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Biomedical subjects

L Abel

Publications and source records attributed to L Abel.

At least 109 records · Page 6Linked to original sources
PubMed1994

Protective effect of BCG against leprosy and its subtypes: a case-control study in southern Vietnam.

A case-control study was conducted to assess the protective effect of intradermal BCG against leprosy and its subtypes in southern Vietnam. A total of 177 cases were selected with a distribution by subtypes as follows: 38 TT, 23 BT, 51 BB, 36 BL, 22 LL, and 7 indeterminate. Two controls were matched with a case for age, sex, ethnic group, socioeconomic status, and district area. The odds ratio assessing the protective effect of BCG varied from 0.44 (0.19-1.03) in the BB subtype to 3.00 (0.24-37.5) in indeterminate leprosy; whereas its overall value was 0.71 (0.45-1.10) for leprosy per se. When all borderline leprosy types were pooled, the protective effect of BCG was found significant with an odds ratio of 0.48 (0.27-0.84). In the polar forms of leprosy, TT and LL, the odds ratio was > 1 with large confidence intervals. It is possible that BCG induces a shift in the immune response to a higher level of cell-mediated immunity. When BCG vaccination is given after primary infection with Mycobacterium leprae, this shift could be the cause of an increase in the risk of the occurrence of milder and transient forms of the disease. In TT forms BCG might reinforce the preexisting subclinical immunopathological reactions, and in stable LL forms BCG might be unable to induce any protective form of immunity. These results confirm the important variability in the protection offered by BCG with respect to the different types of leprosy, and may have important implications for the design and the interpretation of vaccine trials that should take into account the respective proportions of leprosy forms observed in the study region.

Adolescent↗
PubMed1994

[Mutations of RET proto-oncogene in Hirschsprung disease].

Hirschsprung's disease (HSCR) is a common condition (1 in 5,000 live births) resulting in intestinal obstruction in neonates and megacolon in infants and adults. This disease has been ascribed to the absence of autonomic ganglion cells, which are derived from the neural crest, in the terminal hindgut. Segregation analyses have suggested incompletely penetrant dominant inheritance in familial HSCR. Recently, a gene for HSCR has been mapped to chromosome 10q11.2. No recombination was observed between the disease locus and the locus for the RET proto-oncogene, a protein tyrosine kinase gene expressed in the cells derived from the neural crest. Here we report on nonsense and missense mutations in the extracellular domain of the RET protein (exons 2, 3, 5 and 6) in 6 unrelated probands and show that the mutant genotypes segregate with the disease in HSCR families. Mutations of RET have been previously reported in multiple endocrine neoplasia type 2A (MEN 2A). Thus, germ-line mutations of the RET gene may contribute either to developmental anomalies in HSCR or to inherited predisposition to cancer in MEN 2A.

Codon, Nonsense↗
PubMed1993

In vitro analysis of thymic microenvironmental effects on bone marrow cells of severe combined immunodeficient (SCID) mice.

The effect of the thymic microenvironment on thymocyte development from lymphohemopoietic cells was studied in an in vitro experimental model. Fetal thymus explants (FT, 15 days of gestation, C57BL/Ka, Thy1.1) were cocultured with bone marrow (BM) cells of severe combined immunodeficient (SCID, C.B.-17 scid/scid) or of normal BALB/c mice. The FT explants were depleted of their own lymphocytes either by irradiation (10 or 20 Gy) or by 2-deoxyguanosine (dGua) treatment. Development of SCID BM-derived Thy1+ cells was observed in coculture with the severely lymphocyte-depleted FT explants (dGua, 20 Gy), whereas BALB/c BM-type T cells were also apparent in the mildly irradiated (10 Gy) FT. The SCID BM-derived thymocytes were characterized as CD3- subpopulations expressing CD4/CD8 markers, while CD3+ CD4/CD8 subsets developed from the BALB/c mice. In contrast to results on BM-derived cells, cocultures of FT with thymus cells from SCID mice yielded CD3- CD4- CD8- Thy1.2+ cells, as opposed to BALB/c-derived Thy1.2+CD3+ cells exhibiting different CD4/CD8 phenotypes. Our data indicate that the BM cells from SCID mice can be induced to limited differentiation within the thymic microenvironment and this seems to be inhibited in the presence of resident radioresistant thymic cells.

Animals↗
PubMed1993

Effect of ignoring genotype-environment interaction on segregation analysis of quantitative traits.

Thirty replicates of 200 nuclear families (6 members each) were generated under three GxE interaction models. Segregation analyses of these data were performed using a regressive model taking into account an interaction effect or not. Results showed that ignoring the GxE interaction markedly decreased the power for accepting a major gene and led to serious bias in parameter estimates.

Adult↗
PubMed1993

MHC recognition in colonization of the thymus by bone marrow cells.

The role of major histocompatibility complex (MHC) class I and II molecules in the process of colonization of the thymic microenvironment by lymphohemopoietic cells was analyzed in an in vitro experimental model. When lymphoid-depleted fetal thymus (FT) explants were cocultured with a mixture of bone marrow (BM) cells, from donors syngeneic and allogeneic to the FT, the cells syngeneic to the FT showed a developmental preference. Treatment of these cocultures with antibodies to MHC class I (H-2D, H-2K) or class II (I-E, I-A) molecules of the syngeneic cells led to preferential development of the allogeneic donor type cells. Incubation of either the FT or the BM cell inoculum with the antibodies prior to coculture indicated that the effect was exerted on the BM cells rather than on the thymic stroma.

Animals↗
PubMed1993

A mathematical model of the effect of aging on bone marrow cells colonizing the thymus.

The process of T cell generation in the thymus involves complex cell-cell interactions between the various types of thymic stromal cells, thymocyte progenitors, thymocytes at different stages of differentiation and external factors. We applied the tool of mathematical modelling to analyze hypotheses and direct experiments concerning mechanisms underlying the observed developmental inferiority of bone-marrow thymocyte progenitors from old mice. Previous experimental data showed that lower cell numbers were obtained from old bone marrow-derived thymocyte progenitors, compared to young bone marrow-derived progenitors, when colonizing simultaneously the same fetal thymus. In this study, simulations based on the mathematical model indicate that the developmental inferiority of old bone marrow-derived progenitors cannot be explained by a change in a single parameter, such as the observed differences in progenitor frequency, an increase in cell cycle duration, a reduction in the fraction of proliferating cells in old age, and/or an increase in the rate of cell death. We have performed experimental measurements of the fractions of cycling cells. No significant difference was found between these fractions in young and old bone marrow-derived thymocytes. The difference in developmental patterns of young and old bone marrow-derived thymocytes may be due to a combination of more than one mechanism, possibly including interactions between competing thymocytes of old and young bone marrow origin.

Aging↗
PubMed1993

A gene for Hirschsprung disease maps to the proximal long arm of chromosome 10.

Hirschsprung disease (HSCR) is a frequent congenital disorder (1 in 5,000 newborns) of unknown origin characterized by the absence of parasympathetic intrinsic ganglion cells of the hindgut. Taking advantage of a proximal deletion of chromosome 10q (del 10q11.2-q21.2) in a patient with total colonic aganglionosis, and of a high-density genetic map of microsatellite DNA markers, we performed genetic linkage analysis in 15 non-syndromic long-segment and short-segment HSCR families. Multipoint linkage analysis indicated that the most likely location for a HSCR locus is between loci D10S208 and D10S196, suggesting that a dominant gene for HSCR maps to 10q11.2, a region to which other neural crest defects have been mapped.

Base Sequence↗
PubMed1993

Resistance to Schistosoma mansoni in humans: influence of the IgE/IgG4 balance and IgG2 in immunity to reinfection after chemotherapy.

The hypothesis of an association between human resistance to reinfection by the parasite Schistosoma mansoni and anti-larval immunoglobulin isotypes was tested by logistic regression in the presence of the explicative variables water contact, age, and sex. Of the seven isotypes tested (IgM, IgG1, IgG2, IgG3, IgG4, IgA, and IgE), only IgE, IgG4, and IgG2 showed an association (positive for IgE and negative for IgG2 and IgG4) with resistance to reinfection after chemotherapy. The opposite effects of IgE and IgG4 were undissociable in the analysis, indicating that these isotypes probably antagonize each other in protection. The negative association of IgG2 with resistance is consistent with the view that anti-carbohydrate antibodies may facilitate reinfection. Finally, epidemiologic and immunologic studies support the view that there is a progressive but slow development of acquired immunity in children and adolescents.

Adolescent↗
PubMed1993

Risk factors of malaria infection during pregnancy in Burkina Faso: suggestion of a genetic influence.

A cohort of 570 untreated pregnant women from Burkina Faso was studied to assess the influence of epidemiologic factors on malaria infection, which was quantified as the mean of serial, season-adjusted parasitemia measurements (mean parasite density [MPD]) carried out during the last five months of gestation. A significant effect of the area of maternal residence on the MPD was found (P < 0.003) and was probably due to geographic differences in mosquito transmission conditions. The strong relationship observed between parity and malaria infection (P < 0.0001), with MPD levels decreasing as the number of gestations increased, confirms that primigravidae are a high-risk group whose protection should be a priority. After adjustment for two relevant epidemiologic factors (i.e., area of residence and parity), the residual MPD values fitted a mixture of two distributions. This result supports the view that a major gene is involved in the determination of malaria infection intensities and is consistent with the results of a recent familial study in Cameroon.

Adult↗
PubMed1993

An autologistic model for the genetic analysis of familial binary data.

Regressive logistic models specify the probability distribution of familial binary traits by conditioning each individual's phenotype on those of preceding relatives; therefore, the expression of the joint probability of the familial data necessitates ordering the observations. In the present paper, we propose an autologistic model of this familial dependence structure, which does not require specification of a particular ordering of the phenotypic observations. Genetic effects are introduced into the model in order to perform segregation analysis that is aimed at detecting the role of a major locus in the expression of familial phenotypes. In this model, the conditional probabilities have a logistic form, and large patterns of dependence between relatives can be considered with a simple interpretation of the parameters measuring the relationship between two phenotypes. The model is compared with the regressive logistic approach in terms of odds ratios and by using a simulation study.

Computer Simulation↗
PubMed1992

Aging in the T lymphocyte compartment. A developmental view.

A decline in the capacity of bone marrow cells to differentiate to T lymphocytes was found when cells from young and old donors were seeded onto an alymphoid fetal thymus. A step-by-step analysis of cell-cell interactions of the lymphohemopoietic cells and the thymic stroma indicated an effect of age on a variety of cell differentiation parameters. These included a decrease in the affinity of bone marrow cells to the stroma, and in their capacity to compete with the thymic lymphoid resident cells on colonization of the thymus. There was a significant decrease in the ability of cells of old donors to replicate sequentially within the thymic microenvironment. There was a reduced capacity of bone marrow cells from aging mice to express a developmental preference after seeding onto a syngeneic fetal thymus in a mixture with cells from allogeneic donors. We addressed the question whether the aging thymus contains increased levels of immature cells that fail to differentiate in the involuted thymic microenvironment by seeding thymocytes from young and old donors onto the fetal thymic stroma. The values of T cells that developed from the old donor inoculum were lower under these conditions. Our studies suggest that at least some of the manifestations of aging in the T cell compartment are related to developmentally programmed events in the lymphohemopoietic cell compartment.

Aging↗
PubMed1992

Differentiation patterns of CD4/CD8 thymocyte subsets in cocultures of fetal thymus and lymphohemopoietic cells from c-fos transgenic and normal mice.

This study examined the involvement of c-fos protooncogene in thymocyte development from lymphohemopoietic T cell progenitors, within the thymic microenvironment. We first analyzed the thymocytes developing in vitro in the fetal thymus from the c-fos transgenic mice and found a high proportion of CD4+ single positive (SP) cells. We then seeded either fetal liver or bone marrow (BM) cells from normal donors onto lymphocyte-depleted fetal thymus explants of c-fos transgenic mice. The results showed an increased proportion of mature CD4+ SP and decreased CD4+CD8+ double positive (DP) cells. A similar pattern of CD4/CD8 thymocyte subsets was observed when either thymus or BM cells from c-fos transgenic mice developed within a normal thymic stroma. The kinetics of thymocyte development in organ culture (from Days 3 to 11) suggested that the SP cells obtained under these conditions may have bypassed the CD4+CD8+ DP phase. It appears that the altered pattern of thymocyte development manifested in adult c-fos transgenic mice can be induced by the early embryonic thymic stroma, and may also involve cells in the lymphohemopoietic tissues.

Animals↗
PubMed1992

Differential expression of membrane polypeptides on fetal thymic stroma co-cultured with bone marrow cells from young and old mice.

Cell membrane polypeptides from co-cultures of lymphocyte depleted fetal thymuses (C57BL/Ka, H-2b, Thy 1.1) and bone marrow (BM) cells (C57BL/6J, H-2b, Thy 1.2) were analyzed by two-dimensional gel electrophoresis (2D-PAGE). Donors of BM cells were young (3 months) and old (24 months) mice. Two polypeptides, not detected in either the alymphoid thymus itself or the BM cells prior to seeding, were expressed in the co-cultures, and their levels in the presence of old BM cells were higher than in the presence of young BM cells. Two other polypeptides, originally observed in the thymic stroma, exhibited reduced levels by day 3 in cocultures containing BM cells from young donors, but not from old donors. It is concluded that distinct changes in membrane proteins are manifested in the thymic stroma, as well as in the colonizing BM cells.

Aging↗
PubMed1992

Regional cerebral glucose metabolism and attention in adults with a history of childhood autism.

Sixteen high-functioning adults with a history of childhood autism and 26 normal control subjects underwent [18F]fluoro-2-deoxyglucose positron-emission tomography to assess regional cerebral glucose metabolic rate (GMR). Autistic patients had a left > right anterior rectal gyrus asymmetry, as opposed to the normal right > left asymmetry in that region. Patients also showed low GMR in the left posterior putamen and high GMR in the right posterior calcarine cortex. Brain regions with GMR > 3 SD from the normal mean were more prevalent in patients than in control subjects. This variable pattern of abnormal activity is consistent with heterogeneous neurophysiological etiology; group differences in striatum and cortex may represent a final common pathway.

Adolescent↗
PubMed1992

Patterns of dual lymphocyte development in co-cultures of foetal thymus and lymphohaemopoietic cells from young and old mice.

Patterns of lymphocyte development in the thymus were analysed, focusing on newly emigrating bone marrow (BM) and resident thymic cells. We co-cultured foetal (Day 15 of gestation) thymic explants (FT, C57BL/Ka, Thy-1.1), with BM cells from young (2-3 months) or old (24 months) syngeneic, Thy-1 congenic (C57BL/6J, Thy-1.2) mice. When the FT was severely depleted [treated with either 2-deoxyguanosine (dGua) or exposed to an irradiation dose of 20 Gy] BM-type T lymphocytes were dominant, regardless of BM donor age. When the FT was only partially depleted of its proper lymphoid cells (by exposure to 10 Gy), the lymphocytes which developed were from both BM and FT origins, yet the level of donor-type thymocytes from the young mice was higher than that of the old. Under these conditions the proportion of FT-derived double-positive CD4+ CD8+ (DP) cells was higher, and that of single-positive CD4- CD8+ cells was lower, than in the BM-derived cells, irrespective of the BM donor age. The proportions of old BM-derived DP cells were lower than in the young. Co-cultures of thymus cells from young and old mice with partially depleted FT explants resulted in similar proportions of CD4/CD8 subsets from both donor and FT origins, with the exception that in the presence of old-thymus cells there was an increase in the level of FT-type CD4- CD8+ cells. Patterns of T-cell differentiation in the thymus thus seem to be determined by newly emigrating cells and the resident thymocytes.

Aging↗