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D Haddad

Publications and source records attributed to D Haddad.

At least 19 recordsLinked to original sources
PubMed2005

[Dercum's disease: a severe complication in a rare disease. A case report].

Dercum's disease or adiposis dolorasa is unusual and unknown. Four symptoms are typical. It is characterized by painful subcutaneous fatty tumors in postmenopausal woman. We present this disease through the study of an uncommon clinical case: a sceptic choc following the "steato-cutaneous-necrosis" of a fatty tumor. The disease remains rare. The etiology is to this day unknown and different hypothesis (endocrinous, metabolic, genetics) are put forward. Multiple complications can occur but severe septicemia is rare. The treatment can be medical (loss of weight, corticoids, intravenous lidocaine) or surgical (surgical excision or liposuction).

Adiposis Dolorosa↗
PubMed2004

NMR imaging of the honeybee brain.

NMR microscopy provides non-invasively distinct soft-tissue contrast in small biological samples. We were able to visualize the three-dimensional structure of the honeybee brain in its natural shape in the intact head capsule. Thus, in addition to acquiring detailed information about the shapes and volumes of the different brain compartments, we were able to show their relative orientations toward each other within the head capsule. Since the brain was lightly fixed but not dehydrated, and stayed attached to the head capsule and its internal structures, the NMR experiments exhibited larger volumes and a more natural stereo geometry of the various brain structures compared to confocal laser microscopy experiments on dissected, dehydrated and cleared brains.

Animals↗
PubMed2002

Antibody responses to the repetitive Plasmodium falciparum antigen Pf332 in humans naturally primed to the parasite.

Antibodies to the degenerate repeats of EB200, a part of the Plasmodium falciparum antigen Pf332, are protective in monkeys. To analyse the prevalence, magnitude and specificity of antibodies to EB200 in malaria-exposed humans, the IgG antibody reactivity with recombinant EB200 protein as well as with crude malaria antigen was determined in Senegalese donors (n = 100; 4-87 years). Antibody reactivity with EB200 was low or absent in children below 15 years but was prevalent and significantly higher in older donors. In comparison, all individuals displayed reactivity with a crude malaria antigen preparation, which also increased with age. The reactivity with the crude malaria antigen was correlated to the reactivity with EB200, suggesting that the low levels of IgG to EB200 found in some adult donors reflected a limited degree of recent exposure to parasites rather than a selective non-responsiveness to Pf332. Comparison of serological and clinical data showed that high levels of antibodies to crude malaria antigen and to EB200 were predictive of fewer future clinical attacks of malaria. A reactivity pattern very similar to that found in Senegalese donors was observed in Liberian adults where 80% of the sera showed reactivity with EB200 and all peptides were recognized by between 60 and 100% of the donors. This strong reactivity with EB200-derived overlapping peptides suggests that the epitopes in EB200, to a large extent, are linear. In the light of previous data on the parasite neutralizing capacity of antibodies to Pf332, the present results emphasize the potential interest of Pf332-derived sequences for inclusion in a subunit vaccine against P. falciparum malaria.

Adolescent↗
PubMed2000

Plasmid vaccine expressing granulocyte-macrophage colony-stimulating factor attracts infiltrates including immature dendritic cells into injected muscles.

Plasmid-encoded GM-CSF (pGM-CSF) is an adjuvant for genetic vaccines; however, little is known about how pGM-CSF enhances immunogenicity. We now report that pGM-CSF injected into mouse muscle leads to a local infiltration of potential APCs. Infiltrates reached maximal size on days 3 to 5 after injection and appeared in several large discrete clusters within the muscle. Immunohistological studies in muscle sections from mice injected with pGM-CSF showed staining of cells with the macrophage markers CD11b, Mac-3, IA(d)/E(d) and to the granulocyte marker GR-1 from day 1 through day 14. Cells staining with the dendritic cell marker CD11c were detected only on days 3 to 5. Muscles injected with control plasmids did not stain for CD11c but did stain for CD11b, Mac-3, IA(d)/E(d), and GR-1. No staining was observed with the APC activation markers, B7.1 or CD40, or with markers for T or B cells. These findings are consistent with the infiltrating cells in the pGM-CSF-injected muscles being a mixture of neutrophils, macrophages, and immature dendritic cells and suggest that the i.m. APCs may be enhancing immune responses to coinjected plasmid Ags. This hypothesis is supported by data showing that 1) separation of injections with pGM-CSF and Ag-expressing plasmid into different sites did not enhance immune responses and 2) immune enhancement was associated with the presence of CD11c+ cells in the infiltrates. Thus, pGM-CSF enhancement may depend on APC recruitment to the i.m. site of injection.

Adjuvants, Immunologic↗
PubMed1999

Characterization of antibody responses to a Plasmodium falciparum blood-stage antigen induced by a DNA prime/protein boost immunization protocol.

The humoral immune responses elicited by priming with a DNA plasmid and boosting with either the plasmid or the corresponding recombinant protein in alum adjuvant were compared. The plasmid DNA encoded a sequence (M3) derived from the Plasmodium falciparum antigen Pf155/RESA, and the recombinant protein consisted of the identical malarial sequence fused to an albumin-binding region (BB) of streptococcal protein G. Mice of different genetic backgrounds (CBA, Balb/c and C57Bl/6) were primed with plasmid DNA and boosted with either plasmid or recombinant protein. In all strains of mice, boosting with protein elicited higher anti-M3 antibody levels than obtained by boosting with plasmid, yet the kinetics and longevity of the secondary responses were comparable. Antiserum obtained after protein boosting displayed an immunoglobulin (Ig)G subclass profile skewed to the IgG1 isotype, regardless of the mouse strain. In contrast, mice receiving a second injection with plasmid responded with a more mixed IgG subclass profile. Inclusion of a P. falciparum circumsporozoite protein-derived T-helper epitope (CS.T3) in the immunization plasmid as well as in the fusion protein, did not significantly change the humoral responses to M3. The results show the potential of DNA vaccination for the purpose of priming an antibody response against the malarial blood-stage antigen Pf155/RESA. When combined with a protein boost, this DNA priming results in high-titred and long-lasting anamnestic responses.

Amino Acid Sequence↗
PubMed1999

Limited genetic diversity of Plasmodium falciparum in field isolates from Honduras.

The genetic diversity displayed by Plasmodiumfalciparum field isolates, the occurrence of variant forms of the parasite at different frequencies in different geographic areas, and the complexity of the infections represent major obstacles for the development of effective malaria control measures. However, since most of the existing studies have been performed in regions where P. falciparum transmission is high, little is known about the diversity and complexity of parasite populations circulating in areas of low malaria endemicity. We investigated the extent of genetic polymorphism in P. falciparum field isolates from Honduras, a region where its transmission is low and seasonal. Allelic diversity was analyzed in the highly polymorphic parasite genes encoding the merozoite surface proteins- (MSP-1) and -2 (MSP-2) and the glutamate-rich protein (GLURP) by the polymerase chain reaction. Gene polymorphism was also assessed in the EB200 region derived from the highly size polymorphic Pf332 gene. Limited size polymorphism was detected in all genes analyzed, with four and three variants for the MSP-1 and MSP-2 alleles, respectively, and two size variants for the GLURP and Pf332 genes. Moreover, based on the studied genetic markers, most infections consisted of only a few genetically distinct parasite clones. These results suggest that the P. falciparum parasite populations circulating in this region are genetically homogeneous and point to an association between the extent of parasite genetic diversity and the intensity of malaria transmission.

Alleles↗
PubMed1998

Differential induction of immunoglobulin G subclasses by immunization with DNA vectors containing or lacking a signal sequence.

The route and method used to immunize mice with antigen-expressing DNA plasmids have an impact on the resulting T-helper cell response and IgG subclass distribution. Previous findings further indicate that the intracellular targeting of expressed antigens influences the differentiation of naive T-cells into either a Th1 or a Th2 type of response. In the present study, we analyzed the levels of IgG1 and IgG2a antibodies, as correlates of Th2 and Th1 responses, respectively, after intramuscular injection of mice with plasmids encoding a chimeric protein containing a Plasmodium falciparum blood stage antigen expressed in two different forms. One plasmid expresses the antigen in a secreted form as it is preceded by a signal sequence while expression from the other plasmid, lacking this sequence, results in cytoplasmic localization of the antigen. Mice immunized with the plasmid encoding secreted antigen responded with predominantly IgG1 antibodies. In contrast, sera from mice immunized with the plasmid expressing cytosolic protein displayed a mixed IgG1/IgG2a profile. In line with previous findings, our results suggest that the intracellular targeting of proteins expressed by DNA plasmids is an important factor for the differentiation of Th cells and the resulting subclass pattern of IgG responses.

Animals↗
PubMed1997

Predominance of H-2d- and H-2k-restricted T-cell epitopes in the highly repetitive Plasmodium falciparum antigen Pf332.

Genetic restriction of immune responses to malaria antigens is an important issue for a better comprehension of malaria immunity as well as for development of subunit vaccines. To experimentally define the major histocompatibility complex restriction of immune responses to the highly repetitive Plasmodium falciparum high-molecular-weight antigen Pf332, H-2-congenic mice were immunized with EB200, a recombinant fragment of Pf332 consisting of degenerate repeat motifs. Strong B- and T-cell responses were elicited in H-2d and H-2k mice whereas responses in H-2b, H-2q and H-2s mice were of lower magnitude. The T-cell specificity elicited by EB200 was defined by in vitro proliferative responses to a panel of overlapping peptides spanning EB200. Dominant epitopes were identified for H-2d and H-2k mice, respectively, and an additional epitope was recognized by all five mouse strains. Selected EB200-derived peptides were further investigated for their ability to elicit T-cell help when injected as multiple antigen peptides. Defined H-2d- and H-2k-restricted T-cell epitopes generated high antibody levels in the respective mouse strains, as did several peptides lacking defined epitopes indicating the presence of additional H-2d- and H-2k-restricted, cryptic or subdominant T-cell epitopes in EB200. The biased H-2 restriction pattern of T-cell epitopes in Pf332 and, as previously reported, in structurally related repeats in the malaria antigens Pf11.1 and Pf155/RESA may be explained by a shared motif for H-2d and H-2k class II-restricted T-cell epitopes, as revealed by alignment of these sequences.

Amino Acid Sequence↗
PubMed1997

What is core? Guidelines for the core curriculum in paediatrics.

A key point that the UK General Medical Council addressed in its recommendations on the undergraduate medical education was the concept of 'core curriculum' (General Medical Council 1993). Although enthusiastic for the idea of reducing factual overload, many medical teachers found themselves facing the task of how to define what a core curriculum is, what should be included and why. Predictably, our initial response is to include common and important topics, but how common is common, and how does one determine the relative importance of topics? We do not claim to have unravelled all the ambiguities surrounding the subject nor to have resolved all the controversies that are inevitably encountered. We hope, however, to describe some of the principles that governed our approach and put forward some guidelines, that may contribute to the debate.

Child↗
PubMed1997

Comparative study of DNA-based immunization vectors: effect of secretion signals on the antibody responses in mice.

The presence of a signal sequence preceding the gene encoding a target antigen in a DNA vaccine should facilitate secretion of the in vivo translated antigen. The immune responses elicited upon injection with such a vector could differ from those induced by the same vector lacking a signal sequence. In the present study, the humoral responses elicited in mice immunized with two plasmids, either containing or lacking the human tissue plasminogen activator signal sequence, were compared. Both plasmids encode the chimeric antigen ZZN4, containing a malaria antigen Pf332-derived sequence (N4) linked to a bacterial fusion partner (ZZ). In vitro transfection of COS cells with each plasmid and treatment of the transfectants with brefeldin A confirmed that secretion of ZZN4 via the endoplasmic reticulum and Golgi pathway only occurred in cells transfected with the signal peptide-encoding plasmid. Repeated intramuscular injections of mice with either of the plasmids elicited comparable antibody responses to ZZN4 with regard to kinetics, specific IgG levels and persistence. These results indicate that in vivo transfection of muscle cells by either of these two plasmids generated comparable levels of antigen available for B-cell recognition and for uptake by antigen-presenting cells, despite the differential intracellular targeting of the encoded antigen. The relevance of these findings for the design of DNA vaccine vectors is discussed.

Animals↗
PubMed1996

A novel expression system for Salmonella typhimurium allowing high production levels, product secretion and efficient recovery.

A novel expression system for heterologous production in Salmonella typhimurium, taking advantage of the promoter, signal sequence and two IgG-binding domains (ZZ) from staphylococcal protein A, has been investigated. The production of two different fusion proteins, ZZ-M3 and ZZ-M5, was characterized in terms of production levels, product localization (periplasma or culture medium) and product quality after affinity purification. High expression levels and efficient product secretion were obtained, making the system attractive for vaccine development. The potential use of S. typhimurium as host for heterologous production in biotechnology is discussed.

Amino Acid Sequence↗
PubMed1996

Photo quiz.

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Adult↗
PubMed1995

Surface display compared to periplasmic expression of a malarial antigen in Salmonella typhimurium and its implications for immunogenicity.

Two different expression systems were investigated for the production of an 80 amino acid polypeptide, M3, from the C-terminus of the Plasmodium falciparum blood stage antigen Pf155/RESA in an attenuated Salmonella typhimurium vaccine strain. Upon expression, the malarial polypeptide was targeted either to the periplasm as a soluble fusion protein containing two IgG-binding domains (ZZ) from the staphylococcal protein A or, to the bacterial surface as an insert within a chimeric outer membrane protein A (OmpA) derived from Escherichia coli and Shigella dysenteriae. Both the ZZM3 and the OmpAM3 proteins were stably expressed in the periplasm or on the surface of Salmonella, respectively. The ZZ expression system yielded 10-100 times more malarial immunogen than did the OmpA system. Live recombinant Salmonella expressing ZZM3 or OmpAM3 were used to immunize mice intraperitoneally. Both the ZZM3 and OmpAM3 genes persisted for up to three weeks in bacteria isolated from different lymphoid organs. Bacteria expressing ZZM3 induced antibodies to M3, ZZ and to the Pf155/RESA antigen whereas, bacteria producing OmpAM3 induced similar levels of antibodies reactive with M3 but not with Pf155/RESA. Both recombinants induced a memory response of antibodies reactive with both M3 and Pf155/RESA. The high levels of M3 produced by the ZZ expression system make it suitable for the expression of heterologous antigens in Salmonella. Nevertheless, in spite of the quantitative difference in M3 expression, the ZZ and OmpA constructs elicited comparable immune responses to M3.

Animals↗
PubMed1992

[Ioversol 300 and iopamidol 300 in "whole body" computed tomography. A double-blind clinical trial].

The authors compared ioversol 300 to iopamidol 300 by double blind study in patients undergoing enhanced computed body tomography. There was no significant difference in clinical tolerance and efficacy between the two products. Only minor reactions were recorded in both groups. Contrast media were not considered to be responsible for the poor diagnostic quality of a few explorations. Ioversol 300 appears as a well tolerated and effective contrast medium for computed body tomography.

Adult↗
PubMed1992

Efficiency of protective sealants for glass ionomer cements.

This study compared the efficiency of protective sealants for glass ionomer cements. Scotchbond 2, Visar Seal, an experimental light activated silicone and Ketac Glaze were evaluated using liquid scintillation spectrometry. The results showed that Ketac Glaze was a very effective sealant for the newly placed glass ionomer cement and the resin component of Scotchbond 2 is in the same range.

Chi-Square Distribution↗
PubMed1987

Dietitians' development of an enteral nutrition management package.

Several dietitians at the Royal Victoria Hospital, Montreal, examined current hospital practices in enteral feeding and defined three major areas of concern that are known to influence the management of enterally-fed patients. These concerns deal with physicians' perceptions, nursing management and cost. In order to address these concerns and consequently improve the management of enterally-fed patients, an Enteral Nutrition Management Package consisting of an order form, flow sheet and monitoring record was developed. The package provides standardized guidelines for enterally-fed patients and emphasizes the need for monitoring patients' clinical progress. The usefulness of the package is dependent upon the participation of every member of the health care team including the physician, nurse and dietitian. The development of the package is the result of initiative taken by clinical dietitians in addressing patient care concerns in enteral nutrition within a multidisciplinary system.

Dietary Services↗
PubMed1975

Ultrasonic study of normal and fractured bone.

Ultrasonic velocity measurement in bone can be used as a clinical tool that will accurately and objectively monitor the progress of fracture healing. This technique may provide a rational basis for evaluating the effectiveness of various modalities in clinical treatment. The eventual goal of this technique is to determine the status of healing fractures, prescribe appropriate treatment, give the rationale for the timing and form of a rehabilitative program that would accelerate the patient's return to productivity. An instrument has been developed to measure ultrasonic velocity in the long bones of the extremities. Serial measurements of tibial fractures and the measurement of a large group of normals shows no statistically significant differences in ultrasonic measurements have been found on the basis of race, sex, or pregnancy among normals. But a numerically small but statistically significant variation with age was found. While the number of fracture cases observed was small, the evidence is clear that ultrasonic measurement in fractured tibia may give a more reliable indication of the general pattern of healing response than the clinical and roentgenographic examination.

Adult↗