Assessing allergic rhinitis in developing countries.

BACKGROUND: Allergic rhinitis (AR) affects 5% to 40% of the general population. In developing countries, AR is poorly documented and tracked due to a lack of appropriate diagnostic tools. OBJECTIVE: 1) To validate a questionnaire standardised in industrialised countries to ascertain AR, the Score For Allergic Rhinitis (SFAR), in developing countries; 2) to better understand AR prevalence previously reported from developing countries by comparing results from the SFAR and the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires. METHODS: Six African countries were selected for their climates. In each country, 70 individuals with and 30 without nasal symptoms filled out the SFAR and the ISAAC questionnaires. Skin prick tests (SPTs) for allergens were performed by the physician if necessary. RESULTS: The SFAR presented a close match with the gold standard (the physician's diagnosis of AR backed up by SPT where necessary) in terms of various performance parameters. In particular, it showed high sensitivity (0.84) and specificity (0.81). Compared to the ISAAC questionnaire, the SFAR had greater sensitivity and equal specificity. CONCLUSIONS: In the absence of a medical visit, the SFAR is a useful standardised screening instrument for the collection of information needed for the identification of AR in developing countries.

Sex and gender differences in tobacco smoking among adolescents in French secondary schools.

AIM: We investigated the relationship between sex (genetic/biological) and gender (environmental/cultural) factors in relation to adolescent tobacco smoking. METHODS: A representative sample of 11,582 students from French secondary public schools participated in the study by completing a self-administered, standardised questionnaire. RESULTS: Using the WHO classification for smoking in the youth, 15.6% of the adolescents were regular smokers, 7.7% occasional smokers, 17.9% experimental smokers and 4.8% ex-smokers, with no statistically significant gender difference. Taking non-smoking as a reference, puberty had a much greater effect on the likelihood of being a regular smoker [OR = 18.0 (95% Confidence Interval: 9.6-32)] than of being an experimental/occasional smoker [OR = 3.7 (2.9-4.6)] among girls. For boys, the effect of puberty was not as great [OR = 4.7 (3.5-6.5)] for regular vs. [OR = 2.1 (1.8-2.5)] for experimental/occasional smokers). Similarly, illicit drug use had a larger effect on the likelihood of being regular smoker vs. non-smoker [OR = 15.0 (12.0-20.0) in boys and 12 (8.8-16.0) in girls] than of being experimental/occasional smoker vs. a non-smoker [OR = 4.8 (3.7-6.1) and 2.9 (2.1-3.9) respectively]. Other factors related to regular smoking were exposure to passive smoking and regular alcohol consumption. Living with both parents was a protective factor for life and regular smoking in both genders. CONCLUSIONS: Our results show that influential factors of sex-related (puberty), gender-specific (environmental tobacco smoking, alcohol consumption, drug abuse) or sex/gender (regular sexual intercourse) are related to the smoking behaviour in French adolescents.

Questionnaire on health systems and national resources for control of respiratory health in low-income countries.

BACKGROUND: Due to increased exposure to risk factors such as ageing and tobacco smoking, chronic respiratory diseases (CRDs) have become a major cause of morbidity and mortality worldwide. Data on CRDs and their management in developing countries (DC) are nevertheless sparse and not comparable. OBJECTIVE: To implement and validate a standardised self-administered questionnaire to be proposed to health authorities to assess the resources of their health system for dealing with respiratory diseases. METHODS: The questionnaire concerned social security, description of the health system, human resources available within the system, initial training and continuing education of health personnel, existence of a list of essential drugs, vaccine coverage and specific resources involved in CRD and tobacco control. RESULTS: The validity of the criteria of the questionnaire was tested in Reunion Island, where health data are accessible and reliable, and was found to be satisfactory. Its acceptability and relevance were deemed appropriate in Tunisia and in Mozambique. CONCLUSION: The self-administered questionnaire is a simple, reliable and cheap tool. Although designed for the study of respiratory diseases, it can easily be transposed and adapted to other pathologies.

Mobility and the spread of human immunodeficiency virus into rural areas of West Africa.

BACKGROUND: In eastern and southern Africa, the human immunodeficiency virus (HIV) epidemic appeared first in urban centres and then spread to rural areas. Its overall prevalence is lower in West Africa, with the highest levels still found in cities. Rural areas are also threatened, however, because of the population's high mobility. We conducted a study in three different communities with contrasting infection levels to understand the epidemiology of HIV infection in rural West Africa. METHOD: A comparative cross-sectional study using a standardized questionnaire and biological tests was conducted among samples in two rural communities of Senegal (Niakhar and Bandafassi, 866 and 952 adults, respectively) and a rural community of Guinea-Bissau (Caio, 1416 adults). We compared the distribution of population characteristics and analysed risk factors for HIV infection in Caio at the individual level. RESULTS: The level of HIV infection was very low in Niakhar (0.3%) and Bandafassi (0.0%), but 10.5% of the adults in Caio were infected, mostly with HIV type 2 (HIV-2). Mobility was very prevalent in all sites. Short-term mobility was found to be a risk factor for HIV infection among men in Caio (adjusted odds ratio (aOR) = 2.06; 95% CI: 1.06-3.99). Women from Caio who reported casual sex in a city during the past 12 months were much more likely to be infected with HIV (aOR = 5.61 95% CI: 1.56-20.15). Short-term mobility was associated with risk behaviours at all sites. CONCLUSIONS: Mobility appears to be a key factor for HIV spread in rural areas of West Africa, because population movement enables the virus to disseminate and also because of the particularly risky behaviours of those who are mobile. More prevention efforts should be directed at migrants from rural areas who travel to cities with substantial levels of HIV infection.

Seasonality in the transmission of schistosomiasis and in populations of its snail intermediate hosts in and around a sugar irrigation scheme at Richard Toll, Senegal.

Irrigation for intensive sugar cultivation started in the early 1980s at Richard Toll, some 100 km from the mouth of the Senegal River. Infections with Schistosoma mansoni were first seen in late 1988. This study records quantitative snail surveys for over 3 years from 1992 at sites representing different habitats in and around the irrigation scheme. Populations of both Biomphalaria pfeifferi (the intermediate host of S. mansoni) and Bulinus spp. (mainly B. truncatus, the local host of S. boris) peaked in late 'spring' or early 'summer', depending on the habitat, and then remained low until the following spring', B. pfeifferi favoured smaller, man-made habitats with most transmission between May and August each year. The less abundant Bulinus spp. favoured larger natural and man-made habitats with most S. bovis transmission between April and July. S. mansoni infections were more, but S. bovis infections were less abundant than other trematodes in their respective snail hosts. Ecological changes in the early 1980s due to sugar irrigation pre-dated similar, more widespread changes in the late 1980s when the completion of dams across the Senegal River prevented seasonal rain fed floods and sea water intrusion. S. mansoni has since spread rapidly around Richard Toll. The incompatibility of the local S. haematobium strains with the dominant bulinid snails has so far prevented an epidemic of urinary schistosomiasis at Richard Toll, but the invasion of similar downstream habitats by susceptible B. globosus is worrying. The principal control measure, chemotherapy, given in the 'winter' would minimise the rate of reinfection. It could be reinforced by judicious mollusciciding within the sugar irrigation scheme but not elsewhere.

Religion and protective behaviours towards AIDS in rural Senegal.

OBJECTIVES: To describe the association between religion and factors related to sexually transmitted diseases (STD)/AIDS in a country where religious leaders were involved early in prevention. DESIGN: A cross-sectional study conducted in a rural area in central Senegal. METHODS: Questionnaire-based interviews of a random sample of 858 adults from the general population aged 15-59 years and in-depth interviews of four religious leaders and 50 people. RESULTS: Seventy-six per cent of the respondents were Muslim, 24% Catholic, 1% Animist and 0.2% Protestant. A total of 86% of men and 87% of women reported religion to be very important to them. Important prevention-related variables were inversely associated with the importance of religion. Men who considered religion to be very important were less likely to cite AIDS as a major health problem [odds ratio (OR) 0.4, P = 0.008] and were less likely to feel at risk of getting HIV (OR 0.5, P = 0.0005). Women who considered religion to be very important were less likely to report an intention to change to protect themselves from AIDS (OR 0.2, P = 0.0001), less likely to report having discussed AIDS with others (OR 0.4, P = 0.01) and much more likely to feel at risk of getting HIV (OR 9.3, P = 10(-4)). Individuals who considered religion to be very important were not more likely to report intending to or actually having become faithful to protect themselves from AIDS. CONCLUSION: These findings stress the need to intensify the involvement of religious authorities in HIV/STD prevention at the local level.

Preventive attitudes towards the threat of AIDS: process and determinants in rural Senegal.

This report is intended to identify the determinants of preventive attitudes and thereby enable the further elaboration of effective prevention programs in a country where the HIV epidemic has remained controlled. Across-sectional survey using a standardized questionnaire was conducted among a sample of 866 adults of the general population of the rural area of Niakhar, Senegal. The analysis identified psychosocial determinants related to preventive attitudes and the influence of sociodemographic characteristics and of sources of AIDS information on these determinants. Psychosocial determinants of preventive attitudes differed according to gender: Among men, personal risk perception was associated with preventive attitudes. Among women, level of AIDS-related knowledge, communication about AIDS, and optimism about the future were associated with preventive attitudes. Sociodemographic factors and sources of information were similar for men and women: Preventive attitudes were adopted primarily by young, educated subjects who had been exposed to urban life. Religion appeared to be a major obstacle to preventive attitudes. Preventive messages broadcast on radio or television may be determinative. Our results call for a strengthened collaboration with religious leaders and a focus on risk perception to rationalize preventive actions. We also encourage the targeting of vulnerable populations, such as women in rural areas, by developing preventive messages to be delivered through national media (radio, television) and by staff from health centers, which most women visit, at least for prenatal care.

Cellular immune responses of a Senegalese community recently exposed to Schistosoma mansoni: correlations of infection level with age and inflammatory cytokine production by soluble egg antigen-specific cells.

A recently reported epidemic of Schistosoma mansoni infection in Senegal provided an opportunity to study the dynamics of the development of immunity to human schistosomiasis. We report here on the cell-mediated immune response in a population of 99 females and 95 males, with particular emphasis on the relationship between intensity of infection and age. We found that the intensity of infection correlated negatively with age in females but not in males. In men and women, both Th1- and Th2-type cytokines were detected upon in vitro stimulation of PBMCs with soluble egg antigen (SEA) or soluble adult worm antigens (SWAP). In the female group, SEA-induced PBMC proliferation was associated with the production of IFN-gamma, IL-2 and IL-5, all of which correlated negatively with intensity of infection. Most cytokine production correlated positively with age. Spontaneous production of TNF-alpha, IL-6 and IL-10 was higher in the infected population than in an uninfected control group. Our results suggest that immunity to infection could be more pronounced in the female population and associated with a Th0/1 + 2 pattern of cytokine secretion mediated by soluble egg antigen (SEA).

H blood group antigen carried by CD44V modulates tumorigenicity of rat colon carcinoma cells.

Expression of carbohydrate ABH blood group antigens is oncodevelopmentally regulated and their presence on tumor cells constitutes a prognostic factor. However, it is not clear whether they directly affect tumor behavior. Using a rat model of colon carcinoma, we previously observed an association between the presence of H blood group antigens and tumorigenicity in syngeneic animals. In the present study, we show by immunoprecipitation experiments that cell surface H blood group antigens of a highly tumorigenic clone (PROb) are essentially carried by splice variants of the CD44 molecule containing exon V6. PROb cells were then transfected with an antisense fragment of the gene coding for a rat alpha (1-2)fucosyltransferase. This enzyme allows synthesis of H antigens from various beta-galactoside precursors. Transfected subclones of PROb cells were obtained which had significantly decreased enzymatic activity and H antigenic cell surface levels. In contrast, no such changes were observed in control cells transfected with either the empty vector or with a sense fragment of the gene. Compared to controls, the antisense-transfected cells were far less tumorigenic in syngeneic animals. These results show that H blood group antigens at the surface of PROb colon carcinoma cells contribute to tumor progression. The presence of the fucosylated structures on CD44 could modulate the functions of this adhesion molecule.

Evidence for two distinct alpha(1,2)-fucosyltransferase genes differentially expressed throughout the rat colon.

Blood-group-ABH antigens are carbohydrate structures widely distributed in numerous tissues. These structures are fucosylated by an alpha(1,2)-fucosyltransferase. The occurrence of at least two alpha(1,2)-fucosyltransferase genes in the human genome has been strongly suggested by genetic studies, but only one of them has been cloned so far. Specific primers deduced from this human cDNA were used to amplify a fragment of rat genomic DNA (FTA). Screening of a rat colon cDNA library with this probe allowed us to isolate a clearly distinct, but related, cDNA clone (FTB). Both sequences showed considerable sequence similarity to the human alpha(1,2)-fucosyltransferase cDNA previously cloned. Furthermore, cells transfected with these DNA fragments in antisense orientation displayed a decreased alpha(1,2)-fucosyltransferase activity, indicating that they both correspond to fragments of alpha(1,2)-fucosyltransferase genes. Finally, differential expression of these genes was demonstrated in two rat colon-cancer cell lines and throughout the rat colon.

Retinoic acid modulation of alpha(1-->2) fucosyltransferase activity and sensitivity of tumor cells to LAK-mediated cytotoxicity.

We examined the effects of all-trans retinoic acid (RA) on alpha(1-->2) fucosyltransferase activity and sensitivity to LAK-mediated cytotoxicity in two rat colon carcinoma cell lines differing by their glycosylation state and their tumorigenic potential. RA induced a decrease in alpha(1-->2) fucosyltransferase activity in the more tumorigenic variant PROb. Fucosyltransferase mRNA levels were not affected by RA treatment in PROb cells, suggesting a posttranscriptional control. This inhibition was accompanied by a decreased expression of fucosylated membrane glycoconjugates and by a significant increase in the sensitivity to LAK-mediated cytotoxicity. REGb cells, which exhibited a very low enzymatic activity and very few fucosylated glycoconjugates, were more sensitive to LAK-lysis than PROb cells and were not affected by RA treatment.

Phosphorylation sites in human erythrocyte band 3 protein.

The human red cell anion-exchanger, band 3 protein, is one of the main phosphorylated proteins of the erythrocyte membrane. Previous studies from this laboratory have shown that ATP-depletion of the red blood cell decreased the anion-exchange rate, suggesting that band 3 protein phosphorylation could be involved in the regulation of anion transport function (Bursaux et al. (1984) Biochim. Biophys. Acta 777, 253-260). Phosphorylation occurs mainly on the cytoplasmic domain of the protein and the major site of phosphorylation was assigned to tyrosine-8 (Dekowski et al. (1983) J. Biol. Chem. 258, 2750-2753). This site being very far from the integral, anion-exchanger domain, the aim of the present study was to determine whether phosphorylation sites exist in the integral domain. The phosphorylation reaction was carried out on isolated membranes in the presence of [gamma-32P]ATP and phosphorylated band 3 protein was then isolated. Both the cytoplasmic and the membrane spanning domains were purified. The predominant phosphorylation sites were found on the cytoplasmic domain. RP-HPLC analyses of the tryptic peptides of whole band 3 protein, and of the isolated cytoplasmic and membrane-spanning domains allowed for the precise localization of the phosphorylated residues. 80% of the label was found in the N-terminal tryptic peptide (T-1), (residues 1-56). In this region, all the residues susceptible to phosphorylation were labeled but in varying proportion. Under our conditions, the most active membrane kinase was a tyrosine kinase, activated preferentially by Mn2+ but also by Mg2+. Tyrosine-8 was the main phosphate acceptor residue (50-70%) of the protein, tyrosine-21 and tyrosine-46 residues were also phosphorylated but to a much lesser extent. The main targets of membrane casein kinase, preferentially activated by Mg2+, were serine-29, serine-50, and threonine(s)-39, -42, -44, -48, -49, -54 residue(s) located in the T-1 peptide. A tyrosine phosphatase activity was copurified with whole band 3 protein which dephosphorylates specifically P-Tyr-8, indicating a highly exchangeable phosphate. The membrane-spanning fragment was only faintly labeled.

Interleukin 2 stimulates tyrosine phosphorylation in T cell membrane fractions.

Interleukin 2 is a growth factor secreted by T lymphocytes upon antigenic stimulation and inducing the proliferation of T cells bearing at their surface the heterodimeric high-affinity form of its receptor. No enzymatic function has so far been demonstrated in the receptor subunits. In an attempt to elucidate the biochemical pathway of signal transduction, we investigated the capacity of interleukin 2 to modulate tyrosine phosphorylation in T cell membranes. Membrane-rich fractions from T cells were tested for their ability to phosphorylate tyrosine in the presence or absence of added recombinant interleukin 2. Using as substrate a synthetic polymer of glutamic acid and tyrosine, we demonstrated a 3-4-fold stimulation of tyrosine phosphorylation in the presence of interleukin 2; this stimulating effect appeared to be well correlated with interleukin 2 function since (a) it was not observed in insensitive cells, (b) it required the presence of the high-affinity form of the receptor and (c) it was dose-dependent. Confirmatory results were obtained by phosphorylating membrane-rich fractions with [gamma-32P]ATP and by analysing the resulting phosphoproteins: only in fractions from cells with the high-affinity form of the receptor were several membrane proteins specifically phosphorylated on tyrosine residues in response to interleukin 2. At least two proteins of 115 and 58 kDa were consistently hyperphosphorylated on tyrosine in an interleukin-2-dependent manner. This stimulation was strongly dependent on the presence of the protein tyrosine phosphatase inhibitor, sodium orthovanadate. Thus, we propose that interleukin 2 enhances tyrosine phosphorylation by stimulating a tyrosine kinase activity. The nature of the enzyme involved remains to be determined.

The inhibitory effect of PGE2 on T cell activation is not associated with inhibition of PKC translocation.

We have recently reported on the effect of PGE2 on T cell activation and suggested that their immunosuppressive effect may involve the PKC activation pathway. In the present study, we further investigated the potential interference of PGE2 with PHA induced signaling in T lymphocytes. We demonstrate that the PHA mediated increase in IP3, the putative mobilizer of intracellular Ca2+, is slightly affected following cell incubation with PGE2. Treatment of cell culture with the tumor promoter TPA abrogates the suppressive activity of PGE2 whereas exogenous diacylglycerol (1,2-diolein) has only a marginal effect. This suggests that PGE2 affect PKC activity at sites distal to IP3 and DG generation. We also demonstrate that the PGE2 suppressive effect on T lymphocyte activation is not related to an inhibition of PKC translocation.

Comparison of interleukin 2 and 12-O-tetradecanoylphorbol 13-acetate as signals for protein kinase C activation in purified human T lymphocytes.

Interleukin 2 (IL2) and 12-O-tetradecanoylphorbol 13-acetate (TPA) have been compared for their ability to induce translocation of protein kinase C (PKC) in T lymphocytes prestimulated with anti-CD3 monoclonal antibody (mAb), either in the presence or absence of monocytes. TPA alone did not promote purified T cell growth, but it was able to induce a transient, within 30 min, translocation of PKC activity. The profiles of PKC association with the membrane of the T cells under TPA stimulation were quite similar when either the anti-CD3 mAb or the fixed monocytes, or both, were added to the T cells. The decrease of cytosolic PKC under TPA stimulation was less pronounced for the purified T cells stimulated with anti-CD3 mAb, fixed monocytes alone or both than for unstimulated purified T cells. Even in the absence of monocytes, the addition of exogenous IL2 to the anti-CD3 mAb-treated T cells resulted in PKC translocation, with a transient increase in the PKC activity found in both the particulate and cytosolic fractions. When exogenous IL2 was added to the proliferating T cells, the association of PKC with the membrane was prolonged and the activity did not reach a plateau during the first 2 h after the IL2 stimulation. In parallel, the level of PKC associated with the membrane was higher in proliferating cells than in resting cells even 4 days after stimulation. These results suggest that activation of PKC by IL2 might be different from the direct activation of PKC by TPA and that a specific activation pathway, at least kinetically distinct from the classical phosphatidyl inositol diphosphate degradation by phospholipase C, might be involved during IL2 stimulation of T lymphocytes through high-affinity IL2 receptors.

Cation dependence of the phosphorylation of specific residues in red cell membrane protein band 3.

Phosphorylation of anion channel protein (ACP), the major component of erythrocyte protein band 3, was achieved in red cell ghosts in buffers containing vanadate (an inhibitor of phosphatases) and Mg2+ or Mn2+, known specific activators of the various kinases present in the red cell membrane. The anion channel protein was isolated to purity and the phosphorylated aminoacids were determined. The present results show that the phosphorylation of anion channel protein in its membraneous environment leads to an equal phosphorylation of tyrosine and serine plus threonine in the presence of Mg2+. In contrast, phosphotyrosine represents 80% of the total when Mn2+ is the activator.

Vesicular stomatitis virus produced from infected LSTRA lymphoma cells bear tyrosine protein kinase activity (p56).

Murine LSTRA lymphoma cells contain a very active tyrosine protein kinase of 56 kDa (p56) which is not related to any of the other known tyrosine kinases. In the past the purification and characterization of the p56 have been hampered because of the low amount of this protein in LSTRA membranes. In this study, we have utilized a different approach for purification which consisted of trapping the protein in the membrane of vesicular stomatitis virus. Incubation of the virions with [gamma-32P]ATP resulted in the phosphorylation of p56 on tyrosine residues. Moreover, the phosphopeptide digest profile of vesicular stomatitis virus-p56 was identical to that observed with authentic LSTRA-p56. The p56 from such virions could be resolved from other proteins by two-dimensional gels, and furthermore, such virions have been used to prepare several antisera directed against the p56.

Detection of tyrosine-specific protein kinases with gastrin as exogenous substrate.

Gastrin was recently shown to be phosphorylated on its single tyrosine by the epidermal growth factor (EGF)-stimulated tyrosine protein kinase (TPK). The TPK previously detected in the murine lymphoma (LSTRA) induced by the Moloney murine leukemia virus phosphorylates gastrin, the apparent Km is 65 microM and the maximum rate 1900 pmol/min per mg; the kinase is more efficient with MnCl2 than with MgCl2, is stimulated by NaVO3 and inhibited by ZnCl2. Gastrin phosphorylation is observed only when a TPK is expressed by the cell: extracts of fibroblasts infected with a temperature-sensitive mutant of the Rous sarcoma virus had no gastrin kinase activity when grown at the non-permissive temperature whereas cells grown at the permissive temperature were transformed and disclosed a clear gastrin kinase activity. Gastrin kinases were detected in various transformed cells: human lymphomas, K562 cells, cells from a patient with acute proliferative leukemia, and normal cells: human T and B lymphocytes.

Acute myeloblastic leukemia with active tyrosine protein kinase.

High level of tyrosine protein kinase activity was found in a membrane fraction isolated from an acute myeloblastic leukemia, out of 24 leukemias of different origin investigated. The major substrate for tyrosine phosphorylation in vitro was a 58 kDA protein (p58). The phosphorylation proceeded actively at 0 degrees C and was strongly stimulated by Mn2+ ions. Comparison by partial proteolysis of the p58 with similar phosphoproteins from a T-lymphoma line (KE37) and from lectin stimulated lymphocytes showed high similarity. The possible role of the tyrosine kinase activity in this leukemia is discussed.