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S Martin

Publications and source records attributed to S Martin.

At least 235 records · Page 13Linked to original sources
PubMed1999

Humour and alarmism in melanoma prevention: a randomized controlled study of three types of information leaflet.

Effectiveness of melanoma prevention depends on how it is accepted by the population. Humour and alarmism are often used in campaigns, but no information is available about how much they may improve or limit the impact of a campaign. Three different leaflets containing the same information about sun exposure and skin cancers were developed using three different tones of presentation: humoristic (H-leaflet), alarmist (A-leaflet) or neutral information (N-leaflet). In this randomized controlled study, each type of leaflet was mailed to a sample of 300 subjects representative of the sociodemographic population of the South of France. A fourth sample to whom no leaflet was sent was used as a control. Fifteen days after the mailing, the 1200 individuals were interviewed by phone. Four hundred and forty-four of the 900 who received the mail read the leaflet. The percentage of individuals with a good awareness of melanoma was higher in leaflet groups than in controls. The percentage of individuals who read a leaflet was lower in the A-leaflet group and the percentage of individuals knowing what a melanoma is tended to be lower in the H-leaflet group. There was no significant difference between groups with regard to ability for self-assessment of skin sun sensitivity, risk factors and sun exposure. The tone of presentation seems to have a limited impact on the effect of a campaign, but alarmism tends to reduce the number of people reached by the message whereas humour tends to decrease the impact of the message.

Humans↗
PubMed1999

Autografting with CD34+ peripheral blood stem cells: retained engraftment capability and reduced tumour cell content.

The efficacy of an immunomagnetic purging method and the Isolex 300 devices were assessed for selecting CD34+ cells from leukapheresis products of 29 patients with non-Hodgkin's lymphoma (NHL), 39 with multiple myeloma and 34 with breast cancer. The mean purity of the CD34+ cell population was 93.6% and the mean recovery was 67.7%. Following enzymatic cleavage by chymopapain the expression of Thy-1 and Leu-8 was significantly reduced without affecting haematological recovery. The population of selected CD34+ cells of 4/8 patients with follicular lymphoma became PCR-negative. A 2.5 log reduction of tumour cells could be achieved in four patients with multiple myeloma as shown by a quantitative PCR assay. There were no tumour cells detectable in any of the 19 CD34+ cell preparations of patients with breast cancer. In 64 patients who received 94 cycles of high-dose therapy, a mean number of 4.7x 10(6) CD34+ cells/kg were autografted. The time needed for platelet reconstitution was different when a comparison was made with 156 patients, who had received unmanipulated leukapheresis products (10 v 12 d, P = 0.006). No significant differences with regard to neutrophil recovery were noted. Five patients had a graft failure. Two of them died (on day 78 and 88 following PBSCT), and three patients were rescued with unmanipulated back-up transplants. In conclusion, the immunomagnetic selection of CD34+ cells provides autografts with reduced tumour cell content and an engraftment ability similar to that of unmanipulated autografts.

Antigens, CD34↗
PubMed1999

Analysis of mouse dendritic cell migration in vivo upon subcutaneous and intravenous injection.

Dendritic cells (DC) have an increasingly important role in vaccination therapy; therefore, this study sought to determine the migratory capacity and immunogenic function of murine bone-marrow (BM)-derived DC following subcutaneous (s.c.) and intravenous (i.v.) injection in vivo. DC were enriched from BM cultures using metrizamide. Following centrifugation, the low-buoyant density cells, referred to throughout as DC, were CD11c(high), Iab(high), B7-1(high) and B7-2(high) and potently activated alloreactive T cells in mixed lymphocyte reactions (MLR). In contrast, the high-density cells expressed low levels of the above markers, comprised mostly of granulocytes based on GR1 expression, and were poor stimulators in MLR. Following s.c. injection of fluorescently labelled cells into syngeneic recipient mice, DC but not granulocytes migrated to the T-dependent areas of draining lymph nodes (LN). DC numbers in LN were quantified by flow-cytometric analysis, on 1, 2, 3, 5 and 7 days following DC transfer. Peak numbers of around 90 DC per draining LN were found at 2 days. There was very little migration of DC to non-draining LN, thymus or spleen at any of the time-points studied. In contrast, following i.v. injection, DC accumulated mainly in the spleen, liver and lungs of recipient mice but were largely absent from peripheral LN and thymus. The ability of DC to induce T-cell-mediated immune responses was examined using trinitrobenzenesulphate (TNBS)-derivatized DC (TNBS-DC) to sensitize for contact hypersensitivity responses (CHS) in naive syngeneic recipients. Following s.c. injection, as few as 105 TNBS-DC, but not TNBS-granulocytes, sensitized for CHS responses. However, the same number of TNBS-DC failed to induce CHS following i.v. injection. In summary, this study provides new and quantitative data on the organ specific migration of murine BM-derived DC following s.c. and i.v. injection. The demonstration that the route of DC administration determines the potency of CHS induction, strongly suggests that the route of immunization should be considered in the design of vaccine protocols using DC.

Adoptive Transfer↗
PubMed1999

Development of low-dose streptozotocin-induced diabetes in ICAM-1-deficient mice.

Multiple injections of low-dose streptozotocin (LDSZ) induce immune-mediated insulitis and diabetes in C57BL/6 (H-2b) mice. To evaluate the role of the intercellular adhesion molecule-1 (ICAM-1) for LDSZ induced immune-mediated diabetes, we have investigated mice genetically deficient in the ICAM-1 gene (ICAM-1-/-) in comparison to wild-type (ICAM-1+/+) mice. ICAM-1-/- mice, which had a mixed genetic background of C57BL/6 and DBA/2 mice, were backcrossed to C57BL/6 mice and screened for H2b homogenicity. Mice received five daily injections of 40 mg/kg streptozotocin. On day 21 after the first LDSZ injection 55% of the ICAM-1+/+ (female 33%, male 80%) and 50% of the ICAM-1-/- (female 20%, male 100%), mice had blood glucose levels over 200 mg/dl. Mean blood glucose levels increased in response to LDSZ treatment, however, no differences between ICAM-1+/+ and ICAM-1-/- mice were noted. Histological examinations of pancreatic islets revealed mononuclear infiltration of pancreatic islets without significant differences between both groups of mice. In summary, LDSZ-induced immune-mediated insulitis and diabetes development occurs in ICAM-1-/- mice similarly than in ICAM-1+/+ mice. These results do not support the hypothesis that ICAM-1 plays a key role during immune-mediated infiltration and destruction of pancreatic islets in LDSZ induced diabetes.

Animals↗
PubMed1999

A qualitative study of clandestine contraceptive use in urban Mali.

This prospective study uses qualitative methods to examine the social and economic impact of family planning on women's lives in the district of Bamako, Mali. Fifty-five first-time users of contraceptives were interviewed in October 1996. Of particular interest is the high proportion (17/55) of those who had hidden their use of a birth-control method from their husbands. Substantial collusion is found to have occurred between sisters-in-law in assisting each other to gain and hide methods of family planning and to keep their use secret from their spouses and older marital relatives. The main reason for discontinuation among the clandestine users was menstrual disruption, which they feared would make their husbands aware of their contraceptive use. By the end of the study, women were aware that their use of contraceptives had increased their mobility and available time, enabling them to enhance the quantity and efficiency of their work activities. Contraception, therefore, appears to be a valuable resource, permitting women to improve their economic and social status. In settings where clandestine use is prevalent, at least in the short term involving men in family planning programs may not always be beneficial, nor may considering the couple as the unit of intervention and analysis always be appropriate. In the long term, however, the underlying causes of men's objections to contraceptive use need to be addressed so as to facilitate communication and joint decisionmaking about family planning.

Adolescent↗
PubMed1999

Pivotal role of an aspartate residue in sodium sensitivity and coupling to G proteins of neurotensin receptors.

The highly conserved aspartate residue in the second transmembrane domain of G protein-coupled receptors is present in position 113 in the type 1 neurotensin receptor (NTR1) but is replaced by an Ala residue in position 79 in the type 2 neurotensin receptor (NTR2). NTR1 couples to Galphaq to stimulate phospholipase C and its binding affinity for neurotensin is decreased by sodium ions and GTP analogs. By contrast, NTR2 does not seem to couple to any G protein in eukaryotic cells, and its binding of neurotensin is insensitive to sodium and GTP analogs. By using site-directed mutagenesis, we substituted Asp113 of the NTR1 by alanine and the homologous residue Ala79 of NTR2 by aspartate. Both mutant receptors display similar affinity for neurotensin as compared with their respective wild type. We demonstrate that the presence of the Asp residue determines by itself the occurrence of the sodium effect on neurotensin affinity for both wild-type and mutated NTR1 and -2. The introduction of an Asp in the second transmembrane domain of NTR2 is not enough to restore a functional coupling to G proteins. In contrast, replacement of Asp113 by Ala residue in NTR1 strongly decreases its ability to activate inositol turnover, indicating that the functionally active conformation of NTR1 is maintained by interaction of sodium ions with aspartate 113.

Amino Acid Sequence↗
PubMed1999

Lmb, a protein with similarities to the LraI adhesin family, mediates attachment of Streptococcus agalactiae to human laminin.

Streptococcus agalactiae is a leading cause of neonatal sepsis and meningitis. Adherence to extracellular matrix proteins is considered an important factor in the pathogenesis of infection, but the genetic determinants of this process remain largely unknown. We identified and sequenced a gene which codes for a putative lipoprotein that exhibits significant homology to the streptococcal LraI protein family. Mutants of this locus were demonstrated to have substantially reduced adherence to immobilized human laminin. The nucleotide sequence of the gene was subsequently designated lmb (laminin binding) and shown to be present in all of the common serotypes of S. agalactiae. To determine the role of Lmb in the adhesion of S. agalactiae wild-type strains to laminin, a recombinant Lmb protein harboring six consecutive histidine residues at the C terminus was cloned, expressed, and purified from Escherichia coli. Preincubation of immobilized laminin with recombinant Lmb significantly reduced adherence of the wild-type strain O90R to laminin. These results indicate that Lmb mediates the attachment of S. agalactiae to human laminin, which may be essential for the bacterial colonization of damaged epithelium and translocation of bacteria into the bloodstream.

Adhesins, Bacterial↗
PubMed1999

Identification of genetic determinants for the hemolytic activity of Streptococcus agalactiae by ISS1 transposition.

Streptococcus agalactiae is a poorly transformable bacterium and studies of molecular mechanisms are difficult due to the limitations of genetic tools. Employing the novel pGh9:ISS1 transposition vector we generated plasmid-based mutant libraries of S. agalactiae strains O90R and AC475 by random chromosomal integration. A screen for mutants with a nonhemolytic phenotype on sheep blood agar led to the identification of a genetic locus harboring several genes that are essential for the hemolytic function and pigment production of S. agalactiae. Nucleotide sequence analysis of nonhemolytic mutants revealed that four mutants had distinct insertion sites in a single genetic locus of 7 kb that was subsequently designated cyl. Eight different open reading frames were identified: cylX, cylD, cylG, acpC, cylZ, cylA, cylB, and cylE, coding for predicted proteins with molecular masses of 11, 33, 26, 11, 15, 35, 32, and 78 kDa, respectively. The deduced amino acid sequence of the protein encoded by cylA harbors a conserved ATP-binding cassette (ABC) motif, and the predicted proteins encoded by cylA and cylB have significant similarities to the nucleotide binding and transmembrane proteins of typical ABC transporter systems. Transcription analysis by reverse transcription-PCR suggests that cylX to cylE are part of an operon. The requirement of acpC and cylZABE for hemolysin production of S. agalactiae was confirmed either by targeted mutagenesis with the vector pGh5, complementation studies with pAT28, or analysis of insertion elements in naturally occurring nonhemolytic mutants.

Animals↗
PubMed1999

Development and validation of a quality of life measurement for chronic skin disorders in french: VQ-Dermato. The RéseaudEpidémiolo gie en Dermatologie.

BACKGROUND: Quality of life (QoL) assessment is crucial to assess the severity of dermatological diseases. PURPOSE: To construct and validate the first dermatology-specific instrument in French. METHODS: Items were generated from the interview of patients. The final self-administered questionnaire, the VQ-Dermato, included 28 questions. Validity in terms of content and construct, reliability in terms of reproducibility and internal consistency, responsiveness and acceptability were tested in a population of 231 patients with 12 categories of chronic skin disorders, who were recruited and followed in hospital and private practice in France. RESULTS: Item analysis revealed that discrimination indices were high. After factor analysis, 7 dimensions were retained, which accounted for 72% of the total variance. Cronbach's alpha coefficient ranged between 0. 67 and 0.88. A strong correlation was found between dimensions of the VQ-Dermato and the corresponding dimensions of the SF36. Scores were significantly different in each category of chronic skin disease and significantly higher when there was a function restriction or when the lesions were visible to others. The scale was proven to be stable by test-retest correlation. The VQ-Dermato was more responsive to clinical improvement after a 1- or 2-month treatment than the SF36. The percentage of missing responses was under 10 and the time for completing the questionnaire always under 13 min. CONCLUSION: The VQ-Dermato is the first valid and reliable dermatology-specific QoL instrument in French, and the first based on the concept of 'chronic skin disorders'. It is acceptable for routine use and has a better responsiveness than a general health instrument.

Adult↗
PubMed1999

Alternative activation of macrophage by IL-10.

Macrophage activation by proinflammatory stimuli is suppressed by IL-10. We tested the hypothesis that IL-10 induces an alternative state of macrophage activation rather than solely mediating suppression. We therefore searched for genes the expression of which might be up-rather than downregulated in response to IL-10. Total RNA was obtained from mouse macrophages J774 A.1 before or after stimulation with IL-10 (20 ng/ml). Poly(A)+RNA was isolated in both cases in order to obtain driver and tester mRNA. Subtraction suppression hybridization was performed using the PCR-select cDNA subtraction procedure. After evaluation of the subtraction efficiency the subtracted cDNA library was cloned into pCRII.1. A total of 1,300 clones were obtained. Southern blot hybridization analysis was performed as the first screening step of this total number of clones. 140 (10.7%) were identified as upregulated in response to IL-10. Sequence analyses so far showed perfect or near perfect matches with already known genes for the majority of clones. Our results clearly indicate that IL-10 stimulates the expression of a large number of genes in macrophages. We conclude that IL-10 induces in macrophages a noninflammatory state of reactivity which may serve to contain proinflammatory conditions.

Animals↗
PubMed1999

LPS challenge in D-galactosamine-sensitized mice accounts for caspase-dependent fulminant hepatitis, not for septic shock.

Experimental models of sepsis using endotoxin challenges, including studies with sensitized animals with D-galactosamine, have largely contributed to the basic rationale for innovative clinical trials in human septic shock, which have, to date, failed. The ability of these models to reproduce human disease has been highly discussed. We report here that the widely used D-galactosamine/LPS model does not account for septic shock. Treatment with YVAD-CMK, a potent tetrapeptide inhibitor of caspases of the interleukin (IL)-1beta converting enzyme (ICE) family, protects from LPS-induced liver apoptosis and mortality in D-galactosamine-sensitized mice when administered either before or up to 2 h after the lethal challenge. This curative effect is related to complete inhibition of caspase-3 activity in the liver. However, YVAD-CMK does not affect LPS-induced release of IL-1beta and does not protect from a lethal dose of LPS in unsensitized mice. These experiments demonstrate the difference between these two widely recognized experimental models of sepsis. LPS toxicity in D-galactosamine-treated mice, leading to blocked gene transcription, results from tumor necrosis factor (TNF)-alpha-induced caspase-3-dependent liver injury, not from the systemic inflammatory response. These results provide evidence that inhibitors of the ICE caspase family can prevent or even overcome the ongoing hepatic injury induced by TNF-alpha during sepsis, ischemia-reperfusion, or severe hepatitis.

Amino Acid Chloromethyl Ketones↗
PubMed1999

Systems change resulting from HIV/AIDS education and training. A cross-cutting evaluation of nine innovative projects.

An evaluation of nine diverse HIV/AIDS training programs assessed the degree to which the programs produced changes in the ways that health care systems deliver HIV/AIDS care. Participants were interviewed an average of 8 months following completion of training and asked for specific examples of a resulting change in their health care system. More than half of the trainees gave at least one example of a systems change. The examples included the way patient referrals are made, the manner in which agency collaborations are organized, and the way care is delivered.

Adolescent↗
PubMed1999

Regulated, side-directed secretion of proguanylin from isolated rat colonic mucosa.

Guanylin, an activator of the guanylyl cyclase C receptor in the apical membrane of intestinal epithelium, modulates intestinal fluid and electrolyte transport. The bioactive 15-amino acid peptide originally isolated from rat intestine represents the C-terminal part of a longer, 115-residue prepropeptide. The aim of the present study was to characterize the direction and molecular form in which guanylin is secreted from the colonic mucosa, as well as the mechanisms that trigger its secretion. Isolated rat colonic mucosa was mounted in Ussing chambers, allowing the separate determination of apical and basolateral release. After HPLC purification, two different molecular forms of guanylin were identified in the apical incubation media by combining a bioassay for guanylyl cyclase C activation, a specific guanylin enzyme-linked immunosorbent assay and mass spectrometry, as well as sequence analysis: a bioactive form coeluting with synthetic 15-residue guanylin and the 94-residue propeptide, guanylin-22-115. The basal concentration of proguanylin at the apical side of epithelia was about 15-fold higher, compared with that of the small, bioactive peptide. In the basolateral incubation media, no proguanylin and only very low amounts of bioactive guanylin were detected. Incubation with carbachol led to a significant increase of about 7-fold in the release of proguanylin to both sides of the isolated epithelia. On the apical side, a concomitant increase of the small, bioactive peptide was observed; whereas, on the basolateral side, its concentration remained unchanged. Vasoactive intestinal peptide or the NO-donor S-nitroso-N-acetylpenicillamine did not affect guanylin secretion. Our results suggest that, in the intestine, guanylin is secreted mainly to the luminal side of the epithelium. The peptide is released as a 94-residue propeptide, which is then processed to a smaller, bioactive form (luminocrine secretion). Carbachol stimulates the release of proguanylin to both sides of the intestinal mucosa, but a parallel increase in the bioactive C-terminal derivative only occurs on the apical side. In vivo, the basolateral release could be a source of circulating proguanylin, which might be processed proteolytically to the active peptide in distant target tissues (endocrine secretion).

Amino Acid Sequence↗
PubMed1999

Impaired innate immunity in the newborn: newborn neutrophils are deficient in bactericidal/permeability-increasing protein.

OBJECTIVE: The mechanisms by which newborns are at increased risk for invasive bacterial infections have been incompletely defined. A central element of innate immunity to bacterial infection is the neutrophil-a cell that contains cytoplasmic granules replete with antibiotic proteins and peptides. The activity of adult neutrophils against gram-negative bacteria is believed to depend to a significant degree on the presence in neutrophil primary (azurophilic) granules of the 55-kDa bactericidal/permeability-increasing protein (BPI), which binds with high affinity to bacterial lipopolysaccharides and kills gram-negative bacteria. In light of the importance of BPI to antibacterial host defense and to investigate possible factors underlying the risk of neonatal bacterial infections, we determined the relative content of BPI in the neutrophils of adults and newborns. DESIGN: The cellular content of BPI was determined by Western blotting of neutrophils derived from full-term newborn cord blood (n = 21; mean gestational age: 38.6 weeks) and from adult peripheral blood (n = 22; mean age: 29 years). Extracellular levels of BPI in adult and newborn plasma were assessed by enzyme-linked immunosorbent assay. Neutrophil content of other azurophil granule markers also was assessed: myeloperoxidase by Western blotting and defensin peptides by acid-urea polyacrylamide gel electrophoresis and Coomassie staining. Acid extracts of newborn and adult neutrophils were analyzed for antibacterial activity against serum-resistant encapsulated isolate Escherichia coli K1/r. RESULTS: The neutrophils of newborns contain at least threefold to fourfold less BPI per cell than adult neutrophils (67 +/- 13 ng per 10(6) cells vs 234 +/- 27 ng per 10(6) cells). The relative BPI-deficiency of newborn neutrophils apparently was not attributable to perinatal stress-related degranulation of intracellular BPI stores because: 1) newborn and adult neutrophils contained nearly identical amounts of 2 microbicidal constituents derived from the same primary (azurophil) granule compartment as BPI (the enzyme myeloperoxidase as well as defensin peptides), and 2) levels of extracellular BPI in newborn plasma, measured by enzyme-linked immunosorbent assay, represent only approximately 2% of cellular BPI content. As predicted by their lower BPI content, newborn neutrophil acid extracts demonstrated significantly lower antibacterial activity against E coli K1/r than did adult neutrophil acid extracts. CONCLUSION: These data suggest that the neutrophils of newborns are selectively deficient in BPI, a central effector of antibacterial activity against gram-negative bacteria. BPI deficiency correlates with decreased antibacterial activity of newborn neutrophil extracts against serum-resistant E coli and could contribute to the increased incidence of gram-negative sepsis among newborns relative to healthy adults.neonatal sepsis, gram-negative bacteria, endotoxin, neutrophil, polymorphonuclear leukocyte, innate immunity, bactericidal/permeability-increasing protein, defensin, myeloperoxidase.

Adult↗
PubMed1999

FGF-2 dependent angiogenesis is a latent phenotype in basic fibroblast growth factor transgenic mice.

Overexpression of basic fibroblast growth factor (FGF-2) in transgenic (TgFGF2) mice results in a chondrodysplasia as the principle phenotype. Here we report a second phenotype in TgFGF2 mice that was previously undetected: A predisposition to angiogenic reactions with subsequent amplified angiogenesis that are both FGF-2 dependent. We used subcutaneous injection of extracellular matrix as an angiogenic assay. The matrix formed vascularized cysts in the TgFGF2 group after seven days, whereas the non-transgenic (NTg) group developed avascular cysts. Cysts from the TgFGF2 group contained 3-7X more hemoglobin (Hb), two-fold more vonWillebrand Factor (VWF), and 150X more FGF-2 than cysts from the NTg control group. Significant angiogenic reactions occurred only in the TgFGF2 group that express FGF-2 from the transgene. The TgFGF2 mice, therefore, constitute a unique experimental system to study FGF-2 dependent angiogenesis because they have no spontaneous or inherent vascular defects, but provision of an angiogenic substrate results in an amplified angiogenic response. In addition, we report development of an ELISA for VWF that provides a sensitive, quantitative assay for angiogenesis.

Animals↗
PubMed1999

Evaluation of a cut-off value for sperm motility after different hours of incubation to select the suitable reproductive technology (IVF or ICSI).

BACKGROUND: The aim of this study was to enhance the predictability of conventional semen parameters for in-vitro fertilization outcome. The utility of late sperm motility in presence of a cumulus-oocyte complex after different hours of incubation was investigated to predict the outcome of IVF in borderline and normal ejaculates (at least 5 x 10(6) motile sperm). METHODS: The study was done on 52 infertile couples undergoing conventional in-vitro fertilization and embryo transfer. Sperm were prepared by the Percoll cushion centrifugation with swim-down. Cocultures were established by inseminating the cumulus-oocyte complexes with 100000 motile spermatozoa and incubating them for 48 hours. Another 100000 spermatozoa were incubated in culture medium for 48 hours. Sperm motility (WHO a+b) was determined at 0, 4, 24 and 48 hours of incubation. RESULTS: The fertilization rate was 65.5% (42.9-88.1). The conventional semen parameters did not correlate with the fertilization rate. Sperm motility measured after different hours of incubation was found to be significantly positively correlated with the fertilizing ability of sperm in vitro in Spearman's rank correlation test: motility after 0 h (p<0.02), after 4 h (p=0.0025). after 24 h (n.s.) and after 48 h (p=0.0071). Cut-off values for late sperm motility were determined and differences in fertilization rates were calculated for these cut-off values after different hours of incubation. A cut-off value of 20% progressive motile spermatozoa after 48 hours gave the best statistical power (fertilization rate 71.7 vs. 50.2%, p<0.001). Significant differences in the fertilization rates were also observed for a cut-off value of 35% after 24 hours of incubation (70.1 vs. 46.2%, p=0.001) and for a cut-off point of 60% after 4 hours (72.4 vs. 51.5%, p=0.001). CONCLUSIONS: The predictive power of sperm motility after 48 h for fertilization outcome provides support in the decision-making process within the assisted reproduction setting. If less than 20% of sperm are motile after 48 h micromanipulatory techniques should be considered.

Adult↗