of posterior wall: 90 +/- 34 vs 91 +/- 34%, P = NS) function at baseline. Left ventricular diastolic filling was evaluated with Doppler echocardiography. Peak flow velocity in early diastole was increased in thalassemic patients compared to controls (114 +/- 16 vs 96 +/- 18 cm/sec, P < 0.01), and flow velocity deceleration time was reduced (139 +/- 17 vs 157 +/- 20 msec, P < 0.01). At peak dobutamine, thalassemic patients showed a blunted contractile response compared to controls for indexes of both global (ejection fraction: 0.62 +/- 0.06 vs 0.69 +/- 0.05, P < 0.01) and regional (% systolic thickening of posterior wall: 91 +/- 36 vs 130 +/- 39%, P < 0.01) function. When individual patient analysis was performed, echocardiographic parameters were beyond the 95% confidence limits obtained from normal controls in 5 (21%) of the 24 study patients by one or more Doppler diastolic indexes, in 6 (25%) by indexes of contractile reserve, and in 11 (46%) by one of either diastolic function or contractile reserve indexes. These data demonstrate that the "iron heart" of asymptomatic thalassemic patients is a weak heart. Even if the regional and global systolic functions are similar to normals under resting conditions, the application of an inotropic challenge unmasks the weakness of these hearts, which can be identified at an earlier stage of their natural history through the blunted contractile response following the infusion of low dose dobutamine. The information on contractile reserve is not redundant, but rather incremental and in addition to that provided by Doppler echocardiographic indexes, which may be abnormal in these patients. (ECHOCARDIOGRAPHY, Volume 13, September 1996)

Journal Article↗

PubMed2004

Prognostic value of the Tei index combining systolic and diastolic myocardial performance in patients with acute myocardial infarction treated by successful primary angioplasty.

Cardiac systolic (left ventricular ejection fraction) and diastolic (mitral inflow velocity pattern and/or mitral deceleration time) function were reported as predictors of clinical outcome or left ventricular remodeling in patients with acute myocardial infarction (AMI). Recently, a new index (Doppler-derived index combining systolic and diastolic myocardial performance; Tei index) for combined systolic and diastolic ventricular function has been reported to be a useful and convenient method for evaluation of global ventricular function. We therefore investigated the usefulness of the Tei index by echocardiography for evaluation of infarct size and clinical outcome in patients with AMI treated by successful primary angioplasty. We analyzed 10 age-matched control subjects and 43 consecutive patients with first AMI treated by successful primary angioplasty. The Tei index of the AMI patients was significantly greater than that of the control subjects (0.630 +/- 0.106 vs 0.375 +/- 0.036, P << 0.0001). Also, the Tei index showed a significant positive correlation with peak creatine kinase values and (99m)Tc-tetrofosmin scores. Moreover, multiple logistic regression analysis showed that the Tei index >>0.70 ( P = 0.0313, odds ratio = 14.14) was the only significant explanatory factor for cardiac death or developed congestive heart failure. The Tei index combining systolic and diastolic myocardial performance reflects infarct size and might be a predictor of clinical outcome in patients with AMI treated by successful primary angioplasty.

Angioplasty, Balloon, Coronary↗

PubMed2004

The crucial role of sustained attention in community functioning in outpatients with schizophrenia.

The aim was to explore the pattern of associations between visual cognitive performance and community functioning in a sample of outpatients with schizophrenia participating in a rehabilitation program. Visuo-spatial tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were administered to assess cognitive performances in 88 subjects. The Multnomah Community Ability Scale (MCAS) was used to measure dimensions of community functioning. Our results showed that the sustained attention score was significantly associated with the global community functioning score and with two specific dimensions: "adjustment to living" and "behavioral problems". No association was found between other cognitive indices and MCAS scores. Since the sustained attention task mainly involves the executive component of working memory, these findings suggest that attentional control processes are limiting factors for community functioning in schizophrenia outpatients. Measures of such processes could serve as key indices of disability in clinical practice. Attention and working memory training may be helpful to improve community functioning in subjects with schizophrenia.

Adult↗

PubMed1996

A comparison of left ventricular myocardial velocity in diastole measured by magnetic resonance and left ventricular filling measured by Doppler echocardiography.

Abnormal diastolic left ventricular function is an early marker for myocardial disease and may be impaired even when global systolic function is normal. Subendocardial function is affected early in ischaemic heart disease and by altering left ventricular long axis motion, may contribute to abnormal transmitral pressure gradients. Regional myocardial long axis velocity in diastole measured by magnetic resonance was compared with left ventricular filling measured by Doppler echocardiography in 25 patients with coronary artery disease. Fifteen patients also underwent magnetic resonance assessment at the time of onset of early diastolic blood flow. The onset of diastolic long axis velocity preceded flow across the mitral valve by a mean of 46 ms. Mean long axis myocardial velocity correlated with peak early filling velocity (E) (r = 0.73, P < 0.001), early deceleration (r = -0.73, P < 0.001), and the early to late filling ratio (E/A) ratio (r = 0.6, P < 0.01). Maximum myocardial long axis velocity also correlated with peak early filling velocity (r = 0.56, P < 0.01), early deceleration rate (r = 0.63, P < 0.001), and the E/A ratio (r = 0.53, P < 0.01). The variability of long axis velocity around the ventricle correlated inversely with peak early filling, (r = -0.7, P < 0.001), early deceleration (r = -0.56, P < 0.01), and the E/A ratio (r = -0.48, P < 0.02). Peak atrial filling velocity did not correlate with any measure of long axis myocardial velocity. We conclude that early diastolic long axis myocardial velocity has a significant effect on left ventricular filling.

Adult↗

PubMed1999

The rpoS-dependent starvation-stress response locus stiA encodes a nitrate reductase (narZYWV) required for carbon-starvation-inducible thermotolerance and acid tolerance in Salmonella typhimurium.

The starvation-stress response (SSR) of Salmonella typhimurium includes gene products necessary for starvation avoidance, starvation survival and virulence for this bacterium. Numerous genetic loci induced during carbon-source starvation and required for the long-term-starvation survival of this bacterium have been identified. The SSR not only protects the cell against the adverse effects of long-term starvation but also provides cross-resistance to other environmental stresses, e.g. thermal challenge (55 degrees C) or acid-pH challenge (pH 2.8). One carbon-starvation-inducible lac fusion, designated stiA was previously reported to be a sigma(S)-dependent SSR locus that is phosphate-starvation, nitrogen-starvation and H2O2 inducible, positively regulated by (p)ppGpp in a relA-dependent manner, and negatively regulated by cAMP:cAMP receptor protein complex and OxyR. We have discovered through sequence analysis and subsequent biochemical analysis that the stiA::lac fusion, and a similarly regulated lac fusion designated sti-99, lie at separate sites within the first gene (narZ) of an operon encoding a cryptic nitrate reductase (narZYWV) of unknown physiological function. In this study, it was demonstrated that narZ was negatively regulated by the global regulator Fnr during anaerobiosis. Interestingly, narZ(YWV) was required for carbon-starvation-inducible thermotolerance and acid tolerance. In addition, narZ expression was induced approximately 20-fold intracellularly in Madin-Darby canine kidney epithelial cells and 16-fold in intracellular salts medium, which is believed to mimic the intracellular milieu. Also, a narZ1 knock-out mutation increased the LD50 approximately 10-fold for S. typhimurium SL1344 delivered orally in the mouse virulence model. Thus, the previously believed cryptic and constitutive narZYWV operon is in fact highly regulated by a complex network of environmental-stress signals and global regulatory functions, indicating a central role in the physiology of starved and stressed cells.

Amino Acid Sequence↗

PubMed2003

A systematic review of exercise trials post stroke.

OBJECTIVE: To perform a systematic review of exercise trials post stroke. DESIGN: A systematic review of controlled clinical trials. SEARCH STRATEGY: MEDLINE, EMBASE, CINAHL, Amed, Sports Discus, Cochrane controlled trials register and PEDro were searched for relevant trials. INCLUSION CRITERIA: Studies--randomized or quasi-randomized controlled clinical trials. Participants--Adults of any age with a clinical diagnosis of stroke. Interventions--Any cardiovascular exercise intervention aimed at improving cardiovascular fitness and/or function. OUTCOMES: Impairment: gait speed, strength, endurance, balance, flexibility, tonus and exercise capacity. Disability: global dependency, functional independence. Extended activities of daily living. Quality of life. Death. DATA COLLECTION AND ANALYSIS: Two independent reviewers categorized selected trials, documented the methodological quality and extracted the relevant data. Comparisons of cardiovascular exercise interventions versus no cardiovascular intervention were made. Statistical comparisons were carried out using a random effects model to calculate standardized mean differences. RESULTS: We identified three eligible trials. Small numbers and heterogeneous outcomes limited the analyses and comparisons. Based on the limited data available, we found that cardiovascular exercise post stroke was no better than no exercise with respect to disability, impairment, extended activities of daily living, quality of life and death. CONCLUSION: Insufficient evidence was identified to establish if cardiovascular exercise has a positive effect on disability, impairment, extended activities of daily living, quality of life and case fatality post stroke.

Activities of Daily Living↗

PubMed1988

Effects of long term treatment with pinacidil and nifedipine on left ventricular anatomy and function in patients with mild to moderate systemic hypertension.

Hypertrophy of the left ventricle in hypertension is associated with an increased risk of morbidity and mortality. Thus, the prevention of and regression of left ventricular hypertrophy should be essential goals of antihypertensive treatment. Some commonly used antihypertensive drugs do not have this ability, despite achieving adequate blood pressure control. In a double-blind randomised parallel group study, we evaluated the effects of adjunctive long term therapy with either pinacidil or nifedipine on blood pressure and left ventricular function and anatomy (echocardiography) in 22 patients with a diastolic blood pressure above 95mm Hg who were already receiving bendrofluazide 5mg daily. Pinacidil reduced left ventricular mass from 326.3 +/- 126.2g to 251.2 +/- 114.6g (p less than 0.001) compared with nifedipine, which reduced ventricular mass from 293.6 +/- 35.7g to 267.3 +/- 34.7 (p = 0.04). In this respect, pinacidil was more effective than nifedipine (p = 0.013). Pinacidil improved left ventricular diastolic function, measured by the isovolumetric relaxation time, whereas nifedipine did not affect this parameter. Global systolic function was little affected by either drug. However, the end systolic wall stress was significantly reduced by both therapeutic regimens. Pinacidil may, therefore, be a potentially valuable antihypertensive drug.

Aged↗

PubMed1993

Mitochondrial dysfunction in alcoholic patients as assessed by breath analysis.

Mitochondria of patients with alcoholic liver disease are morphologically abnormal, and mitochondria isolated from animals exposed to ethanol exhibit functional deficiencies in vitro. Because the functional consequences of the morphological alterations and the relevance of in vitro observations to mitochondrial function in alcoholic subjects are not clear, we assessed mitochondrial function noninvasively with a breath test. Mitochondrial function was assessed by measuring the exhalation of 14CO2 after administration of 1 microCi 2-keto[1-14C]isocaproic acid, the decarboxylation of which occurs in mitochondria. The results of the 2-keto[1-14C]isocaproic acid breath test in 17 alcoholic subjects were compared with the results in healthy controls and patients with nonalcoholic liver disease. The peak exhalation of 14CO2 and the fraction of the administered dose decarboxylated in 60 min were significantly lower in alcoholic patients than in healthy controls or patients with nonalcoholic liver disease. In alcoholic patients 2-keto[1-14C]isocaproic acid decarboxylation was impaired in the presence of normal conventional and quantitative liver function as assessed by aminopyrine breath test and galactose elimination capacity, indicating that 2-keto[1-14C]isocaproic acid decarboxylation does not simply reflect decreased functional liver mass. We conclude that mitochondrial function as reflected by 2-keto[1-14C]isocaproic acid decarboxylation is impaired in chronic alcoholic patients. The functional impairment is specific for excessive ethanol consumption and not a reflection of decreased global liver function or the presence of cirrhosis. 2-Keto[1-14C]isocaproic acid decarboxylation could thus be useful as a marker of excessive ethanol consumption.

Adult↗

PubMed1987

Evaluation of intraoperative transesophageal two-dimensional echocardiography.

Transesophageal two-dimensional echocardiography (TEE) was evaluated in 11 patients who underwent myocardial revascularization. The TEE transducer was positioned to view the left ventricular (LV) short-axis at the level of the papillary muscles (midcavity). Good quality echocardiographic images were obtainable in ten of 11 patients. Global LV function was assessed by measuring LV end-diastolic and end-systolic area and computing the fractional area change (FAC). Measurements of LV areas and FAC had excellent intraobserver reproducibility. Regional LV function was analyzed in two ways after dividing the short-axis view of the LV into four or five anatomic segments. Systolic wall thickening (SWT) of the myocardium was measured in each of four segments by digitization of the endocardial and epicardial borders of the LV and determining the fractional wall thickening. Measurements of SWT were not reproducible, primarily because of a difficulty in delineating the epicardial border of the LV accurately. In the second method, regional wall motion (RWM) in each of five segments was graded according to a previously developed scoring system. RWM analysis proved to be a measurement with excellent interobserver and intraobserver reproducibility. TEE was performed without complication and found to be a reproducible method for assessing global and regional LV function. Quantitative analysis is tedious and, therefore, currently not available on-line in the operating room.

Echocardiography↗

PubMed2006

Assessment of global and regional left ventricular function and volumes with 64-slice MSCT: a comparison with 2D echocardiography.

BACKGROUND: In patients with coronary artery disease (CAD), LV function and volumes are important parameters for long-term prognosis. Multislice computed tomography (MSCT) allows noninvasive assessment of the coronary arteries, but the accuracy of 64-slice MSCT for the assessment of left ventricular (LV) volumes and function is unknown. METHODS AND RESULTS: A head-to-head comparison between 64-slice MSCT and 2-dimensional (2D) echocardiography was performed in 40 patients with known or suspected CAD. The LV end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV) were determined and the LV ejection fraction (LVEF) was derived. Regional wall motion was assessed visually using a 17-segment model. A 3-point scoring system was used to assign to each segment a wall motion score: 1 = normokinesia, 2 = hypokinesia, 3 = akinesia or dyskinesia. Two-dimensional echocardiography served as the gold standard. MSCT agreed well with 2D echocardiography for assessment of LVEDV (r = 0.97; p < .0001) and LVESV (r = 0.98; p < .0001). An excellent correlation between MSCT and 2D echocardiography was shown for the evaluation of LVEF (r = 0.91; p < .0001). Agreement for the assessment of regional wall motion was excellent (96%, kappa = 0.82). CONCLUSIONS: An accurate assessment of global and regional LV function and volumes is feasible with 64-slice MSCT.

Coronary Artery Disease↗

PubMed2001

Selective tracheal gas insufflation during partial liquid ventilation improves lung function in an animal model of unilateral acute lung injury.

OBJECTIVE: During unilateral lung injury, we hypothesized that we can improve global lung function by applying selective tracheal gas insufflation (TGI) and partial liquid ventilation (PLV) to the injured lung. DESIGN: Prospective, interventional animal study. SETTING: Animal laboratory in a university hospital. SUBJECTS: Adult mixed-breed dogs. INTERVENTIONS: In six anesthetized dogs, left saline lung lavage was performed until PaO(2)/FiO(2) fell below 100 torr (13.3 kPa). The dogs were then reintubated with a Univent single-lumen endotracheal tube, which incorporates an internal catheter to provide TGI. In a consecutive manner, we studied 1) the application of 10 cm H(2)O of positive end-expiratory pressure (PEEP); 2) instillation of 10 mL/kg of perflubron (Liquivent) to the left lung at a PEEP level of 10 cm H(2)O (PLV+PEEP 10 initial); 3) application of selective TGI (PLV+TGI) while maintaining end-expiratory lung volume (EELV) constant; 4) PLV+TGI at reduced tidal volume (VT); and 5) PLV+PEEP 10 final. MEASUREMENTS AND MAIN RESULTS: Application of PLV+PEEP 10 initial did not change gas exchange, lung mechanics, or hemodynamics. PLV+TGI improved PaO(2)/FiO(2) from 189 +/- 13 torr (25.2 +/- 1.7 kPa) to 383 +/- 44 torr (51.1 +/- 5.9 kPa) (p <.01) and decreased PaCO(2) from 55 +/- 5 torr (7.3 +/- 0.7 kPa) to 30 +/- 2 torr (4.0 +/- 0.3 kPa) (p <.01). During ventilation with PLV+TGI, reducing VT from 15 mL/kg to 3.5 mL/kg while keeping EELV constant decreased PaO(2)/FiO(2) to 288 +/- 49 torr (38.4 +/- 6.5 kPa) (not significant) and normalized PaCO(2). At this stage, end-inspiratory plateau pressure decreased from 19.2 +/- 0.7 cm H(2)O to 13.6 +/- 0.7 cm H(2)O (p <.01). At PLV+PEEP 10 final, measurements returned to those observed at previous baseline stage (PLV+PEEP 10 initial). CONCLUSIONS: During unilateral lung injury, PLV with a moderate PEEP did not improve oxygenation, TGI superimposed on PLV improved gas exchange, and combination of TGI and PLV allowed a 77% reduction in VT without any adverse effect on PaCO(2).

Animals↗

PubMed2006

The use of myocardial contrast echocardiography in the assessment of left ventricular function recovery after primary percutaneous coronary intervention in the setting of acute myocardial infarction.

BACKGROUND: Despite successful reperfusion therapy of acute myocardial infarction and complete restoration of infarct-related artery patency, the improvement of systolic function in long-term outcome depends on preserved microvasculature integrity. Myocardial contrast echocardiography (MCE) is a useful technique for identification of viable myocardium. AIM: To assess the value of real-time myocardial contrast echocardiography (rt-MCE) in prediction of left ventricular function improvement in patients with anterior wall acute myocardial infarction as well as selection of the optimal cut-off value for the number of dysfunctional segments with preserved complete perfusion, in order to predict the global left ventricular function improvement during one-month observation. METHODS: Rt-MCE was performed in 74 patients (50 men, aged 58+/-11 years) with anterior wall myocardial infarction, treated with primary percutaneous coronary intervention (PCI) within 12 hours from the onset of symptoms. After estimation of regional contractility disturbances and global systolic function of the left ventricle, rt-MCE was performed with contrast assessment of dysfunctional segments (normal contrast pattern=2, heterogeneous=1, lack of contrast=0). Regional perfusion score index (RPSI) was calculated by adding the perfusion indices and dividing by the number of dysfunctional segments. RESULTS: Of a total of 1184 visualised segments, 344 (29.1%) were dysfunctional (189 hypokinetic, 155 akinetic). Contractility improvement was observed in 192 segments (preserved viability in 105 hypokinetic and 37 akinetic segments). In a group of 44 patients with systolic function improvement, 34 of them had preserved viability, and in a group of 30 patients without LVEF improvement, in 22 of them myocardium viability was not observed. Sensitivity, specificity and accuracy of rt-MCE in prediction of left ventricular global improvement were 72.7%, 73.3% and 73%, respectively, whereas in prediction of regional function improvement these values were 73.9%, 77% and 75.5%, respectively. CONCLUSION: Rt-MCE performed in the early phase of myocardial infarction enables the prediction of left ventricular regional and global function improvement in patients treated with primary PCI.

Aged↗

PubMed1985

Gated blood pool scintigraphy as a tool for non-invasive measurements of left ventricular function.

Gated Blood Pool Scintigraphy (GBPS), i.e. the noninvasive evaluation of ventricular performance following the administration of radionuclides as intravascular tracers has had a major impact on many aspects of cardiology and has proven its clinical value and reliability in the past years. Today it is an accepted method in clinical practice, permitting the assessment of both global and regional cardiac function. The most important parameters derived from GBPS volume curves for the determination of left ventricular global function are ejection fraction (EF) at rest and under exercise and peak filling rate of the left ventricle at rest. In addition, GBPS permits the assessment of regional left ventricular function by determining regional EF and phase shifts. Echocardiography is no true alternative to GBPS due to frequent problems in quantitative evaluation and unpredictable errors in patients with non-uniform heart geometry or dyskinetic left ventricles. Thus, GBPS is not only useful in a wide variety of clinical settings, but has become an accepted tool in the methodological approach for non-invasive evaluation of new drugs and sequential drug therapy monitoring. This application of GBPS can be particularly recommended for the investigation of two different problems: a) exclusion of adverse drug effects on left ventricular performance in the process of drug safety evaluation, and b) demonstration of hemodynamic effects of new drugs particularly after long-term medication. GBPS provides valuable information as to the type, onset and duration of hemodynamic changes, permitting the determination of regional changes in myocardial function as well as its global evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Disease↗

PubMed1994

Measurement of global and regional left ventricular function by cardiac PET.

UNLABELLED: To permit assessment by positron tomography of left ventricular mechanical function, methods were developed to measure ejection fraction and regional wall motion and produce realistic images of the beating heart from ECG-gated PET data. METHODS: Following red cell labeling with 15O-carbon monoxide, seven-slice PET data were collected in list mode and reformatted into 16 time frames. Volume-rendered cine images were created by the depth-weighted maximum-activity method. To determine the left ventricular ejection fraction, background was subtracted in voxels outside the heart and the cubic datasets were rotated to the angle with the best septal separation. Depth weighting was applied to stimulate a 99mTc study, and the beating images were rendered by summing counts along parallel projection rays. These techniques were validated in 16 patients by comparison with planar studies performed with 99mTc-red cells. RESULTS: Visual grading of regional wall motion yielded exact agreement between the PET and 99mTc methods in 62% of walls with agreement with one grade in 94%. Assessment of quantitative regional wall motion agreed closely with an independent threshold edge detection method. CONCLUSION: PET techniques have been developed to measure left-ventricular ejection fraction and regional wall motion and to produce realistic beating images of the cardiac blood pool. This information can be obtained at the same time as measurements of perfusion and metabolism and in the same spatial orientation, thereby permitting quantitative assessment by positron tomography of global and regional mechanical function in relation to flow and metabolism.

Adult↗

PubMed1996

Neuropsychological profiles of three sisters homozygous for the fragile X premutation.

Fragile X syndrome (fraX) is associated with an amplification of a CGG repeat within the fraX mental retardation (FMR-1) gene. We describe an exceptional family in which 3 adult sisters are homozygous for the FMR-1 premutation. Each sister inherited 2 premutation alleles (ca. 80 CGG repeats) from their biologically unrelated parents. The 3 sisters were administered measures of executive function, visual spatial, memory, and verbal skills. Deficiencies in the first 2 of these domains have been reported among females with the full mutation. The sisters' performances were compared with available normative data and with published group means for females affected by fraX. These women did not appear to have verbal or memory difficulties. None of the women demonstrated a global executive function deficit, and none had global deficits in spatial ability. The profiles of these sisters are consistent with reports that the fragile X premutation does not affect cognitive performance.

Adult↗

PubMed2004

The Arabidopsis thaliana chloroplast proteome reveals pathway abundance and novel protein functions.

BACKGROUND: Chloroplasts are plant cell organelles of cyanobacterial origin. They perform essential metabolic and biosynthetic functions of global significance, including photosynthesis and amino acid biosynthesis. Most of the proteins that constitute the functional chloroplast are encoded in the nuclear genome and imported into the chloroplast after translation in the cytosol. Since protein targeting is difficult to predict, many nuclear-encoded plastid proteins are still to be discovered. RESULTS: By tandem mass spectrometry, we identified 690 different proteins from purified Arabidopsis chloroplasts. Most proteins could be assigned to known protein complexes and metabolic pathways, but more than 30% of the proteins have unknown functions, and many are not predicted to localize to the chloroplast. Novel structure and function prediction methods provided more informative annotations for proteins of unknown functions. While near-complete protein coverage was accomplished for key chloroplast pathways such as carbon fixation and photosynthesis, fewer proteins were identified from pathways that are downregulated in the light. Parallel RNA profiling revealed a pathway-dependent correlation between transcript and relative protein abundance, suggesting gene regulation at different levels. CONCLUSIONS: The chloroplast proteome contains many proteins that are of unknown function and not predicted to localize to the chloroplast. Expression of nuclear-encoded chloroplast genes is regulated at multiple levels in a pathway-dependent context. The combined shotgun proteomics and RNA profiling approach is of high potential value to predict metabolic pathway prevalence and to define regulatory levels of gene expression on a pathway scale.

Arabidopsis↗

PubMed1986

Toward a better understanding of the etiology of left ventricular dysfunction after mitral valve replacement: an experimental study with possible clinical implications.

The relatively high morbidity and mortality of mitral valve replacement (MVR) appears to be related to an impairment in left ventricular (LV) function. This two-part investigation was designed to assess the effect of MVR on global LV function in an isolated heart preparation and to evaluate whether a mitral prosthesis with a flexible annulus would be of benefit. In Part I (14 pigs), the effects of each step in MVR were studied. Division of the chordae tendineae caused a severe deterioration in LV function (systolic pressure, 180 +/- 13 versus 120 +/- 10 mm Hg; p less than 0.05; developed pressure, 167 +/- 13 versus 108 +/- 11 mm Hg; p less than 0.05; first derivative of LV pressure [dP/dt], 2,630 +/- 300 versus 1,610 +/- 180 mm Hg/sec; p less than 0.05; balloon volume, 30 ml). Fixation of the mitral annulus prior to division of the chordae tendineae resulted in a small decrease (not significant) in LV function but had no effect after the chordae tendineae were divided. In Part II (10 pigs), two mitral annular prostheses were studied: a standard rigid prosthesis and a prosthesis of identical size but with a flexible annulus. LV function was better with the flexible than the rigid prosthesis (systolic pressure, 118 +/- 10 versus 89 +/- 5% control, p less than 0.02; developed pressure, 120 +/- 11 versus 87 +/- 5% control; p less than 0.02; dP/dt, 119 +/- 10 versus 85 +/- 4% control; p less than 0.02; balloon volume, 30 ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2001

Retrograde cerebral perfusion during thoracic aortic surgery and late neuropsychological dysfunction.

OBJECTIVE: Retrograde cerebral perfusion (RCP) is commonly used in thoracic aortic surgery, ostensibly to provide metabolic support, maintain cerebral hypothermia and/or wash out particulate emboli. We tested the hypothesis that RCP would affect neuropsychological outcome in a clinical cohort. METHODS: Ninety-four patients undergoing elective thoracic aortic repairs requiring deep hypothermic circulatory arrest consented to participate in this study. These patients underwent preoperative neuropsychological evaluation and comprise the reference group. Fifty-six of these patients also underwent neuropsychological evaluation several weeks postoperatively, 12 of whom (21%) had RCP. The neuropsychological domains tested were attention, processing speed, memory, executive function, and fine motor function. A global assessment of impairment, negative neuropsychological outcome (NNO), was defined as a postoperative decrease in function in two or more neuropsychological domains for patients with at least three domains tested both pre- and postoperatively (n=48). The relationship of three potential predictors (RCP, cerebral ischemia time and patient age) to negative outcomes was analyzed using Wilcoxon two-sample tests, chi(2) tests, Mantel-Haenszel tests and multiple logistic regression. P<0.05 was considered significant. RESULTS: Memory dysfunction and NNO had strong associations with RCP. This effect remained significant when controlling separately for age and cerebral ischemia time. CONCLUSIONS: The effects of RCP are difficult to distinguish from those of age and prolonged cerebral ischemia time, because complex thoracic aortic repairs are associated with advanced age, prolonged cerebral ischemia and use of RCP. Despite this limitation, these preliminary data indicated that RCP had no beneficial effect (and most likely a negative effect) upon cognitive outcome.

Adult↗