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F Pages

Publications and source records attributed to F Pages.

18 recordsLinked to original sources

[Medical entomology for the Armed services: preliminary results from the medical entomology unit].

Vector-borne diseases constitutes a threat to the operational capability of armed forces personnel operating outside or stationed overseas. To take this risk into account, the French armed forces medical corps created a medical entomology unit in 2003. The primary function of this unit is to monitor the entomological status of French military bases in sub-Saharan Africa (identification of vectors, study of vector behavior, and measurement of resistance to insecticides) as a means of maintaining an effective vector-control strategy. The French medical entomology unit takes part in the Impact Vector project aimed at evaluating the vector-borne disease risks for troops in combat situations, contributes its expertise to the investigation of epidemic disease, and participates in the development of a global strategy for vector-control for the armed services. To improve understanding and control of vector-borne disease risks, the unit provides basic training in medical entomology to army physicians, veterinarians, and pharmacists as well as to others involved in control programs. The purpose of this article is to present the results of the unit's first activities: investigation of a malaria epidemic that occurred in Ivory Coast in 2003, measurement of malaria exposure over a 4-month period in a combat group on duty in rural Africa, and initial evaluation of control techniques (spraying around living quarters and use of insecticide-impregnated battle dress).

Africa South of the Sahara↗

[Management of American cutaneous leishmaniasis. Outcome apropos of 326 cases treated with high-dose pentamidine isethionate].

The purpose of this retrospective analysis was to evaluate the outcome of pentamidine isethionate treatment (4 mg/kg of Pentamidine by the intramuscular route on Days 1 and 3) of cutaneous leishmaniasis in 326 cases that occurred during an outbreak among French military personnel in French Guyana from 1998 to 1999. A great difference was found between the 205 patients treated in French Guyana (series G) and 32 patients treated at the Laveran Military Hospital in Marseille, France (series L). Failure rate, i.e. 25% in series L versus 5% in series G, was significantly correlated with the delay to treatment which was much longer in series L. Extensive rhabdomyolysis was observed in all cases tested: this side-effect has not been reported. Based on these findings and a review of the literature on pentamidine isethionate, the authors recommend prompt treatment using lower doses. Other treatment alternatives for American cutaneous leishmaniasis are also presented including two of the latest developments in the field, i.e., oral treatment using miltefosine and topical treatment using agents such as paromomycine.

Antiprotozoal Agents↗

[Malaria in military personnel: the case of the Ivory Coast in 2002-2003].

French troops were sent to the Ivory Coast on September 22, 2002 within the framework of Operation Unicorn in response to the political unrest. From September 22 to October 20, a total of 37 cases of malaria were reported, i.e., 35.7 cases per 1000 man-months. As of October 11, the central headquarters of the Armed Services Health Corps decided to use doxycycline as the exclusive agent for drug prophylaxis in military personnel on duty in the Ivory Coast and to enhance vector control measures. The incidence of malaria decreased to 2 cases per 1000 man-months at the sixth month. A recrudescence of malaria to 15 cases per 1000 man-months was observed with the rainy season in April. During this period one person presenting severe malaria with coma required emergency evacuation to France. In May 2003, several studies were undertaken to determine the factors that caused this recrudescence. These studies included surveys to evaluate awareness concerning malaria and monitor compliance with drug prophylaxis and tolerance of doxycycline, a case-control study to identify factors related to malarious episodes and an entomological study. Awareness of malaria was high with 75% of the 477 respondents stating that malaria could be transmitted by single mosquito bite. The case-control study showed a correlation between occurrence of malarious bouts and non-compliance with drug prophylaxis (p < 10(-5)). The odds-ratio was 3.05 (95% confidence interval, 1.52-6.14) for subjects claiming zero to one incident of non-compliance per week and 7.51 (IC95%, 3.24-17.40) for those claiming more than one incident of non-compliance per week. Tolerance of doxycyline was good since 72% of respondents reported no adverse effects. The main vector was Anopheles gambiae. The number of bites per man per night ranged from 25 to 2 and the number of infected bites ranged from 2 to 3 per week. Treatment was initiated promptly using quinine at a total dose of 25 mg/kg in 3 daily doses for 7 days by the intravenous then oral route. This experience shows that malaria remains a major concern for military forces, that standardization of preventive measures in emergency situations is needed, and that enhanced vector control, verification of compliance with drug prophylaxis and prompt treatment based on the presence of a physician in each emergency outpost is crucial. These recommendation must be applied to all French military personnel in the Ivory Coast.

Adult↗

[Disease vector control strategy in the French army].

Disease vector control is a major priority for the Medical Health Corps of the French Armed Forces which maintains around 23,000 troops in tropical areas and is involved in numerous military and humanitarian missions throughout the world. Control strategy includes both general and personal control measures. Personal control measures include wearing permetherin-impregnated combat uniforms, application of repellents to the skin, and use of deltamethrin-impregnated bednets. General measures are implemented in facilities and in the environment. Measures in facilities include not only physical deterrents such as screens on openings and air-conditioning but also application of chemical insecticides to walls, curtains, and screening. Environmental measures include control of larval deposits and elimination of potential breeding areas. Low-volume wide-area spraying of imagocides is a supplemental option used in case of disease outbreak. For units stationed in tropical areas, command and surveillance of vector control operations is under the responsibility of the mosquito control committee which includes personnel from the affected field unit. Strategies are chosen in function of local climate and operational conditions. The efficacy of vector control programs is assessed annually by reviewing the incidence in armed forces personnel of the main vector-transmitted diseases: malaria, dengue fever, and leishmaniasis. Documentation and training are dispensed to all units stationed in tropical areas. To ensure that knowledge of military physicians remains current, three courses on malaria control are offered each year at the Tropical Medicine Institute of the Armed Forces Health Corps (Le Pharo) in Marseille. Field research conducted in collaboration with military or civilian organizations independent of the Armed Services Health Corps makes it possible to keep chiefs of staff informed of state-of-the art vector control measures adapted to use by personnel on assignment or mission in tropical areas.

Animals↗

[Epidemiologic surveillance of dengue fever in the French army from 1996 to 1999].

Dengue fever is a widespread disease that can occur outside tropical areas. Several thousand French military personnel are exposed to this infectious risk each year and exposure is expected to rise with the creation of a professional army and the increasing number of foreign missions. As a result, dengue fever has become a major priority for the Armed Services Health Corps (ASHC). A system of epidemiological surveillance based on the active participation of all military physicians has been designed by the ASHC to collect and analyze all data relevant to cases of dengue fever involving French military personnel stationed overseas or at home. The purpose of this study is to present data compiled for the period from 1996 to 1999. Analysis of these data demonstrated that the incidence of dengue fever peaked in 1997 due to epidemic outbreaks occurring in French Polynesia and Martinique. In response to these outbreaks control measures were adapted especially in regard to vector control. This study shows that the system of surveillance implemented by the ASHC is an effective but still perfectible tool.

Adult↗

[Cholera update at the dawn of the millenium].

Cholera is an ancestral disease belonging to the mythology of numerous societies. In the last two centuries, seven pandemias have been recorded, in which the spatial and temporal modalities of disease transmission are related to the major technical revolutions of the period. The now ongoing seventh pandemia is by far the longest and most widespread with specific features that raise new challenges and hopes. The authors present the situation at the dawn of the third millennium based on a review of current epidemiological, clinical, therapeutic, diagnostic and vaccinal data. This update shows that the field is progressing and may indeed be standing on the verge of significant breakthroughs for management of the disease and vibrion endemicity.

Cholera↗

Control of tumor development by intratumoral cytokines.

The local immune reactions may influence the clinical outcome of human tumors. In carcinoma of the cervix, high gene expression of IL6 with tumor invasiveness whereas lack of gene expression of IFNbeta is correlated with poor prognosis. In colorectal cancer, lack of expression of IFNbeta is associated with the presence of distant metastasis and poor survival. The production of IL17 and IL18, inducers of IL6 and IFNbeta respectively is regulated in these tumors and may control the levels of the effector cytokines, i.e. IL6 and IFNbeta. The mechanisms by which these cytokines act are linked to the recruitment of effector cells such as macrophages.

Animals↗

Two distinct regions of the CD28 intracytoplasmic domain are involved in the tyrosine phosphorylation of Vav and GTPase activating protein-associated p62 protein.

The T cell-associated CD28 molecule plays a key role in T cell co-stimulation. Its ligation induces the tyrosine phosphorylation of numerous proteins including CD28 itself as well as a restricted set of substrates of 97 and 62-68 kDa which are poorly phosphorylated by the tyrosine kinases induced by CD3-TCR triggering. In this study, we identify these substrates as the product of the vav proto-oncogene and as a 62 kDa protein that could correspond at least in part to p62dok, the 62 kDa adaptor molecule associated to p120 Ras-GTPase activating protein. Both p97vav and p62 are tyrosine phosphorylated upon CD28 ligation by mAb or by its counter-receptor B7-1/CD80. Using CD28 mutants, we also show that Vav and p62 tyrosine phosphorylation is regulated by distinct domains within the CD28 cytoplasmic tail: residues 173-181 for Vav and residues 182-202 for p62. Finally, the phosphorylation of Vav and p62 does not require an intact binding site for Grb-2 or p85 SH2 domains. We thus demonstrate that the CD28 cytoplasmic domain contains at least three functionally independent regions involved in CD28-induced signal transduction, since in addition to the Grb-2 and p85 SH2 domain binding site (Tyr173), residues 173-181 and 182-202 are associated with Vav and p62 tyrosine phosphorylation respectively.

Animals↗

[Ser/Thr-phosphatases from bovine retina: detection of cDNA coding for the catalytic subunit of the gamma-isoform PP2B and two homologs of rdgC/PPEF].

The expression of genes for Ser/Thr phosphatases of the PP1/2A/2B class in the bovine retina was analyzed using PCR on cDNA. The mRNAs were found for the following phosphatases: PP1 (alpha- and gamma-isoforms), PP2A (alpha- and beta-isoforms), PPV, and PP2B (beta- and gamma-isoforms). Earlier, PP2B gamma-isoform was considered testis-specific. cDNAs of two phosphatases related to rdgC/PPEF were also detected. Thus, there are mRNAs of at least four phosphatases in retina that may be regulated by Ca2+.

Amino Acid Sequence↗

p53 status does not predict initial clinical response to bacillus Calmette-Guerin intravesical therapy in T1 bladder tumors.

PURPOSE: In superficial urothelial tumors of the bladder, p53 status is currently the most informative pretreatment parameter to define a population at higher risk for invasive carcinoma. Also, in T1 tumors, occurrence of muscular invasion is often related to an early relapse following BCG therapy. With the knowledge of biological parameters able to identify the group of initial BCG therapy non-responders, it would be possible to offer earlier treatment to the patients who need a more aggressive mode of therapy. The aim of this work was to study the predictive value of the p53 tumor status on the early BCG therapy response. MATERIALS AND METHODS: The population included a selected group of 43 patients presenting T1 bladder tumors with no carcinoma in situ (Tis), treated by transurethral resection (TUR) followed by intravesical BCG therapy. Clinical outcome was analyzed in relation to usual clinical and histopathological parameters, and pretreatment p53 tumor status was assayed by an immunohistochemical technique using DO7 monoclonal antibody. For 16 specimens, p53 gene was investigated using a Single Strand Conformation Polymorphism (SSCP) analysis and sequence determination. RESULTS: p53 anomalies were strongly correlated to smoking behavior (p = 0.003) and tumoral grade (p = 0.025). Univariate analysis revealed an absence of correlation between p53 immunostaining and initial, one and two years response-rate to BCG therapy. However, longterm followup revealed a trend between positive staining and disease progression. The p53 molecular study validated the use of DO7 immunostaining in detection of p53 anomalies. CONCLUSIONS: In T1 bladder tumors, pretreatment p53 determination was not useful to define a group of early BCG non-responders. Thus, p53 status and immunological response induced by BCG endovesical therapy are two independent events.

Adult↗

[Fas, fas ligand, immune tolerance, and cancer: implications in cancer of the colon].

Fas and Fas ligand (FasL) are implicated in programmed cell death or apoptosis. In the immunological field, they are particularly important in auto-immunity, graft rejection and anti-tumoral response. Fas ligand expression on thymocytes, activated T lymphocytes, and in sites of immune privilege, suggests the importance of Fas/FasL interactions in negative control of the immune response. The recent description of FasL expression by tumoral cells, represents a new mechanism of immune escape for different cancer, and has been well studied in colon adenocarcinoma.

Apoptosis↗

Cloning of a human phosphoinositide 3-kinase with a C2 domain that displays reduced sensitivity to the inhibitor wortmannin.

The generation of phosphatidylinositide 3-phosphates has been observed in a variety of cellular responses. The enzymes that mediate synthesis are the phosphoinositide 3-kinases (PI3-Ks) that form a family of structurally diverse enzymes with distinct substrate specificities. In this paper, we describe the cloning of a novel human PI3-K, namely PI3-K-C2 alpha, which contains a C-terminal C2 domain. This enzyme can be assigned to the class II PI3-Ks, which was defined by characterization of the Drosophila 68D enzyme and includes the recently described murine enzymes m-cpk and p170. Despite the overall similarity in the amino acid sequence of the murine and human enzymes, which suggests that they are encoded by closely related genes, these molecules show marked sequence heterogeneity at their N-termini. Biochemical analysis of recombinant PI3-K-C2 alpha demonstrates a restricted lipid substrate specificity. As reported for other members of this class, the enzyme only phosphorylates PtdIns and PtdIns4P when the lipids are presented alone. However, when lipids were presented together with phosphatidylserine acting as a carrier, phosphorylation of PtdIns(4,5)P2 was also observed. The catalytic activity of PI3-K-C2 alpha is refractory to concentrations of wortmannin and LY294002 which inhibit the PI3-K activity of other family members. The comparative insensitivity of PI3-K-C2 alpha to these inhibitors suggests that their use should be reevaluated in the study of PI3-Ks.

Amino Acid Sequence↗

Positive prostate-specific antigen circulating cells detected by reverse transcriptase-polymerase chain reaction does not imply the presence of prostatic micrometastases.

OBJECTIVES: Detection of circulating tumor cells may improve the preoperative local staging of prostate cancers. The aim of this study was to perform enhanced reverse transcriptase-polymerase chain reaction (RT-PCR) of prostate-specific antigen (PSA) mRNA to define the predictive value of PSA-positive circulating cells in a large series of patients. METHODS: The study included 46 patients with Stage T1 to T2 prostate cancer, 94 with benign prostatic hyperplasia (BPH), and 51 (including 9 women) with nonprostatic disease. PSA-positive cells from peripheral blood samples were detected by Southern blot analysis of the RT-PCR products. Original oligonucleotide primers were defined to exclusively detect the three PSA mRNA splices. RESULTS: Circulating PSA-positive cells were observed in 8 (8.5%) of 94 patients with BPH, 10 (22%) of 46 with Stage T1 to T2 prostate cancer, and 9 (17.6%) of 51 with nonprostatic disease. The detection rate of PSA-positive circulating cells was significantly increased in patients with prostate cancer versus patients with BPH (P = 0.03). Among clinically localized prostate cancers with a Gleason score less than 8, a correlation was observed between PSA-positive circulating cells and Stage pT3 cancer (P = 0.038), capsular penetration (P = 0.04), and a positive margin (P = 0.038). The specificity of the assay for Stage pT3 cancer detection was 84.6%, with a positive predictive value of 60%. CONCLUSIONS: Although RT-PCR assay may have a role in preoperative local staging, this study demonstrated the absence of tissue and tumor specificity of PSA-positive circulating cells, accounting for the weak positive predictive value of this technique.

Aged↗

IL-6 is a survival prognostic factor in renal cell carcinoma.

It has been reported that a high plasmatic concentration of interleukin-6 (IL-6) is correlated to a lack of response to immunotherapy in several malignancies, suggesting that IL-6 was either a marker of tumour aggressiveness or had only a predictive value of response to immunotherapy. To discriminate between these two possibilities, a retrospective study was performed in a series of 19 patients with metastatic renal cell carcinoma who did not respond to IL-2/IFNalpha/5-FU treatment. Serum levels of IL-6, C-reactive Protein (CRP), soluble IL-2-receptor (sIL-2R), M-CSF and neopterin were assayed before treatment. IL-6 showed a significant correlation with patients median survival time (P < 0.016), suggesting that serum concentration of IL-6 before treatment is a marker of tumour aggressiveness rather than a predictive parameter for an immunological response.

Adult↗

Structural and functional diversity of phosphoinositide 3-kinases.

Phosphoinositide 3-kinases (PI3-kinases) have been shown to be recruited to cell surface receptor signal complexes whose formation is triggered by growth factors, cytokines and other ligands. PI3-kinases are also involved in protein sorting phenomena. A number of PI3-kinase isotypes have been characterised in several laboratories. Here the relations between the PI3-kinases, PI4-kinases and PI5-kinases and other potential phosphoinositide kinases are analysed. A study of the relation of structure to function for sequence motifs defined through the use of homology searches and protein modelling techniques is described and used to assign the family of phosphoinositide kinases to subgroups.

Amino Acid Sequence↗

Phenotypic and functional characterisation of tumour-infiltrating lymphocytes derived from thyroid tumours.

The natural history of thyroid tumours and the hyper-reactivity of the immune system in patients with thyroid cancer suggest that immune surveillance may play a role in the control of this disease. A study was therefore undertaken to analyse the phenotypic and functional features of tumour-infiltrating lymphocytes (TILs) derived from thyroid tumours. In a series of experiments, it was found that, in contrast to TILs derived from patients with melanoma or renal cell carcinoma, thyroid TILs could be efficiently expanded in vitro only in the presence of allogeneic EBV transformed B (B. EBV) cells. Indeed, only one of the seven thyroid-derived TILs grew in vitro without feeder cells, whereas all 16 thyroid-derived TILs could be expanded in the presence of allogeneic B. EBV feeder cells. Phenotypic analysis of these TILs revealed a frequent in vitro expansion of an unusual T cell population that expressed both the CD4 and CD8 markers. Indeed, it was demonstrated that in five of 14 TILs in short-term culture (< day 23) and four of 11 TILs in long-term culture (> day 40), a lymphocyte population that coexpressed CD4 and CD8 antigen accounted for more than 15% of the total TIL population. This double-positive T cell population was not observed in TILs derived from melanoma or renal cell carcinoma. Thyroid-derived TILs also displayed an intense cytolytic activity against NK-sensitive tumour targets with 10 of 11 TILs exhibiting significant cytotoxicity towards the NK-sensitive K562 cell line. Six of 11 TILs were also cytotoxic towards autologous tumour, but when cold target inhibition with K562 was performed with three cultures, unlabelled K562 completely inhibited lysis of autologous tumour cells. A significant expansion of CD3+CD56+ T cells in the different TIL populations may explain this high level of NK-like cytotoxicity. In conclusion, TILs derived from thyroid tumours could be efficiently expanded in vitro under certain culture conditions. Different strategies must be explored to enhance their specific tumour autologous specificity, however, before they can be used in immunotherapy protocols.

Adult↗