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Biomedical subjects

D A Meyers

Publications and source records attributed to D A Meyers.

At least 19 recordsLinked to original sources
PubMed1992

Fetal hemoglobin levels in sickle cell disease and normal individuals are partially controlled by an X-linked gene located at Xp22.2.

Fetal hemoglobin (Hb F) production in sickle cell (SS) disease and in normal individuals varies over a 20-fold range and is under genetic control. Previous studies suggested that variant Hb F levels might be controlled by genetic loci separate from the beta-globin complex on chromosome 11. Using microscopic radial immunodiffusion and flow cytometric immunofluorescent assays to determine the percentage of F reticulocytes and F cells in SS and nonanemic individuals, we observed that F-cell levels were significantly higher in nonanemic females than males (mean +/- SD, 3.8% +/- 3.2% v 2.7% +/- 2.3%). F-cell production as determined by F reticulocyte levels in SS females was also higher than in SS males (17% +/- 10% v 13% +/- 8%). We tested the hypothesis that F-cell production in both normal and anemic SS individuals was controlled by an X-linked locus with two alleles, high (H) and low (L). Using an algorithm to determine the 99.8% confidence interval of a normal distribution in nonanemic individuals, we estimated that males and females with at least one H allele had greater than 3.3% F cells. Comparisons of male-male or female-female SS sib pairs with discordant F reticulocyte levels distinguished two phenotypes in SS males (L, less than 12%; H, greater than 12%) and three phenotypes in SS females (LL, less than 12%; HL, 12% to 24%, HH greater than 24%). Linkage analysis using polymorphic restriction sites along the X chromosome in eight SS and one AA family localized the F-cell production (FCP) locus to Xp22.2, with a maximum lod score (logarithm of odds of linkage v independent assortment) of 4.6 at a recombination fraction of 0.04.

Adult↗
PubMed1992

The influence of weight reduction and exercise regimes upon the personality profiles of overweight males.

In the present study, the MMPI was used to detect personality changes in 53 overweight, yet otherwise healthy, males who were participating in either a weight reduction or an aerobic exercise conditioning program. Analysis of pre- and post-intervention scores revealed that only the participants in the aerobic conditioning group demonstrated the predicted desirable psychological changes. More specifically, this group displayed significant clinically desirable changes on the Hs, PD, and HEA scores. Similar to the weight loss participants, a demographically matched nonintervention comparison group showed none of these desirable changes and actually yielded a significant increase on the D scale. However, when compared to this "normal" group, both intervention programs showed statistically significant differences on at least two MMPI scales.

Age Factors↗
PubMed1992

Evidence for the localization of a malignant hyperthermia susceptibility locus (MHS2) to human chromosome 17q.

Malignant hyperthermia susceptibility is a lethal autosomal dominant disorder of skeletal muscle metabolism that is triggered by all potent inhalation anesthetic gases. Recent linkage studies suggest a genetic locus for this disorder on 19q13.1. We have previously reported three unrelated families diagnosed with MHS that are unlinked to markers surrounding this locus on 19q13.1. In this report we extend these observations and present linkage studies on 16 MHS families. Four families (25%) were found linked to the region 19q12-q13.2 (Zmax = 2.96 with the ryanodine receptor at theta = 0.0). Five families (31%) were found closely linked to the anonymous marker NME1 (previously designated NM23) on chromosome 17q11.2-q24 (Zmax = 3.26 at theta = 0.0). Two families (13%) were clearly unlinked to either of these chromosomal regions. In five additional families, data were insufficient to determine their linkage status (they were potentially linked to two or more sites). The results of our heterogeneity analyses are consistent with the hypothesis that MHS can be caused in humans by any one of at least three distinct genetic loci. Furthermore, we provide preliminary linkage data suggesting the localization of a gene in human MHS to 17q11.2-q24 (MHS2), with a gene frequency of this putative locus approximately equal to that of the MHS1 locus on 19q.

Adult↗
PubMed1992

Atopy and bronchial hyperresponsiveness: exclusion of linkage to markers on chromosomes 11q and 6p.

Previous studies have reported a familial predisposition for the development of atopy, bronchial hyperresponsiveness and clinical asthma, and therefore have suggested the presence of a heritable component to these disorders. The specific contributions of genetic and environmental factors in the pathogenesis of allergic disease and asthma have not been determined although Cookson et al. [1] have postulated linkage between atopy and chromosome 11q. We have studied 20 families (two and three generations) ascertained through a proband identified as having asthma (90% were also allergic) during the period of time between 1962 and 1970. Of those who were originally skin test positive, 82% remained positive. All probands whose pulmonary function allowed retesting (FEV1 > 1.2 l) remained hyperresponsive to histamine. The children of these probands are now in the same age range as their parents when they were originally evaluated; 66% are atopic using criteria described by Cookson et al. (one or more positive skin tests > or = 2 mm, an elevated total serum IgE or a positive specific IgE) and 22% demonstrate bronchial hyperresponsiveness (PC20 FEV1) to histamine. Using the highly polymorphic marker INT2 (which maps 2 cM from p lambda MS.5 l on chromosome 11q) and atopy, we obtained a lod score of -2.00 at a recombination fraction of 0.12. In addition, because many studies have suggested an association between atopy and certain HLA antigens, we investigated the possibility of linkage between atopy and bronchial hyperresponsiveness and D6S105, a polymorphic marker on chromosome 6p, located 7 cM from HLA-DR. For this marker and atopy, we observed a lod score of -2.00 with a recombination fraction of 0.07.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Assessment of lineality in bipolar I linkage studies.

OBJECTIVE: To assess lineality in families of bipolar I probands, the authors used direct interviews of family members to reclassify families initially categorized as unilineal by family history. METHOD: The families of 1,800 treated bipolar I probands were screened by the family history method with multiple informants. If the proband had one or more affected sibs and one apparently unaffected parent, the parents (and then other available first- and second-degree relatives) were directly interviewed by psychiatrists. RESULTS: Of the 1,800 families screened, 56 were apparently suitable unilineal families with multiple affected members; 46 families were interviewed directly. After interviews with the parents, 12 families (26.1%) were found to be bilineal. Direct interviews of all available relatives in the 34 remaining families revealed that only 22 (47.8% of the 46 interviewed families) were unilineal or probably unilineal and 12 were probably bilineal. The probably bilineal families had a significantly higher proportion of siblings with unipolar disorder. In addition, the affected sibs from the probably bilineal families tended to have earlier onsets but had significantly fewer symptoms in the most severe depressive episode. CONCLUSIONS: Fewer than 50% of bipolar I families appearing unilineal according to family history were found to be unilineal by direct interviews. The phenotypic differences between the affected sibs from the probably bilineal families and those from the unilineal and probably unilineal families suggest differences in genetic mechanisms. These findings highlight the need to systematically assess lineality in all families considered for bipolar I linkage studies and support the preferential inclusion of unilineal families in linkage studies.

Adult↗
PubMed1992

Budesonide in grass pollen rhinitis.

To determine the relative efficacy, to compare the incidence of adverse experiences, and to assess the systemic glucocorticoid effect of nasal preparations of budesonide, 200 micrograms bid, and placebo, 50 adult patients with seasonal allergic rhinitis due to grass pollen were studied in a stratified, double-blind parallel group design. After a 2-week baseline period, budesonide nasal spray, 100 microgram per nostril twice a day, was compared with placebo nasal spray over a 4-week treatment period. Supplementary treatment with chlorpheniramine, 4-mg tablets, was permitted when necessary to control symptoms. Daily symptom and medication diaries were kept by the patients. Investigator assessments of symptoms and side effects were made at clinic visits at 2-week intervals. At baseline and again towards the end of the study, blood samples were drawn for the determination of plasma cortisol levels and 24-hour urine samples collected for the measurement of 17-hydroxycorticosteroid output. Of the 24 men and 26 women entering, 49 completed the study. Symptom scores for sneezing, stuffy nose, and nasal secretion all decreased dramatically from baseline when budesonide treatment was started. The decrease in symptoms was greater for budesonide than for placebo (P < .001). There was no difference between budesonide and placebo with regard to eye itch and rescue medication used. Morning nasal washes were taken during the grass season before treatment was started and 16 to 17 days after. They showed a significant decrease in TAME esterase levels in secretions in the budesonide treated patients (P = .03) but not in the placebo-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Genetics of total serum IgE levels: a regressive model approach to segregation analysis.

The genetics of basal total serum IgE levels was investigated in 278 individuals from 42 randomly ascertained nuclear families. The data were analyzed using the regressive model approach to segregation analysis with age, sex, and a measure of skin test responsiveness as covariates in the Class D models. The best fitting model was that of recessive inheritance of high IgE levels with a gene frequency of 0.99 for the "high" allele. Only 3 families showed evidence for segregation of the rare "low" allele, and, if extended further, these families could be useful for molecular genetic linkage studies. These results suggest that there may be a rare allele for very low total serum IgE levels that can be detected even after a measurement of allergic responsiveness (skin test results) is considered as a covariate. Therefore, this major gene for IgE levels appears independent of any similar locus controlling atopy.

Adolescent↗
PubMed1991

Evidence for genetic heterogeneity in malignant hyperthermia susceptibility.

Malignant hyperthermia susceptibility (MHS) is a clinically heterogeneous pharmacogenetic disorder characterized by accelerated metabolism, hyperthermia, and frequently muscle rigidity. MHS is elicited by all commonly used potent inhalation anesthetics and depolarizing neuromuscular blockers and remains an important cause of death due to anesthesia. Recent linkage studies suggest a single genetic locus for this disorder on chromosome 19q13.1. The results of our linkage analyses exclude several loci on 19q13.1 as a site for the gene(s) that produces the MHS phenotype in three unrelated families and clearly establish genetic heterogeneity in this disorder. These results are consistent with the hypothesis that the genetic defect that alters thermoregulation may vary in MHS and that clinical variability in the expression of MHS may be explained by genetic heterogeneity.

Chromosomes, Human, Pair 19↗
PubMed1991

Chromosomal deletion 4p15.32----p14 in a Treacher Collins syndrome patient: exclusion of the disease locus from and mapping of anonymous DNA sequences to this region.

Treacher Collins syndrome is an autosomal dominant condition of bilateral craniofacial abnormalities of structures derived from the first and second branchial arches. A patient with severe manifestations of Treacher Collins syndrome and a de novo chromosomal deletion in region 4p15.32----p14 was identified. Anonymous DNA sequences of loci D4S18, D4S19, D4S20, D4S22, and D4S23 were mapped to the deleted region. DNA probes previously mapped to loci on chromosome 4p (D4S10, D4S15, D4S16, D4S26, D4S35, D4S95, D4S144, RAF1P1, QDPR, and HOX7) were not deleted in this patient. Linkage analysis between the D4S18, D4S23, and QDPR loci and Treacher Collins syndrome in eight families excluded the Treacher Collins syndrome locus from the region of the deletion.

Chromosome Deletion↗
PubMed1991

Alphoid DNA polymorphisms for chromosome 21 can be distinguished from those of chromosome 13 using probes homologous to both.

Although alphoid DNA sequences shared among acrocentric chromosomes have been identified, no human chromosome 21-specific sequence has been isolated from the centromeric region. To identify alphoid DNA restriction fragment length polymorphisms (RFLPs) specific for chromosome 21, we hybridized human genomic DNA with alphoid DNA probes [L1.26; aRI(680),21-208] shared by chromosomes 13 and 21. We detected RFLPs with restriction enzymes ECoRI, HaeIII, MboI,StuI, and TaqI. The segregation of these RFLPs was analyzed in the 40 CEPH families. Linkage analysis between these RFLPs and loci previously mapped to either chromosome 13 or 21 revealed RFLPs that appear to be specific to chromosome 21. These polymorphisms may be useful as genetic markers of the centromeric region of chromosome 21. Different alphoid loci within the centromeric region of chromosome 13 were identified.

Centromere↗
PubMed1991

The Marfan syndrome locus: confirmation of assignment to chromosome 15 and identification of tightly linked markers at 15q15-q21.3.

The Marfan syndrome is a common autosomal dominant disorder of connective tissue. Despite many years of intensive investigation, the primary genetic defect has not yet been identified. Reverse genetic methods, targeted at mapping this disease gene, have resulted in an initial report of linkage of the genetic locus for the Marfan phenotype in Finnish families to two polymorphic markers on chromosome 15. We have investigated four large multiplex American families with classic Marfan syndrome using standard genetic linkage methods. Our data confirm the assignment of the Marfan syndrome gene to chromosome 15, but establish a more centromeric location (defined by markers D15S25 and D15S1) as the most probable site for the genetic defect (lod score = 12.1, theta = 0.00). These data should facilitate identification and characterization of the Marfan syndrome gene and, in selected families, have immediate application to diagnosis of equivocal cases or prenatal counseling.

Chromosome Mapping↗
PubMed1991

Relationship of obesity and physical fitness to cardiopulmonary and metabolic function in healthy older men.

The relationship of obesity and physical fitness (VO2max) to cardiopulmonary and metabolic function was examined in 132 healthy obese, nonsmoking men age 45-79. Obese men with higher VO2max had lower % body fat and waist-to-hip ratio (WHR) than obese men with low VO2max. The obese subjects with high WHR (upper body fat distribution) had higher systolic blood pressure, hyperinsulinemia and impaired glucose tolerance, lower high density lipoprotein cholesterol (HDL-C), and higher triglyceride (TG). VO2max (ml/kg FFM.min) was lower in the older men (r = -0.54, p less than .001), and 32% of the variation was accounted for by age and the one-second forced expiratory volume. Although pulmonary function was normal, 50% of the variability was predicted by age, height, and VO2max or WHR. Glucose tolerance and insulin correlated better with VO2max and indices of body composition than with age, while plasma TG and HDL-C correlated with body composition, not VO2max or age. Thus, while age affects the cardiopulmonary and metabolic function of obese older men, physical inactivity, obesity, and an abdominal body fat distribution (increased WHR) contributed significantly to their reductions in physiological function.

Aged↗
PubMed1991

Mapping the Treacher Collins syndrome locus to 5q31.3----q33.3.

Treacher Collins syndrome is an autosomal dominant disorder of abnormal craniofacial development. Linkage analysis was performed in Treacher Collins families with restriction fragment length or microsatellite polymorphisms associated with eight loci previously mapped to 5q31----qter. Positive lod scores were obtained for four loci, D5S119, D5S207, D5S209, and D5S210, which map to 5q31.3----q33.3. The Treacher Collins syndrome locus was linked closest to locus D5S210, which is associated with microsatellite polymorphisms, with a maximum lod score of 8.65 at theta = 0.02. The Treacher Collins syndrome locus was excluded from locus ADRB2R, which maps to 5q31----q32, and loci D5S22, D5S61, and D5S43, which map to 5q34----qter. There was no evidence for genetic heterogeneity among eight families with variable expression of the condition.

Chromosome Mapping↗
PubMed1990

Clinical trials in asthma and chronic airflow obstruction.

Clinical trials are becoming increasingly important in objectively evaluating therapeutic interventions in pulmonary medicine. Although the overall methodology for clinical trials is similar for most diseases, there are specific questions and problems unique to pulmonary medicine. This review is limited to a discussion of the general design and commonly encountered "problems and pitfalls" for clinical trials in respiratory medicine. Three examples of designs for intervention in asthma and chronic obstructive airways disease are presented.

Asthma↗