Search PubMed⌕ Search

Biomedical subjects

J Feingold

Publications and source records attributed to J Feingold.

At least 217 records · Page 12Linked to original sources
PubMed1978

[Idiopathic hemochromatosis linkage with the HLA system (author's transl)].

Fourteen selected families containing two or more subjects suffering from idiopathic hemochromatosis and 34 unrelated cases have been studied for their HLA markers. A 3 was present in 75% of the unrelated cases vs 26% in the normal population (p less than 10(-8)). The frequencies of B 7 (38% vs 19%) and B 14 (23% vs 9%) were also increased (p lessthan 0,05). Inevitably, in most cases both antigens in the B locus were associated with A 3. Seven of nine affected sib pairs shared both HLA haplotypes, while two shared only one. Significant association between HLA haplotypes and diseases segregation has been demonstrated in family studies. These facts are consistent with the recessive inheritance of a strongly A 3 linked "disease" gene responsible for abnormal iron stores in the heterozygote state. This hypothesis would account for 64% of our present cases. Most of discordances (26%) were females who are physiologically protected, or children under 17 who might later develop the disease. The remaining 10% of disordant cases could be explained by crossing-over between "disease" gene and HLA loci or by an heterogeneity of the disease. This provides a method for screening for high risk subjects and perhaps an opportunity for anticipatory prevention.

Adolescent↗
PubMed1977

Inbreeding in recessive diseases.

The consanguinity of parents (born in France) of individuals who have a recessive disease has been studied. The frequency of first cousin marriages is less than 0.2% in the general French population. Among the parents of affected individuals the following frequencies of first cousin matings were observed: cystic fibrosis: 1.4% cystinosis: 7.1% nephronophtisis: 5.6% spinal muscular atrophy: 4.5% albinism: 5.0% achromatopsia: 12.5% (Albinism and spinal muscular atrophy are heterogeneous conditions). The increase in the frequency of first cousin marriage relative to that of the general population is much greater, as expected, in cystinosis, which is a rare disease, than in cystic fibrosis, which is the most frequent recessive disorder in France. Inbreeding in cystinosis and cystic fibrosis was also studied by computing the distance between parental birth places. This distance is smaller in cystinosis than in cystic fibrosis.

Albinism↗
PubMed1977

Deficient mitogen-induced virus plaque-forming cells in patients with localized cancer.

The virus plaque assay (VPA), an assay capable of enumerating mitogen- or antigen-sensitive T-lymphocytes in a given cell population, was applied to the study of mitogen responses of peripheral blood leukocytes (PBL) in 50 patients with localized, solid cancers and in 29 normal controls. Concanavalin A (Con A)-responsive virus plaque-forming cells (V-PFC) were significantly reduced in the patients as compared with those of the controls. PBL from 20 of the patients but only 2 of the controls failed to show significant increments in V-PFC over background when cultured in the presence of Con A. This deficient response was also present in the patients when phytohemagglutinin was used as the mitogenic agent. Mitogen-stimulated uptake of [3H]thymidine (TdR) in parallel cultures failed to show a statistically significant difference between the patients and the controls, though some patients showed diminished stimulation in this assay. The VPA thus appeared to detect a defect of T-lymphocyte function not found in the [3H]TdR incorporation assay.

Cell Separation↗
PubMed1977

[Genetics of child spinal amyotrophy : existence of 2 autosomal recessive forms].

An analysis of within sibship resemblances in age of onset of symptoms and age of death (or at last examination) was made in families affected with infantile spinal muscular atrophy. The observed correlation coefficients, 0.52 and 0.75, favor the existence of a least two different mutant genes for the disease. In 63 families, the disease was of the acute infantile form and in 71 families it was of the chronic form. Both forms show autosomal recessive transmission.

Age Factors↗
PubMed1976

Polygenic regulation of antibody synthesis to sheep erythrocytes in the mouse: a genetic analysis.

Selective breeding for the character "agglutinin production to heterologous erythrocytes" was performed on random-bred populations of albino mice. Two types of selection were carried out: Selection I: the first 6 generations were immunized with sheep erythrocytes (SE), then SE and pigeon erythrocytes (PE) were alternated at each generation to avoid the interference of maternal antibody. Selection II: all generations were immunized with SE 60-70 days after weaning in order to eliminate the maternal antibody. Both were selected for the character agglutinin titer 14 days after immunization using an optimal dose of erythrocytes. Selection I. The mean response to SE of the foundation population was 7.36 +/- 1.60. The selection limit was attained between the 15th and the 20th generation. The F20--F30 were considered as homozygous for the character investigated. The mean SE agglutinin titers were 9.15 (1/2820) in the high responder line and 2 (1/20) in the low responder line. This corresponds to 140-fold interline difference in agglutinin titers. SE agglutinins determined in F1 hybrids, F2 hybrids and backcrosses obtained from F23--F29 demonstrated incomplete dominance of high responsiveness (23-29%). The inbreeding coefficient produced by close colony breeding was 0.55 in high and 0.71 in low responders at the 20th generation when both lines were homozygous with respect to agglutinin synthesis. Selection II. The mean response of the foundation population to SE was 7.79 +/- 1.56. The selection limit was attained in F14--F17 generations that were considered homozygous for the character investigated. The mean SE agglutinin titer was 9.2 (1/2900) in high responders and 2.8 (1/35) in low responders, which is an 83-fold interline difference in agglutinin titers. The results of both selections indicate that the character agglutinin synthesis is subject to polygenic regulation. The heritability (h2) of this character was estimated to be between 0.18 and 0.36 (range between the extreme values of Selections I and II.

Animals↗
PubMed1976

Mutation theory of carcinogenesis in retinoblastoma.

To test Knudson's hypothesis that two successive mutations are involved in retinoblastoma, we studied the data on 899 cases. Some of the findings appeared to differ from those that might be expected if Knudson's hypothesis were correct. Certain criticisms of Knudson's methodology and model were suggested. Alternative explanations proposed were 1) the role of the sequence in which mutations occur, and 2) the possibility of three mutational events.

Adolescent↗
PubMed1976

Infantile cystinosis in France: genetics, incidence, geographic distribution.

A national distribution of 66 French patients, from 49 sibships, has been studied. Segregation analysis, using the maximum likelihood method, was found to agree with the theoretical values expected in recessive autosomal inheritance. The birthplaces of these patients show an unequal geographic distribution of cystinosis, the incidence being higher in Western France. Compared with the total number of live births during the period 1959 to 1972, the minimum incidence of the condition in the province of Brittany is 1 per 25 909, and the gene frequency 0.0062. In the rest of France, the minimum incidence is 1 per 326,440 and the gene frequency 0.0018. Application of Dahlberg's formula gives a similar result. The mean inbreeding coefficient is 530 X 10(-5), a figure 23 times higher than the mean coefficient of France. An indirect test of inbreeding, the distance between parental birthplaces, was studied, first using the French administrative boundaries, second by using kilometers. This distance was constantly smaller for the parents of patients than for the parents of controls. Analysis of two erythrocyte polymorphisms (ABO and Rh) showed a large excess of group A patients when compared with overall French data. These findings are difficult to interpret on genetic grounds. The genetic reasons for the unequal geographic distribution of cystinosis in France are discussed.

ABO Blood-Group System↗
PubMed1976

[Chromosome effect of cyclophosphamide in various strains of mice].

The chromosomes of four different mouse strains were examined after administration of a single dose of cyclophosphamide, 100 mg/kg. Chromosomal breaks and rearrangements were produced in C3H mice three to four times as frequently and in AKR mice twice as frequently as in C57 B1 and XLII Orl mice. This indicates that cytogenetic investigations in mutation research using mice as in vivo test systems may be variable depending on the mouse strain employed. Because the effect of the alkylating agent was not pronounced in the two strains having a high incidence of cancer and leukemia (C3H and AKR), the possibility of a relationship between chromosomal instability and cancer proneness is discussed.

Animals↗
PubMed1976

[Genetics of diabetes mellitus (author's transl)].

Since Pincus and White's claim in 1933 that diabetes mellitus is an inherited disease, the precise mode of inheritance remains a matter of dispute. The reason for the controversy is that the geneticist is confronted with a number of impediments to genetic analysis. As pointed by Neel, "diabetes mellitus is in many respects a geneticists nightmare". The obstacles are : 1) a precise definition of diabetes is difficult to establish, 2) the frequency of the disease which is sex and age dependent is not well known, 3) the probability of genetic heterogeneity is great but whether early onset and late onset diabetes are different genetic diseases or the same one remains controversial, 4) the basic defect (s) is unknown, 5) environmental factors (e.g. nutritional status) influence the frequency of the disease. Despite these problems many studies have been devoted to the mode of inheritance of diabetes mellitus. Many authors favour an autosomal recessive mechanism. However, low penetrance (25 %) is necessary to support this mode of inheritance. Simple autosomal dominant mode of inheritance has also been suggested, but this pattern fits only few families. The majority of geneticists think, at the present time, that diabetes has a multifactorial mode of inhritance. The heritability which express the extent to which the phenotypes exhibited by parents are transmitted to their offspring is in the neighbourhood of 50%. Many arguments favour this mode of inheritance: 1) low penetrance is necessary to aistinct genetic diseases, and especially in chronic glaucoma, which also have a multifactorial mode of inheritance; in particular, one must note the association between glucose intolerance and ocular hypertension induced by dexamethasone, 3) the association between diabetes and antigen A of the ABO system and antigens HL-A8 and W 15 of the HL-A system.

Diabetes Mellitus↗
PubMed1976

[Risk of recurrence of several congenital malformations: anencephaly, spina bifida, cleft palate and cleft lip].

Recurrence risks were estimated for some congenital malformation from a multifactorial model according to the method given by Smith (1971). Risks were estimated for cleft lip with or without cleft palate, cleft palate alone, anencephaly and spina bifida from data on frequency and heritability collected in France. Results are given in tables representing risks for some 180 specific family histories.

Anencephaly↗
PubMed1976

Chromosomal breakage and scleroderma: studies in family members.

Chromosome studies were performed on 54 apparently healthy relatives of 29 scleroderma patients and on 40 controls. Increased chromosomal breakage is observed in 86 per cent of brothers and sisters and in 68 per cent of children of patients. If the findings in relatives are compared to those obtained in the 29 scleroderma patients of these families, the percentage of abnormal cells does not differ significantly between the two groups (25.8 per cent and 29.1 per cent respectively), and there is no difference for the frequencies of gaps and open breaks. However acentric fragments, "minutes" and morphologically abnormal chromosomes are significantly increased in patients as compared to their asymptomatic relatives with increased breakage. The distribution of breaks is found to be random. The presence of structural chromosome aberrations in relatives of scleroderma patients may have a special importance with regard to the concept of familial autoimmune disease.

Adult↗
PubMed1976

[Genetics of idiopathic scoliosis].

Families of 241 patients among 913 cases of idiopathic scoliosis were surveyed. The data suggest two possible modes of inheritance: either an autosomal dominant inheritance with incomplete penetrance and more frequent manifestation in girls than boys, or a genetic heterogeneity with a mixture of dominant and multifactorial modes of inheritance.

Abnormalities, Multiple↗
PubMed1975

Genetic control of macrophage functions. I. Polygenic regulation of phagocytosis stimulation produced by Glyceryl Trioleate.

The phagocytic index K, established from the rate of blood clearance of colloidal carbon, measures the phagocytic activity of RE macrophages in contact with the circulating blood. The intravenous injection of glyceryl trioleate (triolein) produces a marked stimulation of the phagocytic activity of RE macrophages. This response is higher in the female than in the male mice. The phenotypic character "responsiveness of macrophage to triolein" presents large individual variants in population of random bred albinos mice. This character is submitted to polygenic regulation. Starting from a foundation population of 25 males and 25 females random bred albinos, mice, two lines were separated by selective breeding for the character "responsiveness to triolein": a "high" responder line, KTH, and a "low" responder line, KTL. After 26 consecutive generations of selective breeding, KTH mice present a very high response to triolein while KTL mice are almost irresponsive. The heritability of this character (h2) calculated from the interline divergence is of 12% plus or minus 1. This value of h2 indicates that the character investigated is determined by the cumulative effect of a group of about 27 independently segregating loci. The distribution of the character in (KTH plus KTL)F1 and their backcrosses with parental lines suggests that low responsiveness is dominant over high responsiveness. The genetic regulation of responsiveness to triolein is independent from the dose administered. These results are discussed in relation to the importance of genetic factors controlling macrophage functions involved in lipid metabolism and in the specific mechanisms of immunity.

Animals↗