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Assessment of myocardial reinnervation in cardiac transplants by positron emission tomography: functional significance tested by heart rate variability.

While it is known that scintigraphically measured uptake of [C-11] hydroxyephedrine (HED) correlates well with the catecholamine uptake and storage in the nerve terminals of the myocardium, the functional significance of this morphologic marker remains unclear. It had been shown that normal, innervated myocardium exhibits pronounced heart rate variability (HRV). In this study, parallel to the scintigraphic determination of regional HED uptake, the functional sympathetic innervation of the left ventricle was measured by spectral analysis of HRV. Prior to PET scanning, changes in the low frequency HRV after tilt were determined as validated marker of sympathetic function in 12 patients with cardiac transplants (mean time after transplantation 4.7 years). Dynamic PET data acquisition allowed the definition of a retention index as regional marker for sympathetic nerve terminals. Intensity as well as regional extent of this marker were then compared to the results of HRV studies. Two groups were defined based on the scintigraphic findings: 8 of 12 patients displayed regionally increased HED retention (11.5 +/- 3.1%/min.) in the anteroseptal region of the left ventricle, while 4 patients showed little HED uptake (4.3 +/- 0.5%/min.). Uptake values tended to increase for longer times after surgery. Average HRV in the first group (7.57 +/- 7.47 ms2/Hz) was significantly higher (p < 0.05) compared to the low HED uptake group (1.17 +/- 1.08 ms2/Hz). HRV was lower than normal values even in the first group. These independent electrophysiological measurements prove the significance of HED retention for the functional characterization of reinnervation in cardiac transplants.

Adult↗

Pear blister canker viroid: sequence variability and causal role in pear blister canker disease.

The sequences of several cDNA clones of pear blister canker viroid (PBCVd) P1914T and P47A isolates have been determined. Seven out of eight P1914T clones analysed have a constant sequence which differs at six positions from that of the P2098T isolate reported previously. The remaining P1914T clone (8) has a single nucleotide substitution. The same six changes have been also observed in most of the ten P47A clones sequenced. However, some P47A clones show additional variability in positions on both strands of the central conserved region (CCR) and in another conserved sequence at the left-terminal region. This is the first report of a change affecting the upper strand of a viroid CCR. Reasons why such a change is tolerated are discussed. Infectivity bioassays have demonstrated that PBCVd is the causal agent of PBC disease.

Base Sequence↗

MR Imaging of arrhythmogenic right ventricular cardiomyopathy: morphologic findings and interobserver reliability.

BACKGROUND: Magnetic resonance (MR) imaging is frequently used to diagnose arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). However, the reliability of various MR imaging features for diagnosing ARVC/D is unknown. The purpose of this study was to determine which morphologic MR imaging features have the greatest interobserver reliability for diagnosing ARVC/D. METHODS: Forty-five sets of films of cardiac MR images were sent to 8 radiologists and 5 cardiologists with experience in this field. There were 7 cases of definite ARVC/D as defined by the Task Force criteria. Six cases were controls. The remaining 32 cases had MR imaging because of clinical suspicion of ARVC/D. Readers evaluated the images for the presence of (a) right ventricle (RV) enlargement, (b) RV abnormal morphology, (c) left ventricle enlargement, (d) presence of high T(1) signal (fat) in the myocardium, and (e) location of high T(1) signal (fat) on a Likert scale with formatted responses. RESULTS: Readers indicated that the Task Force ARVC/D cases had significantly more (chi(2) = 119.93, d.f. = 10, p < 0.0001) RV chamber size enlargement (58%) than either the suspected ARVC/D (12%) or no ARVC/D (14%) cases. When readers reported the RV chamber size as enlarged they were significantly more likely to report the case as ARVC/D present (chi(2)(= )33.98, d.f. = 1, p < 0.0001). When readers reported the morphology as abnormal they were more likely to diagnose the case as ARVC/D present (chi(2) = 78.4, d.f. = 1, p < 0.0001), and the Task Force ARVC/D (47%) cases received significantly more abnormal reports than either suspected ARVC/D (20%) or non-ARVC/D (15%) cases. There was no significant difference between patient groups in the reported presence of high signal intensity (fat) in the RV (chi(2) = 0.9, d.f. = 2, p > 0.05). CONCLUSIONS: Reviewers found that the size and shape of abnormalities in the RV are key MR imaging discriminates of ARVD. Subsequent protocol development and multicenter trials need to address these parameters. Essential steps in improving accuracy and reducing variability include a standardized acquisition protocol and standardized analysis with dynamic cine review of regional RV function and quantification of RV and left ventricle volumes.

Adult↗

Evaluation of left ventricular contractile pattern by intravenous digital subtraction ventriculography: comparison with cineangiography and assessment of interobserver variability.

The accuracy and reproducibility of measurements of left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF) and regional wall motion obtained by digital subtraction ventriculography (DSV) were compared with values of direct cineangiography in 40 patients, 21 of whom were ambulatory. DSV was performed with a 1-second, 30-ml contrast injection, which yielded real-time fluoroimages composed of 512 X 512 pixels at 30 frames/s. Single-plane right anterior oblique LV volumes were calculated by area-length methods for both DSV and cineangiography. Wall motion was assessed as percent area shortening for 12 equal myocardial segments, with results classified as abnormal if greater than 2 standard deviations below the mean of 20 normal values. DSV exhibited close correlation with angiography for EDV (r = 0.88), ESV (r = 0.92) and EF (r = 0.93). Intravenous DSV and direct cineangiography were concordant in classification of LV contractile pattern in 436 of 480 (91%) myocardial segments. Measurements of DSV obtained by 2 observers showed close correlations for EDV (r = 0.88), ESV (r = 0.95) and EF (r = 0.94), and wall motion classification was in agreement in 434 of 480 (90%) LV segments. Artifacts induced by respiratory motion, persistence of contrast in the right ventricle or left atrium, or low cardiac output may have contributed to the discrepancies observed. These data indicate that DSV is accurate in assessing LV volume and EF, correlates well with cineangiography and exhibits good interobserver reproducibility.

Analog-Digital Conversion↗

[The variability in the interrelations of the terminal portions of the thoracic duct and the left vertebral vein and its importance in applying a lymphovenous anastomosis].

Peculiarities of interrelations between the thoracic duct terminal regions and left vertebral vein were studied in 158 human cadavers. In case of long and thin neck trunks of the thoracic duct and vertebral vein ere established not to adjoin. Here a lympho-venous end-to-side anastomosis may be applied in vertebral vein mobilization. In short and thick neck intercrossing of the trunks was observed. In this case any type of lympho-venous anastomosis may be applied.

Anastomosis, Surgical↗

Measurement of regional myocardial perfusion using collimated miniature radiation detectors and the method of 133-xenon washout.

A new approach to the measurement of local myocardial perfusion based on the application of highly-collimated miniature cadmium telluride radiation detectors to measure washout of 133-Xenon from well-defined tissue volumes is presented. Single-hole collimators with length/diameter ratios of 1 (L = 4 mm, D = 4 mm) and 4 (L = 12 mm, D = 3 mm) were employed as prototype designs. The probe field of view was characterized theoretically using a spherical model of the myocardium in conjunction with experimental point source response measurements for each collimator. Method evaluation using two medium resolution collimators (L/D = 1) was effected by performing left main and circumflex coronary artery perfusion studies at controlled but variable flows in the dog heart. An excellent correlation (r greater than 0.99) between actual and estimated perfusion determined from 65 washout curves over the flow range 0.38 to 3.18 ml/min/gm was demonstrated. The ability to resolve regional flow differences was verified by measuring tracer washout from circumflex and left anterior descending regions of the myocardium, using two high resolution collimators (L/D = 4), in a preparation where the left main coronary artery was cannulated and a snare was placed around the circumflex coronary artery to selectively reduce flow to that region.

Biomedical Engineering↗

Clinical significance of pericardial rub with regional ventricular dilatation.

To elucidate the clinical characteristics associated with regional ventricular dilatation in the early phase of myocardial infarction (MI), 228 patients with acute Q-wave anterior MI were studied. Forty-nine patients (21 percent) had echocardiographically demonstrated regional ventricular dilatation (an abnormal bulge in the left ventricular contour during both systole and diastole) on the third hospital day. Careful auscultation revealed that a pericardial rub was present in 49 patients (21 patients with and 28 patients without regional ventricular dilatation) during the first three days after hospital admission. Multivariate analysis was performed to determine the relative importance of pericardial rub with six other clinical variables related to regional ventricular dilatation. Pericardial rub and cardiac output were the significant factors related to the presence of regional ventricular dilatation. Thus, a pericardial rub, in concert with impaired left ventricular function, is a physical sign associated with regional ventricular dilatation, and anatomically transmural infarction is the possible factor explaining their association.

Aged↗

Functional significance of predischarge exercise thallium-201 findings following intravenous streptokinase therapy during acute myocardial infarction.

The purpose of this study was to determine which predischarge exercise thallium-201 imaging pattern(s) best correlate with myocardial salvage following intravenous streptokinase therapy (IVSK). Myocardial salvage was defined as improvement in regional left ventricular function determined by two-dimensional echocardiography between the time of admission and time of discharge in 21 prospectively studied patients receiving IVSK within 4 hours of chest pain. All patients had coronary angiography 2 hours following IVSK. Whereas 16 of the 21 patients (76%) had patent infarct-related vessels, only seven (33%) showed significant improvement in regional function at hospital discharge. Eleven patients demonstrated persistent defects (PD), and five each showed delayed and reverse redistribution. Patients with both delayed and reverse redistribution demonstrated significant improvement in regional left ventricular function score, while those with PD did not (+3.9 +/- 3.3 versus -0.5 +/- 2.9, p = 0.004). All other clinical, exercise, electrocardiographic, scintigraphic, and angiographic variables were similar between all patients, with the exception of the interval between chest pain and the institution of IVSK, which was longer in patients with reverse compared to delayed redistribution (3.5 +/- 0.4 versus 2.2 +/- 0.4 hours, p = 0.001). It is concluded that both delayed and reverse redistribution seen on predischarge exercise thallium-201 imaging are associated with myocardial salvage, defined as serial improvement in regional systolic function. Despite a high infarct vessel patency rate in patients with acute myocardial infarction receiving IVSK within 4 hours of onset of symptoms, only one third demonstrated improvement in regional function that was associated with either delayed or reverse redistribution seen on predischarge exercise thallium-201 imaging.

Adult↗

Regional heterogeneity in gene expression profiles: a transcript analysis in human and rat heart.

BACKGROUND: Investigations involving biopsies of human cardiac tissue often assume that myocardial samples from a specific location are representative of the entire heart. HYPOTHESIS: There are significant regional differences in gene expression in the heart. METHODS: We used two models. In the first model, seven whole human hearts were cut in 1-cm slices from apex to base and 11 distinct regions were sampled. Full thickness left ventricular tissue was further subdivided equally into an inner, outer, and middle region. In the second model, hearts were removed from adult Sprague-Dawley rats and were divided into 4 regions. Using species-specific quantitative reverse transcriptase-polymerase chain reaction, we measured transcript levels of myosin heavy chain beta (MHC-beta), glucose transporter 1 (GLUT 1), and atrial natriuretic factor (ANF) in tissue samples from both models. RESULTS: In human heart, there were significant differences in transcript levels between regions. The following patterns could be recognized among the seven hearts. ANF expression was highest in the subendocardial region. MHC-beta and GLUT 1 transcript levels were higher in the right ventricle than the left ventricle. As expected, ANF transcript levels were highest in the atria, where MHC-beta and GLUT 1 expression was low. Analogous to the human studies, MHC-beta and GLUT 1 transcript levels were low in rat atria as compared to ventricles. In rat heart, MHC-beta expression was higher in the left ventricle than the right ventricle while GLUT 1 expression was not significantly different between ventricles. CONCLUSION: Despite the large variability in transcript levels among different regions in human hearts, certain patterns in gene expression emerged suggesting that different anatomical regions of the heart also differ in respect to gene expression.

Adolescent↗

Sweat gland carcinoma with regional lymph node metastasis.

Description of a 63-year-old man with a sweat gland carcinoma low in the left axilla, and an axillary lymph node metastasis. A five-year survival was obtained. The histological picture of a sweat gland carcinoma may be highly variable. The best treatment seems to be local excision. If the primary tumour is situated close to a regional lymph gland station, regional lymph node extirpation should be seriously considered.

Carcinoma↗

Hemodynamic effects of portal triad clamping with and without pneumoperitoneum: an echocardiographic study.

The decrease of cardiac index observed during portal triad clamping (PTC) with and without pneumoperitoneum has been studied only with right heart catheterization. To better understand this decrease of cardiac index, we investigated the balance between the adequacy of preload and the ability of the heart to pump against an increased afterload, by using transesophageal echocardiography. Ten patients with PTC performed during laparoscopy and 10 with PTC performed during laparotomy were studied. Five minutes after PTC, the stroke volume, the left ventricular (LV) fractional area change (FAC), and the LV end-systolic wall stress (LVESWS) were measured as the conventional hemodynamic variables. Regional wall motion abnormalities (RWMA) were also recorded. In the laparotomy group, LV end-diastolic area decreased, and LVESWS did not increase significantly. FAC remained stable, and one patient developed RWMA. In the laparoscopic group, LV end-diastolic area remained stable, and LVESWS increased. FAC decreased significantly, and five patients developed RWMA. A decrease in preload was the main important change in the laparotomy group, and in the laparoscopic group a decrease in LV function was demonstrated that was likely a consequence of decreased LV preload and increased LV afterload. However, these did not necessitate stopping the procedure or releasing PTC in these study patients without cardiac disease.

Adult↗

Reproducibility of quantitative hexakis-2-methoxyisobutylisonitrile single photon emission tomography in stable coronary artery disease.

The quantification of myocardial perfusion abnormalities is necessary to allow comparison of repeated studies, especially in the evaluation of the success of medical, interventional or combined treatment in stable coronary artery disease or in evolving myocardial infarction. The purpose of this study was to assess inter-observer reproducibility of tomographic study processing using a semi-automatic quantitative programme. Technetium 99m hexakis-2-methoxyisobutylisonitrile (99mTc-Sestamibi) was chosen for tomographic imaging of repeated rest-stress studies in patients with stable coronary artery disease. The quantification was performed using a modification of the Cedars polar coding and comparison with the normal data base. The perfusion defects were quantified separately for each standard perfusion area [left anterior descending (LAD), right coronary (RCA) and left circumflex (LCX) arteries] and total area of hypoperfused myocardium. The inter-observer variability for 40 tomographic studies was accomplished. The defects were the largest in the LAD perfusion area (average 19.7% of the normalized LAD supply area) with an inter-observer correlation of 0.84 for this region. The greatest variability was found for the LCX region (r = 0.55) and is attributed to a small average perfusion defect (7.1%), only 18 studies having abnormal perfusion in this area. In total, an average 14.3% of the left ventricular myocardium was significantly hypoperfused, and the inter-observer correlation was 0.87. These results show good inter-observer reproducibility using semi-automatic quantitation of perfusion defects. Careful interpretation of smaller defects in the evaluation of treatment results is advised when repeated 99mTc-Sestamibi single photon emission tomography studies are processed by more than one observer.

Coronary Disease↗

Birth of a retroposon: the Twin SINE family from the vector mosquito Culex pipiens may have originated from a dimeric tRNA precursor.

SINEs are short interspersed repetitive elements found in many eukaryotic genomes and are believed to propagate by retroposition. Almost all SINEs reported to date have a composite structure made of a 5' tRNA-related region followed by a tRNA-unrelated region. Here, we describe a new type of tRNA-derived SINEs from the genome of the mosquito Culex pipiens. These elements, called TWINs, are approximately 220 bp long and reiterated at approximately 500 copies per haploid genome. TWINs have a unique structure compared with other tRNA-SINEs described so far. They consist of two tRNA(Arg)-related regions separated by a 39-bp spacer. Other tRNA-unrelated sequences include a 5-bp leader preceding the left tRNA-like unit and a short trailer located downstream of the right tRNA-like region. This 3' trailer is a 10-bp sequence that is ended by a TTTT motif and followed by a polyA tract of variable length. The right tRNA-like unit also contains a 16-bp sequence which is absent in the left one and appears to be located in the ancestral anticodon stem precisely at a position expected for a nuclear tRNA intron. According to this singular structure, we hypothesize that the TWIN: SINE family originated from an unprocessed polymerase III transcript containing two tRNA sequences. We suggest that some peculiar properties acquired by this dicistronic transcript, such as a polyA tail and a 3' stem-loop secondary structure, promote its retroposition by increasing its chances of being recognized by a reverse transcriptase encoded elsewhere in the C. pipiens genome.

Animals↗

Structural characterization of chromosome I size variants from a natural yeast strain.

Many yeast strains isolated from the wild show karyotype instability during vegetative growth, with rearrangement rates of up to 10(-2) chromosomal changes per generation. Physical isolation and analysis of several chromosome I size variants of one of these strains revealed that they differed only in their subtelomeric regions, leaving the central 150 Kb unaltered. Fine mapping of these subtelomeric variable regions revealed gross alterations of two very similar loci, FLO1 and FLO9. These loci are located on the right and left arms, respectively, of chromosome I and encompass internal repetitive DNA sequences. Furthermore, some chromosome I variants lacking the FLO1 locus showed evidence of recombination at a DNA region on their right arm that is enriched in repeated sequences, including Ty LTRs. We propose that repetitive sequences in many subtelomeric regions in S. cerevisiae play a key role in karyotype hypervariability. As these regions encode several membrane-associated proteins, subtelomeric plasticity may allow rapid adaptive changes of the yeast strain to specific substrates. This pattern of semi-conservative chromosomal rearrangement may have profound implications, both in terms of evolution of wild strains and for biotechnological processes.

Blotting, Southern↗

Hemispheric specialization for language.

Hemispheric specialization for language is one of the most robust findings of cognitive neuroscience. In this review, we first present the main hypotheses about the origins of this important aspect of brain organization. These theories are based in part on the main approaches to hemispheric specialization: studies of aphasia, anatomical asymmetries and, nowadays, neuroimaging. All these approaches uncovered a large inter-individual variability which became the bulk of research on hemispheric specialization. This is why, in a second part of the review, we present the main facts about inter-individual variability, trying to relate findings to the theories presented in the first part. This review focuses on neuroimaging as it has recently given important results, thanks to investigations of both anatomical and functional asymmetries in healthy subjects. Such investigations have confirmed that left-handers, especially "familial left-handers", are more likely to have an atypical pattern of hemispheric specialization for language. Differences between men and women seem less evident although a less marked hemispheric specialization for language was depicted in women. As for the supposed relationship between anatomical and functional asymmetries, it has been shown that the size of the left (not the right) planum temporale could explain part of the variability of left hemispheric specialization for language comprehension. Taken as a whole, findings seem to vary with language tasks and brain regions, therefore showing that hemispheric specialization for language is multi-dimensional. This is not accounted for in the existing models of hemispheric specialization.

Animals↗

Manipulating smoking motivation: impact on an electrophysiological index of approach motivation.

A chief goal of this research was to determine whether stimuli and events known to enhance smoking motivation also influence a physiological variable with the potential to index approach motivation. Asymmetry of electroencephalographic (EEG) activity across the frontal regions of the 2 hemispheres (left minus right hemisphere activation) was used to index approach motivation. In theory, if EEG asymmetry sensitively indexes approach dispositions, it should be influenced by manipulations known to affect smoking motivation, that is, exposure to smoking cues and tobacco deprivation. Seventy-two smokers participated in this research and were selectively exposed to a smoking-anticipation condition (cigarettes plus expectation of imminent smoking) following either 24 hr of tobacco withdrawal or ad libitum smoking. Results indicated that EEG asymmetry was increased by smoking anticipation and that smoking itself reduced EEG asymmetry. Results also suggested that smoking anticipation increased overall (bihemispheric) EEG activation. Results were interpreted in terms of major theories of drug motivation.

Adult↗

Antigenic and genomic identity between simian herpesvirus aotus type 2 and bovine herpesvirus type 4.

Herpesvirus aotus type 2 (HVA-2) was isolated from a culture of kidney cells from a healthy owl monkey (Aotus trivirgatus). Bovine herpesvirus type 4 (BHV-4) is frequently isolated from diseased and even healthy cattle and occasionally from sheep, wild ruminants and cats. The two viruses are related antigenically, as was revealed by an indirect fluorescent antibody test using polyclonal antisera from experimentally infected rabbits or monoclonal antibodies raised against six BHV-4 proteins, three of which were glycosylated. The genome structures of the two viruses consist of a unique central sequence flanked at both ends by G + C-rich tandem repeats. Restriction maps (produced using EcoRI, BamHI and HindIII) of these two viruses were nearly identical but the unique sequence of the HVA-2 genome possessed two additional BamHI sites. Four genomic regions of variable size were detected, two located in the unique part, one in the repetitive part and one in the left junction between the unique and the repeated part of the genome; these slight variations were similar to those observed between various BHV-4 isolates. These results suggest that HVA-2 and BHV-4 belong to the same virus species; HVA-2 could be either a BHV-4 contaminant of owl monkey kidney cell cultures or an isolate from an owl monkey accidentally infected with BHV-4.

Animals↗

Functional anatomical correlates of controlled and automatic processing.

Behavioral studies have shown that consistent practice of a cognitive task can increase the speed of performance and reduce variability of responses and error rate, reflecting a shift from controlled to automatic processing. This study examines how the shift from controlled to automatic processing changes brain activity. A verbal Sternberg task was used with continuously changing targets (novel task, NT) and with constant, practiced targets (practiced task, PT). NT and PT were presented in a blocked design and contrasted to a choice reaction time (RT) control task (CT) to isolate working memory (WM)-related activity. The three-dimensional (3-D) PRESTO functional magnetic resonance imaging (fMRI) sequence was used to measure hemodynamic responses. Behavioral data revealed that task processing became automated after practice, as responses were faster, less variable, and more accurate. This was accompanied specifically by a decrease in activation in regions related to WM (bilateral but predominantly left dorsolateral prefrontal cortex (DLPFC), right superior frontal cortex (SFC), and right frontopolar area) and the supplementary motor area. Results showed no evidence for a shift of foci of activity within or across regions of the brain. The findings have theoretical implications for understanding the functional anatomical substrates of automatic and controlled processing, indicating that these types of information processing have the same functional anatomical substrate, but differ in efficiency. In addition, there are practical implications for interpreting activity as a measure for task performance, such as in patient studies. Whereas reduced activity can reflect poor performance if a task is not sensitive to practice effects, it can reflect good performance if a task is sensitive to practice effects.

Adult↗