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Biomedical subjects

P Even

Publications and source records attributed to P Even.

At least 19 recordsLinked to original sources
PubMed2005

Dysregulation of energy homeostasis in mice overexpressing insulin-like growth factor-binding protein 6 in the brain.

AIMS/HYPOTHESIS: IGFs, IGF receptors and IGF binding proteins (IGFBPs) are widely expressed in the central nervous system. To investigate the physiological significance of IGFBP-6 in the brain we established two transgenic mouse lines overexpressing human (h)-IGFBP-6 under the control of glial fibrillary acidic protein promoter. Increasing evidence suggests that insulin/IGF signalling pathways could be implicated in the neuroendocrine regulation of energy homeostasis. We explored the impact of brain IGFBP-6 overexpression on the regulation of food intake and energy balance. METHODS: Transgenic mice were fed either a control diet or a high-fat diet for up to 3 months. Glucose and insulin tolerance tests were carried out before and after the diet period. Plasma parameters (insulin, leptin, glucose, NEFAs and triglycerides) were measured, and uncoupling protein 1 (UCP-1) expression was quantified in brown adipose tissue. Oxygen consumption was also measured in both groups. RESULTS: The transgenic mice fed a high-fat diet for 3 months developed obesity, showing increases in plasma leptin, glucose and insulin levels and mild insulin resistance. As compared with wild-type mice, no significant differences were found in the quantity of food intake. However, UCP-1 expression was down-regulated in the brown adipose tissue of the transgenic mice. CONCLUSIONS/INTERPRETATION: Our results show that brain IGFBP-6 has an impact on the regulation of energy homeostasis. These transgenic h-IGFBP-6 mice may be considered a new tool for studies of the involvement of the brain IGF system in metabolism control and obesity.

Adipose Tissue, Brown↗
PubMed2003

Coumarin-like fluorescent molecular rotors for bioactive polymers probing.

Polysaccharides are interesting and often essential macromolecules but are difficult to analyse due to their lack of convenient chromophores. We propose an efficient labelling procedure for polysaccharides such as functionalized dextrans with coumarin derivatives: the fluorescent tracers present inter alia properties of emission of fluorescence dependent on the molecular environment (polarity, viscosity, temperature, pH, etc.). Hence, with in mind the understanding of cell-polysaccharide interactions, the labelled polymers were studied by in vitro tests on a line of endothelial cells sensitive to the proliferative effect of these dextran polysaccharides. Using 3D fluorescence microscopy, the fixation and internalization of fluorescent functionalized dextrans were observed in endothelial cells.

Cell Division↗
PubMed1995

Long-term follow-up of HIV positive asymptomatic patients having received cyclosporin A.

The data of the 27 asymptomatic HIV-1 seropositive patients with CD4+ cell count between 300 and 600/microliters treated by Cyclosporin A (CSA) (7.5 mg/kg/day) in our institution between October 1985 and 1987 were reviewed in October 1993. Hemoglobin concentration, platelet count, total lymphocytes, CD4+ and CD8+ cell counts and serum core protein p24 antigenemia, as well as creatininemia measured before CSA onset, at CSA cessation and twice a year were recorded as well as clinical signs and CSA toxicities. In October 1993 median duration of CSA treatment was 11 months, median follow-up after CSA cessation was 45 months and median total follow-up was 67 months. Toxicities of CSA were those commonly encountered in other pathologies. Under CSA no patient progressed toward clinical AIDS (1987 definition). The mean CD4+ cell count of the 27 patients remained unchanged (gain of 1 cell/year) under CSA treatment, while it decreased at a rate of 50 cells/year after CSA cessation (p < 0,005). On the other hand CSA treatment had no significant impact on the evolution of total lymphocyte count, CD8+ cell counts, and P24 antigenémia.

Adult↗
PubMed1993

Peripheral selection of V delta 1+ cells with restricted T cell receptor delta gene junctional repertoire in the peripheral blood of healthy donors.

To characterize the T cell receptor (TCR) repertoire expressed by the V delta 1+ gamma/delta T cell population, we have studied the V delta 1-J delta 1 junctional sequences from peripheral blood samples of healthy donors. We show that, surprisingly, this repertoire is restricted in most healthy adults, with a donor-specific and relatively stable pattern, whereas this repertoire remains unrestricted in infants, and is similar to that of thymocytes. These data contrast with the general assumption that the junctional repertoire of V delta 1+ gamma/delta T cells is extensive, and strongly suggest that peripheral recruitment of V delta 1+ cells bearing particular TCR occurs in humans during the postnatal stage.

Adult↗
PubMed1993

Human immunodeficiency virus production by alveolar lymphocytes is increased during Pneumocystis carinii pneumonia.

Several factors are known to upregulate in vitro HIV expression by infected T cells, such as certain cytokines and cell-cell interactions. The effect of such factors, involved in immune responses, has never been evaluated in relation to HIV production by infected cells in vivo. To do so, we assessed HIV production by enriched alveolar and blood lymphocytes using a quantitative p24 antigen coculture. This was performed in 32 HIV-seropositive subjects in relation to their pulmonary infectious status, that is, with no current infection (Group 1, n = 17) or with Pneumocystis carinii pneumonia (PCP) (Group 2, n = 15). We showed that HIV core p24 antigen production by enriched alveolar lymphocytes is strongly related to the presence or absence of PC. Although the prevalence of p24-positive alveolar lymphocytes cocultures was 100% in subjects with PCP (15 of 15) compared with 65% in those without lung infection (p = 0.02), all blood lymphocytes tested were positive. In addition, the viral production of alveolar lymphocytes was 40-fold and 8-fold increased at Days 4 and 6 of the culture period in Group 2 compared with Group 1, respectively (p < 0.005). Finally, p24 antigen production by alveolar lymphocytes was significantly higher than that by the corresponding blood lymphocytes in subjects with PCP (p = 0.03) and lower in subjects without lung infection (p = 0.025). Altogether, these data strongly suggest that the HIV burden is markedly enhanced in the lung during PCP. This increased viral production is, at least initially, compartmentalized to the affected organ.

AIDS-Related Opportunistic Infections↗
PubMed1992

Effectiveness and safety of bolus administration of alteplase in massive pulmonary embolism.

Animal studies have demonstrated that thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) is accelerated and that bleeding is reduced when rt-PA is infused over a short period. Previous clinical studies in patients with venous thromboembolism have shown that rt-PA is an effective thrombolytic agent when administered by continuous infusion over 2 to 24 hours. Clinical experience of bolus rt-PA administration in patients with massive acute pulmonary embolism (PE) is, however, limited. A prospective open study was conducted in which 54 patients with massive PE (Miller index > or = 20 of 34) received a 10-minute infusion of rt-PA at a dose of 1 mg/kg. Perfusion lung scanning was used to assess the change in pulmonary perfusion after drug administration. At 48 hours and 10 days, the mean absolute improvements in the perfusion defect were 11 and 31%, respectively. In addition, a significant clinical improvement occurred within 2 hours in 11 of the 15 shocked patients. Five patients died (9%) as a result of persistent shock (3 patients), neurologic damage (1 patient) or intracranial bleeding (1 patient). Major bleeding occurred in 8 patients (15%). Long-term follow-up information was available for 44 of the 49 discharged patients: 2 had died and 12 (27%) complained of persistent exertional dyspnea, 7 of whom had an associated heart or lung disease or chronic thromboembolism at admission. These results suggest that a bolus regimen of rt-PA could provide a convenient approach to thrombolytic therapy in patients with massive PE.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Elevation of IgE in HIV-infected subjects: a marker of poor prognosis.

The IgE synthesis is tightly controlled by a complex network of T and B cells. Because human immunodeficiency virus (HIV) disease associates T cell activation and depletion, polyclonal B cell activation, atopic symptoms, drug hypersensitivity, and autoimmune activity, we have evaluated IgE, as well as IgA, IgG, and IgM, in 315 HIV-seropositive individuals with or without acquired immunodeficiency syndrome (AIDS) and compared the results to those of 100 HIV-seronegative subjects. IgE levels were higher in HIV-infected subjects as a whole, compared to levels in seronegative control subjects (p less than 0.05). This difference was particularly marked between patients with AIDS and control subjects (p less than 0.005). A strong relationship appeared between IgE and the immune status as assessed by CD4 cell counts (p less than 0.001 between IgE values in patients with CD4 less than 300 or greater than 300/microliters). In addition, we assessed the predictive value of IgE elevation over disease progression: in subjects with a CD4 count less than 300/microliters, the survival analysis disclosed a 24-month occurrence rate of AIDS of 83% in individuals with IgE greater than 150 KIU/L versus 44% in individuals with IgE less than 150 (p = 0.016). In subjects with an AIDS-related complex, IgE greater than 150 indicated a 100% rate of AIDS versus 9% in individuals with IgE less than 150 (p = 0.003). Thus, IgE levels appear to be a very discriminative marker between patients in late stages of HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Biology of small-cell bronchogenic carcinoma: recent advances].

In the last ten years considerable progress has been made in small-cell lung carcinoma (SCLC) biology, along with the technical progress made in molecular biology. This progress now allows us to propose a model for the genesis and the development of this type of tumor. Tobacco, the principal causal factor plays a dual role. In bringing about secretion of growth factors by the bronchial epithelia, usually involved in the normal development of lungs, and by functioning autocrinally and paracrinally, it facilitates the occurrence of mitotic mutations. Without directly contributing to cellular transformation, this autocrine functioning also gives a selective advantage to cells going through transformation or immortalization. The procarcinogenic or carcinogenic agents contained in tobacco smoke, whose level of production could be genetically determined, would also contribute to the accumulation of mutations affecting both suppressor genes and oncogenes. Two tumour suppressor genes have been identified: RB1 and P53. At least one other putative tumour suppressor gene has constantly been implied. It lies on the short arm of chromosome 3. There could also be the possibility of detecting subjects susceptible to developing an SCLC, a functional hemizygote still needing evaluation. The activated oncogenes principally belongs to the myc family. Their activation could correspond with the appearance of cellular clones having aggressive behavior independent of growth factors, chemoresistant and more metastatic. SCLC may be distinguished from other malignant lung tumors by a fairly characteristic pattern consisting of the loss of suppressor genes and the activation of oncogenes. The links between the neuroendocrine properties of this type of tumor and its characteristic description are being clarified and will contribute to a better understanding of the relationship between the different types of lung tumors. From this biologic knowledge follow several therapeutic applications under investigation (blocking autocrine loop through anti-GRP antibodies), as well as potential applications (concerning the products of suppressor genes) and possible applications such as prevention oriented towards detection of high-risk subjects.

Carcinoma, Bronchogenic↗
PubMed1992

The metabolic signal of hunger and satiety, and its pharmacological manipulation.

Hunger is elicited by the depletion of available macronutrients to the cells. The question is how the depletion is sensed and transduced into a biologically meaningful signal of hunger. Accumulating data show that the signal comes not from depletion of carbohydrates alone or from one of the other major macronutrients. Instead, the signal is generated by the overall cellular power production that induces hunger when it decreases and satiety when it increases. As for satiation, i.e. the state that causes the termination of a meal before nutrients cross the intestinal barrier, it is induced by early metabolic events elicited reflexly from orogastric afferences and tuning the preprandial metabolism towards the level of the postprandial metabolism. Neuronal responses from the medial hypothalamus suggest that they may integrate information on the degree of utilization of glucose and of lipids. Some of the pharmacological agents that reduce feeding seem to operate by increasing the metabolic rate in a way similar to that induced by a meal. These pharmacological agents are active because they mobilize endogenous metabolites, such as lipids, so inducing a sort of 'autocanibalic' meal.

Animals↗
PubMed1991

[Small cell lung cancers: intensive and short chemotherapy followed by irradiation. Results of a pilot study].

Twenty-six patients with localized small cell lung cancer received 3 monthly courses of intensive chemotherapy consisting of cisplatin (40 mg/m2/day on days 1, 2, 3), cyclophosphamide (750 mg/m2/day on days 4 and 5), adriamycin (50 mg/m2/day on day 5), vindesine (2 mg/m2/day on days 1 and 5), etoposide (100 mg/m2/day on days 1, 2, 3) and methylprednisolone (120 mg/m2/day on days 1 to 5). The first 10 patients received radiotherapy of the chest (3 Gy/day on days 7 and 8) and brain (2 Gy/day on days 7 and 8) after each course of chemotherapy, followed by complementary chest (27 Gy) and brain (22 Gy) radiotherapy after the end of the aplasia induced by the 3rd course of chemo-radiotherapy (alternate protocol: AP). In view of the toxicity of this protocol (4 deaths) and of the occurrence of 2 epidural relapses, the remaining 16 patients received the same 3 courses of chemotherapy followed by radiotherapy of the chest (55 Gy), brain (34 Gy) and spinal cord (34 Gy) (sequential protocol: SP). Haematological toxicity was controlled without problem in a medical oncology intensive care unit. The complete response rate (AP + SP) was 100 percent. The median survival rate was 26 months. Survival at 2 years was 20 percent with AP and 78 percent with SP (P = 0.002), this difference being due to the absence of iatrogenic deaths and epidural relapses. Intensive chemotherapy combined with radiotherapy deserves to be developed in the management of localized small cell lung cancer.

Actuarial Analysis↗
PubMed1991

Tumor necrosis factor production in HIV-seropositive subjects. Relationship with lung opportunistic infections and HIV expression in alveolar macrophages.

We have evaluated the TNF production by alveolar macrophages (AM) in 43 HIV-infected subjects in relation with 1) their clinical and biologic status; 2) the presence of lung opportunistic infections (OI); and 3) the expression of HIV by AM. This production was assessed in a standard chromium release test, using monocytic U937 cells as targets. The spontaneous TNF production by AM from patients without lung OI was higher than that from seronegative controls (p less than 0.02). This production by AM was similar to that of blood monocytes, suggesting that it was not related, in these subjects, to any particular lung status. The extent of TNF release by AM was correlated to the presence of a lymphocytic alveolitis (p less than 0.05), and not to the patients' clinical presentation nor to their CD4 cell count. Finally, AM from these subjects could be normally stimulated in vitro by IFN-gamma. On the other hand, it appeared that the spontaneous TNF release by AM shown in vitro to express HIV (p24+ AM) was significantly higher than that by their p24- counterparts (p less than 0.05) and by controls (p less than 0.01). In addition, contrasting with the marked increase of TNF release by p24- AM after their stimulation with IFN-gamma (p less than 0.001), p24+ AM appeared to be refractory to any stimulation by IFN, arguing for their activation in vivo. Finally, the spontaneous TNF release by AM was significantly increased during lung OI, compared with controls (p less than 0.01) as well as with AIDS patients without OI (p less than 0.01). In addition, the production of TNF by AM in these subjects was higher than that by the corresponding blood monocytes (p less than 0.02), suggesting a compartmentalization of this response within the lungs. In conclusion, it appears that the TNF production by AM of seropositive patients is highly related to the presence of lung OI as well as to the expression of HIV by these cells. In the context of the up-regulation of HIV expression induced by TNF in vitro, our data could suggest that the in vivo release of TNF by AM could participate in viral dissemination. Moreover, we hypothesize that the generation of activated AM refractory to any further stimulation could in turn lead to the development of additional pulmonary infections.

Gene Products, gag↗
PubMed1991

Pulmonary embolectomy: a 20-year experience at one center.

Between 1968 and 1988, 96 consecutive patients with acute massive pulmonary embolism underwent pulmonary embolectomy under cardiopulmonary bypass. The operative mortality rate was 37.5%. We analyzed 12 clinical and hemodynamic variables by univariate and multivariate analyses to assess the predictive factors of postoperative outcome. Multivariate analysis disclosed that cardiac arrest and associated cardiopulmonary disease were independent predictors of operative death. Long-term follow-up (range, 2 to 144 months; mean, 56 months) information was available for 55 of the 60 discharged patients: 6 had died, and 5 complained of persistent mild or severe exertional dyspnea (New York Heart Association class II). These results help assess the preoperative risk in patients undergoing pulmonary embolectomy. They also show that, in the few patients who do not benefit from optimal medical therapy, pulmonary embolectomy remains an acceptable procedure in view of the long-term results.

Adult↗
PubMed1991

Effects on metabolic and hormonal parameters of monosodium glutamate (umami taste) ingestion in the rat.

Umami taste appears to signal, at the gustatory level, the intake of proteins, therefore the working hypothesis was: does umami taste of a monosodium glutamate (MSG) solution elicit changes in both glucagon and insulin release, similar to those elicited by amino acids, and consequently, changes in plasma glucose and in overall cellular metabolism? In a first experiment, rats were equipped with indwelling jugular and oral catheter and serial samplings were made in the free moving, undisturbed rat before and after an oral or IV infusion of MSG (0.05 M). None of the plasma parameters showed any significant response. In a second experiment, energy expenditure was monitored by means of an original computer-based calorimeter capable of calculating, besides the classical parameters, resting metabolism in a moving animal (designated by background metabolism). The addition of MSG to a low calorie, low-protein meal did not modify background metabolism or respiratory quotient. Therefore MSG ingestion does not by itself affect plasma levels of hormones of glucose and protein metabolism, total metabolism rate, or nutrient utilization. However, examination of individual data and those from a pilot experiment for future work suggests that MSG becomes an efficient metabolic effector if added to a caloric diet, and so enhances proper thermogenesis of macronutrients.

Animals↗
PubMed1991

HIV isolation from pulmonary cells derived from bronchoalveolar lavage.

In a study of 75 alveolar cell co-cultures from 55 HIV-seropositive subjects, p24 antigen production was identified by ELISA in 11 out of 26 (42%) of unseparated cell cultures, 15 out of 39 (38%) purified alveolar macrophage cultures and eight out of 10 purified alveolar lymphocyte samples. Positivity in unseparated cell cultures was associated with an alveolar lymphocytosis greater than 30%. Negative macrophage cultures were significantly more likely in the early stages of HIV infection with none positive when the subject had a peripheral CD4+ cell count greater than 300/microliters. Alveolar macrophage infection thus appears to increase with HIV disease progression.

Bronchoalveolar Lavage Fluid↗
PubMed1990

Actuarial rate of clinical and biological progression in a cohort of 250 HIV-1-seropositive subjects. Laennec HIV Study Group.

This study was undertaken to define the risk of AIDS in a cohort of 250 HIV-seropositive patients identified by their clinical and biological status. All patients were enrolled between October 1985 and March 1988. They were classified according to clinical classes A, asymptomatic (n = 97); B, lymphadenopathic (n = 123); and C, AIDS-related complex, (n = 30). Also as CD4 cell stages 1 (CD4 greater than or equal to 600/microliters; n = 126); 2 (CD4 less than 600 and greater than or equal to 300/microliters; n = 83); and 3 (CD4 less than 300/microliters; n = 41); and serum p24 antigen positive (n = 48) or negative (n = 202). All patients were evaluated every 3-6 months, until AIDS development or April 1989: 29 cases of AIDS occurred during the follow-up period. The risk of AIDS in class C is very high (64% at 2 years) compared with the 3-year risk of classes A (13%) and B (25%). On the other hand the three CD4 stages have significantly different prognosis (stage 1 6%; stage 2 22%; and stage 3 89%; P less than 10(-2]. Antigen p24 negative and positive patients have also different prognosis (18% and 53%; P less than 10(-4]. Interestingly, p24 antigen conserved its prognostic value in stage 2 (positive 37%, negative 16%) while stages 1 are at low risk of AIDS and stages 3 at high risk whatever their p24 antigen status. We have also identified the risk of becoming stage 3 and/or p24 antigen positive in p24 antigen negative patients at stages 1 and 2 (respectively, 18% and 47%). This classification should serve to design randomized trials better with experimental drugs with earlier end-points than AIDS onset.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Autoreactive cytotoxicity in HIV-infected individuals.

A possible role for autoimmunity in the pathogenesis of HIV infection has been suggested, based upon the certain degree of homology shared by HIV gp41 and MHC class II molecules. A number of humoral markers of autoimmunity have since been found in seropositive subjects. We have evaluated the cellular autoreactive response in HIV-infected individuals. Our study demonstrates the existence of a cytolytic activity, present in seropositive but not in seronegative subjects. This activity is mediated by CD3+ T cells, which only occasionally express the CD8 or the CD4 surface markers. Effector cells do not appear to exert their activity in a MHC-restricted fashion, since allogeneic target cells could also be killed, recovered from allogeneic seropositive as well as from seronegative subjects. Several types of target cells were lysed: T cell blasts and Epstein-Barr virus (EBV) transformed B cells, suggesting that the target antigen is common to at least these two cell types. The fact that cells from seronegative individuals were lysed argues against the recognition of an HIV-specific antigen. The nature of the target determinants and the identity of the effector cells are discussed.

Antigens, CD↗
PubMed1989

[Continuous high-dose corticosteroid pressured aerosol therapy in steroid-dependent asthma].

Two therapeutic trials aimed at determining whether a high-dose inhaled corticosteroid, beclomethasone dipropionate (BDP), could reduce or suppress a long term and continuous treatment with a systemic corticosteroid, triamcinolone acetonide (TA), were carried out in a homogeneous population of severe, steroid-dependent asthmatics. The first one was a controlled, double-blind versus placebo trial involving 25 patients followed up for 5 months. The second one was an open trial involving 105 patients followed up for 12 months. In both trials the mean doses of TA were reduced by 60 to 65 per cent, and TA could be totally or nearly totally suppressed in almost 60 per cent of the cases with clinical and functional results that were equal or superior to those previously obtained with systemic corticosteroid therapy. It is concluded that: (a) continuous systemic corticosteroid therapy in mean doses of more than 5 mg/day of prednisone equivalent is now rarely indicated in patients with steroid-dependent asthma, and (b) inhaled corticosteroid therapy with BDP could be extended to cases of non steroid-dependent asthma inadequately controlled by bronchodilators.

Administration, Inhalation↗