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Biomedical subjects

A F Wilson

Publications and source records attributed to A F Wilson.

At least 91 records · Page 5Linked to original sources

Linkage analysis of pure depressive disease.

In a study of the subgroups of unipolar affective disease, 13 families were ascertained as pure depressive disease (PDD) families. Here we investigate linkage relationships between PDD and 30 genetic markers in these families. Using the robust sib-pair method of linkage analysis, evidence for possible linkage or association was found with five loci: the ABO and MNS blood groups, immunoglobulin kappa (IGK), proline rich parotid salivary protein (PR) and glyoxylase-1 (GLO1). Weak evidence of linkage with ABO was supported using the lod score method of analysis. The maximum lod score between PDD and ABO was 1.42 at a male recombination fraction of 0.09 and a female recombination fraction of 0.03. When these results from the sib-pair analysis were combined with the results from two previous sib-pair studies on PDD, the ABO, MNS and IGK loci were found to be significant (P = 0.05, P = 0.005, P = 0.05, respectively, not allowing for multiple tests).

Adolescent↗

Evaluation of consistency among different electrical impedance indices of relative cerebral blood flow in normal resting individuals.

Significant correlation was observed, in normal resting individuals, of interregional variation of classical amplitude-dependent electrical impedance indices of cerebral blood flow (CBF) with three quantitative rheographic measures of cerebral blood flow which have been themselves radioisotopically validated. Since these amplitude-related CBF indices are derived from the Nyboer model relating blood volume changes to change of impedance, the data support the correctness and applicability of this model to the head. Interrelationship among the CBF parameters obtained with the use of this technique was found to be markedly affected by differing electrode placements; it was not apparently affected by extracranial circulation. It is concluded that under proper recording conditions, several assumptions underlying rheoencephalography are consistent and that it may be a useful tool for the study of relative regional cerebral blood flow in normal individuals.

Adult↗

Double-blind cross-over placebo controlled study of flunarizine in patients with therapy resistant epilepsy.

Twenty-five patients with long-standing therapy resistant epilepsy were studied in an eight-month double-blind cross-over add-on trial with a daily dose of 15 mg flunarizine. In five patients the seizure frequency decreased 50% or more. The mean seizure frequency reduction in the patients on flunarizine was 35%. Particularly the control of secondary generalized seizures improved. Flunarizine did not significantly alter the plasma levels of the regular anticonvulsant drugs. Minimal adverse side effects were reported equally in the flunarizine and the placebo group. In three patients depressive symptoms improved and two patients became free of postictal headaches. Flunarizine appears to be a safe adjuvant anticonvulsant.

Adolescent↗

Determination of anaerobic threshold by ventilatory frequency.

Detection of anaerobic threshold (AT) requires either invasive techniques or expensive gas analyzers and somewhat complicated procedures. The purpose of this study was to determine if ventilatory frequency (f) could be used to detect AT. Thirteen (seven females) healthy, non-smoking, physically active adults (21-44 years) volunteered to perform progressive cycle exercise. A protocol of either 22.5- or 45-W increments every 2 min was used according to the subject's weight and fitness to assure steady state. Expiratory gas was measured using a computerized breath-by-breath system. Mean values of oxygen uptake (VO2, 1.min-1), ventilation (VE, 1.min-1), and f(br.min-1) were calculated each min. Peak VO2 ranged from 24.8 to 58.9 ml.kg-1.min with a group mean (+/- SD) of 45.1 +/- 11.6 ml.kg-1.min. Mean (+/- SD) VO2 at AT, as determined by disproportionate increase of VE, was 2.11 +/- 0.57 1.min-1. Mean (+/- SD) VO2 at the point of disproportionate increase of f was 2.09 +/- 0.58 1.min-1. A significant (P less than 0.05) correlation (r = 0.834) was found between the point of disproportionate increase in f and that of VE for individual data. A Student's t test indicated there was no significant difference in mean VO2 at AT. It was concluded that AT could be detected by f in healthy, physically active adults, thus providing a simplified and less expensive alternative method. This finding may have implications with regard to establishing and monitoring exercise intensity.

Adult↗

Effects of thoracic gas compression on maximal and partial flow-volume maneuvers.

Airway hysteresis can be evaluated by comparing maximal (MEFV) and partial (PEFV) expiratory flow-volume curves. The maneuvers are often obtained from pulmonary function systems that are subject to gas-compression artifacts. Because gas-compression artifacts might differentially affect PEFV vs. MEFV curves, we simultaneously obtained MEFV and PEFV curves by use of a spirometer and a volume-displacement plethysmograph (a method not subject to gas-compression artifacts) in normal and asthmatic subjects. Plethysmographic flow rates exceeded spirometric flow rates on all MEFV and PEFV maneuvers. When maximal flow exceeded partial flow (or vice versa) in the plethysmograph, the same result was virtually always observed for spirometric measurements. Alveolar pressure (PA) was higher on MEFV than on PEFV maneuvers in asthmatic subjects; comparisons between PA (on PEFV and MEFV maneuvers) in normal subjects varied at different lung volumes. Ratios of Vmax on PEFV maneuvers to Vmax on MEFV maneuvers (Vmax-p/Vmax-c) obtained from a volume-displacement plethysmograph differ quantitatively from ratios determined in systems subject to gas-compression artifacts; qualitatively, however, failure to account for thoracic gas compression ordinarily will not influence the ability to identify airway hysteresis (or lack thereof) by use of Vmax-p-to-Vmax-c ratios.

Adult↗

Is lung sequestration of indium-111-labeled granulocytes organ specific?

Transient sequestration of polymorphonuclear leukocytes (PMN) in the normal lungs of animals occurred immediately following intravenous injection of 111In-labeled PMN. We investigated the organ specificity of this process. Equal amounts of homologous PMN, derived from the intravascular space and labeled with [111In]oxine, were infused either intravenously (i.v.) or intraarterially (i.a.) into pairs of rats. Changes in radioactivity emitted from three regions--representing lung, liver and spleen, and lower body--were determined from images during the following hour. A nonspecific character was demonstrated by the transient sequestration of activity in the lower body following i.a. infusions. However, the rate of initial clearance of activity (first 30 min) from the lungs of i.v.-infused rats was relatively slower than from the lower body of i.a.-infused rats. This suggests the presence of a lung-specific as well, which may be important for localization of PMN-related events to the lung.

Animals↗

Evidence for possible linkage between genetic markers and affective disorders.

Studies of the underlying components of affective disorders are particularly difficult because of the confounding effects of both genetic and environmental factors. Linkage analysis is a useful tool in delineating the etiology of affective disorders, as it is unlikely that linkage between behavioral traits and blood group polymorphisms could result from environmental effects. The present study used the robust Haseman and Elston sibpair method to analyze linkage between 24 genetic markers and affective disorder in 34 nuclear families from 25 pedigrees (195 people). The probands were ascertained as part of the ongoing NIMH Collaborative Depression Study. Indications of linkage between familial pure depressive disease and MNS and depression spectrum disease and ORM were found, as had been previously suggested. There was also suggestive evidence for linkage between the latter and GC. Results are discussed in terms of methodological differences with previous studies.

Bipolar Disorder↗

Hypotheses for testing deviations from random integration: evidence for nonrandom retroviral integration.

The use of a recently developed in vitro model for retroviral integration provides a means of statistically testing hypotheses concerning the distribution of integration sites and hypotheses about the sequence of proviral orientations. In this study, three null hypotheses are formulated and applied to previously published data. Statistical analyses of these data suggest that the distribution of integration sites may not be uniform, and the sequence of proviral orientations is not random. On the basis of these results and the observed clustering of orientations, it was postulated that if a DNA sequence was involved in nonrandom proviral integration, that sequence would be found in the regions where the orientations change direction with respect to the target DNA ("I" regions). Computer analyses for homologous and complementary DNA sequences were performed on all possible pairs of identifiable "I" regions. A common sequence (at least 8 bp in size) was found in three out of four regions and that sequence was absent elsewhere in the target DNA. A model, with features of recombination reminiscent of chi sequences in bacteria, is proposed that may account for these results.

Biometry↗

Mechanisms of expiratory valves resistance.

Expiratory valves are the major source of resistance in ventilator circuits. Some valves, particularly under certain conditions, cause high resistances. To establish the mechanisms of expiratory valve resistance (R), we measured R of 4 commercial valves under several experimental conditions. The pressure above the diaphragm of one of the valves was also measured. The results reveal that all valves produce significant resistance to air outflow. This resistance is the result of the physical and functional interplay of several valve components. (1) In most valves, the dimensions of the air pathway through the valve contribute minimally to resistance in spite of its tortuosity. (2) The diaphragm adds a major contribution to valve resistance particularly at low flows. The diaphragm effect has 2 components: its weight--a gravity-dependent, fixed effect most predominant at very low flows and evident in all the valves--and a spring-like effect--a component related to the resistance of the diaphragm to deformation and of variable magnitude in different valves. Because of diaphragm-related components at low flows, valves behave as variable threshold resistors. (3) There is limitation to air egress from above the diaphragm at higher exhaled flows, which further contributes to valve resistance. The first and last components cause the valves to function also as flow resistors. Constant flows effectively counteract the diaphragm spring-like effect. Measuring valve resistance during constant flow underestimates the resistance that occurs under dynamic flow conditions characteristic of clinical situations.

Equipment Design↗

Possible linkage between alcoholism and esterase-D.

Association and linkage relationships between alcoholism and 30 polymorphic marker loci were studied in a total of 42 families: 27 families originally collected as part of a study on depression spectrum disease, 14 previously reported families with depression spectrum disease, and 1 family with familial alcoholism. Since heterogeneity within a sample can confound genetic linkage analysis, obscuring linkage relationships, alcoholism was studied in these families as a disorder unrelated to depression or antisocial personality. No allelic associations were found to be significant after allowing for the multiple tests. In a sib-pair linkage analysis, significant differences between the mean proportion of genes identical by descent in concordant and discordant sib pairs were found for the esterase-D (ESD) marker locus (p less than or equal to .01). This suggested that a linkage may exist between a gene for alcoholism and the ESD locus on chromosome 13q. Lod score linkage analysis yielded odds in favor of linkage to ESD of 44 to 1, most of the information relevant to linkage residing in a single family in which three offspring were classified as alcoholic and five were not.

Adult↗

Linkage of a gene regulating dopamine-beta-hydroxylase activity and the ABO blood group locus.

Previous studies have presented evidence suggesting that levels of dopamine-beta-hydroxylase (DBH) activity are controlled by a gene linked to the ABO blood group locus. In this study, linkage analyses in four large families of whites and one family of blacks were performed on the untransformed and on the square root--and natural log--transformed DBH activity. In the families of white individuals, the results of both the sib-pair and lod-score linkage analyses strongly indicate that a gene regulating DBH activity is linked to the ABO blood group locus on chromosome 9q (i.e., lod score 5.88 at a recombination fraction of .0). However, the transformation used has a large effect on the maximum lod score and estimated recombination fraction. This putative gene does not appear to be polymorphic in the family of blacks.

ABO Blood-Group System↗

A linkage study of panic disorder.

We tested for linkage between panic disorder and a battery of 29 genetic markers in 26 families. Linkage between panic disorder and 18 of the marker loci could be excluded at a recombination fraction of 0.00, nine at a recombination fraction of 0.05, and four at a recombination fraction of 0.10. The 18 loci are distributed over ten chromosomes. One locus was suggestive of linkage. The maximum lod score for alpha-haptoglobin was 2.27 at a recombination fraction of 0.0, representing odds in favor of linkage of 186.1. alpha-Haptoglobin has been mapped to chromosome 16q22. The results demonstrate that linkage studies of psychiatric disorders can yield informative results by identifying tentative linkages that merit further investigation and by excluding regions of the genome from future linkage searches.

Adult↗

Segregation and linkage analyses of dopamine-beta-hydroxylase activity in a six-generation pedigree.

Serum dopamine-beta-hydroxylase (DBH) levels and 30 polymorphic markers were determined on 178 individuals of the HGAR 29 family, ascertained through six probands who had clinical and electrocardiographic evidence of myocardial infarction. Individuals in this pedigree with a history of heart attack had significantly lower levels of DBH, but this difference was partly confounded with age differences. Pedigree segregation analysis showed evidence of a codominant gene for DBH segregating in the family. Linkage analysis between the putative DBH locus and 30 polymorphic marker loci, assuming a codominant model, yielded a largest lod score of 0.53, with ABO at 20% recombination. Adding this to the lod scores obtained by Elston et al [1979] and Goldin et al [1982], we obtain combined lod scores of 2.49 and 2.50 at 0.0 and 10% recombination respectively.

ABO Blood-Group System↗

A major gene model for the familial aggregation of plasma IgA concentration.

Plasma IgA concentration was determined on 94 individuals of an eastern Kentucky family (IGANI) with some members having clinical and biopsy-proven IgA nephropathy, and on 197 individuals of a large Louisiana family (HGAR29) with no clinical history of IgA nephropathy but on whom 30 polymorphic markers had previously been typed. Pedigree segregation analysis was used to fit a major gene model, and a moderately large lod score for linkage to the ABO locus (1.50 at 0% recombination) suggested the existence of a recessive allele for high plasma IgA concentration. This allele is only slightly more prevalent in pedigree IGANI than in pedigree HGAR29, indicating that it is a minor, rather than a major, etiologic factor in IgA nephropathy.

Adult↗

Linkage and segregation analyses of apolipoproteins A1 and B, and lipoprotein cholesterol levels in a large pedigree with excess coronary heart disease: the Bogalusa Heart Study.

Robust methods were employed, using data from a single large pedigree, to screen serum apolipoprotein A1 and B levels, serum lipoprotein cholesterol levels, and ratios of serum lipoprotein cholesterol fractions to apolipoprotein A1 and B levels for genetic linkage to 31 polymorphic markers. Segregation analyses were performed for each of the apolipoprotein and lipoprotein cholesterol fractions to obtain estimates for use in applying likelihood methods of linkage analysis. Trait-marker combinations for which linkages were suggested from the robust methods were then reexamined for linkage using the likelihood (lod score) method. Results from the segregation analyses were consistent with major gene determination of apo B and HDL-C levels, the HDL-C to apo A1 ratio, the LDL-C to apo B ratio, and a measure of relative content of cholesterol in HDL-C and LDL-C. Linkage between haptoglobin and the HDL-C/apo A1 ratio was suggested, with a lod score of 1.72 at theta = 0.05.

Apolipoprotein A-I↗

Effects of cortical lesions on middle-latency auditory evoked responses (MLR).

Middle-latency auditory evoked responses (MLRs) were recorded simultaneously at 3 or 4 electrode locations in the coronal plane in 5 normal subjects, 11 patients with temporal lobe lesions and in 5 patients with cortical lesions not involving the temporal lobes. In patients with unilateral temporal lobe lesions, the amplitude of Pa and hence that of the Na-Pa complex was reduced over the involved hemisphere but remained intact over the contralateral hemisphere. No MLR asymmetries were demonstrated in patients with cortical lesions that did not affect the temporal lobes or in 2 cases with unilateral anterior temporal lobectomy. The latency of wave V of the auditory brain-stem response was within normal limits in the majority of the patients studied regardless of the site of their cortical lesion.

Adult↗