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Biomedical subjects

N Franck

Publications and source records attributed to N Franck.

At least 19 recordsLinked to original sources
PubMed2006

Peroxisome proliferator activated receptor gamma activity is low in mature primary human visceral adipocytes.

AIMS/HYPOTHESIS: The amount of visceral fat mass strongly relates to insulin resistance in humans. The transcription factor peroxisome proliferator activated receptor gamma (PPARG) is abundant in adipocytes and regulates genes of importance for insulin sensitivity. Our objective was to study PPARG activity in human visceral and subcutaneous adipocytes and to compare this with the most common model for human disease, the mouse. MATERIALS AND METHODS: We transfected primary human adipocytes with a plasmid encoding firefly luciferase controlled by PPARG response element (PPRE) from the acyl-CoA-oxidase gene and measured PPRE activity by emission of light. RESULTS: We found that PPRE activity was 6.6-fold higher (median) in adipocytes from subcutaneous than from omental fat from the same subjects (n = 23). The activity was also 6.2-fold higher in subcutaneous than in intra-abdominal fat cells when we used a PPARG ligand-binding domain-GAL4 fusion protein as reporter, demonstrating that the difference in PPRE activity was due to different levels of activity of the PPARG receptor in the two fat depots. Stimulation with 5 micromol/l rosiglitazone did not induce a PPRE activity in visceral adipocytes that was as high as basal levels in subcutaneous adipocytes. Interestingly, in mice of two different strains the PPRE activity was similar in visceral and subcutaneous fat cells. CONCLUSIONS/INTERPRETATION: We found considerably lower PPARG activity in visceral than in subcutaneous primary human adipocytes. Further studies of the molecular mechanisms behind this difference could lead to development of drugs that target the adverse effects of visceral obesity.

Adipocytes↗
PubMed2003

The role of proprioception in action recognition.

This study aimed at evaluating the role of proprioception in the process of matching the final position of one's limbs with an intentional movement. Two experiments were realised with the same paradigm of conscious recognition of one's own limb position from a distorted position. In the first experiment, 22 healthy subjects performed the task in an active and in a passive condition. In the latter condition, proprioception was the only available information since the central signals related to the motor command were likely to be absent. The second experiment was realised with a deafferented patient who suffers from a complete haptic deafferentation, including loss of proprioception. The results first argue in favour of a dominant role of proprioception in action recognition, but they also stress the possible role of central signals. The process of matching the final position of one's limbs with an intended movement and thus of action recognition would be achieved through a comparison process between the predicted sensory consequences of the action, which are stored in its internal model, and the actual sensory consequences of that action.

Adult↗
PubMed2003

Modulating the experience of agency: a positron emission tomography study.

This study investigated agency, the feeling of being causally involved in an action. This is the feeling that leads us to attribute an action to ourselves rather than to another person. We were interested in the effects of experimentally modulating this experience on brain areas known to be involved in action recognition and self-recognition. We used a device that allowed us to modify the subject's degree of control of the movements of a virtual hand presented on a screen. Four main conditions were used: (1) a condition where the subject had a full control of the movements of the virtual hand, (2) a condition where the movements of the virtual hand appeared rotated by 25 degrees with respect to the movements made by the subject, (3) a condition where the movements of the virtual hand appeared rotated by 50 degrees, and (4) a condition where the movements of the virtual hand were produced by another person and did not correspond to the subject's movements. The activity of two main brain areas appeared to be modulated by the degree of discrepancy between the movement executed and the movement seen on the screen. In the inferior part of the parietal lobe, specifically on the right side, the less the subject felt in control of the movements of the virtual hand, the higher the level of activation. A reverse covariation was observed in the insula. These results demonstrate that the level of activity of specific brain areas maps onto the experience of causing or controlling an action. The implication of these results for understanding pathological conditions is discussed.

Adult↗
PubMed2001

Self-monitoring in schizophrenia revisited.

According to a widespread theory, the first-rank symptoms such as delusions of control or thought insertion met in schizophrenia result from a failure in predicting the consequences of an action on the basis of a forward model based of the intended motor commands (efference copy). This assumption of an impairment in the central monitoring of their own actions is inferred from experiments showing that it is more difficult for schizophrenic patients than for controls to correct erroneous movements in the absence of visual feedback. In our study, 19 schizophrenic patients (10 with Schneiderian symptoms and nine without) and 19 paired control subjects were subjected to a sensorimotor adjustment task to reassess this hypothesis. We show that the patients who succeeded the task not differently from the control subjects were those who were aware of the manual correction (n = 9). Surprisingly, most of them presented Schneiderian symptoms. This suggests that the experience of alien control observed in certain schizophrenic patients cannot be directly related to an underlying cognitive deficit in the conscious monitoring of their own actions.

Adult↗
PubMed2001

Anticipating incoming events: an impaired cognitive process in schizophrenia.

Intentions are central to guiding actions to their completion because they generate expectations which precede the realization of a task. This ability to manage time was investigated by using a cognitive task which involves several highly integrated processes: sequential learning, explicit processing, and working memory. In this task, participants are required to explicitly learn a repeating color sequence before receiving an instruction to give an anticipatory motor response concerning the next element. Two types of sequences (temporal and spatial) and three experimental conditions were tested in both a group of normal participants and a group of schizophrenic patients. Schizophrenics were included because their condition is known to alter conscious executive function. Our results showed that schizophrenic patients have a strong deficit in performing anticipation tasks. Although they learned the sequences almost normally, their anticipatory ability was reduced in comparison to normal participants in all the tested conditions. These results expand the notion of a working memory deficit in schizophrenia and bear strong implications for understanding executive disorders observed in such patients.

Adult↗
PubMed2001

Defective recognition of one's own actions in patients with schizophrenia.

OBJECTIVE: The possibility that delusions of influence could be related to abnormal recognition of one's own actions was investigated in persons with schizophrenia. METHOD: Schizophrenic patients with (N=6) and without (N=18) delusions of influence were compared with normal subjects (N=29) on an action recognition task. The image of a virtual right hand holding a joystick was presented to the subjects through a mirror so that the image was superimposed on their real hand holding a real joystick. Subjects executed discrete movements in different directions. Angular biases and temporal delays were randomly introduced in some trials, such that the movement of the virtual hand departed from the movement executed by the subjects. After each trial, subjects were asked whether the movement they saw was their own. RESULTS: Compared with normal subjects, both patient groups made significantly more recognition errors in trials with temporal delays. In trials with angular biases, the error rate of patients with delusions of influence significantly differed from that of comparison subjects and from that of patients without delusions of influence. CONCLUSIONS: The findings support the hypothesis that delusions of influence are associated with a quantifiable difficulty in correct self-attribution of actions. This difficulty may be related to a specific impairment of a neural action attribution system.

Adult↗
PubMed2000

Cognitive sequence processing and syntactic comprehension in schizophrenia.

It has been repeatedly demonstrated that schizophrenic patients are impaired in the comprehension of sentences with complex syntax. We investigated the hypothesis that this syntactic comprehension impairment in schizophrenia is not a purely linguistic dysfunction, but rather the reflection of a cognitive sequence processing impairment that is revealed as task complexity increases. We tested 10 schizophrenic patients using a standard measure of syntactic comprehension, and a non-linguistic sequence processing task, both of which required simple and complex transformation processing. Patients' performance impairment on the two tasks was highly correlated (r2 = 0.84), and there was a significant effect for complexity, independent of the task. These results are quite similar to those of aphasic patients with left hemisphere lesions. This suggests that syntactic comprehension deficits in schizophrenia reveal the dysfunction of cognitive sequence processing mechanisms that can be expressed both in linguistic and non-linguistic sequence tasks.

Adult↗
PubMed2000

Transformation of mycosis fungoides: clinicopathological and prognostic features of 45 cases. French Study Group of Cutaneious Lymphomas.

The course of mycosis fungoides (MF) is indolent except when transformation to a large T-cell lymphoma occurs. The diagnosis of transformed MF (T-MF) relies on the presence of more than 25% of large cells on biopsy of an MF lesion. We analyzed 45 patients with T-MF recorded by the French Study Group on Cutaneous Lymphomas to better determine clinicopathological features of MF transformation and to analyze their impact on prognosis. Median time from diagnosis of MF to transformation was 6.5 years. Extracutaneous progression was present in 20 patients. Mean survival from transformation to death was 22 months. In univariate analysis, only an extracutaneous progression was associated with a worse prognosis (5-year actuarial survival: 7.8% versus 32%). Neither sex, age, clinical and skin disease stage at transformation, transformation speed, nor percentage of large cells or CD30 expression (14 of 45) had a prognostic value. When performing multivariate analysis, age (at least 60 years), and extracutaneous spreading were found to be associated with a poor prognosis. There was no difference between survival curves of patients with T-MF and with pleomorphic large T-cell CD30- lymphomas. The main diagnostic pitfall was "histiocytic-rich" MF, requiring CD68 staining for the diagnosis of T-MF. Out of 45 patients, 6 presented an histologic transformation before clinical progression, suggesting that an early histopathological diagnosis may be performed by histological follow-up. The prognostic value of such early histopathological diagnosis must be confirmed by prospective studies.

Adult↗
PubMed2000

Confusion between silent and overt reading in schizophrenia.

The present study was aimed at investigating whether schizophrenic patients are impaired in monitoring their own speech. In particular, we attempted to assess their ability to discriminate between overt and covert speech in a reading task, in order to verify whether they can correctly recollect the modality in which an internally generated action is produced. Subjects were asked to read either silently or aloud, items from a list of words. After a delay of 5 min, they were required to indicate in a new list which words had been read previously (either silently or overtly), or had never been presented during the reading task. With respect to normal controls, schizophrenic patients showed a significant bias to report that they had read aloud words which they had actually read silently, or which were absent during the reading task. The results are discussed in relation to recent neuroimaging studies on inner and overt speech in hallucinating schizophrenic patients. Our data favour the hypothesis that the inability to correctly discriminate between inner and overt speech may play a role in the onset of schizophrenic hallucinations.

Adult↗
PubMed1999

Prognostic factors in primary cutaneous lymphomas other than mycosis fungoides and the Sézary syndrome. The French Study Group on Cutaneous Lymphomas.

Prognostic studies of primary cutaneous lymphomas (PCL) other than mycosis fungoides (MF) and the Sézary syndrome (SS; non-MF/SS PCL) have been mainly performed on subgroups or on small numbers of patients by using univariate analyses. Our aim was to identify independent prognostic factors in a large series of patients with non-MF/SS PCL. We evaluated 158 patients who were registered in the French Study Group on Cutaneous Lymphomas database from January 1, 1986 to March 1, 1997. Variables analyzed for prognostic value were: age; sex; type of clinical lesions; maximum diameter, location, and number of skin lesions; cutaneous distribution (ie, local, regional, or generalized); prognostic group according to the European Organization for Research and Treatment of Cancer (EORTC) classification for PCL; B- or T-cell phenotype; serum lactate dehydrogenase (LDH) level; and B symptoms. Univariate and multivariate analyses were performed using a model of relative survival. Forty-nine patients (31%) died. The median relative survival time was 81 months. In univariate analysis, EORTC prognostic group, serum LDH level, B symptoms, and variables related to tumor extension (ie, distribution, maximum diameter, and number of skin lesions) were significantly associated with survival. When these variables were considered together in a multivariate analysis, EORTC prognostic group and distribution of skin lesions remained statistically significant, independent prognostic factors. This study confirms the good predictive value of the EORTC classification for PCL and shows that the distribution of skin lesions at initial evaluation is an important prognostic indicator.

Adolescent↗
PubMed1999

Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma.

Human herpesvirus 8 (HHV-8, also called KSHV) is linked to the etiopathogenesis of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and primary effusion lymphoma (PEL). The universal presence of HHV-8 in early KS has not yet been shown. We used a mAb (LN53) against latent nuclear antigen-1 (LNA-1) of HHV-8 encoded by ORF73 to study the distribution of the cell types latently infected by HHV-8 in patch, plaque, and nodular KS, MCD, and PEL. In early KS, HHV-8 is present in <10% of cells forming the walls of ectatic vessels. In nodular KS, HHV-8 is present in cells surrounding slit-like vessels and in >90% of spindle cells, but not in normal vascular endothelium. In addition, HHV-8 colocalizes with vascular endothelial growth factor receptor-3 (VEGFR-3), a marker of lymphatic and precursor endothelium. In early KS lesions, VEGFR-3 is more extensively expressed than LNA-1, indicating that HHV-8 is not inducing the proliferation of VEGFR-3-positive endothelium directly. In MCD, HHV-8 is present in mantle zone large immunoblastic B cells. No staining for LNA-1 is seen in samples from multiple myeloma, prostate cancer, and angiosarcoma, supporting the absence of any etiological link between these diseases and HHV-8.

Antigens, CD↗
PubMed1999

Perception of self-generated movement following left parietal lesion.

Three apraxic patients with lesions in the left parietal cortex were required to execute finger movements with either hand, while the visual feedback they received about the movement was manipulated systematically. We used a device which allowed us to present on a video monitor either the patient's hand or the examiner's hand simultaneously performing an identical or a different movement. In each trial, patients were required to decide whether the hand shown on the screen was their own or not. Hand movements produced in response to verbal command included simple (single-finger extension) and complex gestures (multi-finger extension). Ownership judgements were analysed and compared with those produced by six normal controls and two non-apraxic neurological patients. Apraxic patients and controls accurately recognized their own hand on the screen (own movement condition) and correctly identified the viewed hand as the examiner's when it performed a movement different from their own movement (incongruent movement condition). However, when the viewed hand was the examiner's hand executing their own movement (congruent movement condition), apraxic patients were significantly more impaired than controls. When the results were analysed as a function of gesture type, the number of correct responses was significantly lower for apraxic patients with respect to controls only for complex gestures. Interestingly, when patients executed the finger gestures inaccurately, they still failed to recognize the examiner's hand as alien, and claimed that the correct movement presented on the screen was their own. These results confirm that parietal lesions alter the representational aspects of gestures, and suggest a failure in evaluating and comparing internal and external feedback about movement. We conclude that the parietal cortex plays an important role in generating and maintaining a kinaesthetic model of ongoing movements.

Aged↗
PubMed1999

The Spectrum of Cutaneous Lymphomas in HIV infection: a study of 21 cases.

We studied 21 HIV-associated lymphomas with cutaneous presentation to determine whether they showed features of primary cutaneous lymphoma arising fortuitously or whether they represented the cutaneous involvement of AIDS systemic lymphoma. Besides rare mycosis fungoides (n = 3), which shared typical clinicopathologic lesions, nonepidermotropic large-cell lymphomas (n = 18) were predominant. They frequently presented as a solitary nodule or tumor. Seven of the eight large T-cell lymphomas had a CD30-positive (CD30+) phenotype but did not express ALK protein. Overexpression of p53 protein was observed in six cases. Although EBV-EBER transcripts were detected in two of them, LMP1 protein was absent. Except for their original prevalence, the features of these T-cell CD30+ cutaneous lymphomas were the same as in immunocompetent patients. The 10 B-cell cutaneous lymphoma were immunoblastic or centroblastic lymphomas, with a differential expression of BCL-6 and Syndecan. Four of them expressed CD30, EBER-EBV transcripts, and LMP1 and p53 proteins. This B-cell CD30+ EBV+ phenotype contrasts with cutaneous lymphoma in immunocompetent patients. Human herpesvirus 8 was not involved in lymphomagenesis since its sequences were detected in a single patient with Kaposi's sarcoma and Castleman's disease. These lymphomas occurred in severely immunocompromised patients with a low CD4 count. Death was due to immunodepression rather than to lymphoma spread, suggesting avoiding aggressive immunosuppressive treatment in such patients.

Adult↗
PubMed1998

Gaze discrimination is unimpaired in schizophrenia.

Interpersonal communication is largely dependent on interpretation of facial expression and emotion. Difficulties in face processing, and more specifically in gaze discrimination, have been described in schizophrenic patients. According to Baron-Cohen (Mindblindness. M.I.T. Press, Cambridge, MA, 1995), gaze discrimination relies on the functioning of a specific cognitive module, the Eye Direction Detector (EDD). It has been proposed [Rosse et al. (1994) Gaze discrimination in patients with schizophrenia: preliminary report. American Journal of Psychiatry 151, 919-921] that an impairment in gaze discrimination is present in schizophrenia, and plays a fundamental role in inducing the paranoid symptoms reported by many patients. However, in the previous studies, gaze direction detection and interpretation of gaze have never been completely dissociated. The present experiment attempts to test the schizophrenics' skill in a simple gaze direction detection task. A series of photographic portraits of models looking at different directions have been presented to 22 schizophrenic patients and 36 control subjects. For each portrait subjects were asked to determine whether gaze was directed to the right or to the left by pressing a keyboard key. A forced choice paradigm was used. No differences were reported between schizophrenic patients and control subjects. That is, in the present paradigm, schizophrenic patients did not show any specific impairment in detecting the direction of gaze of the portraits. The results are discussed according to the notion that a dissociation is present in schizophrenia between implicit and explicit processes. The present case illustrates how the more automatic elementary functions, such as the detection of gaze direction, may be spared in schizophrenic patients, whereas explicit cognitive functions are likely more affected.

Adult↗
PubMed1998

Prevalence of human herpesvirus 8 infection measured by antibodies to a latent nuclear antigen in patients with various dermatologic diseases.

BACKGROUND: Human herpesvirus 8 (HHV-8) has been detected in all epidemiological forms of Kaposi sarcoma (KS). The role of HHV-8 in dermatologic diseases other than KS is controversial. Some studies based on polymerase chain reaction findings suggest an association between HHV-8 and epithelial tumors of the skin, lymphoproliferative disorders, or pemphigus. OBJECTIVE: To assess the prevalence of antibodies against a latent nuclear antigen of HHV-8 in patients with various dermatologic diseases. DESIGN: An indirect immunofluorescence assay was used to search for HHV-8 antibodies. SETTING: Ambulatory or hospitalized patients from a university hospital associated with a research laboratory. PATIENTS: Eighty-three patients with various non-KS dermatologic diseases and 16 patients with KS who were seronegative for the human immunodeficiency virus. Controls were 100 healthy subjects living in the same area. RESULTS: Antibodies to HHV-8 were found in 100% (16/16) of the patients with KS and 3.6% (3/83) of the patients with non-KS dermatologic diseases: 1 patient with pemphigus vulgaris, 1 with discoid lupus erythematosus, and 1 with bullous pemphigoid. The prevalence of antibodies to HHV-8 in controls was 2% (2/100) and was not significantly different than the prevalence in patients with dermatologic diseases other than KS (P =.28). CONCLUSIONS: Our serologic study confirms the higher prevalence of HHV-8 antibodies in patients with KS and demonstrates that contrary to other human herpesviruses, HHV-8 is not a ubiquitous virus in France. We could not determine any causal association between HHV-8 and pemphigus or lymphoproliferative disorders of the skin.

Adult↗
PubMed1997

Looking for the agent: an investigation into consciousness of action and self-consciousness in schizophrenic patients.

The abilities to attribute an action to its proper agent and to understand its meaning when it is produced by someone else are basic aspects of human social communication. Several psychiatric syndromes, such as schizophrenia, seem to lead to a dysfunction of the awareness of one's own action as well as of recognition of actions performed by others. Such syndromes offer a framework for studying the determinants of agency, the ability to correctly attribute actions to their veridical source. Thirty normal subjects and 30 schizophrenic patients with and without hallucinations and/or delusional experiences were required to execute simple finger and wrist movements, without direct visual control of their hand. The image of either their own hand or an alien hand executing the same or a different movement was presented on a TV-screen in real time. The task for the subjects was to discriminate whether the hand presented on the screen was their own or not. Hallucinating and deluded schizophrenic patients were more impaired in discriminating their own hand from the alien one than the non-hallucinating ones, and tended to misattribute the alien hand to themselves. Results are discussed according to a model of action control. A tentative description of the mechanisms leading to action consciousness is proposed.

Adult↗