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At least 1,387 records · Page 77Linked to original sources
PubMed2004

Multilocus analysis of hypertension: a hierarchical approach.

While hypertension is a complex disease with a well-documented genetic component, genetic studies often fail to replicate findings. One possibility for such inconsistency is that the underlying genetics of hypertension is not based on single genes of major effect, but on interactions among genes. To test this hypothesis, we studied both single locus and multilocus effects, using a case-control design of subjects from Ghana. Thirteen polymorphisms in eight candidate genes were studied. Each candidate gene has been shown to play a physiological role in blood pressure regulation and affects one of four pathways that modulate blood pressure: vasoconstriction (angiotensinogen, angiotensin converting enzyme - ACE, angiotensin II receptor), nitric oxide (NO) dependent and NO independent vasodilation pathways and sodium balance (G protein-coupled receptor kinase, GRK4). We evaluated single site allelic and genotypic associations, multilocus genotype equilibrium and multilocus genotype associations, using multifactor dimensionality reduction (MDR). For MDR, we performed systematic reanalysis of the data to address the role of various physiological pathways. We found no significant single site associations, but the hypertensive class deviated significantly from genotype equilibrium in more than 25% of all multilocus comparisons (2,162 of 8,178), whereas the normotensive class rarely did (11 of 8,178). The MDR analysis identified a two-locus model including ACE and GRK4 that successfully predicted blood pressure phenotype 70.5% of the time. Thus, our data indicate epistatic interactions play a major role in hypertension susceptibility. Our data also support a model where multiple pathways need to be affected in order to predispose to hypertension.

Alleles↗
PubMed2006

A retrospective study of preimplantation embryos diagnosed with monosomy by fluorescence in situ hybridization (FISH).

This report is a retrospective study of preimplantation embryos diagnosed with monosomy for chromosomes 13, 15, 16, 18, 21, 22, X and Y on day 3 to determine the rate of true positives, false positives and/or mosaicism and to assess if these embryos are suitable for in vitro fertilization (IVF) transfer. In a one year period, 80 patients went through preimplantation genetic diagnosis for aneuploidy screening (PGD-AS). Monosomy was diagnosed in 51 embryos. Fluorescence in situ hybridization (FISH) was then performed on the blastomeres at day 5-7 with commercially available probes using the same probe set that initially identified monosomy for chromosomes 13, 16, 21 and 22 or chromosomes 15, 18, X and Y. Based on FISH analysis, the monosomy diagnosed during routine PGD-AS analysis was confirmed in 17 of the 51 embryos. A euploid result for the specific chromosomes tested was observed in 16 of the 51 embryos while mosaicism was found in the remaining 18 embryos. This results in an estimated false positive rate of 3.8% for a diagnosis of monosomy. Reanalysis of these embryos demonstrates that the majority of monosomy diagnoses represents true monosomy or mosaicism and should be excluded for transfer in IVF. Furthermore, improved understanding from recent emerging data regarding the fate of oocytes in women with advanced maternal age undergoing IVF to the development of early embryos may provide a valuable insight into the mechanism of chromosome mosaicism.

Adult↗
PubMed1980

Affective illness and HLA frequencies: no compelling association.

114 patients suffering from an endogenomorphic affective illness were typed for HLA antigens at the A and B loci, and the frequencies were compared with those of a control panel numbering 439 individuals. Using new analytical procedures, a large number of tests were conducted, but no convincing evidence for an association of HLA types with affective disorders was obtained. A reanalysis of the same data, where patients are classified according to Danish diagnostic criteria, yields a marginally significant association of the B locus alleles. The sample sizes for this latter analysis were small, the test criteria are undoubtedly inflated, and no compelling case can be made for a useful association.

Alleles↗
PubMed1982

Encephalization in mammals in relation to the size of the cerebral cortex.

A new index of encephalization has been proposed based on a reanalysis of the brain-body weight relationship in mammals. The new index, c, is related to the volume of the whole brain as well as to the surface and volume of the cerebral cortex. From an evolutionary point of view the index-cortex relationship is particularly interesting, since the structure of the brain which contributes most to its evolutionary progression is the cerebral cortex. A theory of corticalization has been developed in which the surface of the cerebral cortex is analyzed into two components, Sb, determined by the size of the animal, and Se, associated with an increase in the information-processing capacity. An analogue division has been performed for the cortical volume. Furthermore, an inquiry has been made into the brain structure which can serve as an estimator of body weight. The medulla oblongata appears to be such a structure.

Animals↗
PubMed1981

Adult male positioning in baboon progressions: order and chaos revisited.

Evidence of nonrandom positioning among adult males is crucial for a protection theory of the spatial organization of baboon progressions. In a recent study it was suggested that systematic positioning of troop members other than mothers and infants is so slight and rare that progressions may be regarded as essentially random. This suggestion depends upon debatable methodological points presumably downgrading previous findings of nonrandom order. Reanalysis of data from this study revealed numerous analytical and statistical problems, as well as serious calculation and other errors, and showed that the findings are consistent with results of the present and previous research. Adult males tended toward the front or back of progressions, a tendency which was intensified in potentially dangerous situations. Dominant males were disproportionately more often frontward and subordinate males rearward. Nonrandom order, which was found for a variety of circumstances at high levels of statistical significance, was unusually general in that it occurred in 6 studies, 7 troops, 2 species, and 5 locations. Such generality is consistent with a protection theory postulating phylogenetic underpinnings of a sociospatial organization which allows an advanced primate to adapt to terrestrial coexistence with predators.

Animals↗
PubMed1982

The nonlinear tissue-binding character of fluoride kinetics in normal and anephric subjects. Graphical analysis of serum fluoride data from man and rabbit.

A study has been made of the fluoride kinetics in man, with a series of 5 healthy subjects and 4 patients with renal insufficiency. The fluoride metabolism was found to conform to nonlinear tissue-binding kinetics. Reanalysis of findings on the rabbit reported in the literature yielded equivalent results. The tissue-binding constants elicited - probably associated with the fluoride metabolism of bone - presented no differences between healthy subjects and uremics. Uremics had a clearly lower fractional fluoride elimination rate (K) compared with the healthy controls. A significant correlation of creatinine clearance on the K value was noted.

Adult↗
PubMed1995

Psychopathology of Schizophrenia: initial validation of a 5-factor model.

Schizophrenic psychopathology is heterogeneous and multidimensional. One of the more fruitful strategies to investigate more homogenous domains of psychopathology has been the positive-negative syndrome approach. However, this approach is unable to address a number of important issues. Most schizophrenics present a mixed syndrome; the criteria for what constitutes a positive and negative syndrome are variable; distinguishing primary from secondary negative symptoms can be difficult. In order to address some of these problems, we propose the introduction of a 5-syndrome model based on a reanalysis of factor-analytic procedures used on 240 schizophrenics assessed with the Positive and Negative Syndrome Scale: A negative, positive, excitement, cognitive and depression/anxiety factor. This 5-factor solution is supported by 4 independent and comparable factor analyses. Data on internal consistency of the 5 factors and on initial validation using demographic and clinical variables are presented.

Adolescent↗
PubMed2005

Evaluation of carotid-femoral pulse wave velocity: influence of timing algorithm and heart rate.

Carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, is determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. Propagation time is measured variously from the foot of the waveform or point of maximum upslope. We investigated whether these methods give comparable values of PWV at rest, during beta-adrenergic stimulation, and pacing-induced tachycardia. In subjects at rest (n=43), values obtained using the foot-to-foot method (SphygmoCor system) were 1.7+/-0.75 m/s (mean+/-SD) greater than those obtained using the maximum slope (Complior system) at a mean value of 12 m/s. Isoprotenerol (0.5 to 1.5 microg/min; n=10), and pacing (in subjects with permanent pacemakers; n=11) increased heart rate but had differential effects on systolic blood pressure and pulse pressure. The increase in heart rate produced by isoprotenerol (18+/-3 bpm) and pacing (40 bpm) was associated with an increase in PWV measured using both systems (increases of 0.7+/-0.2 m/s and 0.9+/-0.2 m/s for SphygmoCor and Complior, respectively, during isoprotenerol and increases of 2.1+/-0.5 m/s and 1.1+/-0.2 m/s for SphygmoCor and Complior, respectively, during pacing, each P<0.001). Reanalysis of waveforms recorded from the Complior system using the foot-to-foot method produced similar values of PWV to those obtained with the SphygmoCor, confirming that the difference between these systems was attributable to the timing algorithm rather than other aspects of signal acquisition. Carotid-femoral PWV is critically dependent on the method used to determine propagation time, but this does not account for variation of PWV with heart rate.

Adrenergic beta-Agonists↗
PubMed1994

Confirmation of mutant alpha 1 Na,K-ATPase gene and transcript in Dahl salt-sensitive/JR rats.

As the sole renal Na,K-ATPase isozyme, the alpha 1 Na,K-ATPase accounts for all active transport of Na+ throughout the nephron. This role in renal Na+ reabsorption and the primacy of the kidney in hypertension pathogenesis make it a logical candidate gene for salt-sensitive genetic hypertension. An adenine (A)1079-->thymine (T) transversion, resulting in the substitution of glutamine276 with leucine and associated with decreased net 86Rb+ (K+) influx, was identified in Dahl salt-sensitive/JR rat kidney alpha 1 Na,K-ATPase cDNA. However, because a Taq polymerase chain reaction amplification-based reanalysis did not detect the mutant T1079 but rather only the wild-type A1079 alpha 1 Na,K-ATPase allele in Dahl salt-sensitive rat genomic DNA, we reexamined alpha 1 Na,K-ATPase sequences using Taq polymerase error-independent amplification-based analyses of genomic DNA (by polymerase allele-specific amplification and ligase chain reaction analysis) and kidney RNA (by mRNA-specific thermostable reverse transcriptase-polymerase chain reaction analysis). We also performed modified 3' mismatched correction analysis of genomic DNA using an exonuclease-positive thermostable DNA polymerase. All the confirmatory test results were concordant, confirming the A1079-->T transversion in the Dahl salt-sensitive alpha 1 Na,K-ATPase allele and its transcript, as well as the wild-type A1079 sequence in the Dahl salt-resistant alpha 1 Na,K-ATPase allele and its transcript. Documentation of a consistent Taq polymerase error that selectively substituted A at T1079 (sense strand) was obtained from Taq polymerase chain reaction amplification and subsequent cycle sequencing of reconfirmed known Dahl salt-sensitive/JR rat mutant T1079 alpha 1 cDNA M13 subclones. This Taq polymerase error results in the reversion of mutant sequence back to the wild-type alpha 1 Na,K-ATPase sequence. This identifies a site- and nucleotide-specific Taq polymerase misincorporation, suggesting that a structural basis might underlie a predisposition to nonrandom Taq polymerase errors.

Alleles↗
PubMed1981

"Pressure-volume" relations in isolated cat trabecula.

We studied isolated cat trabecula under conditions closely resembling those present for muscle fibers in the left ventricular wall. The purpose of the study was to see if muscle contraction under those circumstances could be described by a time-varying compliance as reported for intact canine left ventricle. We found the time of the end of systole to depend on the history of contraction. This time varied between 100 and 160 msec as measured from the onset of contraction. Similar dependency, although less percentage-wise, was found by reanalysis for intact feline left ventricles. We conclude that the behavior of the canine left ventricle as a time-varying compliance may be related to the complex organization of the cardiac muscle fibers in the wall of the heart rather than to muscle properties.

Animals↗
PubMed2004

Targeting neuroprotection clinical trials to ischemic stroke patients with potential to benefit from therapy.

BACKGROUND AND PURPOSE: Clinical trials of neuroprotective drugs have had limited success. We investigated whether selecting patients according to prognostic features would improve the statistical power of a trial to identify an efficacious treatment. METHODS: Using placebo data from the Glycine Antagonist in Neuroprotection (GAIN) International and National Institute of Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator (rtPA) clinical trials, we developed and validated simple prognostic models for stroke trial end points: Barthel Index > or =95, modified Rankin Scale < or =1, National Institutes of Health Stroke Scale < or =1, and Glasgow Outcome Scale=1. Using these models, we simulated 1000 clinical trials and estimated, under several hypothetical treatment effect patterns of neuroprotection, the effect on statistical power of including only patients with moderate prognosis. We calculated the number of patients that would have to be enrolled to maintain the statistical power achieved in selecting the whole trial population. Reanalysis of actual data from the NINDS rtPA trials confirmed the results independently. RESULTS: Selecting patients with moderate prognosis (predicted probability of favorable outcome 0.2 to 0.8) enabled a sample size reduction, without loss of statistical power, of between 54.6% (51.3% to 57.6%) and 68.6% (66.0% to 71.1%), depending on the treatment effect pattern and outcome measure. These benefits were largely due to the exclusion of patients with poor prognosis. CONCLUSIONS: Targeting patients with potential to benefit enables a substantial sample size reduction without compromising statistical power or duration of recruitment. As part of a broader trial design strategy, informed use of prognostic data available acutely would help in identifying effective neuroprotective treatments.

Aged↗
PubMed2005

Viral persistence in the myocardium is associated with progressive cardiac dysfunction.

BACKGROUND: Cardiotropic viral infections have been suspected as one possible cause of myocarditis and dilated cardiomyopathy. Although adverse outcomes in dilated cardiomyopathy patients have been documented, the natural course of heart diseases caused by cardiotropic viruses is unknown. METHODS AND RESULTS: Consecutive patients (n=172) with biopsy-proven viral infection in endomyocardial biopsies (EMBs) were followed up by reanalysis of EMBs and hemodynamic measurements after a median period of 6.8 months (range, 5.4 to 11.9). Nested polymerase chain reaction (PCR) and reverse transcription-PCR were performed to analyze the genomic sequences. Myocardial inflammation was assessed by histology and immunohistology. At baseline, 32.6% of EMBs in the study group contained enteroviral (EV) RNA, 8.1% adenovirus (ADV) DNA, 36.6% parvovirus B19 (PVB19) DNA, and 10.5% human herpesvirus type 6 (HHV6) DNA. In 12.2% of the samples, dual infection with PVB19 and HHV6 was present. Follow-up analysis of EMBs by PCR documented spontaneous clearance of viral genomes in 36.2% (55/151) of all patients with single infections. Virus-specific clearance rates were 50% for EV, 35.7% for ADV, 22.2% for PVB19, and 44.4% for HHV6. In patients with dual infection with PVB19+ and HHV6(+)-, HHV6 was cleared in 42.8% (9/21), whereas PVB19 persisted in all 21 patients. Clearance of viral genomes was associated with a significant improvement in left ventricular ejection fraction (LVEF), improving from 50.2+/-19.1% to 58.1+/-15.9% (P<0.001). In contrast, LV function decreased in patients with persisting viral genomes (LVEF, 54.3+/-16.1% versus 51.4+/-16.1%, P<0.01). CONCLUSIONS: In this first biopsy-based analysis of the course of viral heart disease, we show that EV, ADV, PVB19, and HHV6 persistence detected in the myocardium of patients with LV dysfunction was associated with a progressive impairment of LVEF, whereas spontaneous viral elimination was associated with a significant improvement in LV function.

Adenoviridae↗
PubMed2004

The faces of development: a review of early face processing over childhood.

The understanding of the adult proficiency in recognizing and extracting information from faces is still limited despite the number of studies over the last decade. Our knowledge on the development of these capacities is even more restricted, as only a handful of such studies exist. Here we present a combined reanalysis of four ERP studies in children from 4 to 15 years of age and adults (n = 424, across the studies), which investigated face processing in implicit and explicit tasks. We restricted these analyses to what was common across studies: early ERP components and upright face processing across all four studies and the inversion effect, investigated in three of the studies. These data demonstrated that processing faces implicates very rapid neural activity, even in young children--at the P1 component--with protracted age-related change in both P1 and N170, that were sensitive to the different task demands. Inversion produced latency and amplitude effects on the P1 from the youngest group, but on N170 only starting in mid childhood. These developmental data suggest that there are functionally different sources of the P1 and N170, related to the processing of different aspects of faces.

Adolescent↗
PubMed2004

The BOLD hemodynamic response in healthy aging.

Several previous studies have compared the blood oxygen level-dependent (BOLD) hemodynamic response (HDR) in healthy elderly subjects to the HDR in young subjects. Some studies have found a relative decreased amplitude in the elderly in the visual cortex, whereas other studies have found the elderly HDR amplitude in the visual cortex to be nearly identical to that in young subjects. A possible explanation for the different findings is that the peak voxel HDR is similar between the groups, but that the HDR in the group-averaged region-of-interest (ROI) is "washed out" by the inclusion of less significant voxels (due to a smaller extent of activation in the elderly) or by the inclusion of negative-peaking voxels. We tested this hypothesis using event-related functional magnetic resonance imaging (fMRI ). While undergoing fMRI, subjects performed a simple visual and motor task, pressing with their index fingers in response to visual presentation of the word tap. Data from 18 subjects, 8 young and 10 elderly, were analyzed. For each subject, a visual and a motor ROI was selected by choosing the most significant positive voxels within the anatomically defined ROI. This individual subject approach excluded both low-significance and negative-peaking voxels. Similar peaks were found for the elderly and the young subjects in both motor and visual regions and a more sustained BOLD response was found for the elderly in both regions. Additionally, as predicted, a greater percentage of voxels with a negative HDR was found for the elderly in the visual region; this finding was also replicated in our reanalysis of an independent fMRI and aging study from the fMRI Data Center. Functional neuroimaging observations of negative HDRs in visual areas have been interpreted as the effect of unconstrained processing during rest. Our results suggest that the elderly may have more unconstrained visual processing during the rest condition in the scanner. The observation that the group differences in the BOLD response are sensitive to voxel selection (e.g., inclusion of low-significance and/or negative voxels) underscores the importance of ROI selection criteria in the interpretation of fMRI studies using elderly populations.

Adult↗
PubMed2005

Pronominal reference in sentences about persons or things: an electrophysiological approach.

German pronouns (er(MALE/masculine), sie(FEMALE/feminine)) that refer to a person are determined by the biological gender (MALE/FEMALE) and/or syntactic gender (masculine/feminine) of the person. Pronouns (er(masculine), sie(feminine)) that refer to a thing are determined by the syntactic gender of this thing (Garten [garden]masculine, Tasche [hand-bag]feminine). The study aimed to investigate whether semantic integration, syntactic integration, or both are involved in establishing co-reference between pronoun and subject/antecedent in sentences. Here we focused on two event-related potential components: the SPS/P600, related to syntactic violation and reanalysis, and the N400 component, related to semantic integration problems. In one condition, a person was introduced as antecedent and later referred to by a pronoun, which either agreed in biological/syntactic gender or not (biological/syntactic gender violation). In a second condition, a thing was introduced as antecedent and the corresponding pronoun either agreed in syntactic gender or not (syntactic gender violation). Results at critical pronouns showed a P600 effect for incongruent compared with congruent pronouns in both conditions with a centro-parietal maximum. This effect was larger for the person compared to the thing condition. We interpreted this finding as reflecting a syntactic integration process that can be influenced by conceptual/semantic and syntactic information of the antecedent type. Furthermore, at the word following the pronoun, we observed an N400 for the thing but not for the person condition. We suggest, supported by the results of a control experiment, that this effect reflects continuous integration processes for things, whereas for persons the integration seems to be finished at pronoun position.

Adult↗
PubMed2006

The impact of proficiency on syntactic second-language processing of German and Italian: evidence from event-related potentials.

The present study investigated the role of proficiency in late second-language (L2) processing using comparable stimuli in German and Italian. Both sets of stimuli consisted of simple active sentences including a word category violation, a morphosyntactic agreement violation, or a combination of the two. Four experiments were conducted to study high- and low-proficiency L2 learners of German as well as high- and low-proficiency L2 learners of Italian. High-proficiency L2 learners in both languages showed the same event-related potential (ERP) components as native speakers for all syntactic violations. For the word category violation, they displayed an early anterior negativity (ELAN), an additional negativity reflecting reference-related processes, and a late P600 evidencing processes of reanalysis. For the processing of the morphosyntactic error, an anterior negativity (LAN) and a P600 were observed, whereas for the combined violation, the same ERP components were found as in the pure category violation. In high-proficiency L2 learners, the timing of the processing steps was equivalent to that of native speakers, although some amplitude differences were present. Low-proficiency L2 learners, however, showed qualitative differences in the agreement violation characterized by the absence of the LAN and quantitative differences reflected in a delayed P600 in every violation condition. These findings emphasize that with a high proficiency, late L2 learners can indeed show native-like neural responses with the timing approximating that of native speakers. This challenges the idea that there are fundamental differences in language processing in the brain between natives and late L2 learners.

Adult↗
PubMed1996

Bronchoscopic surfactant administration in patients with severe adult respiratory distress syndrome and sepsis.

The present study was performed on 10 patients with severe adult respiratory distress syndrome (ARDS), all suffering from sepsis (mean lung injury score [LIS] (1): 3.25 +/- 0.1; duration of mechanical ventilation upon study entry: 3.1 +/- 0.6 d). Ex vivo analysis of the alveolar surfactant system, obtained by bronchoalveolar lavage (BAL), showed severe impairment of surfactant function. Three hundred milligrams of natural surfactant/kg body weight (Alveofact) was delivered bronchoscopically in separate doses to each segment of both lungs. This caused an immediate increase in PaO2/FlO2 from 85 +/- 7 mm Hg to 200 +/- 20 mm Hg (p < 0.001), mainly due to a decrease in shunt flow (42 +/- 4 to 20 +/- 2% [p < 0.001]). Reanalysis of the alveolar surfactant showed that its function was significantly improved. In five patients the increase in arterial oxygenation was partially lost within the next few hours, and a second dose of 200 mg/kg surfactant was applied 18 to 24 h later, again increasing PaO2/FlO2 values. Eight patients survived the subsequent 14-d observation period with progressive improvement of gas exchange, and five patients were definitely weaned from the respirator. All fatalities were due to non-respiratory causes. We conclude that the bronchoscopic application of a high dose of surfactant aimed at overcoming inhibitory factors in the alveolar space of these patients, may offer a feasible and safe approach to improving gas exchange in severe ARDS.

Adolescent↗
PubMed2000

Association of beta(2)-adrenoreceptor variants with bronchial hyperresponsiveness.

Because of its involvement in the regulation of airway tone, the beta(2)-adrenoreceptor is considered a candidate for bronchial hyperresponsiveness (BHR) associated with asthma. This notion is supported by several reports that have implicated the chromosomal region 5q31-q33 harboring the gene for the beta(2)-adrenoreceptor in the genetics of asthma and related phenotypes. We performed a population-based association study focusing on BHR as a qualitative trait and omitting other asthma-related phenotypes. From a German population sample of 1,150 individuals we extracted all 152 bronchohyperreactive probands, who were compared with 295 bronchonormoreactive control subjects. All individuals were genotyped for three single nucleotide polymorphisms of the beta(2)-adrenoreceptor gene resulting in variants at the amino acid positions 16, 27, and 164. The genotyping protocol used allowed the determination of haplotypes of these polymorphisms. Whereas no individual polymorphism was associated with BHR, the Gly16/Gln27/Th164 haplotype was significantly underrepresented in the case group indicating a protective effect of this haplotype with regard to BHR. Upon reanalysis by sex a significant association persisted only for female probands.

Airway Resistance↗