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PubMed1981

"Abnormal" responses of ejection fraction to exercise, in healthy subjects, caused by region-of-interest selection.

We performed serial exercise equilibrium radionuclide angiography in eight normal subjects with each subject executing three tests: control, after nitroglycerin, and after propranolol. The left-ventricular ejection fraction (EF) was calculated by two methods: (a) fixed region-of-interest (FROI) using a single end-diastolic ROI, and (b) variable region-of-interest (VROI) where an end-diastolic and end-systolic region of interest were used. Abnormal maximal EF responses occurred in five of eight subjects during control using FROI but in zero of eight employing VROI (p < 0.05). After nitroglycerin, three of eight subjects had abnormal responses by FROI, but zero of eight were abnormal by VROI (p < 0.05). After propranolol, blunted EF responses occurred in three of seven by both methods. Falsely abnormal EF responses to execrise RNA may occur due to the method of region-of-interest selection in normal subjects with normal or high ejection fractions.

Adult↗

PubMed1985

Effect of long-term oral nifedipine therapy on left ventricular regional wall function at rest and during supine bicycle exercise.

15 patients, 1 to 3 year after coronary bypass surgery, underwent symptom limited supine bicycle exercise tests without nifedipine and after acute and chronic (3 months) administration of the drug. Haemodynamic variables were monitored as was epicardial marker motion, using biplane cineradiography during exercise, the markers having been implanted at the time of surgery. We found significant (P less than 0.001) reductions in end-diastolic and end-systolic regional dimensions at maximal exercise after oral nifedipine, associated with a significant reduction in exertional angina, which persisted during long-term treatment. No adverse effects of the drug were observed.

Administration, Oral↗

PubMed1988

Substrate regulation of the nucleotide pool during regional ischaemia and reperfusion in an isolated rat heart preparation: a phosphorus-31 magnetic resonance spectroscopy analysis.

Isolated rat heart preparations were studied to characterise the alterations in high energy phosphates that occur during reversible regional ischaemia and to determine whether pyruvate, as the sole exogenous energy substrate, would attenuate the ischaemia induced depletion of the nucleotide pool when compared with glucose. Using phosphorus-31 magnetic resonance spectroscopy baseline concentrations of adenosine triphosphate, phosphocreatine, inorganic phosphate, and intracellular pH were compared with values during 30 min of left coronary artery occlusion followed by 30 min of reperfusion. These variables were related to changes in developed pressure, coronary flow, and oxygen consumption. In addition, the total nucleotide pool was evaluated by biochemical analysis of myocardial tissue extracts and coronary effluent. The ischaemic region was characterised by a dye staining technique and cross sectional echocardiographic measurements of regional myocardial wall thinning. In both glucose and pyruvate perfused groups, coronary flow and oxygen consumption decreased to 50-60% of control within 1 min of ischaemia and returned to baseline values with reflow. Developed pressure decreased to 50(9) and 74(8)% (mean(SEM] of control after 30 min of ischaemia in glucose and pyruvate perfused groups respectively. Reperfusion resulted in complete recovery of developed pressure in hearts perfused with pyruvate but not in the glucose group. Glucose perfused hearts had a greater decrease in intracellular pH during ischaemia (7.07(0.01) to 6.36(0.1] than pyruvate perfused hearts (7.06(0.02) to 6.83(0.04]. Reperfusion resulted in a rapid return to baseline intracellular pH in both groups. During ischaemia, adenosine triphosphate values decreased to a greater degree in glucose than in pyruvate perfused hearts (57(4) and 79(5)% of baseline respectively). Thirty minutes of reperfusion did not significantly improve adenosine triphosphate concentrations in either group. Phosphocreatine concentrations decreased to 52(7) and 75(6)% of baseline in glucose and pyruvate perfused groups respectively after the ischaemic period. Reperfusion resulted in normalisation of phosphocreatine values in the pyruvate but not in the glucose perfused group. Biochemical analysis of myocardial tissue extracts confirmed the spectroscopy data and showed that pyruvate inhibits the efflux of adenine nucleotide derivatives. Tissue concentrations of adenosine monophosphate were three times greater and adenosine 50% less after 30 min of ischaemia in the pyruvate perfused group.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Evaluation of factors influencing myocardial infarct size in unconscious dogs.

STUDY OBJECTIVE: The aim was to evaluate the factors determining myocardial infarct size in unconscious dogs. DESIGN: In anaesthetised open chest dogs, the left anterior descending coronary artery was occluded either by ligation or by thrombosis for different time periods (1.5 h, 4 h, 24 h), with or without reperfusion. Haemodynamic variables were recorded throughout the experiment. Radioactive microspheres (15 microns) were injected at the end of the ischaemic period to measure regional myocardial blood flow. Infarct size and area at risk were determined by the Evans blue triphenyltetrazolium staining technique followed by planimetry. SUBJECTS: Mongrel dogs of either sex (n = 16-42 per experiment), weight 18-25 kg, were used. MEASUREMENTS AND MAIN RESULTS: A large interindividual variability in infarct size was observed after occlusion of the left anterior descending coronary artery at a standardised location for a well defined period. An examination of the factors responsible for this variability was carried out in order to develop a statistical model which would make it possible to predict infarct size. Using multiple regression analysis, it was found that in most protocols (except 90 min thrombosis) more than 85% of the variability in infarct size could be explained by the size of the area at risk and the amount of collateral flow. Thus, knowing the area at risk and the collateral flow, a fairly accurate prediction can be made of the size of the infarct that the dog will develop after a defined occlusion period. Furthermore, it was found that the infarct size increased with duration of occlusion, while duration of reperfusion had no effect. In the 90 min occlusion group thrombosis induced a larger final infarct than ligature. CONCLUSIONS: A correction for baseline variables is necessary in order to compare infarct size between experimental groups. The usefulness of this procedure is shown by an example of an experimental intervention, i.e., R 56,865, a drug with known cardioprotective effects.

Animals↗

PubMed1991

Early restoration of cardiac function in hearts with acute regional ischaemia. The importance of beta-adrenergic stimulation.

The effects of acute coronary artery occlusion in anaesthetized cats has been studied with regard to changes in cardiac function and regional myocardial blood flow. Occlusion of the left anterior decending coronary artery (LAD) is followed by a rapid reduction of peak systolic blood pressure (LVSP) and contractility (dP/dt) and increased left ventricular end-diastolic pressure (LVEDP). Five minutes after coronary occlusion heart rate, LVSP, and (dP/dt) was reduced and LVEDP increased. Global cardiac function measured by these variables was gradually restored to preocclusion values; LVSP after 10 min., heart rate and dP/dt after 20 min. After 40 and 60 min these variables were stable at preocclusion levels. LVEDP remained permanently elevated. In hearts with regional ischaemia and paced heart rate global cardiac function was mainly restored 20 min after coronary occlusion except for increased LVEDP, both in cats pretreated with non-selective beta-adrenergic blockade (propranolol) and in unblocked cats. In general, blood flow in non-ischaemic myocardium adjacent to the ischaemic region increased following coronary occlusion, although not significantly in the endocardium. The endocardial/epicardial blood flow ratio was stable in unblocked hearts and was reduced in beta-blocked hearts. In normally perfused myocardium remote from the ischaemic region, blood flow increased following occlusion both in beta-blocked and unblocked cats, most pronounced in the epicardium; the endo/epicardial blood flow ratio decreased.

Adaptation, Physiological↗

PubMedDate not supplied

Quantitative assessment of regional right ventricular myocardial velocities in awake dogs by Doppler tissue imaging: repeatability, reproducibility, effect of body weight and breed, and comparison with left ventricular myocardial velocities.

Right ventricular myocardial (RVM) motion is poorly documented. The objective of this study was to determine the variability of RVM velocities by tissue Doppler imaging (TDI) in healthy dogs (study 1), to analyze RVM motion in a large healthy canine population (study 2), and to compare the results with those obtained for the left ventricular free wall. Six healthy Beagle Dogs were monitored in study 1, and 64 healthy dogs of 14 different breeds were monitored in study 2. Velocities were recorded in 2 segments (basal and apical) of the right and left myocardial walls. In study 1, 36 TDI examinations were performed for 4 days, whereas a single TDI examination was performed on each dog in study 2. All velocity profiles included 1 positive systolic wave and 2 negative diastolic waves. The lowest intraday and interday coefficient of variation values of the right TDI variables were observed at the base (3.5-16.1%). The variability of the right apical velocities was much higher, with most coefficient of variation values > 15%. RVM velocities were higher in the basal than in the apical segments (P < .001) and were higher than the left velocities of the corresponding segment (P < .01). Body weight and breed had an effect on only a few right and left TDI variables. TDI provides a repeatable and reproducible method for evaluating basal RV function in the dog. These data also demonstrate the heterogeneity of the myocardial velocities between the left and the right ventricles and between the base and the apex.

Aging↗

PubMed1987

Structural elements highly preserved during the evolution of the D-loop-containing region in vertebrate mitochondrial DNA.

A detailed comparative study of the regions surrounding the origin of replication in vertebrate mitochondrial DNA (mtDNA) has revealed a number of interesting properties. This region, called the D-loop-containing region, can be divided into three domains. The left (L) and right (R) domains, which have a low G content and contain the 5' and the 3' D-loop ends, respectively, are highly variable for both base sequence and length. They, however, contain thermodynamically stable secondary structures which include the conserved sequence blocks called CSB-1 and TAS which are associated with the start and stop sites, respectively, for D-loop strand synthesis. We have found that a "mirror symmetry" exists between the CSB-1 and TAS elements, which suggests that they can act as specific recognition sites for regulatory, probably dimeric, proteins. Long, statistically significant repeats are found in the L and R domains. Between the L and R domains we observed in all mtDNA sequences a region with a higher G content which was apparently free of complex secondary structure. This central domain, well preserved in mammals, contains an open reading frame of variable length in the organisms considered. The identification of common features well preserved in evolution despite the high primary structural divergence of the D-loop-containing region of vertebrate mtDNA suggests that these properties are of prime importance for the mitochondrial processes that occur in this region and may be useful for singling out the sites on which one should operate experimentally in order to discover functionally important elements.

Amino Acid Sequence↗

PubMed1987

[EEG changes during the performance of verbal and non-verbal tasks].

EEGs were recorded from 12 positions of the scalp (10-20 system) in 30 normal right-handed subjects. Powers of alpha component obtained from contralateral loci during their performance of verbal tasks (definition of nouns, tongue twisting) and non-verbal tasks (memorization of shapes, imagination of a face) were compared. At the frontal and occipital regions, the right hemisphere dominance of the alpha component was more distinctly demonstrated during the verbal tasks than the non-verbal tasks, while at the occipito-temporal region, the left hemisphere dominance was distinctly demonstrated during the non-verbal tasks than the verbal tasks. However, the alpha components were dominant at the left occipito-temporal region during the verbal tasks and at the right frontal and occipital regions during the non-verbal tasks. The latter result was discussed in relation to the findings of Moss, Davidson, & Saron (1985) and noise generated by apparatuses. Component analysis was carried out for a correlation matrix made by four task variables and 12 samples of electrode positions. Two factors were derived; the first factor was loaded on the verbal tasks whereas the second factor on non-verbal tasks. The factor scores of the first factor were high at the right temporal region and those of the second factor at the left temporal region. These results proved the utility of principal factor method onto general patterns of alpha component during the tasks.

Adolescent↗

PubMed1996

An alternative to radioactive microspheres for measuring regional myocardial blood flow, Part 1: Colored microspheres.

OBJECTIVE: To compare measurements of regional myocardial blood flow between color and radioactive microspheres. DESIGN: Prospective, randomized, controlled. SETTING: University research laboratory. PARTICIPANTS: Pigs. INTERVENTIONS: Pigs underwent constriction of the left anterior descending artery, either incremental and then 0 constriction with epinephrine, 0.5 to 3 mu/kg/min (n = 5; "variable") or only 0% and 100% constriction without epinephrine (n = 4, "single"). Radioactive and color microspheres were injected simultaneously. For variable constriction, 5 colors (3 x 10(6)/mL) were tested in random order and, for single, red and yellow (6 x 10(6)/2 mL). MEASUREMENTS AND MAIN RESULTS: Measurements of regional endocardial, epicardial, and transmural myocardial blood flow were compared by regression analysis (linear and nonlinear). With radioactive measurements as the point of reference, when regional flow was 50 to 150 mL/min/100 g, correlation was high (r = 0.85), although regression slope was low. With endocardial and epicardial flow between 30 and 100 mL/min/100 g, correlation was close (r = 0.84). Overall nonlinear correlation was higher with single than variable constriction (r = 0.72). When regional flow was less than 100 mL/min/100 g, linear correlation was r = 0.72. When transmural flow measured by color microspheres was less than 25 mL/min/100 g, correlation was high (r = 0.86) but, with endocardial or epicardial flow, low (r = 0.67). When transmural flow was greater than 100 mL/min/100 g, correlation was extremely low (r = 0.1; n = 26 data points). The overall correlations for regional endocardial and epicardial flows were also low, except in the ischemic zone. CONCLUSIONS: Color and radioactive measurements correlate well during moderate and ischemic regional myocardial blood flow, ischemic blood flow requiring a higher concentration of color microspheres. A major limitation of using color microspheres is imprecision when flow is greater than 150 mL/min 100 g.

Animals↗

PubMed2006

Functional imaging of working memory following normal sleep and after 24 and 35 h of sleep deprivation: Correlations of fronto-parietal activation with performance.

Working memory was evaluated after normal sleep, and at 24 and 35 h of sleep deprivation (SD) in 26 healthy young adults to examine the neural correlates of inter-individual differences in performance. The extent of performance decline was not significantly different between the two SD test periods although there was greater variability in performance at SD35. In both SD sessions, there was reduced task-related activation (relative to normal sleep) in both superior parietal regions and the left thalamus. Activation of the left parietal and left frontal regions after normal sleep was negatively correlated with performance accuracy decline from normal sleep to SD24 thus differentiating persons who maintained working memory performance following SD from those who were vulnerable to its effects.

Adult↗

PubMed1985

Functional and pathologic effects of multiple echocardiographic contrast injections on the myocardium, brain and kidney.

Myocardial contrast echocardiography can define in vivo the area at risk for necrosis after coronary occlusion. However, if this technique is to be used, it cannot be intrinsically toxic to the heart or other critical organs. To determine the functional and pathologic effects of contrast echocardiography, six intracoronary, six intrarenal and six intracarotid artery injections of 2 to 6 cc of a commonly employed contrast agent (agitated Renografin-saline solution) were performed in five dogs. A sixth dog served as a sham to assess any deleterious effects of the model preparation. Two-dimensional echocardiographic images and electrocardiograms were recorded during intracoronary injections, and heart rate, blood pressure, left ventricular end-diastolic pressure and rate of rise of left ventricular pressure (dP/dt) were continuously monitored. At 24 hours, echocardiographic and hemodynamic measurements were repeated, the dogs were killed and the heart, brain and kidneys were removed and prepared for light microscopic examination. Quantitative analysis of left ventricular wall motion was performed on control, peak contrast, post-contrast and 24 hour studies. With each intracoronary injection, there were transient decreases in blood pressure (p = 0.05 versus control) and increases in left ventricular end-diastolic pressure (p = 0.04 versus control). These were associated with depression of wall motion in contrast-enhanced regions (p = 0.01 versus control) and ST-T segment changes on the electrocardiogram. No significant change in heart rate or left ventricular dP/dt was noted. All variables normalized with the clearance of the contrast effect and remained normal to 24 hours. Light microscopic examination revealed no myocardial or cerebral changes attributable to the contrast agent injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2004

Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition.

Germ-line mutations in the BRCA1 gene predispose affected individuals to breast and ovarian cancer syndromes. In an attempt to systematically analyze a broader spectrum of genetic changes ranging from frequent exon deletions and duplications to amino acid replacements and protein truncations, we isolated and characterized full size BRCA1 homologues from a representative group of non-human primates. Our analysis represents the first comprehensive sequence comparison of primate BRCA1 loci and corresponding proteins. The comparison revealed an unusually high proportion of indels in non-coding DNA. The major force driving evolutionary changes in non-coding BRCA1 sequences was Alu-mediated rearrangements, including Alu transpositions and Alu-associated deletions, indicating that structural instability of this locus may be intrinsic in anthropoids. Analysis of the non-synonymous/synonymous ratio in coding portions of the gene revealed the presence of both conserved and rapidly evolving regions in the BRCA1 protein. Previously, a rapidly evolving region with evidence of positive evolutionary selection in human and chimpanzee had been identified only in exon 11. Here, we show that most of the internal BRCA1 sequence is variable between primates and evolved under positive selection. In contrast, the terminal regions of BRCA1, which encode the RING finger and BRCT domains, experienced negative selection, which left them almost identical between the compared primates. Distribution of the reported missense mutations, but not frameshift and nonsense mutations, is positively correlated with BRCA1 protein conservation. Finally, on the basis of protein sequence conservation, we identified missense changes that are likely to compromise BRCA1 function.

Alu Elements↗

PubMed1986

Tx1: a transposable element from Xenopus laevis with some unusual properties.

A family of transposable genetic elements in the genome of the frog, Xenopus laevis, is described. They are designated Tx1. Transposability of the elements was deduced by characterization of a chromosomal locus which is polymorphic for the presence or absence of a Tx1 element. Nucleotide sequence analysis suggested that Tx1 elements show target site specificity, as they are inserted at the pentanucleotide TTTAA in all four cases that were examined. The elements appear to have 19-base-pair (bp) inverted terminal repeats, and they are flanked by 4-bp target duplications (TTAA), although the possibility that they do not create target site duplications is discussed. Tx1 elements have several unusual characteristics: the central portion of each element is comprised of a variable number of two types of 393-bp repeating units; the rightmost 1,000 bp of the element contains separate regions potentially capable of forming bends, left-handed Z-form DNA, and alternative stem-loop structures. Comparisons among single frogs suggest that germ line transposition is relatively infrequent and that variations in numbers of internal repeats accumulate quite slowly at any locus.

Animals↗

PubMed2004

Structural brain abnormalities in multiple sclerosis patients with major depression.

OBJECTIVE: To assess the association between major depression and structural brain abnormalities in patients with multiple sclerosis (MS). METHODS: Two groups of patients with clinically definite MS were studied: 21 with Diagnostic and Statistical Manual of Mental Disorders (4th ed.)-defined major depression and 19 without. The groups did not differ on demographic, disease, or cognitive measures. All subjects underwent brain MRI. Tissue segmentation and regional brain masking were applied to the MRI data. RESULTS: Compared with the euthymic subjects, those with major depression had a greater T2-weighted lesion volume (p = 0.003) and more extensive T1-weighted lesion volume in the left medial inferior prefrontal cortex (p = 0.01) and less gray matter volume (p = 0.01) and more CSF volume in the left anterior temporal region (p = 0.005). A logistic regression analysis identified two independent predictors of depression: left medial inferior prefrontal cortex T2 lesion volume and left anterior temporal CSF volume. These variables accounted for 42% of the depression variance score. CONCLUSION: Whereas both lesion burden and atrophy are important in the pathogenesis of depression in MS, psychosocial influences should also be considered.

Adult↗

PubMed1982

Detection of one-millimeter motion under conditions simulating equilibrium blood-pool scinitgraphy.

The widespread clinical applications of multiple-gated equilibrium cardiac blood-pool scintigraphy for qualitative assessment of regional left-ventricular wall motion has raised questions regarding the limits of detectable motion. Under conditions simulating some of the elements of cardiac motion, and using variables associated with multiple-gated equilibrium scintigraphy, we have studied these limits both theoretically and experimentally. The theory of detecting simple edge motion as a function of motion magnitude, system resolution, and counts per pixel is studied both conceptually and by statistical analysis using a line-source activity distribution represented as Gaussian. The experiment involves six independent observers in the qualitative evaluation of the presence and location of edge motion of two cylindrical activity distributions as displayed by a computer.

Computers↗

PubMed1992

Analysis of beat-to-beat cardiovascular hemodynamic variables obtained from long-term biotelemetry.

Manual methods of large volume data storage, retrieval, and analysis are difficult, time consuming, and present numerous opportunities for calculation errors. We have designed and implemented a comprehensive computer-based system for performing these functions. Development of this system was necessary since left ventricular (LV) blood pressure and two regional LV wall thickness measurements were obtained during long-term extracorporeal biotelemetry of miniswine for 24-h periods. During a single recording period over 100,000 individual cardiac cycles were recorded on analog tape and later analysed for determination of global myocardial oxygen demand and regional myocardial function. In addition, custom designed software was developed to determine the extent and duration of myocardial dysfunction. Batch file commands enabled the customized software to operate without prompting by the user thus optimizing the time usage of the computer, and the computer based data acquisition and analysis system. Although this system was designed specifically for analysing cardiovascular hemodynamic variables, it is flexible and can be applied to other experimental applications.

Analog-Digital Conversion↗

PubMed1993

Cloning of cDNAs encoding the variable domains of antibody BrE-3 and construction of a chimeric antibody.

BrE-3 is an IgG1,kappa murine monoclonal antibody that binds to human breast epithelial mucin and that has been shown to be promising for imaging and treatment of breast cancer. We have cloned and sequenced cDNAs encoding the variable regions of the light (VL) and heavy (VH) chains of BrE-3. VL belongs to group II and resulted from a V kappa-J kappa 1 fusion. VH belongs to group IIIc and arose from a V-D-JH3 non-conservative fusion which left little or nothing of the original D minigene. Thus, the third VH CDR contains only 4 amino-acids. We constructed an IgG1,kappa human/mouse chimeric antibody (by joining the murine variable domains to human constant domains) and expressed it in SP2/0 myeloma cells. This chimeric monoclonal antibody stains breast carcinoma tissue sections by the ABC immunoperoxidase method. Its affinity for the BrE-3 antigen is 2.68 x 10(8) M-1, which, considering the experimental error, is indistinguishable from the affinity of the original murine antibody (3.75 x 10(8) M-1). The VL and VH domains alone are respectively 73%, and 63% identical to the human V kappa II and VHIII consensus sequences. If the CDRs are excluded, these numbers become respectively 82% and 80%. Therefore, we expect the reported chimeric BrE-3 to be considerably less immunogenic to humans than the original murine antibody, while retaining the original binding properties.

Amino Acid Sequence↗

PubMed2006

How do brain tumors alter functional connectivity? A magnetoencephalography study.

OBJECTIVE: This study was undertaken to test the hypothesis that brain tumors interfere with normal brain function by disrupting functional connectivity of brain networks. METHODS: Functional connectivity was assessed by computing the synchronization likelihood in a broad band (0.5-60Hz) or in the gamma band (30-60Hz) between all pairwise combinations of magnetoencephalography signals. Magnetoencephalography recordings were made at rest in 17 brain tumor patients and 15 healthy control subjects. For a given threshold of synchronization likelihood values, graphs of the suprathreshold connections between each magnetoencephalography channel and the others channels were built. RESULTS: In some regions, a variable number of channels without connectivity (missing connective points) at this threshold was found. The number of missing connective points was higher in patients with brain tumors than in control subjects (p < 0.0001, broad and gamma band) and was higher for left-sided than right-sided tumors (p = 0.008, broad band; p < 0.0001, gamma band). Individual results analysis indicates that the majority of brain tumor patients display several regions with missing connective point alterations in the affected and in the contralateral hemisphere. INTERPRETATION: Our findings suggest that brain tumors induce a loss of functional connectivity that affects multiple brain regions, and that left side brain tumors have the more severe consequences in this respect.

Adult↗