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L Chatenoud

Publications and source records attributed to L Chatenoud.

At least 37 records · Page 2Linked to original sources
PubMed2001

Suppressor T cells--they're back and critical for regulation of autoimmunity!

Regulation of the immune response to self-antigens is a complex process that depends on maintaining self-tolerance while retaining the capacity to mount a robust immune response to foreign antigens. Autoreactive T cells specific for these autoantigens are present in most normal individuals but are kept under control by multiple diverse peripheral tolerance mechanisms. In the last few years, there has been a re-emergence of suppressor cells as among the most central of these regulatory mechanisms. These cells, which express CD4, CD25, and CD62L, develop in the thymus and survive in a CD28-dependent manner in the periphery to maintain the homeostatic equilibrium of immunity and tolerance. In this review, we will summarize studies of these regulatory cells as they relate to autoimmune diseases and more specifically to type 1 diabetes and attempt to address some of the many outstanding questions. Finally, evidence is provided to support the ability of anti-CD3 mAbs to stimulate the regulatory T cells and reset the rheostat of immune tolerance in an animal model of autoimmune diabetes, the NOD mouse.

Animals↗
PubMed2001

Selected food intake and risk of multiple pregnancies.

In order to explore the association between multiple birth risk and diet, data were analysed from a case-control study on risk factors for multiple births conducted in Italy between 1988 and 1998. A total of 185 cases (median age 30 years) were interviewed: 36 women delivered monozygotic and 149 delivered spontaneous dizygotic multiple births. The control group comprised 498 women who gave birth at term (>37 weeks gestation) to healthy infants on randomly selected days at the same clinic. Women were specifically excluded if they reported a history of multiple pregnancy or they had received treatment for infertility for the index pregnancy. No marked differences emerged in daily intake between cases and controls and a total of 35 foods items, including the major sources of beta-carotene, retinol, ascorbic acid, vitamin D, E, methionine folate and calcium in the Italian diet. Likewise intake of selected micronutrients was largely similar in dizygotic cases, monozygotic cases and controls, with the only exception of a slightly lower intake of folates in dizygotic pregnancies in comparison with controls: this difference was statistically significant (P < 0.05), but limited in quantitative terms (mean daily intake of folate 192.4, 183.2 and 191.4 microg respectively in monozygotic, dizygotic cases and controls). In conclusion, the results of this study do not support the role of diet in the development of multiple births.

Adult↗
PubMed2001

Time trends of major coronary risk factors in a northern Italian population (1986-1994). How remarkable are socioeconomic differences in an industrialized low CHD incidence country?

BACKGROUND: The goals are to estimate time trends (1986-1994) of major coronary risk factors in an industrialized low CHD incidence population and to assess education class (EC) differences in risk factor prevalence and in time trends. METHODS: Three population surveys were conducted in 1986-1987, 1989-1990 and 1993- 1994 on independent and two-stage age- and gender-stratified random samples (1906 men and 1941 women) of 35-64 year old residents of Brianza, an affluent region of northern Italy. The protocol for data collection, clinical measurements and biochemical determinations adhered to the WHO MONICA manual and underwent repeated quality control assessments. EC were identified according to gender- and 5-year birth-cohort specific tertiles. RESULTS: In the initial, middle and final surveys 1258, 1259 and 1330 subjects were enrolled, corresponding to participation rates of 70.1%, 70.3% and 74.3%, respectively. Over the 8-year period, in men systolic blood pressure and smoking habits declined, body mass index and serum total cholesterol increased. In women systolic blood pressure showed a constant reduction, total cholesterol and BMI increased and the prevalence of smokers remained stable. Overall inverse associations with EC were found for body mass index, for prevalence of cigarette smokers in men and for systolic blood pressure in women. Decreases in blood pressure were more evident in the lowest EC. Cigarette smoking was on the decline in the higher EC in men. BMI and total cholesterol increased in all EC with the notable exception of the 'low' EC in women. CONCLUSIONS: Favourable changes of the risk factor profile in the low socio-economic classes may have contributed to reduce CHD rates in this population. Specific policies oriented to lowest socio-economic classes are needed to continue to combat the smoking epidemic.

Adult↗
PubMed2001

Tolerance to islet autoantigens in type 1 diabetes.

Tolerance to beta cell autoantigens represents a fragile equilibrium. Autoreactive T cells specific to these autoantigens are present in most normal individuals but are kept under control by a number of peripheral tolerance mechanisms, among which CD4(+) CD25(+) CD62L(+) T cell-mediated regulation probably plays a central role. The equilibrium may be disrupted by inappropriate activation of autoantigen-specific T cells, notably following to local inflammation that enhances the expression of the various molecules contributing to antigen recognition by T cells. Even when T cell activation finally overrides regulation, stimulation of regulatory cells by CD3 antibodies may reset the control of autoimmunity. Other procedures may also lead to disease prevention. These procedures are essentially focused on Th2 cytokines, whether used systemically or produced by Th2 cells after specific stimulation by autoantigens. Protection can also be obtained by NK T cell stimulation. Administration of beta cell antigens or CD3 antibodies is now being tested in clinical trials in prediabetics and/or recently diagnosed diabetes.

Animals↗
PubMed2001

Cigarette smoking: a risk factor for erectile dysfunction in diabetics.

OBJECTIVES: Diabetes is one of the systemic disorders most frequently associated with erectile dysfunction (ED). An extensive literature documents well the relationship between ED and several factors related to diabetic pathology, but the role of risk factors mainly related to life-style, e.g. cigarette smoking, is still not defined. METHODS: Eligible for the study were men aged 20-70 years with a diagnosis of insulin-dependent (type 1---IDDM) or non-insulin-dependent (type 2--NIDDM) diabetes who were observed on randomly selected days in 178 diabetes centers in Italy. ED was defined as a failure to achieve and maintain an erection sufficient for satisfactory sexual performance. RESULTS: The study population consisted of 9,670 diabetic men. Of these 2,962 (30%) were never smokers, 2,877 (30%) current smokers and 3,831 (40%) ex-smokers. After taking into account the effect of age, the odds ratios of ED in comparison with never smokers was 1.4 (95% confidence interval 1.3-1.6) for smokers and 1.5 (95% confidence interval 1.3-1.6) for ex-smokers. Duration and intensity of the smoking habit was associated with an increased risk of ED. Among ex-smokers, the risk of ED significantly decreased; with increase in the number of years since the patient quit smoking. CONCLUSION: The study offers an assessment of the association between smoking habit and ED and its potential interaction with other risk factors in diabetic men.

Adult↗
PubMed2001

Report from the 1st International NOD Mouse T-Cell Workshop and the follow-up mini-workshop.

A workshop on autoreactive T-cell responses in NOD mice was held to optimize autoreactive T-cell detection methodologies. Using different proliferation assay protocols, 1 of the 11 participating laboratories detected spontaneous T-cell responses to GAD(524-543) and insulin(9-23) in their NOD mice. Two other laboratories were able to detect autoreactive responses when using enzyme-linked immunospot assay (ELISPOT) and enzyme-linked immunosorbent assay (ELISA) analysis of cytokines in culture supernatants, suggesting that these assays provided greater sensitivity. To address the divergent findings, a follow-up mini-workshop tested NOD mice from four different colonies side-by-side for T-cell proliferative responses to an expanded panel of autoantigens, using the protocol that had enabled detection of responses in the 1st International NOD Mouse T-Cell Workshop. Under these assay conditions, 16 of 16 NOD mice displayed proliferative responses to whole GAD65, 13 of 16 to GAD(524-543), 9 of 16 to GAD(217-236), 7 of 16 to insulin(9-23), and 5 of 16 to HSP277. Thus, spontaneous proliferative T-cell responses can be consistently detected to some beta-cell autoantigens and peptides thereof. Overall, the results suggest that more sensitive assays (e.g., ELISPOT, ELISA analysis of cytokines in supernatants, or tetramer staining) may be preferred for the detection of autoreactive T-cells.

Animals↗
PubMed2001

Nutrition and health: epidemiology of diet, cancer and cardiovascular disease in Italy.

Most epidemiological data suggest a protective role for fruits and vegetables in the prevention of several common epithelial cancers, including digestive and major non-digestive neoplasms. The relation between frequency of consumption of vegetables and fruit and cancer and myocardial infarction risk was analysed using data from a series of case-control studies conducted in Italy. For digestive tract cancer, population attributable risks for low intake of vegetables and fruit ranged between 15 and 40%. A selected number of antioxidants showed a significant inverse relation with breast and colorectal cancer risk, although the main components responsible for the favourable effect of a diet rich in vegetables and fruit remain undefined. Fish tends to be another favourable indicator of reduced cancer risk. In contrast, subjects reporting frequent red meat intake showed a relative risk consistently above unity for several common neoplasms. Whole grain food intake was consistently related to reduced risk of several types of cancer, particularly of the upper digestive tract neoplasms. Epidemiological evidence of the relation between fiber and colorectal cancer indicated a possible protections. In contrast, refined grain intake was associated to increased risk of different types of cancer, pointing to a potential role of insulin-like growth factor 1 (IGF-1). A low risk diet for cardiovascular disease includes high consumption of fish, vegetables and fruit, and hence rich in ascorbic acid and other antioxidants, thus sharing several aspects with a favourable diet for cancer.

Animals↗
PubMed2000

Determinants of elevated blood pressure in women around menopause: results from a cross-sectional study in Italy.

OBJECTIVE: To analyse the determinants of high blood pressure in women around menopause. METHODS: Eligible women were consecutively identified among patients who asked for a visit of their general practitioner during the period March November 1997. A total of 22919 women aged 44-66 years (median age 55 years), were identified. Women whose mean of the second and third of the three measures of diastolic blood pressure values performed during interview was > 90 mm of mercury and/or reporting any type of current pharmacological treatment for elevated blood pressure were considered hypertensive. RESULTS: In comparison with women aged 40-50 years, the multivariate odds ratio (OR) of elevated blood pressure were 1.4 in women aged 51-55, 2.0 in those aged 56-60 and 2.7 in those aged > or = 61. In comparison with women with a body mass index (kg m(-2)) < 25, the OR of elevated blood pressure was 1.7 and 2.7, respectively, for women with a BMI of 25 28 and > or = 29. In comparison with women reporting a low level of physical activity, the OR of elevated blood pressure were 0.9 (95%, confidence interval, CI 0.7-1.0) and 0.7 (95% CI 0.4-0.9), respectively, for those reporting an intermediate or high level of activity. In comparison with premenopausal women, the OR of elevated blood pressure was, after taking into account the confounding effect of age, 1.6 (95% CI 1.0-1.4) in post menopausal ones. The OR of elevated blood pressure was 0.8 (95% CI 0.7-0.9), for current users of hormone replacement therapy (HRT), but no clear association emerged with duration of HRT pressure. CONCLUSIONS: This study suggests that, after taking into account the effect of age, post-menopausal women are at higher risk of the condition, and current HRT use decreases the risk. Other main determinants of risk of elevated blood pressure were overweight and low physical activity.

Adult↗
PubMed2000

Risk factors for ovarian cancer in central Italy.

OBJECTIVE: We conducted a case-control study to analyze risk factors for ovarian cancer. METHODS: Cases included 440 women (age range 13-80 years, median 54) with a histologically confirmed diagnosis of epithelial ovarian cancer who were admitted to the Gynecological Oncological Department of Gynecologic Oncology at the Catholic University Hospital in Rome, Italy. Controls were women admitted to the same hospital where cases were identified for acute nongynecological, nonhormonal, and nonneoplastic conditions. A total of 868 control women (age range 19-80 years, median 55) were interviewed. RESULTS: In comparison with ever married women, the multivariate odds ratios (OR) of ovarian cancers was 2.0 (95% confidence interval, CI 1.3-3.2) for never married women. Cases and controls were similar as regards educational status and body mass index. No clear relation emerged between ovarian cancer and age at menarche, menopausal status, and age at menopause. In comparison with nulliparae, the estimated ORs were 0.8, 0.9, and 0.7, respectively, in women reporting one, two, or three births. Women reporting two or more induced abortions were at decreased risk of ovarian cancer (OR 0.5, 95% CI 0.3-1.0). In comparison with women reporting their first birth before 20 years of age, the multivariate ORs were 1.8, 2.0, and 2.8, respectively, for women reporting their first birth at age 20-24, 25-30, and >/=31 (chi(2) trend = 10.1). Breast-feeding for more than 1 year was associated with an OR of 0.5 (95% CI, 0.4-0.8). Forty-two (9.5%) cases and 164 (18.9%) controls reported ever oral contraceptive use: in comparison with never users, the multivariate OR was 0.4 (95% CI 0.3-0.6) for ever users, and the risk decreased with duration of use. The OR for ovarian cancer was 2.9 (95% CI, 1.5-5.8) for women with a family history of the disease. CONCLUSION: This study, conducted on a relatively low-risk population, confirms the role of oral contraceptive on ovarian cancer risk and the direct association with family history of ovarian cancer. It also indicates that a later age at first birth is directly, and induced abortion and breast-feeding are inversely, related to the risk of the disease.

Adolescent↗
PubMed2000

Estroprogestin vs. gonadotrophin agonists plus estroprogestin in the treatment of endometriosis-related pelvic pain: a randomized trial. Gruppo Italiano per lo Studio dell'Endometriosi.

OBJECTIVE: This is a randomized clinical trial comparing estroprogestin (E/P) pill given for 12 months vs. gonadotrophin releasing hormone agonist (GNRHa) given for 4 months followed by E/P pill treatment for 8 months in the relief of endometriosis-related pelvic pain. METHODS: Eligible for the study were women with laparoscopically confirmed endometriosis and pelvic pain lasting 3-12 months after diagnosis. Eligible women were randomly assigned to treatment with E/P pill (gestroden 0.75 mg and ethynlestradiol 0.03 mg) for 12 months (47 patients) vs. tryptorelin 3.75 mg slow release every 28 days for 4 months followed by E/P pill for 8 months (55 patients). RESULTS: At baseline, dysmenorrhea was reported in 46 women allocated to E/P pill only (97.9%), and in all the 55 women allocated to GNRHa+E/P pill. The corresponding value at the 12 months follow-up visit was 14 subjects (35.9%) and 16 subjects (34.8%). The baseline median values of the multidimensional and analog scale were for dysmenorrhea 4 and 6 in the EP only and 3 and 6 in the GNRHa+E/P group. The corresponding value at the 12 months follow-up visit were 2 and 6 and 0 and 5. Non-menstrual pain was reported, respectively, at baseline and 12 month visit by 46 (97.9%) and 15 (38.5%) subjects in the E/P pill group and 49 (89.1%) and 17 (37.0%) of the GNRHa+E/P pill one. The baseline median values of the multidimensional and analog scale were for non-menstrual pain 3 and 5 in the E/P only and 2 and 6 in the GNRHa+E/P group. The corresponding values at the 12 month follow-up visit were 0 and 4 and 0 and 4. These differences between the two groups were not statistically significant. CONCLUSIONS: 1 year after randomization, the two treatment schedules show similar relief of pelvic pain in women with endometriosis.

Adult↗
PubMed2000

Population attributable risk for ovarian cancer.

Parity, oral contraceptive (OC) use, age at menopause, a family history of the disease and selected aspects of diet have been related to the risk of ovarian cancer. The quantification of their impact on a population level may help focus and rank the importance of potential prevention strategies. Using data from a case-control study conducted in Italy between 1983 and 1991 on 971 ovarian cancer cases and 2758 control women we computed the multivariate relative risk estimates, and population attributable risks (PARs), i.e. the proportion of ovarian cancers that would have been avoided if a given exposure had not been present in the population. Overall, the PARs were 5% for nulliparity, 12% for never OC use and 4% for a family history of breast or ovarian cancer in first-degree relatives. Among women aged >/=50 years, later age at menopause accounted for 16% of all ovarian cancer cases. Low intake of green vegetables accounted for 24% of cases and a high fat score for 7%. All these factors together explained 51% of cases. In conclusion, even if the PAR estimates were based on several arbitrary assumptions, available knowledge could, in principle, explain over 50% of all ovarian cancer cases in this Italian population, thus indicating and quantifying the theoretical scope for prevention.

Adult↗
PubMed2000

Wine drinking and diet in Italy.

OBJECTIVE: To investigate the relation between wine drinking and intake of selected indicator foods, which may vary in various populations. DESIGN: Cross-sectional analysis of the comparison group of a case- control study. SETTING: A network of teaching and general hospitals from six Italian areas. SUBJECTS: 5642 control subjects (3261 females and 2381 males) aged 20-74 y (median age 58 y), admitted for acute, non-neoplastic conditions unrelated to alcohol consumption. Participation rate was over 95%. INTERVENTION: Trained interviewers collected information using a structured and validated questionnaire. The average intakes of selected food items were computed, together with the multivariate odds ratios (OR) of eating above the median of each food. RESULTS: No appreciable difference in either sex for any food indicator considered (fruit, raw vegetables, cooked vegetables, salad and fish) was observed between abstainers, wine, and other alcoholic beverage drinkers. If anything, female wine drinkers reported less frequently high consumption of salad (OR=0.8) and raw vegetables (OR=0.8), both estimates being of borderline significance. CONCLUSIONS: In no instance did wine drinkers or mixed drinkers (who include a large proportion of wine drinkers, too) show an association with indicators of healthy diet. SPONSORSHIP: Italian Association for Cancer Research, Milan, Italy. European Journal of Clinical Nutrition (2000) 54, 177-179

Adult↗
PubMed2000

Refined and whole grain cereals and the risk of oral, oesophageal and laryngeal cancer.

OBJECTIVE: To investigate the possible differential role of refined and whole grain cereals on the risk of upper digestive and respiratory tract neoplasms. DESIGN: Hospital-based case-control study. SETTING: University Hospital of Lausanne, Switzerland. SUBJECTS: A total of 156 incident cases of cancers of the oral cavity and pharynx, 101 of the oesophagus, 40 of the larynx, and 349 control subjects admitted for a wide spectrum of acute non-neoplastic conditions. INTERVENTION: Trained interviewers collected information using a structured and validated questionnaire. Odds ratios (OR) of various cancers for a tertile increment of intake of refined and whole grains were estimated using unconditional multiple logistic regression. RESULTS: Refined grains were directly related to the risk of cancer of the oral cavity and pharynx (OR=1.9 for the highest tertile), oesophagus (OR=3.7) and larynx (OR=4.0). In contrast, whole grain cereals were protective, with OR of 0.6 for oral cavity and pharynx, 0.3 for oesophagus, and 0.7 for larynx. For the three sites combined, the OR for the highest tertile was 5.7 for refined grains and 0.5 for wholegrains. The trends in risk for refined grains were significant for all sites and their combination, and for wholegrain for oesophageal cancer and all sites. CONCLUSIONS: Even if inference on causality and the biological interpretation remain open to discussion, the present data indicate and further quantify that refined cereals are an unfavourable, but whole grain ones a favourable indicator of the risk of upper aerodigestive and respiratory tract neoplasms.

Adult↗
PubMed2000

Autoantibodies in recent onset type-1 diabetic patients to a Mr 60K microsomal hepatic protein: new evidence for autoantibodies to the type-2 glucose transporter.

Here we describe the presence of IgG antibodies, in the sera of patients presenting with insulin-dependent diabetes mellitus (IDDM), that react in Western blots with a 60-kD protein (Mr 60K) from rat hepatic microsomal extracts. Sera from 60 IDDM patients were screened and 31.6% were positive for the Mr 60K band. This antibody reactivity was indistinguishable in terms of both molecular weight and isoelectric point (pI 5.4) from that described in some patients presenting with autoimmune hepatitis who may also develop IDDM. We hypothesized that the type-2 glucose transporter (Glut-2) that is expressed on both hepatocytes and pancreatic beta cells could be a putative target for the detected antibodies. A polyclonal antisera to rat Glut-2 used in the liver microsome Western blot identified a 60-kD band superimposable upon that evidenced by IDDM sera. Antisera to Glut-2 successfully inhibited the binding of the patient's IgGs to liver microsomes, further suggesting that the two proteins may be identical. Using protein extracts from a rat insulinoma cell line (RIN) transfected with the human Glut-2 cDNA, further evidence was obtained suggesting that these IDDM IgGs are specific for the human Glut-2 transporter.

Animals↗
PubMed2000

Role of cytotoxic T cells in chronic alopecia areata.

Cytokines play a role in alopecia areata. We used immunohistochemical and in situ hybridization studies to demonstrate the persistence of pro-inflammatory as well as apoptotic mechanisms in skin biopsies from patients with chronic alopecia areata. In situ hybridization allows the visualization of the distribution of immunocompetent cells in vivo. We studied skin biopsies from 11 untreated alopecia areata patients and two normal controls. In situ hybridization was performed on frozen sections using 35S-radio-labeled riboprobes, specific for IL-1beta, IL-2, IL-6, INFgamma, and granzyme B mRNA. Immunohistochemistry was carried out using an anti-IL-1beta monoclonal antibody, and a monoclonal antibody directed against the human Fas protein. We demonstrated the presence of cells labeled with IL-1beta, IL-6, INFgamma, and granzyme B antisense probes. Similarly, cells labeled with anti-IL-1beta were found in 10 of 11 cases. The labeled cells were located in the mononuclear peri- and intrafollicular infiltrate. Cells expressing granzyme B were found in close contact with the follicle. Fas positivity was demonstrated in four of four cases at the level of the cytoplasmic membrane of the hair follicle keratinocytes. These results, based on visualizing the labeled cells, demonstrate that pro-inflammatory cytokines are produced by the mononuclear cell infiltrate in close contact with follicles in alopecia areata. Furthermore, they demonstrate for the first time that apoptotic mechanisms involving granzyme B and Fas-Fas ligand pathways may play a major role in the persistence of chronic alopecia areata.

Alopecia Areata↗