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J Alcouffe

Publications and source records attributed to J Alcouffe.

5 recordsLinked to original sources
PubMed1999

Mildly oxidized low-density lipoproteins decrease early production of interleukin 2 and nuclear factor kappaB binding to DNA in activated T-lymphocytes.

Activated T-lymphocytes are found early in atherosclerosis lesions, but little is known about their role. Oxidized low-density lipoproteins (oxLDLs) are considered to be involved in the pathogenesis of the lesions, and we have previously demonstrated that oxLDLs inhibit not only interleukin (IL)-2-receptor expression on the surface of in vitro-activated T-lymphocytes but also their proliferation. We have now investigated the effect of oxLDLs on blast differentiation, on IL-2 synthesis and on the activation of the nuclear factor kappaB (NF-kappaB) system in activated lymphocytes. Mildly oxLDLs (50 and 100 microgram/ml) decreased the number of lymphoblasts and the level of IL-2 concentration in the culture supernatants after activation of lymphocytes by phytohaemagglutinin and PMA+ionomycin. The inhibition of IL-2 production was observed in the CD3(+) T-lymphocyte cytoplasm as early as 4 h after activation by PMA+ionomycin. The study of NF-kappaB showed that oxLDLs led to a decrease of activation-induced p65/p50 NF-kappaB heterodimer binding to DNA, whereas the presence of the constitutive nuclear form of p50 dimer was unchanged. This was correlated with an unchanged level of the active form of the cytosolic inhibitor protein IkappaB-alpha. Taken together, these observations suggest that the immunosuppressive effect of oxLDLs might operate via a dysregulation of the T-lymphocyte activation mechanisms.

Arteriosclerosis↗
PubMed1999

Analysis by sex of low back pain among workers from small companies in the Paris area: severity and occupational consequences.

OBJECTIVES: To describe workers with low back symptoms, to identify risk factors and to assess the occupational consequences separately in men and women. METHODS: A descriptive study was conducted between 1 October 1996 and 31 December 1996 in a sample of workers selected at random from all types of small companies in the Paris area. A group of 202 occupational physicians interviewed 7129 workers with a standardised questionnaire including the Nordic questionnaire. Data analysis was performed by sex in the two groups: with low back pain and without low back pain over the previous 12 months. The group with low back pain was then divided into four subgroups: mild cases (without referred pain), moderate cases (with referred pain above the knee), serious cases (with referred pain below the knee), and low back pain with occupational consequences. RESULTS: 7010 questionnaires were able to be evaluated. The sample consisted of 54.8% of men (3842) and 45.2% of women (3168), with a mean age of 37.8 and 37.0 years, respectively (p < 0.05). The following risk factors occurred significantly more often in men: high weight, height, body mass index (BMI), smoking, number of children, increased driving time and work time, material handling tasks, uncomfortable working positions. Most women were clerks (53%). Non-conditional logistic regression applied to the whole sample identified female sex as a risk factor (odds ratio (OR) = 1.85, 95% confidence interval (95% CI) 1.58 to 2.13). The following risk factors were common to both sexes: lifting weights > 10 kg, in women (OR 1.69, 95% CI 1.27 to 2.25) and in men (OR 1.27, 95% CI 1.06 to 1.53), uncomfortable working positions (OR 2.04, 95% CI 1.58 to 2.17 and OR 1.85, 95% CI 1.69 to 2.43), and absence of means to achieve good quality work (OR 1.39, 95% CI 1.19 to 1.63 and OR 1.38, 95% CI 1.15 to 1.65), respectively. Driving was a risk factor only in men and its importance increased with driving time (driving > 4 hours a day (OR 1.61, 95% CI 1.24 to 2.09)). Severe low back pain was linked to female sex (10.2% of women v 6.6% of men), high BMI, aging, and uncomfortable working positions. Low back pain with occupational consequences (n = 258) was not linked to sex, but only to aging and severity. CONCLUSIONS: The incidence and severity of low back pain were higher in women, although they seemed to be less exposed to known occupational risk factors. However, our results indicate a preponderance of these risk factors among female workers. Particular attention must therefore be paid to lifting of weights and uncomfortable working positions in female jobs (clerk, trading, health care staff).

Adult↗
PubMed1999

Oxidized low density lipoproteins induce apoptosis in PHA-activated peripheral blood mononuclear cells and in the Jurkat T-cell line.

Oxidized low density lipoproteins (oxLDLs) and activated T lymphocytes are present in early atherosclerotic plaques. It has been shown that oxLDLs are cytotoxic to cultured vascular cells but their possible toxic action on T lymphocytes has not been described. Peripheral blood lymphocytes from healthy individuals were stimulated in vitro with the polyclonal activator phytohemagglutinin and treated with various doses of native and mildly oxidized LDLs. Low doses of oxLDLs inhibited cell growth and DNA synthesis after 48 h culture and at 200 microg apoB/ml we observed a loss of cell viability. Dead cells did not exhibit significant increase of alteration of membrane integrity (i.e., necrosis) but showed chromatin fragmentation evaluated by DNA staining with 4', 6-diamidino-2-phenylindole and propidium iodide. This fragmentation increased with TBARS and hydroperoxide levels. The expression of early apoptosis marker Apo2.7 rose among the CD3(+) T-cell population. In addition, morphological analysis showed apoptotic features (cell shrinking, nucleus condensation, and fragmentation). Study of phosphatidylserine expression using Annexin V confirmed that oxLDLs induced apoptosis in activated lymphocytes. In the Jurkat T-cell line cultured with oxLDLs, apoptotic morphological changes (condensation and nucleus fragmentation) were observed and they were accompanied by DNA fragmentation visualized by propidium iodide staining and electrophoresis showing apoptotic ladder. These results demonstrate that mildly oxidized LDLs induce apoptosis in a part of activated and proliferating T cells. T-lymphocyte apoptosis induction in atherosclerotic lesions might contribute to the development of an inappropriate local T cell response.

Apoptosis↗