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Biomedical subjects

L Chatenoud

Publications and source records attributed to L Chatenoud.

At least 109 records · Page 6Linked to original sources

Reproductive factors and risk of uterine fibroids.

We analyzed the relation between reproductive history and risk of uterine fibroids using data from a case-control study. Cases were 621 women with histologically confirmed diagnosis of uterine fibroids. Controls were 1,051 non-hysterectomized patients. Compared with nulliparae, parous women had a relative risk (RR) of fibroids of 0.5 [95% confidence interval (CI) = 0.4-0.6], and the risk declined with number of births. The risk of fibroids also decreased with number of induced abortions (RR = 0.8 and 0.6 for women reporting one or two or more abortions, respectively). A total of 24 cases (3.9%) and 19 controls (1.8%) reported a history of infertility (RR = 2.0; 95% CI = 1.1-3.7).

Adult↗

In vitro T cell unresponsiveness following low-dose injection of anti-CD3 MoAb.

Anti-CD3 MoAb treatment is widely used as an immunosuppressive therapy. In the present study we examined the in vitro T cell response in mice having received 24 h before a single i.v. injection of 10 microgram of anti-CD3 MoAb. We found that splenocytes from these mice displayed a dramatically decreased proliferative response to the T cell mitogens concanavalin A (Con A), anti-CD3, phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) + calcium ionophore, while the effect of lipopolysaccharide (LPS) was not impaired. T cell suppression persisted for about 10 days after anti-CD3 injection, returning to normal within 15 days. The F(ab')2 fragment of anti-CD3 had no such effect, indicating the requirement for in vivo activation. At the dose used, anti-CD3 resulted neither in T cell depletion nor in down-modulation of the CD3/T cell receptor (TCR) complex. The low proliferation was also not explained by apoptosis, following secondary challenge with Con A. Splenocytes from anti-CD3-injected mice were highly responsive to IL-2, but generated little or no IL-2, IL-3, IL-4 and interferon-gamma (IFN-gamma) when exposed to Con A. Normal cytokine production could not be restored by the addition of optimal doses of IL-2 during Con A stimulation. Transforming growth factor-beta (TGF-beta) was the only cytokine whose mRNA expression was not modified in stimulated splenocytes from anti-CD3-injected mice. Furthermore, anti-TGF-beta antibodies increased Con A-induced T cell proliferation, but not cytokine production.

Animals↗

Sexually transmitted diseases and risk of HIV infection.

We have analyzed the association between sexually transmitted diseases (STD) and HIV infection, using data from a cross-sectional survey of subjects attending STD clinics in Northern Italy conducted since 1988. A total of 1,711 subjects (1,259 males, 452 females), who had referred themselves to three STD clinics in Northern Italy for suspected STD or STD treatment, were included for the study. Out of these, 145 subjects (113 males and 32 females) were HIV-positive. A total of 58 HIV-positive and 368 HIV-negative subjects reported a history of STD; the corresponding odds ratio (OR) was 2.3 (95% confidence interval (CI) 1.5-3.6) for subjects reporting a history of STD. Considering various STD in details, the estimated OR was 1.8 (95% CI 0.8-3.8) for a history of gonorrhoea and 1.5 (95% CI 0.8-2.7) of syphilis, and the OR was 1.8 (95% CI 1.0-3.2) and 2.2 (95% CI 1.3-3.8), respectively, for a positive TPHA and VDRL test. The results of the test for HbsAg were available in 50 HIV-positive and 1,028 HIV-negative subjects; the OR of HIV infection in subjects with HbSAg was 3.9 (95% CI 1.7-9.0). Presence of genital ulcers at clinical examination was not significantly associated with the risk of HIV infection (OR yes vs no genital ulcers 1.5, 95% CI 0.6-2.8).

Adolescent↗

Early defect of immunoregulatory T cells in autoimmune diabetes.

A potential immunoregulatory function has recently been attributed to the discrete subset of major histocompatibility complex (MHC) class I-restricted TCR-alpha beta mature thymocytes expressing an unusual V beta 8-biased T cell receptor repertoire. This T cell subset which also selectively express the CD44 marker is the main IL-4 producer in the thymus. Nonobese diabetic (NOD) mice were found to have a marked deficit in the number and functional capacity of CD44+ TCR-alpha beta+ thymocytes from as early as 3 weeks of age. The deficiency in IL-4 production was completely corrected after incubation with interleukin-7 (IL-7), a selective growth factor for CD44+ TCR-alpha beta+ mature thymocytes. This abnormality in T cell differentiation could explain the Th2 functional deficiency that may be a key element in the emergence of Th1-driven autoimmune disease in NOD mice.

Animals↗

T cells and B cells in chronic renal failure.

Recent knowledge into the pathophysiological mechanisms mediating the immune abnormalities characteristic of end-stage renal disease (ESRD) has focused on the dual activation versus deficiency state of immunocompetent cells. Despite major advances in renal replacement therapy, notably hemodialysis, no significant improvement in the immune status of uremic patients has been achieved. After a brief review of the role of T cells and B cells in the normal immune response, the functional and phenotypic T and B cell abnormalities observed in uremic patients are presented. Special emphasis is placed on our recent findings indicating that these abnormalities are observed at an early stage in the course of chronic renal failure, worsen with the progression of uremia, and are exacerbated by the dialysis procedure. The previous hypotheses that could reconcile the so-called Janus-faced behavior of T cells in uremia are updated in light of the recent findings obtained in the search of therapeutic strategies that could counteract the impaired responsiveness of patients with ESRD to vaccination against hepatitis B virus. Perspectives of research aimed at elucidating the respective role of T helper cell subpopulations (Th1 and Th2) could contribute to understanding of the mechanisms of the multifaceted process of uremia-related immune dysregulation and of the rationale for possible immunointervention strategies.

Animals↗

Dietary factors and the risk of psoriasis. Results of an Italian case-control study.

We have conducted a case-control study to explore the relation between the consumption of selected foods and psoriasis. The out-patient services of nine teaching hospitals and five general hospitals in northern and southern Italy took part. Cases were newly diagnosed psoriatics with a history of skin problems of no more than 2 years. As controls, we selected subjects with newly diagnosed skin conditions, other than psoriasis, who were seen in the same out-patient clinics. Inclusion of cases and controls was limited to the age group 16-65 years. A total of 316 psoriatics and 366 controls were recruited. Anthropometric measures, including height and weight, were obtained. Diet was assessed by a semiquantitative food frequency questionnaire. Psoriasis appeared to be positively associated with body mass index (chi 2(1) trend 4.3, P < 0.05). Significant inverse relations with psoriasis were also observed for the intake of carrots (chi 2(1) trend 4.8, P < 0.05), tomatoes (chi 2(1) trend 26.3, P < 0.01), fresh fruit (chi 2(1) trend 11.7, P < 0.01) and index of beta-carotene intake (chi 2(1) trend 9.1, P < 0.01). Although largely explorative, these results provide some evidence for a potential role of diet in psoriasis.

Adolescent↗

In vivo soluble tumor necrosis factor receptor release in OKT3-treated patients. Differential regulation of TNF-sR55 and TNF-sR75.

Administration of monoclonal antibodies to CD3 triggers acute and massive release of several cytokines, including tumor necrosis factor alpha (TNF-alpha), essentially T cell-derived. This cytokine release is responsible for the spontaneously reversible acute clinical syndrome observed in most OKT3-treated patients. We found that the first OKT3 injection in human renal allograft recipients led to the release in significant amounts of soluble TNF receptors (TNF-sR55 and TNF-sR75) that are considered main natural inhibitors of TNF bioactivity. As for OKT3-induced TNF-alpha, peak TNF-sR levels were observed 1 hr postinjection, and this release was limited to the first monoclonal antibody injection. A distinct regulation of OKT3-mediated release of TNF-sR75 and TNF-sR55 was observed, since (1) in clear contrast with OKT3-mediated TNF-sR75 induction, TNF-sR55 release was completely blocked by a high dose of corticosteroids prior to OKT3 injection and (2) secretion of TNF-sR75 but not TNF-sR55 correlated with immunoreactive TNF-alpha release. In hemodialyzed patients prior to transplantation and OKT3 treatment, a condition characterized by chronic TNF-alpha release, TNF-sR efficiently block TNF bioactivity. In contrast, the system is overwhelmed by the massive acute TNF-alpha release that follows the first OKT3 injection: in such a condition TNF-sR looses its capacity to counteract TNF bioactivity.

Adrenal Cortex Hormones↗

The effects of donor and recipient endotoxemia on TNF alpha production and mortality in the rat model of syngenic orthotopic liver transplantation.

The effects of administration of endotoxin to donors or recipients on the mortality rate, evolution of endotoxin levels, and tumor necrosis factor alpha (TNF-alpha) release were investigated in a syngenic orthotopic liver transplantation model in Lewis rats with portal reperfusion only. No significant recipient endotoxemia, TNF-alpha release, or mortality occurred in control recipients following transplantation from normal donors. The doses of endotoxin needed to kill 50% and 100% of animals after hepatic artery ligation were, respectively, 4 mg/kg and 10 mg/kg. Transplantation of animals' livers with no preservation phase from donors who were administered a lethal dose of endotoxin for this combination (10 mg/kg) produced significant recipient endotoxemia at 10 min (6.9 +/- 2.5 x 10(3) endotoxin unit/ml (EU/ml), P < 0.01), 45 min (8.8 +/- 1.1 x 10(3) EU/ml, P < 0.001) and 8 hr (18.5 +/- 3.5 x 10(3) EU/ml, P < 0.001) after graft reperfusion. Significant levels of TNF-alpha were also detected in these animals at 45 min (280 +/- 70 pg/ml, P < 0.007) and 8 hr (80 +/- 40 pg/ml, P < 0.05) when compared with the controls. Mortalities in recipients of OLT from donor animals that had received endotoxin (2 mg/kg or 4 mg/kg) immediately prior to the harvesting procedure was 0% and 20%, respectively, compared with no death in the control group. When recipient animals were administered endotoxin immediately after graft reperfusion the resistance to endotoxin administration was significantly reduced compared with animals that had not received OLT (LD50 < 2 mg/kg versus 4 mg/kg; LD100 4 mg/kg versus 10 mg/kg, respectively). These results show that endotoxin and its effects can be transferred from the liver graft donor to the recipient and that OLT per se reduces the recipient resistance to endotoxin with subsequent increase in mortality.

Animals↗

[Dysregulation of the immune system in chronic uremic and hemodialysed patients].

Concomitant immune deficiency and activation of immuno-competent cells, together with a disequilibrium between inflammation-inducing cytokines and their specific natural inhibitors is the basis of our current understanding of immune system dysregulation in patients with chronic uraemia. These anomalies may even be accentuated by dialysis. Clinically, bacterial infections, viral hepatitis and amyloidosis all play important roles. Humoral factors include abnormal immunoglobulin response to specific antibodies and complement activation. The response of T lymphocytes, long sought as the origin of the immunodeficiency associated with chronic uraemia, is also significantly decreased in these patients. The decreased antibody responses to specific stimuli may be related to B cell dysfunction. Monocyte and polymorphonuclear cell reactions are also perturbed. A deficiency in natural killer cells is observed although the mechanisms involved and the consequences are still debated. The factors determining the anomalies leading to immune system dysregulation in chronic uraemia and dialysis and their relationship with the reduction in active nephron mass as well as their metabolic and/or endocrine consequences remain to be fully described. A better understanding of the mechanisms involved should lead to new strategies for immuno-intervention in patients with chronic renal failure and help in optimizing haemodialysis.

Chronic Disease↗

Smoking and risk of endometrial cancer: results from an Italian case-control study.

To determine the relationship between cigarette smoking and endometrial cancer, we conducted a case-control study. The cases were 726 patients with histologically confirmed endometrial cancers 74 years of age or less (median age, 59 years; range, 31-74) admitted between 1983 and 1992 to the Ospedale Maggiore (including the four largest teaching and general hospitals in the greater Milan area), to the Obstetrics and Gynecology University Clinics, and to the National Cancer Institute of Milan. The controls were 1452 patients younger than 75 years (median age, 59; range, 25-74) admitted for acute, nongynecological, nonhormonal, nonneoplastic conditions to the same network of hospitals where cases had been identified. Cases were less frequently ever-smokers (19%) than controls (25%). In comparison with never-smokers, the relative risk (RR) of endometrial cancer was 0.8 (95% confidence interval, CI, 0.7-1.1) in current smokers and 0.6 (95% CI 0.4-0.9) in ex-smokers. The risk of endometrial cancer decreased with number of cigarettes smoked per day and duration of habit. The estimated RR were, in comparison with never-smokers, 0.8 and 0.6 respectively in smokers of less than 20 and 20 or more cigarettes per day (chi 2(1) trend 5.48, P = 0.02) and 1.0 and 0.5 in ever-smokers for less than 20 and for 20 years or more. There was no clear relation with time since first smoking, but the RR was lower in ex-smokers who had stopped smoking less than 10 years before the interview (RR, 0.4; 95% CI, 0.2-0.8) than in those who had stopped 10 years or more before (RR, 0.8; 95% CI, 0.5-1.4). The estimated RR for ever-smokers was close to unity in premenopausal women, but apparently stronger in premenopause. Likewise the RR was 0.9 in lean (< 25 Quetelet's index) smoking women in comparison with lean nonsmokers, but smoking appeared to reduce the association with overweight. The estimated RR of endometrial cancer, in comparison with nonsmokers with Quetelet's index < 25 was 2.0 in nonsmokers with Quetelet's index > or = 25, and 1.3 in smokers with Quetelet's index > or = 25. These findings confirm the role of smoking on endometrial cancer risk. The risk reduction is, however, moderate in relative terms, and negligible from a public health point of view, in consideration of the negative consequences of smoking in several other diseases.

Adult↗

Determinants of high-grade dysplasia among women with mild dyskaryosis on cervical smear.

OBJECTIVE: To identify the epidemiologic characteristics of women who have mild dyskaryosis on cervical smear but cervical intraepithelial neoplasia (CIN) grade II or III at biopsy. METHODS: We analyzed information from 291 women (median age 33 years, range 17-69) observed for the first time with a single smear test showing mild dyskaryosis. All subjects underwent colposcopy, and histologic confirmation was obtained by biopsy. We compared the characteristics of women who had CIN I or no evidence of CIN with those of women with CIN II or III at biopsy. RESULTS: Twenty-eight women (10%) had CIN I at biopsy, 46 (15%) CIN II, and 23 (8%) CIN III. The frequency of CIN II or III tended to decrease with increasing education; compared with women reporting 11 or fewer years of education, the multivariate odds ratios (OR) of CIN II or III lesions was 0.5 (95% confidence interval [CI] 0.3-0.9) in those reporting 11 years of education or more. Compared with nulliparas, the OR of CIN II or III was 1.8 (95% CI 1.1-3.5) for parous women. Furthermore, compared with never-smokers, the OR of CIN II or III was 2.3 (95% CI 1.0-5.4) for current smokers. Ex-smokers were at increased risk, too; the estimated multivariate OR was 3.8 (95% CI 1.9-7.6). Compared with women reporting one sexual partner, the multivariate ORs of CIN II or III were 1.4 and 2.3 for women reporting two to three or four or more sexual partners, respectively (chi 2(1) trend = 6.65, P < .05). CONCLUSION: Our results show that smoking is a risk indicator of CIN II or III in women with a single smear showing mild dyskaryosis. Parous women, those of low social standing, and those reporting multiple sexual partners also are at increased risk of CIN II or III.

Adolescent↗

Alcohol and endometrial cancer risk: findings from an Italian case-control study.

Using data from a case-control study conducted in Northern Italy, we analyzed the relation between alcohol drinking and risk of endometrial cancer. Cases were 726 patients, < 75 years of age, admitted to the Ospedale Maggiore (including the 4 largest teaching and general hospitals in the Greater Milan area), the University Obstetrics and Gynecology Clinics, and the National Cancer Institute of Milan with histologically confirmed endometrial cancer. Controls were 2,123 nonhysterectomized patients, < 75 years of age, admitted for acute nongynecological non-hormone-related nonneoplastic conditions to the same network of hospitals where cases had been identified. When total consumption of all alcoholic beverages was considered, 68.2% of cases and 63.9% of controls were drinkers and 12% of cases and 9.3% of controls reported > or = 2 drinks/day. Considering total alcohol drinking, the relative risk for alcohol drinkers vs. nondrinkers was 1.3 (95% confidence interval 1.1-1.5), and the RR estimates for subsequent levels of intake were 1.1, 1.4, and 1.6 for women drinking > 0 < or = 1, > 1 < or = 2 drinks/day (chi 2(1) trend 11.33, p < 0.001). The estimates were similar when wine only (which represents the large majority of all alcohol intake in Italy) was considered, whereas data were less informative for beer and spirits intake only. No relation emerged between duration of alcohol consumption and risk of endometrial cancer. These findings suggest a potential link between alcohol drinking and endometrial cancer risk and are, in any case, inconsistent with a protective role of alcohol in endometrial carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Family history and the risk of endometrial cancer.

The association between a family history of endometrial, breast and ovarian cancer and the risk of endometrial cancer was analyzed on the basis of data from a case-control study conducted in northern Italy between 1983 and 1993. A total of 726 histologically confirmed endometrial-cancer patients (median age 61) admitted to a network of general and teaching hospitals in the Greater Milan area were interviewed. The controls were 2,123 women (median age 59), admitted for acute, non-neoplastic, non-hormone-related diseases to the same network of hospitals where the cases had been identified, with admission diagnoses unrelated to any of the known or suspected risk factors for endometrial cancer. Among cases, 37 (5.1%) reported a history of endometrial cancer in first-degree relatives. The corresponding figure among controls was 77 (3.6%). In comparison with women with no family history of endometrial cancer, the odds ratio (OR) of endometrial cancer was 1.5 (95% CI [confidence interval], 1.0-2.3) in women with a history of endometrial cancer in first-degree relatives. No relation emerged between endometrial cancer and a family history of breast or ovarian cancer. These results suggest that a family history of endometrial cancer increases the risk of contracting the same disease. However, the proportion of cases attributable to this factor was small: less than 1% of endometrial cancers in this population were attributable to familial (and hence potentially genetic) factors.

Adult↗