Search PubMed⌕ Search

Biomedical subjects

François Lang

Publications and source records attributed to François Lang.

At least 19 recordsLinked to original sources
PubMed2006

Energy expenditure adjusted for body composition differentiates constitutional thinness from both normal subjects and anorexia nervosa.

Constitutional thinness (CT) is characterized by a low and stable body mass index (BMI) without any hormonal abnormality. To understand the weight steadiness, energetic metabolism was evaluated. Seven CT, seven controls, and six anorexia nervosa (AN) young women were compared. CT and AN had a BMI <16.5 kg/m(2). Four criteria were evaluated: 1) energy balance including diet record, resting metabolic rate (RMR) (indirect calorimetry), total energy expenditure (TEE) (doubly labeled water), physical activity; 2) body composition (dual-energy X-ray absorptiometry); 3) biological markers (leptin, IGF-I, free T3); 4) psychological profile of eating behavior. The normality of free T3 (3.7 +/- 0.5 pmol/l), IGF-I (225 +/- 93 ng/ml), and leptin (8.3 +/- 3.4 ng/ml) confirmed the absence of undernutrition in CT. Their psychological profiles revealed a weight gain desire. TEE (kJ/day) in CT (8,382 +/- 988) was not found significantly different from that of controls (8,793 +/- 845) and AN (8,001 +/- 2,152). CT food intake (7,565 +/- 908 kJ/day) was found similar to that of controls (7,961 +/- 1,452 kJ/day) and higher than in AN (4,894 +/- 703 kJ/day), thus explaining the energy metabolism balance. Fat-free mass (FFM) (kg) was similar in CT and AN (32.5 +/- 2.9 vs. 34.1 +/- 1.9) and higher in controls (37.8 +/- 1.6). While RMR absolute values (kJ/day) were lower in CT (4,839 +/- 473) than in controls (5,576 +/- 209), RMR values adjusted for FFM were the highest in CT. TEE-to-FFM ratio was also higher in CT than in controls. Energetic metabolism balance maintains a stable low weight in CT. An increased energy expenditure-to-FFM ratio differentiates CT from controls and could account for the resistance to weight gain observed in CT.

Adipose Tissue↗
PubMed2006

Does the frequency of anxiety and depressive disorders differ between diagnostic subtypes of anorexia nervosa and bulimia?

OBJECTIVE: The objective of the present work is to determine whether the prevalence of depressive and anxiety disorders varies in subgroups of eating disorders (ED) according to age, ED duration, mode of care provision, and body mass index (BMI). METHOD: Using the Mini International Neuropsychiatric Interview (MINI), the frequency of anxiety and depressive disorders was evaluated in 271 ED participants. Their prevalence was compared in subgroups of anorexics (AN-R and AN-BN) and bulimics (BN), both before and after controlling for potential confounding variables. RESULTS: Current or lifetime comorbidity of anxiety and depressive disorders did not differ between AN-R and AN-BN groups. Social phobia, panic disorders, and obsessive-compulsive disorder (OCD) were significantly more frequent in AN-BN and AN-R groups. Panic disorder was more frequent in the BN group. CONCLUSION: Several confounding factors, in particular those identified in the present study, may explain previous conflicting results on the frequency of anxiety and depressive disorders in ED. Nevertheless, the study confirmed that OCD is more frequent in AN, even after controlling for confounding factors.

Adolescent↗
PubMed2005

Dependency and suicidality in addictive disorders.

Excessive interpersonal dependency has been described in depression and addictive disorders. Moreover, excessive dependency and suicidality are linked in psychiatric subjects, but their relationships have not been studied in specific addictions. Separate samples of female anorectic patients (n=150), female bulimic patients (n=95), male (n=150) or female (n=68) alcoholics, male (n=94) or female (n=54) drug abusers and non-psychiatric control subjects (n=683) were included in the study. On the basis of a structured interview, suicidal ideations, number of previous suicide attempts and diagnoses of dependent personality disorder (DSM-IV) were collected, and the subjects completed the Interpersonal Dependency Inventory and the Beck Depression Inventory. Logistic regression analysis revealed that excessive dependency and notably dependent personality disorder increased the likelihood of suicidal ideation or suicide attempts with a range of 2.65 to 9.42 in bulimic patients, female alcoholics and male drug abusers. Excessive dependency in specific addictive disorders as well as in male non-psychiatric subjects could constitute a risk factor for suicide. This hypothesis must be confirmed using prospective studies.

Adolescent↗
PubMed2005

Production of recombinant human trimeric CD137L (4-1BBL). Cross-linking is essential to its T cell co-stimulation activity.

The interaction between 4-1BB ligand (CD137L), a member of the tumor necrosis factor superfamily, and its receptor 4-1BB provides a co-stimulatory signal for T lymphocyte proliferation and survival. However, the structure of 4-1BBL has not been thoroughly investigated, and none of the human recombinant 4-1BBL molecules available have been described as capable of co-stimulating T cells. The present work provides a model of the three-dimensional structure of the tumor necrosis factor homology domain of 4-1BBL and describes the production of a recombinant human soluble 4-1BBL whose originality lies in that it contains the whole extracellular tail preceding the tumor necrosis factor homology domain and an AviTag peptide (AviTag-4-1BBL) allowing enzymatic biotinylation and multimerization via streptavidin. We provide evidence that this chimeric protein exists as a homotrimer, whereas commercial FLAG-tagged 4-1BBL does not. This resulted in a much higher affinity for 4-1BB (1.2 nM) as compared with FLAG-4-1BBL (55.2 nM). We demonstrate that the single extracellular cysteine residue in the tail (Cys-51) could form a disulfide bond, both in our recombinant protein and in physiologically expressed 4-1BBL. The mutation of this cysteine residue exerted no effect on trimerization but increased the dissociation rate of AviTag-4-1BBL from 4-1BB. In its soluble form, AviTag-4-1BBL did not stimulate purified T cells but dramatically inhibited proliferation of peripheral blood mononuclear cells stimulated with anti-CD3 mAb. In contrast, a very significant co-stimulatory effect was observed on purified T cells once AviTag-4-1BBL was immobilized onto streptavidin beads. In addition, we show that the cross-linking of two trimeric AviTag-4-1BBL molecules was the minimum step required to elicit significant costimulatory activity.

4-1BB Ligand↗
PubMed2005

Adoptive transfer of tumor-reactive Melan-A-specific CTL clones in melanoma patients is followed by increased frequencies of additional Melan-A-specific T cells.

In this study, we report the adoptive transfer of highly tumor-reactive Melan-A-specific T cell clones to patients with metastatic melanoma, and the follow-up of these injected cells. These clones were generated from HLA-A*0201 patients by in vitro stimulations of total PBMC with the HLA-A*0201-binding Melan-A peptide analog ELAGIGILTV. Ten stage IV melanoma patients were treated by infusion of these CTL clones with IL-2 and IFN-alpha. The generated T cell clones, of effector/memory phenotype were selected on the basis of their ability to produce IL-2 in response to HLA-A*0201 Melan-A-positive melanoma lines. Infused clones were detected, by quantitative PCR, in the blood of three patients for periods ranging from 7 to 60 days. Six patients showed regression of individual metastases or disease stabilization, and one patient experienced a complete response, but no correlation was found between the detection of the infused clones in PBMC or tumor samples and clinical responses. Nonetheless, frequencies of Melan-A/A2-specific lymphocytes, measured by tetramer labeling, increased after treatment in most patients. In one of these patients, who showed a complete response, this increase corresponded to the expansion of new clonotypes of higher avidity than those detected before treatment. Together, our results suggest that infused CTL clones may have initiated an antitumor response that may have resulted in the expansion of a Melan-A-specific CTL repertoire.

Adoptive Transfer↗
PubMed2005

Refeeding normalizes the QT rate dependence of female anorexic patients.

We postulated that dynamic alterations in QT interval adaptation could characterize patients with anorexia nervosa (AN) and could be restored after weight gain. To assess ventricular repolarization features, we evaluated the QT dynamicity along RR intervals from 24-hour electrocardiographic data of patients with AN before and after refeeding. Ten young women with AN (19 +/- 3 years) were included in the study. The QT/RR slope was found significantly enhanced compared with normals (-1.82 +/- 0.62 vs -1.40 +/- 0.30; p < 0.05). This slope returned to normal range values after refeeding. The QT/RR slope was significantly correlated with the body mass index (r = 0.59; p < 0.007) in the patient group.

Adult↗
PubMed2005

A new carboxamide compound exerts immuno-suppressive activity by inhibiting dendritic cell maturation.

The immunosuppressive properties of a benzamide derivative, JM34, previously characterized as an anti-inflammatory compound are described. The immunosuppressive potential of JM34 was evidenced by inhibition of PBMC proliferation in vitro with an IC50 of 20 microM. In contrast with classical immunosuppressive drugs, JM34 affected neither cytokine production nor IL-2R expression from activated T cell clones, and displayed only moderate inhibition of IL-2-induced or anti-CD3/anti-CD28-induced proliferation. We investigated its effects on dendritic cells (DC) in vitro. Addition of JM34 during DC maturation inhibited the expression of some maturation markers: specifically, MHC molecule up-regulation was totally inhibited and CD83 expression was significantly reduced, while up-regulation of CD86, CD80 or CD40 was less affected. Moreover, JM34-treated DC showed impaired IL-12 but not IL-10 secretion, and a markedly reduced ability to present antigens to naive T lymphocytes in vitro. We provide evidence that these JM34-induced alterations of DC were associated with a marked inhibition of NF-kappaB nuclear translocation. Finally, JM34 inhibited delayed type hypersensitivity dose dependently in mice. In conclusion, our data suggest that JM34 inhibited T lymphocyte activation mainly by targeting DC, and thus may represent a new class of therapeutic agents in the fields of transplantation and autoimmune diseases.

Animals↗
PubMed2004

Alexithymia, depressive experiences, and dependency in addictive disorders.

Alexithymia, depressive feelings, and dependency are interrelated dimensions that are considered potential "risk factors" for addictive disorders. The aim of this study was to investigate the relationships between these dimensions and to define a comprehensive model of addiction in a large sample of addicted subjects, whether affected by an eating disorder or presenting an alcohol- or a drug use-related disorder. The participants in this study were gathered from a multicenter collaborative study on addictive behaviors conducted in several psychiatric departments in France, Switzerland, and Belgium between January 1995 and March 1999. The clinical sample was composed of 564 patients (149 anorexics, 84 bulimics, 208 alcoholics, 123 drug addicts) of both genders with a mean age of 27.3 +/- 8 years. A path analysis was conducted on the 564 dependent patients and 518 matched controls using the scores of the Toronto Alexithymia Scale, the Depressive Experiences Questionnaire, and the Interpersonal Dependency Inventory. Statistical analyses showed good adjustment (Goodness of Fit Index = 0.977) between the observable data and the assumed model, thus supporting the hypothesis that a depressive dimension, whether anaclitic or self-critical, can facilitate the development of dependency in vulnerable alexithymic subjects. This result has interesting clinical implications because identifying specific patterns of relationships leading from alexithymia to dependency can provide clues to the development of targeted strategies for at-risk subjects.

Adolescent↗
PubMed2003

Retrovirus-mediated gene transfer in polyclonal T cells results in lower apoptosis and enhanced ex vivo cell expansion of CMV-reactive CD8 T cells as compared with EBV-reactive CD8 T cells.

To modulate alloreactivity after hematopoietic stem cell transplantation, "suicide" gene-modified donor T cells (GMCs) have been administered with an allogeneic T-cell-depleted marrow graft. We previously demonstrated that such GMCs, generated after CD3 activation, retrovirus-mediated transduction, and G418 selection, had an impaired Epstein-Barr virus (EBV) reactivity, likely to result in an altered control of EBV-induced lymphoproliferative disease. To further characterize the antiviral potential of GMCs, we compared the frequencies of cytomegalovirus (CMV)-specific CD8+ T (CMV-T) cells and EBV-specific CD8+ T (EBV-T) cells within GMCs from CMV- and EBV-double seropositive donors. Unlike anti-EBV responses, the anti-CMV responses were not altered by GMC preparation. During the first days of culture, CMV-T cells exhibited a lower level of CD3-induced apoptosis than did EBV-T cells. In addition, the CMV-T cells escaping initial apoptosis subsequently underwent a higher expansion rate than EBV-T cells. The differential early sensitivity to apoptosis could be in relation to the "recent activation" phenotype of EBV-T cells as evidenced by a higher level of CD69 expression. Furthermore, EBV-T cells were found to have a CD45RA-CD27+CCR7- effector memory phenotype, whereas CMV-T cells had a CD45RA+CD27-CCR7- terminal effector phenotype. Such differences could be contributive, because bulk CD8+CD27- cells had a higher expansion than did bulk CD8+CD27+ cells. Overall, ex vivo T-cell culture differentially affects apoptosis, long-term proliferation, and overall survival of CMV-T and EBV-T cells. Such functional differences need to be taken into account when designing cell and/or gene therapy protocols involving ex vivo T-cell manipulation.

Antigens, CD↗
PubMed2003

Anxiety disorders in subjects seeking treatment for eating disorders: a DSM-IV controlled study.

Women who were referred with an eating disorder (ED) were compared with a matched normal control group to answer the following questions: What are the frequencies of anxiety disorders in cases of anorexia and bulimia nervosa diagnosed according to DSM-IV criteria? Are anxiety disorders significantly more frequent among women with an eating disorder than among women from the community? We assessed the frequencies of six specific anxiety disorders among 271 women with a current diagnosis of anorexia or bulimia nervosa and 271 controls, using the Mini-International Neuropsychiatric Interview, French DSM-IV version. A lifetime comorbidity with at least one anxiety disorder was found in 71% of both the anorexic and the bulimic subjects, significantly higher than the percentage of controls with an anxiety disorder. The prevalence was significantly higher in the eating disorder groups than in controls for most types of anxiety disorder, and between 41.8 and 53.3% of comorbid cases had an anxiety disorder preceding the onset of the eating disorder. Anxiety disorders are significantly more frequent in subjects with eating disorders than in volunteers from the community, a finding that has important etiological and therapeutic implications.

Adolescent↗
PubMed2003

Depressive psychopathology and adverse childhood experiences in eating disorders.

PURPOSE: The aim of this paper was to investigate the diagnostic specificity of the self-critical and dependent depressive experiences in a clinical sample of eating disorder patients and to explore the impact of adverse childhood experiences on these dimensions of personality. METHOD: A sample of 94 anorexic and 61 bulimic patients meeting DSM-IV criteria and 236 matched controls were assessed with the Depressive Experience Questionnaire (DEQ), the abridged version of the Beck Depression Inventory (BDI) and the AMDP Life Events Inventory. Subjects presenting a major depression or a comorbid addictive disorder were excluded from the sample using the Mini International Neuropsychiatric Interview (MINI). RESULTS: Anorexic and bulimic patients showed higher scores than controls on both self-criticism and dependency sub-scales of the DEQ. Bulimic patients scored significantly higher than anorexic patients on self-criticism and reported more adverse childhood experiences. Finally, negative life events correlated only with self-criticism in the whole sample. DISCUSSION: Differences in the DEQ Self-Criticism between anorexics and bulimics could not be accounted for by depression since bulimic patients did not show higher BDI levels compared to anorexic patients and depressive symptoms measured with the BDI were not found to be significant predictors of diagnostic grouping in a logistic multiple regression. CONCLUSION: This study supports the diagnostic specificity of the dependent and self-critical depressive dimensions in eating disorders and strengthens previous research on the role of early experiences in the development of these disorders.

Adolescent↗
PubMed2003

Balance in ghrelin and leptin plasma levels in anorexia nervosa patients and constitutionally thin women.

Ghrelin, a 28-amino acid octanoylated peptide, has recently been identified in rat stomach as an endogenous ligand for the GH secretagogue receptor. In addition to GH-releasing properties, exogenous ghrelin injections exert orexigenic effects in both rodents and humans. As the endogenous peptide appears directly related to feeding behavior, we assessed its plasma levels in anorexia nervosa (AN) patients before and after renutrition and in constitutionally thin subjects with body mass indexes (BMIs) equivalent to those of AN women but with no abnormal feeding behavior. The relationships between plasma ghrelin levels and other neuroendocrine and nutritional parameters, such as GH, leptin, T3, and cortisol, were also investigated. In AN patients, morning fasting plasma ghrelin levels were doubled compared with levels in controls, constitutionally thin subjects, and AN patients after renutrition. Twenty-four-hour plasma ghrelin, GH, and cortisol levels determined every 4 h were significantly increased, whereas 24-h plasma leptin levels were decreased in AN patients compared with controls and constitutionally thin subjects. Both plasma ghrelin and leptin levels returned to control values in AN patients after renutrition. Constitutionally thin subjects displayed intermediate 24-h plasma ghrelin and leptin levels, significantly different from controls and AN patients, whereas GH and cortisol were not modified. Ghrelin was negatively correlated with BMI, leptin, and T(3) in controls, constitutionally thin subjects, and AN patients, whereas no correlation was found between GH and ghrelin or between cortisol and ghrelin. Ghrelin and BMI or T3 were still correlated after renutrition, suggesting that ghrelin is also a good nutritional indicator. Basal and GHRH-stimulated GH release were significantly increased in AN patients only. In conclusion, ghrelin is increased in AN and constitutionally thin subjects who display very low BMI but different eating behaviors, suggesting that not only is ghrelin dependent on body fat mass, but it is also influenced by nutritional status. Even though endogenous ghrelin is not strictly correlated with basal GH secretion, it may be involved in the magnitude of GHRH-induced GH release in AN patients.

Adolescent↗
PubMed2003

[Are anxiety disorders more frequent in subjects with eating disorders?].

OBJECTIVE: We designed a controlled study comparing referred women with an eating disorder (ED) to a matched normal control group to answer the following questions: what are the frequencies of anxiety disorders (AD) in anorexia nervosa (AN) and bulimia nervosa (BN), according to DSM-IV criteria? Are AD significantly more frequent among women with an ED than among women from the community? METHOD: We assessed frequencies of six specific AD among 271 women with a current diagnosis of AN or BN and 271 controls, using the Mini International Neuropsychiatric Interview (MINI), French DSM-IV version. RESULTS: Seventy-one percent of both the AN and the BN subjects had a lifetime comorbidity with at least one AD, significantly more (p<0.001) than the percentage of controls with an AD. Prevalence was significantly higher in the ED groups than in controls for most types of AD, and between 41.8% and 53.3% of comorbid cases had an AD preceding the onset of the ED. CONCLUSION: Evidence that AD are significantly more frequent in subjects with ED than in the community has important etiological and therapeutic implications.

Adolescent↗
PubMed2002

Apoptotic body-loaded dendritic cells efficiently cross-prime cytotoxic T lymphocytes specific for NA17-A antigen but not for Melan-A/MART-1 antigen.

DCs hold promise for cancer immunotherapy due to their functional ambivalence: iDCs internalize antigens, then mDCs trigger naive T-cell activation. However, no consensus has been reached concerning the optimal mode of antigen acquisition for efficient cross-priming of TAA-specific CTLs, and this remains a field of investigation. Here, we used highly purified apobodies derived from an HLA-A*0201-negative melanoma line as a source of tumor antigens for HLA-A*0201 DCs. We compared in vitro mDCs loaded with apobodies to DCs loaded with antigenic peptides, NA17-A(1-9) and Melan-A/MART-1(26-35) A27L analogue, for their capacity to stimulate melanoma antigen-specific T cells from autologous PBLs. Apobody phagocytosis did not induce spontaneous DC maturation, but phagocytic DCs were still responsive to maturation signals, resulting in a functional ability to activate antigen-specific lymphocytes. NA17-A-specific T lymphocytes were activated by both types of stimulation, whereas only peptide-pulsed DCs stimulated the growth of Melan-A/MART-1-specific lymphocytes. We also observed a lack of staining of melanoma-derived apobodies with a Melan-A-specific MAb, suggesting protein alteration during apoptosis induction. After HLA-A*0201/NA17-A multimer sorting, antigen-specific lymphocytes induced by mature DCs loaded with either peptide or apobodies displayed similar functional capacity against peptide-pulsed T2 cells and melanoma cells. Therefore, apobody-loaded DCs can achieve T-cell priming similar to that induced by peptide-pulsed DCs, provided that the apoptotic process allows the preservation of antigen expression.

Antigen Presentation↗
PubMed2002

Retrovirus-mediated gene transfer in primary T lymphocytes impairs their anti-Epstein-Barr virus potential through both culture-dependent and selection process-dependent mechanisms.

To modulate alloreactivity after hematopoietic stem cell transplantation, suicide gene-expressing donor T cells can be administered with an allogeneic T-cell-depleted bone marrow graft. Immune competence of such cells is a critical issue. The impact of the ex vivo gene transfer protocol (12-day culture period including CD3/interleukin-2 [IL-2] activation, retroviral-mediated gene transfer, and G418-based selection) on the anti-Epstein-Barr virus (EBV) potential of gene-modified cells has been examined. Cytotoxic (pCTL) and helper (pTh) cell precursor limiting dilution assays, interferon-gamma enzyme-linked immunospot, or fluorescence-activated cell sorter analysis after tetrameric HLA-A2/EBV peptide complexes revealed that the frequency of anti-EBV T cells was lower in gene-modified cells (GMCs) than in similarly cultured but untransduced T cells and was even lower than in fresh peripheral blood mononuclear cells, demonstrating both an effect of the culture and of the transduction or selection. The culture-dependent loss of EBV-reactive cells resulted from the preferential induction of activation-induced cell death in tetramer(+) cells. Replacing the initial CD3/IL-2 activation by CD3/CD28/IL-2 partially restored the anti-EBV response of GMCs by reducing the initial activation-induced cell death and enhancing the proliferation of EBV-tetramer(+) cells. Moreover, the G418 selection, and not the transduction, was directly toxic to transduced tetramer(+) cells. Replacing the G418 selection by an immunomagnetic selection significantly prevented the selection-dependent loss of EBV-specific cells. Overall, ex vivo gene modification of primary T cells can result in a significant reduction in EBV-reactive T cells through both culture-dependent and selection-dependent mechanisms. Improving immune functions of GMCs through modifications of the cell culture conditions and transduction/selection processes is critical for further clinical studies.

Cell Culture Techniques↗
PubMed2002

Criterion validity of the interpersonal dependency inventory: a preliminary study on 621 addictive subjects.

The interpersonal dependency inventory comprised three subscales called Emotional reliance of another person (ER), lack of social self confidence (LSS) and Assertion of autonomy (AUT). Several formula have been developed for deriving whole-scale scores. The aim of the study on 621 addictive subjects was to determine the best formula using the DSM-IV dependent personality disorder as gold standard. The formula 3 ER + LSS - AUT yielded the best values of sensitivity and specificity.

Adult↗
PubMed2002

[The translation of questionnaires and of tests: techniques and problems].

OBJECTIVES: To summarize the difficulties involved in translating tests, to describe the translation methods and the test validation procedures, and to apply those to a personality test. METHOD: The revised Freiburg Personality Inventory (FPI-R) was translated, then subjected to the following test validation methods: backtranslation, pretest, and review by a carefully selected expert committee. RESULTS: We used a literature review to clarify FPI-R translation problems. These include in particular the different types of equivalence between the source language and the target language (for example, semantics and idioms, as well as experiential and conceptual equivalence). Statistical validation procedures are employed in principle only. CONCLUSION: The current method combining translation with backtranslation is not sufficient and must be used with, at least, a pretest and step-by-step review by an expert committee. The presence of unilingual experts to explain the smallest details of the target language, which bilingual experts could miss, seems to be mandatory.

Culture↗