A new CX3 CR1 genotype with implications for HIV disease progression.
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Biomedical subjects
Publications and source records attributed to N Franck.
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Autoantibodies characteristic of autoimmune bullous skin diseases (AIBDs) can be detected by immunoblotting on epidermal, dermal, or bovine muzzle extracts. However, none of those substrates contain all the autoantigens involved in AIBDs, and the diagnosis requires the use of various substrates. Human keratinocytes were cultured under such conditions that they expressed the major autoantigens associated with AIBDs. Forty-two sera with antiepidermal antibodies were immunoblotted on the keratinocyte extract. Bands corresponding to desmoglein III, desmoglein I, BPAg2, BPAg1, and type VII collagen were found in 38 sera. Desmoplakins I and II were revealed by specific monoclonal antibodies. A review of the patients' charts showed a perfect correlation between the blots and the diagnoses of pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, cicatricial pemphigoid, and epidermolysis bullosa acquisita. Four sera revealing no band typical of AIBD were from patients with no autoimmune skin disease. Therefore, a single extract of keratinocytes can be used for the differential diagnosis of AIBDs.
Human herpesvirus 8 (HHV-8) is a new virus which has been reported in Kaposi's sarcoma and some lymphoproliferative disorders such as Castleman's disease and body-cavity-based lymphoma. Because HHV-8 shares homology with Epstein-Barr virus (EBV), we searched for the presence of HHV-8 DNA sequences in various cutaneous T- and B-cell lymphoma by the polymerase chain reaction (PCR). Forty-seven HIV-negative patients with cutaneous lymphoma or large plaque parapsoriasis were enrolled in the study. For the detection of HHV-8 DNA sequences we used PCR followed by a hybridization with a digoxigenin-labelled probe and nested-PCR. HHV-8 DNA sequences could only be detected in a patient with large plaque parapsoriasis. Our study does not suggest any direct implication of HHV-8 in the pathogenesis of most cutaneous lymphoma. Serological studies will be helpful to appreciate if there is an epidemiological link between HHV-8 and cutaneous lymphomas.
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