ABH non-secretor status, blood group O, and chronic airflow limitation.
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Biomedical subjects
Publications and source records attributed to J Feingold.
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The frequencies of cleft lip with or without cleft palate (CL(P)) and isolated cleft palate (CP) have been estimated in France to be 0.082% and 0.035%, respectively, after exclusion of malformation syndromes. A genetic and epidemiological study has been carried out on 468 patients with CL(P) and 163 with CP. The results are given in detail and some specific points are discussed: the apparently low incidence in France, the relationship between sex ratio and abortion rates, the maternal effects, and the possibility of an association between CL(P) and CP.
The descendance of 2 lines from NZB/bl mice which differ by the frequency of chromosome breaks has been studied. The analysis of reciprocal crosses and of "back cross" shows that the character of the chromosome breaks is perhaps dominant. This result is correlated with the observation that the autoimmunity (17) and viral expression (1, 13, 17) are also dominant.
Net fluxes of sodium and potassium ions were determined in sodium-loaded, potassium-depleted erythrocytes from 370 white subjects, 194 of whom had essential hypertension or had been born to parents with essential hypertension. Findings were compared with those in 86 controls who were normotensive and did not have a family history of hypertension. Compared with controls all patients with essential hypertension had a low sodium to potassium ratio secondary to a deficit in the sodium-potassium cotransport system. A similar abnormality was found in subjects born to parents with essential hypertension, the prevalences of a deficient cotransport system in such subjects being 53.6% (52 out of 97) among those with one hypertensive parent and 73.7% (14 out of 19) among those with two hypertensive parents. Both sexes were equally affected. Studies in 14 families over two or three generations showed the erythrocyte cation abnormality in one or more members of each consecutive generation. No close association was evident between the deficient erythrocyte sodium-potassium cotransport system and either blood groups ABO, Rh, Kidd, Duffy, P, and MNS or the major histocompatibility HLA antigens. Out of 90 consecutive unrelated and normotensive white blood donors, 36 showed a low erythrocyte sodium-potassium net flux ratio. It is concluded that in white people abnormal erythrocyte cation transport is a biochemical disorder characteristic of essential hypertension and transmitted by a dominant and autosomal mode expressing a single abnormal gene.
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The relationship between sickle cell trait and falciparum malaria was studied in the village of Djoumouna, twenty kilometers south west of Brazzaville. Malaria is characterized by a stable high intensity of transmission on the average one infective mosquito bite by night and by child contrasting with a relatively low malarial infection rate. The prevalence of carriers of an S gene (AS) does not change with age: 22.2% for children under 5 years, 22.1% for childrern between 5 and 15 years, and 22.9% in adults. Malarial infection rates are 32% in homozygous AA children under five years and 38% in AS children, an insignificant difference. Our data for this region of the Congo fail to confirm the hypothesis that the AS genotype protects the carrier against Plasmodium falciparum infection.
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Geographical variation in the incidence of an Anencephaly and Spina-Bifida is well documented. The highest rates for these malformations were found in Ireland, Wales, Scotland and in Western regions of England. These rates decrease progressively towards eastern Europe. In France the highest rates were found in some regions of Brittany. The geographical correlations between the mortality rates of Spina-Bifida and incidence of Spina-Bifida and Anencephaly and the HLA antigen frequencies are studied. There is a positive correlation with A1 and B8 and a negative one with B5 and BW35. The role of the HLA system in these associations is discussed.
HLA markers (A, B, C, DR loci) were determined for the members of 52 unrelated families with at least one child suffering from congenital adrenal hyperplasia due to 21 hydroxylase deficiency, permitting genotyping. The gene frequencies of the 52 index cases were compared with those obtained from the patients' normal haplotypes and with those of a control reference panel. No significant differences were observed, except a clear decrease in the frequency of HLA-B8 among the haplotypes that carry the gene for congenital adrenal hyperplasia.
HLA, Pi, Gm and Km phenotypes were determined in 53 cases of spina bifida with myelomeningocele. Family studies were possible in 42 cases. An increase in the frequency of HLA-B5 antigen was found. Some phenotype frequencies were also increased without reaching significant levels.
The geographical correlation between the incidence of spina bifida and anencephaly and the HLA and ABO antigen frequencies are studied. There is a positive correlation between these malformations and A1 and B8, and a negative correlation with B5 and Bw35. The role of the HLA system itself, or of a human T-like locus, is discussed. This study provides evidence of a possible genetic background of susceptibility to these malformations.
Increased chromosome breakage observed in NZB mice was studied. Breeding experiments with mice selected according to breakage frequencies provided evidence that the proportion of mice with high breakage (HB) and low breakage (LB) figures in the progeny depends on the phenotype of the parents. Selective breeding for the "chromosome breakage" characteristic was successful and resulted in the separation of a breeding line with LB incidence. However, the selection could not be continued beyond the fourth generation for the mice with HB incidence because of lethal factors. Comparative studies of HB mice from the HB line and LB mice from the LB line showed significant differences for tumor incidence and positivity of the Coombs' test.
The effects of levamisole on human chromosomes have been studied using lymphocyte cultures. A slight excess of chromatid and chromosome breaks and gaps was observed in both in vitro and in vivo studies. An excess of SCE was observed in vivo but not in vitro when similar levamisole concentrations were used.
A methodical study of the alpha-1-antitrypsin serum level and the Pi type in 69 CF children, 156 CF heterozygote parents and 200 blood donors from Paris, has been made. Although the PiZ allele frequency was found to be higher in the CF population, especially in fathers, than in the reference population, the difference is not statistically relevant. Therefore there does not seem to be a relation between cystic fibrosis and the Pi alleles system.
The incidence of neural tube defects among the siblings of 311 index cases has been estimated at 1.9%. The recurrence risk is higher for a same type malformation i.e. spina bifida after the birth of a child with spina bifida. The same features appear in other surveys from the literature although the general recurrence risk is lower in our series. The sex ratio appears to be inversely correlated with the incidence of the malformation, being higher in France than in Britain. Interpretation of the segregation analysis of the data is difficult. Genetic counseling is based upon the empirical risk (1.25% in the studied cases). Indications of antenatal diagnosis are discussed.
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