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Biomedical subjects

J R David

Publications and source records attributed to J R David.

At least 55 records · Page 3Linked to original sources
PubMed1998

The PACAP-type I receptor agonist maxadilan from sand fly saliva protects mice against lethal endotoxemia by a mechanism partially dependent on IL-10.

Sand fly saliva contains maxadilan, a peptide that causes vasodilation and modifies the secretion of pro-inflammatory cytokines by macrophages. We show that 1 to 10 microg maxadilan protected BALB/c mice against a lethal dose of LPS. Maxadilan reduced serum levels of TNF-alpha by approximately tenfold, while it caused a threefold increase in IL-6 and IL-10. The protective effect of maxadilan is partially dependent on its ability to induce IL-10 production since maxadilan did not prevent death from endotoxic shock in IL-10(-/-) mice. Finally, maxadilan is a selective agonist of the pituitary adenylate cyclase-activating peptide (PACAP) type I receptor, and we found that the natural ligand of this receptor (PACAP 38) also protected mice against lethal endotoxemia. These results indicate that activation of the PACAP type I receptor may contribute to the control of systemic inflammation by a mechanism that is partially dependent on IL-10.

Animals↗
PubMed1998

Latitudinal clines for morphometrical traits in Drosophila kikkawai: a study of natural populations from the Indian subcontinent.

Natural populations of Drosophila kikkawai were collected in India and Sri Lanka, along a latitudinal transect ranging from 6.8 degrees to 31.8 degrees N latitude. Six morphometrical traits were analysed: wing and thorax length, body weight, ovariole number, and abdominal and sternopleural bristle numbers. Significant clines were observed for the three-size related traits and for ovariole number, corresponding to a regular increase in the mean value with latitude, but not for bristle numbers. Due to the utilization of two types of laboratory food, data were distributed into two separate data sets. A low-nutrient food produced smaller flies on average because of more intense crowding. The two rearing conditions produced significant clines but with significantly different slopes. The wing/thorax ratio, which is inversely related to wing loading, also increased with latitude. The analysis of Indian climatic conditions suggested that winter temperature, decreasing from south to north, could be more efficient than summer temperature, which varies in an opposite way, as a selective factor for inducing the clinal variations. The sibling species D. leontia, which is known only from the humid tropics, was found to be much smaller than D. kikkawai and did not fit the clinal regressions. Such morphological differences should help to identify the two species when found in sympatry.

Animals↗
PubMed1998

Genetic analysis of Drosophila sechellia specialization: oviposition behavior toward the major aliphatic acids of its host plant.

Oviposition behavior of the four species in the Drosophila melanogaster complex (D. melanogaster, D. simulans, D. mauritiana, D. sechellia) was investigated versus natural morinda fruit (the normal resource of D. sechellia) and the two major aliphatic acids of this fruit (hexanoic acid, C6, and octanoic acid, C8). Two different experimental techniques were compared. When control and experimental food were set on the same egg laying plate, three species (D. sechellia, D. mauritiana, D. melanogaster) exhibited a significant preference for morinda; with aliphatic acids, only D. sechellia manifested a preference. With separate oviposition sites, a preference was found in D. sechellia for morinda and acids, and a general avoidance behavior in the three other species. Genetic analysis of the behavioral response toward C6 and C8 was done with the two plates technique on D. sechellia, D. simulans, F1 hybrids and backcrosses. Significant behavioral differences were observed with major effects due to genotype, concentration and their interaction. Hybrid behaviors were intermediate between those of their parents. In several cases, a qualitative reversal from preference to avoidance was observed with increasing concentration. In F1 flies, a dominance reversal was observed with increasing C8 concentration. Different reaction thresholds in different receptors might explain such observations.

Animals↗
PubMed1998

Larval tolerance in the Drosophila melanogaster species complex toward the two toxic acids of the D. sechellia host plant.

The toxicity of hexanoic (C6) and octanoic (C8) acids, the two major components of the host plant of Drosophila sechellia, was investigated upon larvae of the four species included in the D. melanogaster complex and on interspecific hybrids between D. sechellia and D. simulans. Specific methods had to be devised for obtaining reproducible toxicity results. The three generalist species (D. melanogaster, D. mauritiana and D. simulans) were found to be very sensitive, as indicated by low lethal concentrations and an increase in development duration. By contrast D. sechellia was much more tolerant, especially toward C8 which is the most abundant product in the natural resource. Interspecific hybrids (F1 and backcrosses) exhibited intermediate characteristic, but a dominance of D. simulans sensitivity was observed for both acids and especially for C8. Data on larvae are quite different from those previously obtained on adults, and are more likely to reflect the natural selective pressures existing in the wild.

Animals↗
PubMed1998

Studies on control of visceral leishmaniasis: impact of dog control on canine and human visceral leishmaniasis in Jacobina, Bahia, Brazil.

To assess the effect of removing leishmania-infected dogs on the incidence of visceral leishmaniasis, a controlled intervention study was performed in northeast Brazil. The attempted elimination of seropositive dogs resulted in an initial significant decrease in the annual incidence of seroconversion among dogs from 36% to 6% over the first two years. In the following two years, the incidence increased to 11% and 14%, respectively. In a control area in which dogs were surveyed but seropositive dogs were not removed, the cumulative incidence did not vary significantly from year to year, ranging from 16% to 27%. In the intervention area, the prevalence of dog seropositivity decreased from 36% before the intervention to 10% and remained stable. These findings suggest that attempting to remove seropositive dogs is insufficient as a measure for eradicating visceral leishmaniasis in dogs. However, the force of transmission of infection among dogs can be reduced by such programs. Also, when the number of human cases before and after the start of the intervention was calculated, a significant decrease in incidence of disease in the intervention area was observed among children less than 15 years of age (P < 0.01). The results of this intervention study suggest that the elimination of the majority of seropositive dogs may affect the cumulative incidence of seroconversion in dogs temporarily and may also diminish the incidence of human cases of visceral leishmaniasis.

Adolescent↗
PubMed1997

Evolutionary changes of nonlinear reaction norms according to thermal adaptation: a comparison of two Drosophila species.

While the adaptive significance of discontinuous reaction norms is generally accepted, the evolutionary interpretation of continuous response curves remains speculative, and the occurrence of internal constraints is often suggested as an explanation of experimental observations. In Drosophila melanogaster, various morphometrical traits exhibit convex reaction norms to growth temperature, with a maximum value within the developmental thermal range. We compared a cold-adapted species (D. subobscura) with a mid thermal range at 16 degrees C, to the warm-adapted D. melanogaster (mid thermal range at 22 degrees C) for three different morphometrical traits: wing and thorax length in both sexes and ovariole number in females. Maximum value temperatures were ordered in the same way for the three traits in both species: ovariole number > thorax length > wing length. Significant differences were also observed between the two species for the curvature parameter of the quadratic adjustment. The major observation was a significant lateral shift in the reaction norms: maximum values were observed at much lower temperatures in the cold-adapted species than in the warm-adapted one. The parallelism between mid thermal range variation and the position of the maximum value strongly suggests an adaptive displacement of the response curves. Natural selection may thus act not only on trait mean values but also on phenotypic plasticity and on the shape of reaction norms.

Animals↗
PubMed1997

Evolution of a lesser fitness trait: egg production in the specialist Drosophila sechellia.

In the evolutionary process during which Drosophila sechellia became specialized on a toxic fruit (morinda), a spectacular decrease in female reproductive capacity took place when compared with the species' generalist relatives D. mauritiana and D. simulans. Comparisons of species and interspecific crosses showed that two different traits were modified: number of ovarioles and rate of egg production. During the conservation of a D. sechellia strain on usual food, adaptation to laboratory conditions led to an increase in the rate of oogenesis but not in ovariole number. Comparison of F1 and backcross progeny also suggests that the two traits are determined by different genes (ovariole number has already been shown to be polygenic). When morinda is available as a resource, the low rate of egg production in D. sechellia is partly compensated by a stimulating effect, while an inhibition occurs in D. simulans. It is assumed that D. sechellia progressively adapted itself from rotten, non-toxic morinda to a fresher and more toxic resource. During this process the rate of oogenesis evolved from an inhibition to a stimulation by morinda. Simultaneously a spectacular decrease in ovariole number took place, either as a consequence of stochastic events related to the small population size of D. sechellia and a metapopulation dynamics, or as an adaptive process favouring dispersal capacities of the female.

Animal Feed↗
PubMed1997

Gammadelta T cells are not essential for control of cutaneous Leishmania major infection in genetically resistant C57BL/6 mice.

As gammadelta T cells are believed to be involved in host defense against Leishmania major, the role of gammadelta T cells in immunity against this parasite was investigated. The growth of L. major was measured in alphabeta (T cell receptor [TCR] alpha -/-) and gammadelta (TCR delta -/-) TCR-deficient C57BL/6 mice and compared with growth in control (C57BL/6) mice. While TCR alpha -/- mice developed nonhealing lesions containing large numbers of parasites following L. major infection, TCR delta -/- and C57BL/6 mice effectively controlled the infection. Following in vitro stimulation, lymph node cells from C57BL/6 mice produced significantly more interferon (IFN)-gamma than those from TCR delta -/- mice during early and late phases of infection; however, both produced similar levels of IFN-gamma at postinfection week 6. Culture supernatants from both TCR delta -/- and C57BL/6 mice contained interleukin-4, at postinfection week 2 only. These results indicate that gammadelta CD3 T cells are not essential for mediating protection against cutaneous L. major infection in C57BL/6 mice.

Animals↗
PubMed1997

An in vitro model for infection with Leishmania major that mimics the immune response in mice.

By using a primary in vitro response specific for Leishmania major, normal T cells from resistant CBA/CaH-T6J and susceptible BALB/c mice commit to a Th1 and a Th2 response, respectively. Since commitment occurred, we measured the production of gamma interferon (IFN-gamma), interleukin-1 (IL-1), IL-2, IL-4, IL-5, IL-10, and IL-12, prostaglandin E2 (PGE2), transforming growth factor beta (TGF-beta), and nitric oxide in the first 7 days of the response to identify factors that are critical for Th1 and Th2 development. While cells from resistant CBA mice produced more IFN-gamma, IL-10, and nitric oxide, cells from susceptible BALB/c mice produced more IL-1alpha, IL-5, PGE2, and TGF-beta. Although substantial amounts of IL-12 were detected, IL-12 did not associate with either Th1 or Th2 development. We did not anticipate that cells from resistant CBA mice would make more IL-10 in vitro. However, this also occurred in vivo since CBA mice produced substantial amounts of IL-10 following infection with L. major. Moreover, adding anti-IL-10 to primary in vitro responses enhanced production of IFN-gamma and nitric oxide by cells from CBA and BALB/c mice. Therefore, IL-10 cannot be regarded as a cytokine that associates with susceptibility to infection with L. major. Finally, the data presented here suggest that a collection of factors that can be produced by accessory cells influence Th commitment (e.g., IL-1, PGE2, and TGF-beta favor Th2 development).

Animals↗
PubMed1996

The mariner transposable element in natural populations of Drosophila teissieri.

The mariner transposable elements of several natural populations of Drosophila teissieri, a rainforest species endemic to tropical Africa, were studied. Natural populations trapped along a transect from Zimbabwe to the Ivory Coast were analyzed by Southern blotting, in situ hybridization, cloning, and sequencing of PCR products. The Brazzaville population had some full-length elements, while the remaining populations had mainly deleted elements. The main class of deleted elements lacked a 500-bp segment. A mechanism is proposed that could generate such elements rapidly. In situ hybridizations showed that there are no mariner elements in pericentromeric heterochromatin. Finally, the phylogeny of the Mos1-like mariner full-length elements is consistent with vertical transmission from the ancestor of the melanogaster subgroup.

Africa↗
PubMed1996

rK39: a cloned antigen of Leishmania chagasi that predicts active visceral leishmaniasis.

The diagnosis of visceral leishmaniasis (VL), a serious and often fatal parasitic disease caused by members of the Leishmania donovani complex, remains problematic. Current methods rely on clinical criteria, parasite identification in aspirate material, and serology. The latter methods use crude antigen preparations lacking in specificity. A previously described cloned antigen, rK39, of Leishmania specific for all members of the L. donovani complex (L. chagasi, L. donovani, L. infantum) was very useful in the serodiagnosis by ELISA of both human and canine VL. The present study demonstrated that rK39 seroreactivity correlated with active disease. The sera from early or self-healing infected subjects reacted with leishmanial lysate and were generally nonreactive with rK39. These data demonstrate the utility of rK39 in the serodiagnosis of VL and as an indicator of active disease.

Animals↗
PubMed1996

Association of hepatosplenic schistosomiasis with HLA-DQB1*0201.

Major histocompatibility class II alleles of 351 persons living in an area endemic for Schistosoma mansoni in northeastern Brazil were characterized at three loci (DRB1, DQA1, and DQB1). Contingency analyses were used to compare allele frequencies with high egg excretion, proliferative response to schistosome soluble egg antigens (SEA), and occurrence of severe, biopsy-confirmed hepatosplenic disease. There were no associations of HLA-DR or DQ with egg excretion. Patients positive for DRB1*01, DQA1*0101, or DQB1*0501 were less likely to respond to SEA than was the overall study population. However, using stringent Bonferroni correction (multiplying P values by the number of alleles tested; P x 35), none of these associations with SEA responsiveness remained significant. Hepatosplenic disease was less likely in patients positive for DRB1*11 and was more likely in patients positive for DRB1*07 or DQB1*0201. However, only the DQB1*0201 association remained significant (odds ratio = 3.72; P < .005) following Bonferroni correction.

Adolescent↗
PubMed1995

Genetic basis of some morphological differences between temperate and equatorial populations of Drosophila melanogaster.

The genetic basis of three morphological traits (ovariole number, sternopleural bristle number and wing length) of Drosophila melanogaster has been investigated in natural populations that show great differences in these traits, i.e. Bordeaux (France) and Loua (Congo). F1 and F2 crosses, and chromosome substitutions between these two populations, were analysed. Maternal and/or X chromosome effects were found for sternopleural bristle number and wing length. For all traits, significant effects from each of the three chromosomes were found, but in general only one or two chromosomes had a major effect. Moreover, in all cases significant interactions between chromosomes were observed, suggesting the existence of epistatic effects. Our results are discussed and compared to those obtained from the analysis of selected laboratory strains.

Animals↗
PubMed1995

Structural characterization and chromosomal location of the mouse macrophage migration inhibitory factor gene and pseudogenes.

Macrophage migration inhibitory factor, MIF, is a cytokine released by T-lymphocytes, macrophages, and the pituitary gland that serves to integrate peripheral and central inflammatory responses. Ubiquitous expression and developmental regulation suggest that MIF may have additional roles outside of the immune system. Here we report the structure and chromosomal location of the mouse Mif gene and the partial characterization of five Mif pseudogenes. The mouse Mif gene spans less than 0.7 kb of chromosomal DNA and is composed of three exons. A comparison between the mouse and the human genes shows a similar gene structure and common regulatory elements in both promoter regions. The mouse Mif gene maps to the middle region of chromosome 10, between Bcr and S100b, which have been mapped to human chromosomes 22q11 and 21q22.3, respectively. The entire sequence of two pseudogenes demonstrates the absence of introns, the presence of the 5' untranslated region of the cDNA, a 3' poly(A) tail, and the lack of sequence similarity with untranscribed regions of the gene. The five pseudogenes are highly homologous to the cDNA, but contain a variable number of mutations that would produce mutated or truncated MIF-like proteins. Phylogenetic analyses of MIF genes and pseudogenes indicate several independent genetic events that can account for multiple genomic integrations. Three of the Mif pseudogenes were also mapped by interspecific backcross to chromosomes 1, 9, and 17. These results suggest that Mif pseudogenes originated by retrotransposition.

Amino Acid Sequence↗
PubMed1995

Genetic characterization of geographic populations using morphometrical traits in Drosophila melanogaster: isogroups versus isofemale lines.

Studies of short or medium range geographic variations play an increasing role in ecological genetics, and sensitive techniques are required to detect them. In this respect, two sampling techniques were compared in D. melanogaster. The biological data were provided by the analysis of four natural populations from the same geographic area, Spain (one) and Southern France (three), for four morphometrical traits: abdomen and thoracic pigmentation, and wing and thorax lengths. Traits were measured on wild living females and on their progeny reared in the laboratory at 25 degrees C. For progeny analyses, two techniques were compared: the usual isofemale line technique, sib families issued from a single female, and a new isogroup technique, the progeny produced by a group of 20 wild-collected parents. Large phenotypic variations were observed in wild living flies, corresponding to the unstability of natural environmental conditions during their development. Among laboratory grown flies, variations were much smaller. Between isogroups, differences were small, due to sampling error and some common environment effects. Variations between lines were much greater, thus demonstrating a strong genetic component. When different populations have to be compared, the isogroup technique should be preferred since, for the same amount of work, the lesser variability between groups provides a more precise characterization of the population means.

Animals↗
PubMed1995

Mating propensity of Indian Drosophila melanogaster populations with D. simulans: a nonadaptive latitudinal cline.

Crosses were investigated between a single strain of Drosophila simulans and 28 natural Indian populations of D. melanogaster. In each case, a mass culture and 10 isofemale lines of D. melanogaster were studied. Crosses were much easier between D. melanogaster females and D. simulans males than in the reciprocal case. Also, hybrid offspring were easier to obtain by using D. melanogaster flies (either males or females) from isofemale lines than from mass cultures. Finally, the crossability, estimated by progeny production, showed a clear-cut latitudinal cline: hybrids were easier to obtain with D. melanogaster populations from higher latitudes. As D. simulans does not occur in India, this cline does not reflect an evolutionary interaction between the two sibling species.

Adaptation, Physiological↗
PubMed1995

Bubonic leishmaniasis: a common manifestation of Leishmania (Viannia) braziliensis infection in Ceara, Brazil.

Enlarged regional lymph nodes have been reported to accompany the cutaneous lesions of Leishmania (Viannia) braziliensis (= L. braziliensis). A survey in Ceara State, Brazil indicated that 77% of persons (456 of 595) with parasitologically confirmed cutaneous leishmaniasis reported lymphadenopathy in addition to skin lesions. A group of 169 persons with recently diagnosed leishmaniasis and lymph nodes measuring > or = 2 cm in diameter (mean = 3.6 cm, maximum = 10.5 cm) underwent detailed clinical examination. Lymphadenopathy preceded the skin lesions in more than two-thirds of these, on the average by two weeks. Cultures of lymph node aspirates yielded Leishmania more frequently (86%) than cultures of aspirates of skin (53%) or biopsies of skin (74%). Parasites were isolated from the peripheral blood of one patient. Persons with lymphadenopathy gave a history of fever and had enlarged livers or spleens more often than a comparison group of 50 persons with cutaneous lesions but no lymphadenopathy. Persons with lymphadenopathy had more intense leishmanin skin reactions and lymphocyte proliferation following stimulation with specific antigens, whereas persons without lymphadenopathy had a higher frequency of previous infection. Isolates of parasites from both groups were identified as L. braziliensis. These data demonstrate the early spread of L. braziliensis beyond the skin and suggest differences in host immunity between persons with and without lymphadenopathy. Leishmaniasis braziliensis should be considered in cases of unexplained lymphadenopathy in endemic areas.

Adolescent↗