Power and type I error in affected sib-pair methods under restricted estimation conditions.
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Alleles↗
Biomedical subjects
D V Dawson
Publications and source records attributed to D V Dawson.
Genetic analysis of HLA in the U.S. Schmiedenleut Hutterites.
The Hutterites are an Anabaptist population, highly inbred, with large family sizes and extensively documented pedigrees. As part of genetic-epidemiologic studies of the impact of HLA on fertility, HLA-A, -B, -C, -DR, and -DQ typing was performed on a total of 650 Schmiedenleut Hutterities in South Dakota. An extraordinary degree of homogeneity was found. HLA-A1, -A2, -A3, -A24, and -A26 accounted for 83%, HLA-B8, -B27, -B35, -B51, -Bw60, and -Bw62 for 75%, and HLA-DR1, -DR2, -DR3, and -DR4 for 66% of the antigens at the respective HLA-A, -B, and -DR loci. All Hutterites characterized for HLA were descendants of no more than 78 ancestors. However, family analysis identified only 45 unique HLA haplotypes thought to reflect the original gene pool. Eight haplotypes were particularly frequent, accounting for nearly 50% of all observed haplotypes; four of these were consistent with a European ancestry. Coefficients measuring linkage disequilibrium were computed from haplotypes identified by family analysis. Overall, HLA analysis portrayed the Schmiedenleut Hutterities as a homogeneous and unique population, with disequilibrium among particular alleles and a spectrum of common and uncommon European haplotypes.
Alleles↗
Evidence that amphetamine with physical therapy promotes recovery of motor function in stroke patients.
We conducted a double-blind pilot study of 8 patients with established cerebral infarction to evaluate the effect of a single dose of amphetamine on recovery of motor function using the Fugl-Meyer scale. Four patients received amphetamine; the rest were given placebo. All underwent a session of physical therapy. Patients treated with amphetamine obtained greater increments in motor scores than the controls. Along with animal studies, these findings may allow the development of a pharmacological approach to stroke rehabilitation.
Aged↗
Depression in early-onset Alzheimer's disease: clinical and neuroendocrine correlates.
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Aged↗
Alloantibody responses in multiply transfused sickle cell patients.
Fifty-six adult and 15 pediatric black patients with sickle cell disease were studied to determine their antibody responses to repeated transfusions of red cells. Red cell antibodies were determined retrospectively; anti-lymphocyte antibodies (class I and II) were determined on the single, most recently drawn blood sample. All adults were HLA-A, B, C, DR and DQ typed. Ten percent of the individuals with less than 50 transfusions, but greater than 50% with 100 transfusions or more, had red cell antibodies. The percentage of patients producing anti-red cell antibodies increased consistently with the number of transfusions (p = 0.0062). Women were more likely to become sensitized to red cell antigens than men (p = 0.008), and nulliparous women more likely than multiparous women. Children were also sensitized to red cell antigens (20%), and to a high degree to lymphocyte antigens (73%). No HLA association was found with increased propensity to red cell sensitization. A weak association of HLA DR5 and DR7 with failure to become sensitized to lymphocyte alloantigens was observed, but did not reach statistical significance. Our results suggest that, while genetic factors influencing transfusion response almost certainly exist, other factors such as number of transfusions, age, sex and parity need to be examined to provide accurate projections of risk in chronic transfusion.
Age Factors↗
Hereditary motor and sensory neuropathy, X-linked: a half century follow-up.
The existence of an X-linked sensorimotor peripheral neuropathy has been debated. We reevaluated the original family, and present data on 13 affected males and 25 obligate or probable heterozygous females, documenting the devastating nature of the disease in the men and the extremely variable degree of clinical involvement in the carriers. Use of DNA probes indicates that the gene lies in the DXYS1-p58-1 region of the X-chromosome.
Adolescent↗
Probabilistic assessment of the degree of antigen sharing in couples with impaired reproductive performance.
Increased histocompatibility antigen sharing has been reported in couples experiencing recurrent infertility problems. Mathematical expressions describing the probability distribution of the number of antigens shared by randomly mating couples are derived for a single locus, two linked loci, and multiple independent systems. These theoretical frequencies are applied in concert with conventional statistical procedures to evaluate hypotheses concerning antigen distributions. Extensions for simultaneous consideration of other genetic systems are discussed.
Abortion, Habitual↗
Genetic control of susceptibility to mite-associated ulcerative dermatitis.
Variable susceptibility to mite-associated ulcerative dermatitis (MAUD) attributable to Myobia musculi infestation was studied in breeding stocks of sixteen inbred strains of mice. Statistical evaluation of 41 occurrences of lesion among 1,517 mice of the various strains indicated that significant differences in the frequency of MAUD were associated with differences in genetic background and in the H-2 type. These findings suggest that the occurrence of an ulcerative skin lesion in inbred mice exposed to M. musculi is controlled by at least two genes. Lesion susceptibility appears to be profoundly affected by a non-H-2 linked gene or gene combination shared by all C57Bl background strains. In addition, a major influence is exerted by one or more genes within the H-2 complex.
Animals↗
A bivariate problem in human genetics: ascertainment of families through a correlated trait.
In genetic analysis of pedigree data, nonrandom sampling occurs commonly and appropriate adjustments for the ascertainment procedure are necessary for the correct interpretation of results. In this paper we consider ascertainment models for the situation in which proband selection is made on the basis of one trait, but the desired object of analysis is another related trait for which the individuals in the pedigree also are measured. The ascertainment function corresponding to the most useful bivariate form, that involving two correlated quantitative traits, is described explicitly under suitable assumptions. As its form is mathematically intractable for purposes of pedigree analysis, an approximation is developed. Such ascertainment models accomplish corrections for ascertainment while permitting adjustment for covariates, analysis of traits correlated with the trait used in selection, and multivariate analysis of nonrandomly sampled pedigrees using linear combinations of traits.
Gene Expression Regulation↗
Autologous mixed lymphocyte reaction in patients with myasthenia gravis: correlation with disease activity.
Enriched subpopulations of peripheral blood mononuclear cells from patients with myasthenia gravis and from normal control individuals were tested for proliferative ability in the autologous mixed lymphocyte reactions. Myasthenia gravis patients were studied at various phases of therapy. Longitudinal patient populations were studied. Purified T cells from untreated patients with active myasthenia gravis demonstrated enhanced proliferative responses when co-cultured with nonmodified autologous non-T cells. Furthermore, treatment by thymectomy with or without prior plasmapheresis was associated with a consequent normalization of the autologous reaction. The enhanced autologous mixed lymphocyte reaction in the pre-treatment group of myasthenia gravis patients was significantly different from the post-treatment and normal control groups (Stimulation Index, p less than 0.01 and p less than 0.02, respectively). This difference in activity was also confirmed in a longitudinal study of 10 patients followed pre- and post-treatment (Stimulation Index, p less than 0.02). There was no difference between the responses of post-treatment patients and normal control individuals. There was no evidence of altered T cell responsiveness or non-T cell stimulation, as measured by the allogeneic mixed lymphocyte reaction or by mitogen-induced lymphocyte proliferation, between pretreatment and post-treatment patients as compared to controls. The responses were not affected by serum substitution experiments whereby myasthenic responder T cells were co-cultured with pooled normal human sera. Other parameters studied included clinical status, anti-acetylcholine receptor antibody levels, and thymic pathology. An intriguing connection between abnormalities in the thymic cell populations and the autoaggressive state in myasthenia may be reflected by the in vitro autologous mixed lymphocyte reaction.
Adolescent↗
Age-of-onset heterogeneity in Huntington disease families.
Ten Huntington disease (HD) families are analyzed using maximum likelihood methods to study age-of-onset (AO) heterogeneity. Both age of onset and age at examination are used in calculating an individual's likelihood of being affected; familial correlations and family structure are not included in the model. The model allows for differences in current age distributions by considering the distribution of age of onset conditional on age at examination. Families are grouped according to family type (ie, juvenile-onset families and adult-onset families) and then analyzed within each family type as well as between the two types, using both a chi-square test for heterogeneity and F-ratios. The results of the chi-square analyses indicate heterogeneity in AO among the individual families as well as between the two family types. However, the results of the F-ratios show no significant difference between the two family types, indicating that the difference in the chi-square analysis between the two family types is mostly owing to variation among the families. Thus, the results demonstrate that the existing variation in age of onset between these two family types is dwarfed by the magnitude of the variation among the families within each type. This implies that families of sufficient size should be evaluated individually for age-of-onset data for the purpose of either genetic counseling or linkage studies.
Adolescent↗
The predictive value of 2,-4, dinitrochlorobenzene skin testing in patients with bilharzial bladder cancer.
A group of 40 patients with bilharzial bladder cancer underwent quantitative skin testing with dinitrochlorobenzene and purified protein derivative of tuberculin before radical surgery. Correlations were made between various clinical parameters, patient outcome, skin test results and pathologic changes in the resected bladder and draining lymph nodes. Striking associations between dinitrochlorobenzene responses and tumor stage, tumor recurrence and several specific parameters of lymph node stimulation were found, while no correlations were made with the pathologic grade, size or type of tumor, degree of schistosomal infestation or tumor bed inflammation. Purified protein derivative responses showed no correlation with any parameter examined. Patient outcome also showed a good correlation with tumor stage and draining lymph node reaction. These findings indicate that dinitrochlorobenzene skin testing as a presumptive test of cell-mediated immunity may represent a good predictor of clinical outcome in patients with bilharzial bladder cancer, and correlates well with draining lymph node stimulation.
Dinitrochlorobenzene↗
Histocompatibility testing for keratoplasty in high-risk patients.
Forty-eight consecutive patients at high risk for corneal graft rejection were transplanted with corneas from donors selected on the basis of a negative lymphocyte crossmatch, ABO blood group compatibility, and maximized HLA-A, -B matching. Graft survival in this study group was compared to a retrospective control group of 72 consecutive high-risk transplants performed in patients receiving randomly obtained corneal donors. Demographic parameters, cause of primary disease, and incidence of prior graft rejection were no different between the two groups. Graft survival at one year, calculated by the Kaplan-Meier method, was 78% for the negative crossmatch study group vs 52% in the uncrossmatched control group (P less than 0.05%). All graft failures in the negative crossmatch group were in poorly HLA matched recipients. While patients with evidence of nondonor specific humoral presensitization to HLA antigens experienced earlier graft rejection, overall graft survival was not associated with such nonspecific presensitization. These findings indicate that prospective histocompatibility testing can improve corneal allograft survival for high-risk patients by better identification of appropriate donors.
Adult↗
HLA-B15 association with erythema multiforme.
Erythema multiforme (EM) is a cutaneous reaction pattern which follows numerous infections, drugs, neoplastic and inflammatory disorders in some individuals. We undertook a prospective study of thirty-eight HLA specificities of the -A, -B, and -C series in 16 Caucasian patients with EM and in 140 local Caucasian controls. Seven of 16 patients (44%) with EM and 5 of 9 patients (55%) with EM following herpes simplex infections possessed the HLA-B15 antigen, compared to 7% of local controls and 11.6% of the 1980 WHO Workshop Caucasian controls. Both associations were highly significant (p = 0.0125 and p = 0.02) when corrected for 38 HLA antigens. This is the first reported HLA association for erythema multiforme, a disease which may be a host-specific immune response to various antigens, determined in part by genes linked to HLA-B15.
Erythema Multiforme↗
Studies of random Black and White populations in North Carolina: hla antigen profile.
As HLA testing is becoming a major vehicle for parentage determination with non-excluded, alleged fathers being compared to their racial peers, it is important to ensure that the population data used accurately reflect the genetic profile of the region from which the alleged fathers are drawn. This paper presents data on the HLA profile of Black and White residents of North Carolina. Significant differences were observed for certain antigens when the North Carolina data were compared to nationally derived population tables. Differences were observed for B7 (increase) and Bw16 (decrease) in Whites and A10 (decrease), B7 (increase) and Bw42 (decrease) in Blacks. Internal controls comparing the testing from the two participating centers showed complete agreement for White persons, but a significant difference for B5 between the two Black populations.
Adult↗
IgA nephropathy. Correlation of clinical and histologic features.
The clinical and histologic features of 81 patients with IgA nephropathy were analyzed. Azotemia was present in 32 per cent of the patients, proteinuria was present in 88 per cent, and gross or microscopic hematuria was present in all of the patients tested. The median age of histologic diagnosis was 27 years. The median age at onset of clinical signs was 20 years. There was no increased incidence in any HLA-A or -B antigen within the patient population over our control population. All patients had glomerular mesangial IgA deposition (by definition) greater than or equal to IgG or IgM. Histologic changes were quantitated and ranged from normal to necrotizing and/or crescentic glomerulonephritis. Many patients (48 per cent) had mild or moderate generalized glomerlular hypercellularity. Nonparametric statistical analysis showed strong correlations among patient age at histologic diagnosis, creatinine, proteinuria, global glomerular sclerosis, and interstital fibrosis. Our analysis suggests that IgA nephropathy is an indolent disease generally beginning in childhood. It is a cause of renal insufficiency in a significant number of patients. Interpretation of this series and other reported studies suggests that most cases of IgA nephropathy in the United States are best considered idiopathic but that hereditary and secondary forms may exist.
Adolescent↗
Confidence bands for the growth of head circumference in achondroplastic children during the first year of life.
Confidence bands are established for the growth of head circumference in achondroplastic children during their first year of life. the model of (formula see text), where a = (1, t,t2) and t is aged expressed in months provides the best estimated population mean curve with 95% confidence limits.
Cephalometry↗
Identifying carriers of mild haemophilia.
The problems of carrier identification in mild haemophilia were examined by studying a large kindred transmitting VIII:C levels which average 17 u/dl in affected males. Fifteen obligatory carriers and 13 normal women from this kindred were used as reference groups to produce a set of linear discriminants. The utility of these discriminants in identifying carriers of mild haemophilia was compared with that of a similar set of discriminants which had been prepared for use with carriers of severe haemophilia, each set of discriminants being tested against both data bases. It was found that both sets of discriminants had large error rates when applied to the mild data base, and that both had much smaller error rates when applied to the severe data base. This outcome resulted from the greater overlap between the factor VII-related activities of mild carriers and normal women than the overlap of these activities between severe carriers and normal women. Our conclusions were that (i) correct classification of many but not all women from families of mild haemophilia would be difficult, (ii) discriminants prepared using obligatory carriers of severe haemophilia were not more inefficient in mild haemophilia than those prepared using obligatory carriers of mild haemophilia, (iii) a single set of discriminants prepared from reference groups of normal women and obligatory carriers of severe haemophilia may be used for identifying potential carriers of all grades of haemophilia, and (iv), statistically speaking, VIIIR:Ag assays provide a limited amount of information for this purpose.
Age Factors↗