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Biomedical subjects

L Cohen

Publications and source records attributed to L Cohen.

At least 19 recordsLinked to original sources
PubMed2006

Polymorphisms in the dopamine D4 receptor gene (DRD4) contribute to individual differences in human sexual behavior: desire, arousal and sexual function.

Although there is some evidence from twin studies that individual differences in sexual behavior are heritable, little is known about the specific molecular genetic design of human sexuality. Recently, a specific dopamine D4 receptor (DRD4) agonist was shown in rats to induce penile erection through a central mechanism. These findings prompted us to examine possible association between the well-characterized DRD4 gene and core phenotypes of human sexual behavior that included desire, arousal and function in a group of 148 nonclinical university students. We observed association between the exon 3 repeat region, and the C-521T and C-616G promoter region SNPs, with scores on scales that measure human sexual behavior. The single most common DRD4 5-locus haplotype (19%) was significantly associated with Desire, Function and Arousal scores. The current results are consistent with animal studies that show a role for dopamine and specifically the DRD4 receptor in sexual behavior and suggest that one pathway by which individual variation in human desire, arousal and function are mediated is based on allelic variants coding for differences in DRD4 receptor gene expression and protein concentrations in key brain areas.

Family Health↗
PubMed2006

[Obstetrical management of patients at risk of neonatal lupus syndrome: review of the literature].

Fetuses and infants of women with anti-SSA/Ro and anti-SSB/La antibodies are at risk of neonatal lupus syndrome, featuring skin lesions, hematological and hepatic disorders, and congenital heart block (CHB) in the absence of severe cardiac malformation. The prevalence of CHB in newborns of anti-SSA/Ro positive women with known connective tissue disease is 1 to 2% and the risk of recurrence ranges from 10 to 17%. CHB is definitive and is associated with significant morbidity (pacemaker must be implanted in 2/3 of cases) and mortality (16 to 19%). Myocardial involvement may either be associated or appear subsequently. Other manifestations are discussed. For anti-SSA/Ro positive pregnant women, echocardiograms should be performed every 2 weeks from 16 to 24 weeks of gestation, and every week in case of past history of CHB. Electrocardiogram should be performed in the first days of life for all children to detect incomplete CHB. Therapy for CHB detected in utero is based on fluorinated steroids, especially betamethasone. Its efficiency is variable.

Antibodies, Antinuclear↗
PubMed2005

[A clinical study of the number processing system: decimal size effects on reading numbers in patients with left parieto-occipital gliomas].

An increasing number of studies are focusing on the anatomo-functional organisation of number processing and some cognitive models have been recently developed. Nevertheless, relationships between areas implicated in number processing, and language areas and circuits remain unclear. Recently, Dehaene and Cohen, in their "triple-code model of number processing", (Dehaene and Cohen, 1995) distinguished two alternative number representation and processing systems: one depending on verbal processes, the other representing a quantity manipulation. According to this model, the retrieval of "arithmetical facts" (AF), learned by rote at school and memorised in a verbal form (such as the multiplication table or simple addition problems) can be considered as a verbal automatism; conversely, subtraction problems, which require mental manipulation of the quantities, represent an abstract, semantic elaboration: "Actual Calculation" (AC). The anatomical correlate of the retrieval of AF (depending on automatic verbal associations) seems to correspond to the left-hemispheric perisylvian areas, while impairment of the actual calculation (AC) depends on the intraparietal region, particularly in the left dominant hemisphere. The present study describes the neuropsychological assessment of three patients, tested after surgery for left parieto-occipital tumors. Two of them were affected by an anaplasic glioma, the third by a low-grade glioma. The cognitive evaluation included: words of Rey, numeral (directed and reversed) span, reading of "simple" numbers (from 1 to 10) and of "complex" numbers (many decimals), writing (dictation) and reading a standard text, finger denomination and right-left distinction. All patients showed language disturbances, dysgraphia and severe dyslexia. In reading numbers, we identified two types of errors: lexical and syntactic. "Lexical errors" consisted in a wrong choice among words in the number's lexicon. For instance, all patients made errors in reading "complex" numbers composed by many decimals, switching single numbers but respecting the decimal size and the structure of the whole number (such as 69107 instead of 68107). On the other hand, only one patient committed syntactic errors, misunderstanding the decimal size and the structure of the number. We considered lexical errors as verbal errors, and syntactic errors as semantic errors, affecting the notion of quantity. We tried to explain verbal disturbances as well as lexical errors as a consequence of lesion of the left-hemispheric perisylvian areas, while syntactic errors as a consequence of impairment of the intraparietal region.

Adult↗
PubMed2005

Recombinant NY-ESO-1 cancer antigen: production and purification under cGMP conditions.

The cancer-testis antigen, NY-ESO-1, has been engineered into a bacterial expression plasmid which incorporates a His6-tag. The plasmid was transfected into E. coli strain BL21 and Master and Working cell banks generated from this expression system. Three 15-litre fermentations were performed under cGMP (code of Good Manufacturing Practice) conditions and the crude NY-ESO-1 tagged protein isolated as solubilised inclusion bodies. A three-step cGMP chromatography process (immobilised metal affinity, anion exchange, and hydrophobic interaction) was utilised to purify the protein. The purified NY-ESO-1 is being used in early stage human cancer vaccine trials in Australia and the U.S.A.

Antigens, Neoplasm↗
PubMed2004

Brain anatomy in Turner syndrome: evidence for impaired social and spatial-numerical networks.

Analysis of brain structure in Turner syndrome (TS) provides the opportunity to identify the consequences of the loss of one X chromosome on brain anatomy and to characterize the neural bases underlying the specific cognitive profile of TS subjects which includes deficits in spatial-numerical processing and social cognition. Fourteen subjects with TS and fourteen controls were investigated using voxel-based analysis of high resolution anatomical and diffusion tensor images and using sulcal morphometry. The analysis of anatomical images provided evidence for macroscopical changes in cortical regions involved in social cognition such as the left superior temporal sulcus and orbito-frontal cortex and in a region involved in spatial and numerical cognition such as the right intraparietal sulcus. Diffusion tensor images showed a displacement of the grey-white matter interface of the left and right superior temporal sulcus and revealed bilateral microstructural anomalies in the temporal white matter. The analysis of fiber orientation suggests specific alterations of fiber tracts connecting posterior to anterior temporal regions. Last, sulcal morphometry confirmed the anomalies of the left and right superior temporal sulci and of the right intraparietal sulcus. Our results thus provide converging evidence of regionally specific structural changes in TS that are highly consistent with the hallmark symptoms associated with TS.

Adolescent↗
PubMed2004

Letter binding and invariant recognition of masked words: behavioral and neuroimaging evidence.

Fluent readers recognize visual words across changes in case and retinal location, while maintaining a high sensitivity to the arrangement of letters. To evaluate the automaticity and functional anatomy of invariant word recognition, we measured brain activity during subliminal masked priming. By preceding target words with an unrelated prime, a repeated prime, or an anagram made of the same letters, we separated letter-level and whole-word codes. By changing the case and the retinal location of primes and targets, we evaluated the invariance of those codes. Our results indicate that an invariant binding of letters into words is achieved unconsciously through a series of increasingly invariant stages in the left occipito-temporal pathway.

Adult↗
PubMed2003

Postoperative speech disorder after medial frontal surgery: role of the supplementary motor area.

BACKGROUND: Patients undergoing surgical resection of medial frontal lesions may present transient postoperative speech disorders that remain largely unpredictable. OBJECTIVE: To relate the occurrence of this speech deficit to the specific surgical lesion of the supplementary motor area (SMA) involved during language tasks using fMRI. METHODS: Twelve patients were studied using a verbal fluency task before resection of a low-grade glioma of the medial frontal lobe and compared with six healthy subjects. Pre- and postoperative MR variables including the hemispheric dominance for language, the extent of SMA removal, and the volume of resection were compared to the clinical outcome. RESULTS: Following surgery, 6 of 12 patients presented speech disorders. The deficit was similar across patients, consisting of a global reduction in spontaneous speech, ranging from a complete mutism to a less severe speech reduction, which recovered within a few weeks or months. The occurrence of the deficit was related to the resection of the activation in the SMA of the dominant hemisphere for language (p < 0.01). Increased activation in the SMA of the healthy hemisphere on the preoperative fMRI was observed in patients with postoperative speech deficit. CONCLUSIONS: fMRI is able to identify the area at risk in the SMA, of which resection is related to the occurrence of characteristic transient postoperative speech disorders. Increased SMA activation in the healthy hemisphere suggested that a plastic change of SMA function occurred in these patients.

Adult↗
PubMed2003

A jeep trip with young adult cancer survivors: lessons to be learned.

The paper describes major areas of concern and preferred coping mechanisms among 17 young survivors of childhood cancer who participated in an 8-day adventure jeep trip in Greece. The paper also deals with various aspects of "adventure therapeutic activity." The participants were videotaped and interviewed during and after the trip. The data gathered were studied through a process of content analysis. Survivors' main areas of concern included: coping with uncertainty, dependency versus autonomy, social exclusion, separation processes, body image, intimacy, sexuality and fertility, and occupation. Preferred coping styles included use of humor, religious beliefs, cognitive reframing, and use of imagination. The trip provided the young adults with an opportunity for physical challenges, and they reported improvements in self-confidence, independence, and social contacts. The trip served as a catalyst for further group activities and group support. An adventure trip seems to be a suitable therapeutic milieu for young adult cancer survivors, where they can profit from a nurturing setting in which rehabilitation-promoting resources are available. It still remains to be seen which components of such an activity are more health promoting, what contraindications there could be, if any, for participation in such a trip, and what role health professionals should play in this kind of activity.

Adaptation, Psychological↗
PubMed2003

Aberrant T-cell receptor signalling of interferon-gamma- and tumour necrosis factor-alpha-producing cytotoxic CD8+ Vdelta1/Vbeta16 T cells in a patient with chronic neutropenia.

We previously found that the peripheral blood (PB) mononuclear cells (MCs) (PBMCs) of a patient with chronic neutropenia contained an expanded population of cytotoxic CD8+ T cells using a variable (V) region delta1 gene product in the T-cell receptor-alpha (TCR-alpha) polypeptide [Vdelta1-constant(C)alpha+ T cells]. Sequencing of polymerase chain reaction (PCR) amplification products have now revealed a productive Vdelta1/joining (J)alphaIGRJa03/Calpha rearrangement of the TCR-alpha gene, predominantly associated with a Vbeta16/Dbeta2.1/Jbeta2.1/Cbeta2 TCR-beta gene, in these cells. Furthermore, we detected a markedly deficient proliferative response of the patient PBMCs to triggering with monoclonal antibodies (MoAbs) to the CD3 molecule, contrasting with a substantial response to the Vbeta3, 12, 14, 15, 17 and 20-specific staphylococcal enterotoxin B (SEB) superantigen, suggesting defective TCR-mediated activation of the Vdelta1+/Vbeta16+ clone. Moreover, whereas triggering of Vdelta1- T cells cultured with interleukin-2 (IL-2) by MoAb to the CD3 molecule enhanced proliferation, Vdelta1-Calpha+ T cells were inhibited by MoAbs to either CD3 or Vdelta1. Vdelta1-Calpha+ T-cell clones spontaneously secrete interferon-gamma (IFN-gamma) and were further induced to release tumour necrosis factor (TNF-alpha) when triggered by anti-CD3 plus phorbol ester. Aberrant signalling by the clonotypic TCR together with the functional properties of the CD8+ Vdelta1+/Vbeta16+ clone may thus contribute to the immunohaematological abnormalities observed in this patient.

Amino Acid Sequence↗
PubMed2003

New insights into septal anterior wall motion velocities at end-systole in normal and hypertrophied left ventricles.

AIMS: It was two-fold (1) to define tissue Doppler echocardiographic characteristics of the end-systolic septal anterior motion: passive due to heart translation, or active motion free of translational effects, substantiated by a myocardial velocity gradient. (2) to specify the temporal features of this septal anterior motion on normal and hypertrophied left ventricles since it occurs while the posterior wall contracts during late ejection. METHODS AND RESULTS: Myocardial velocity gradient was calculated during the anterior motion in simultaneously colour M-mode imaged septal and posterior walls of 21 controls (49+/-12 years) and 17 patients (49+/-13 years) with left ventricle hypertrophy. Timings of septal motion were compared with flow and posterior wall motion. In controls, septal anterior motion started prior to, and overlapped the end of subaortic flow and that of the posterior wall anterior motion. Myocardial velocity gradient was found, exceeding that at the posterior wall (2.5+/-1.6 vs 0.9+/-0.5s(-1), P=0.001). In patients, septal myocardial velocity gradient was lower than in controls (1.2+/-1.04 s(-1)P=0.006). The anterior motion had a longer duration than in controls (75+/-37 vs 50+/-17ms, P=0.003). Myocardial velocity gradient and duration were correlated with septal thickness (P=<0.01). CONCLUSIONS: The septal anterior motion was active. Patients showed a decreased myocardial velocity gradient, while wall asynchrony increased. Unusual higher septal than posterior wall systolic velocities at tissue Doppler echocardiography may suggest a relaxation pattern, in spite of its end-systolic onset.

Adult↗
PubMed2003

Visual word recognition in the left and right hemispheres: anatomical and functional correlates of peripheral alexias.

According to a simple anatomical and functional model of word reading, letters displayed in one hemifield are first analysed through a cascade of contralateral retinotopic areas, which compute increasingly abstract representations. Eventually, an invariant representation of letter identities is created in the visual word form area (VWFA), reproducibly located within the left occipito-temporal sulcus. The VWFA then projects to structures involved in phonological or lexico-semantic processing. This model yields detailed predictions on the reading impairments that may follow left occipitotemporal lesions. Those predictions were confronted to behavioural, anatomical and functional MRI data gathered in normals and in patients suffering from left posterior cerebral artery infarcts. In normal subjects, alphabetic stimuli activated both the VWFA and the right-hemispheric symmetrical region (R-VWFA) relative to fixation, but only the VWFA showed a preference for alphabetic strings over simple chequerboards. The comparison of normalized brain lesions with reading-induced activations showed that the critical lesion site for the classical syndrome of pure alexia can be tightly localized to the VWFA. Reading impairments resulting from deafferentation of an intact VWFA from right- or left-hemispheric input were dissected using the same methods, shedding light on the connectivity of the VWFA. Finally, the putative role of right-hemispheric processing in the letter-by-letter reading strategy was clarified. In a letter-by-letter reader, the R-VWFA assumed some of the functional properties normally specific to the VWFA. These data corroborate our initial model of normal word perception and underline that an alternative right-hemispheric pathway can underlie functional recovery from alexia.

Adult↗
PubMed2003

Therapeutic vaccine to control stromal tumor-induced immunosuppression in human uterine cervixc cancer.

Cancer cells may escape immune surveillance by secreting in their microenvironment soluble factors that may locally paralyze the stromal effector immune cells. In the human uterine cervix cancer, HPV-16 E7 protein, released in the stroma, should contribute to cancer cells immune escape since this protein inhibits the cellular immune response to recall antigens or alloantigens and strongly enhances the release of immunosuppressive cytokines by APCs. This prompted us to prepare a therapeutic vaccine triggering anti-E7 neutralizing Abs to antagonize the E7-induced stromal immunosuppressive effects and allow cellular immune reaction towards cancer cells including specific CTLs, induced by conventional vaccine, to be effective. Since HPV-16 is a mucosotropic virus, this therapeutic vaccine has been prepared to generate systemic as well as mucosal immunity.

Animals↗
PubMed2002

Transcranial magnetic stimulation for the treatment of seizures: a controlled study.

OBJECTIVE: To perform a controlled trial of transcranial magnetic stimulation (TMS). METHODS: Twenty-four patients with localization-related epilepsy were randomized to blinded active or placebo stimulation. Weekly seizure frequency was compared for 8 weeks before and after 1 week of 1-Hz TMS for 15 minutes twice daily. RESULTS: When the 8-week baseline and post-stimulation periods were compared, active patients had a mean seizure frequency reduction of 0.045 +/- 0.13 and sham-stimulated control subjects -0.004 +/- 0.20. Over 2 weeks, actively treated patients had a mean reduction in weekly seizure frequency of 0.16 +/- 0.18 and sham-stimulated control subjects 0.01 +/- 0.24. Neither difference was significant. CONCLUSION: The effect of TMS on seizure frequency was mild and short lived.

Adult↗
PubMed2002

Visualizing the neural bases of a disconnection syndrome with diffusion tensor imaging.

Disconnection syndromes are often conceptualized exclusively within cognitive box-and-arrow diagrams unrelated to brain anatomy. In a patient with alexia in his left visual field resulting from a posterior callosal lesion, we illustrate how diffusion tensor imaging can reveal the anatomical bases of a disconnection syndrome by tracking the degeneration of neural pathways and relating it to impaired fMRI activations and behavior. Compared to controls, an abnormal pattern of brain activity was observed in the patient during word reading, with a lack of activation of the left visual word form area (VWFA) by left hemifield words. Statistical analyses of diffusion images revealed a damaged fiber tract linking the left ventral occipito-temporal region to its right homolog across the lesioned area of corpus callosum and stopping close to the areas found active in fMRI. The behavioral disconnection syndrome could, thus, be related functionally to abnormal fMRI activations and anatomically to the absence of a connection between those activations. The present approach, based on the "negative tracking" of degenerated bundles, provides new perspectives on the understanding of human brain connections and disconnections.

Adult↗
PubMed2002

Analysis of mismatch repair defects in the familial occurrence of lymphoma and colorectal cancer.

Hereditary non-polyposis colon cancer (HNPCC) is an autosomal dominant disorder featuring familial clustering of colorectal and/or endometrial cancer, and other malignancies. Except for a rare case report, Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) have not been considered part of HNPCC. Recent murine models for HNPCC have shown an increased incidence of B- and T-cell lymphoma, as well as tumors of the gastrointestinal tract and other organ systems, involving defects in genes resulting in faulty mismatch repair (MMR) of DNA. These MMR genes include MLH1, MSH2, MSH3, MSH6, PMS1 and PMS2. We sought to analyze the occurrence of NHL and HD in families with clusters of colorectal cancers (CRC). Probands from 21 kindreds were classified as HNPCC (3), HNPCC-like (5), and HNPCC-variant (13); seen and followed by Clinical Genetics at Memorial Hospital the kindreds were assessed for the occurrence of NHL or HD. Of the 21 pedigrees, a total of 37 patients were identified who were diagnosed with leukemia, lymphoma, or HD. Fourteen of the 37 patients with a diagnosis of NHL or HD were further classified and showed varying histologies ranging from chronic lymphocytic leukemia/small lymphocytic lymphoma (2), mycosis fungoides (1), follicular lymphoma (1), extranodal marginal zone lymphoma of MALT type (2), diffuse large B-cell lymphoma (4), nodular sclerosis HD (3), and mixed cellularity HD (1). Microsatellite instability studies were performed on 6 cases but none showed evidence of replication error repair defects. Immunohistochemical stains performed on paraffin sections from these 6 representative cases showed differential protein expression of MLH1, MSH2, MSH6, and PMS2 when compared to normal reactive tissues from the same patient but showed no significant differences when compared to controls of non-familial, sporadic lymphomas. These results suggest that lymphomas arising in the setting of familial CRC do not bear the molecular hallmarks of HNPCC. Further studies are needed to explain the differential patterns of expression of RER-associated proteins in lymphomas, as well as the association of lymphomas and possibly renal cell cancers in a subset of kindreds in which CRC clustering is evident.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Quality of life in patients with malignant melanoma participating in a phase I trial of an autologous tumour-derived vaccine.

Quality of life (QOL) plays an increasingly important role in the decision-making process and the ultimate acceptability of particular treatments for patients. We prospectively examined QOL in patients with advanced melanoma treated with surgery followed by heat-shock protein peptide complex 96 (HSPPC-96) vaccine, an active, patient-specific immunotherapy. QOL (the RAND 36-Item Health Survey; SF-36) and cancer-related intrusive thoughts (Impact of Event Scale; IES) were measured at the start of treatment, 3 weeks later on the final day of treatment, and at follow-up 1 month later in 30 patients with stage III or IV malignant melanoma. Mixed model analyses revealed no significant change over time in the SF-36 Physical or Mental Component Summary scores, or the IES scores. In comparisons with other populations, at the 1 month follow-up assessment, melanoma patients reported similar QOL to patients with metastatic renal cell carcinoma who received the same treatment, significantly worse QOL on the physical dimensions and similar QOL on the psychosocial and emotional dimensions compared with the general population, similar QOL to patients with type II diabetes, and significantly better QOL on all three dimensions than patients with congestive heart failure. There was also a significant negative association between IES scores at baseline and mental health scores at each time point ( < 0.002 for all). QOL remained stable during treatment with the HSPPC-96 vaccine. In addition, patients who reported high levels of cancer-related intrusive thoughts at the start of treatment reported worse mental health at the end of the treatment.

Adult↗
PubMed2002

gammadelta T cell subsets in patients with arthritis and chronic neutropenia.

BACKGROUND: An abnormal distribution of subsets of gammadelta T cells, which are a component of the inflammatory infiltrate in arthritic synovium, has been demonstrated in the peripheral blood (PB) of patients with arthritis and neutropenia. OBJECTIVE: To evaluate whether the clinical manifestations of patients with arthritis and neutropenia are related to the specific gammadelta T cell subset predominant in the PB. METHODS: Flow cytometry of PB lymphocytes in six consecutive patients with chronic neutropenia and arthritis was performed. Variable (V) gamma and delta gene families were analysed by polymerase chain reaction. cDNA was subjected to direct automated sequencing of T cell receptor (TCR) genes. RESULTS: Three patients had non-deforming and non-erosive rheumatoid factor (RF)(+) polyarticular rheumatoid arthritis, RF(+) oligoarticular arthritis, or RF(-) non-deforming oligoarticular psoriatic arthritis with persistent expansions of Vgamma1(+)/Vdelta2(+), Vgamma2(+)/Vdelta2(+), or Vgamma1(+)/Vdelta (undetermined (2- 1-)) T cells, respectively. The other three patients, without persistent expansion of gammadelta T cells, had either non-deforming and non-erosive oligo- or polyarthritis with a balanced distribution of several Vdelta and Vgamma genes, or severe erosive RF(+) arthritis with deficiency of all but Vgamma1(+)/Vdelta1(+) T cells. CONCLUSIONS: gammadelta T cell lymphoproliferations in chronic neutropenia and arthritis use different Vgamma and Vdelta gene families, often forming T cell receptor (TCR) structures that are infrequent in normal adult PB. Arthritis with Vgamma1(+)/Vdelta2(+), Vgamma2(+)/Vdelta2(+), or Vgamma1(+)/Vdelta2(-)/Vdelta1(-) gammadelta T cells in the PB is non-deforming and non-erosive, suggesting a protective effect of these cells, as opposed to a more pathogenic contribution of Vgamma1(+)/Vdelta1(+) cells.

Aged↗