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Biomedical subjects

L Cohen

Publications and source records attributed to L Cohen.

At least 145 records · Page 8Linked to original sources
PubMed1996

Brain processing of native and foreign languages.

We used positron emission tomography to study brain activity in adults while they were listening to stories in their native language, in a second language acquired after the age of seven, and in a third unknown language. Several areas, similar to those previously observed in monolinguals, were activated by the native but not by the second language. Both the second and the unknown language yielded distinct left-hemispheric activations in areas specialized for phonological processing, which were not engaged by a backward speech control task. These results indicate that some brain areas are shaped by early exposure to the maternal language, and are not necessarily activated by the processing of a second language to which they have been exposed for a limited time later in life.

Adult↗
PubMed1996

Purification and characterization of a novel restricted antigen expressed by normal and transformed human colonic epithelium.

A cell surface antigen that is expressed by normal and 95% of transformed colonic epithelium and is recognized by the monoclonal antibody A33 (Welt, S., Divgi, C. R., Real, F. X., Yeh, S. D., Garin-Chesa, P., Finstad, C. L., Sakamoto, J., Cohen, A., Sigurdson, E. R., Kemeny, N., Carswell, E. A., Oettgen, H. F., and Old, L. J. (1990) J. Clin. Oncol. 8, 1894-1906) has been purified to homogeneity from the human colonic carcinoma cell line LIM1215. The A33 protein was purified from Triton X-114 extracts of LIM1215 cells under nondenaturing conditions. These extracts were applied sequentially to Green-Sepharose HE-4BD, Mono-Q HR 10/10, Superose 12 HR 10/30, and micropreparative Brownlee Aquapore RP 300. The purification was monitored by biosensor analysis using surface plasmon resonance detection with a F(ab')2 fragment of the humanized A33 monoclonal antibody immobilized on the sensor surface and Western blot analysis following SDS-polyacrylamide gel electrophoresis (PAGE) under nonreducing conditions using humanized A33 monoclonal antibody. The purified A33 antigen has a Mr on SDS-PAGE of 43,000 under nonreducing conditions. By contrast, the purified protein displayed a Mr of approximately 180,000 under native conditions on both size exclusion chromatography and native PAGE, possibly due to the formation of a homotetramer. N-terminal amino acid sequence analysis of the purified protein identified 34 amino acid residues of a unique sequence: ISVETPQDVLRASQGKSVTLPXTYHTSXXXREGLIQWD. A polyclonal antibody was raised against a synthetic peptide corresponding to residues 2-20 of this sequence. The antipeptide serum recognized the purified protein using Western blot analysis under both nonreducing (Mr 43,000) and reducing (Mr 49,000) conditions.

Amino Acid Sequence↗
PubMed1996

Effects of P2 cleavage site mutations on poliovirus polyprotein processing.

The poliovirus genome comprises a single open reading frame which is translated to give one large polyprotein. The proteolytic cascade involved in the processing of this polyprotein is not yet understood in full detail,particularly concerning the processing of P2-P3, the precursor to the viral nonstructural polypeptides, 2A, 2B, 2C, 3A, 3B, 3C, and 3D. To investigate the possibility that the cleavage events within P2 and at the 2C/3A junction occur in an ordered fashion, we used oligonucleotide-directed mutagenesis of poliovirus cDNA to modify the 3C(prn)-mediated cleavage sites. The Gin residue of the Gin-Gly sequence at the 2A/2B, 2B/2C, and 2C/3A junctions in the poliovirus polyprotein was replaced by Asn, Glu, Asp, or Lys. The effects of each of these substitutions were studied in vivo after transfection onto HeLa cells and in vitro in a cell-free translation assay, using full-length mutated RNA transcripts. Only the mutant with the Glu-Gly sequence at the 2C/3A junction was viable. Analysis of the in vitro processing profiles showed that the efficiency of the 3C protease cleavage at any of the sites in P2 was in the following order: Gin-Gly > Glu-Gly > Asn-Gly. No cleavage could be detected with the Asp-Gly or Lys-Gly sequence at any junction. Lack of 2A/2B or 2B/2C cleavage had no consequences on the cleavage efficiency at other Gin-Gly sites in the polyprotein. Abolition of cleavage at the 2C/3A junction did not prevent the generation of the 2A, 2B, and 3CD polypeptides. Thus, these polypeptides. Thus, these polypeptides could be produced independently of the generation of the P2 and P3 precursors.

Binding Sites↗
PubMed1996

m-Chlorophenylpiperazine challenge in borderline personality disorder: relationship of neuroendocrine response, behavioral response, and clinical measures.

We have previously found that a subgroup of patients with impulsive personality disorders respond to m-chlorophenylpiperazine (m-CPP) administration with a distinctive spacy/high behavioral reaction and with increased cortisol responses. In this report we analyzed the relationship between behavioral and neuroendocrine responses to m-CPP in an enlarged sample of patients with borderline personality disorder (BPD). We also assessed the association of behavioral and neuroendocrine responses with clinical symptoms and with m-CPP blood levels. We found that in BPD patients the presence of a spacy/high behavioral response was significantly associated with increased prolactin and cortisol responses to m-CPP. In BPD patients increased m-CPP levels were significantly associated with neuroendocrine hypersensitivity and with a spacy/high behavioral response, while in controls increased m-CPP levels were not significantly associated with neuroendocrine hypersensitivity but were significantly associated with dysphoric behavioral responses. Taken together with previous work on m-CPP in obsessive-compulsive disorder, these results are partially consistent with the hypothesis that compulsive and impulsive symptoms fall at opposite ends of a phenomenologic and neurobiologic spectrum.

Adult↗
PubMed1996

The mental representation of hand movements after parietal cortex damage.

Recent neuroimagery findings showed that the patterns of cerebral activation during the mental rehearsal of a motor act are similar to those produced by its actual execution. This concurs with the notion that part of the distributed neural activity taking place during movement involves internal simulations, but it is not yet clear what specific contribution the different brain areas involved bring to this process. Here, patients with lesions restricted to the parietal cortex were found to be impaired selectively at predicting, through mental imagery, the time necessary to perform differentiated finger movements and visually guided pointing gestures, in comparison to normal individuals and to a patient with damage to the primary motor area. These results suggest that the parietal cortex is important for the ability to generate mental movement representations.

Adult↗
PubMed1996

Issue of fraud raised as MD self-referral comes under spotlight in Ontario.

Physician self-referral, fraud and conflict of interest are causing increasing concern in Ontario, where 100 physicians are now being investigated for such activities. These and related offences recently have been pushed to the top of the agenda of the provincial college, which recently asked physicians to vote on what kind of self-referral regulations they prefer.

Disclosure↗
PubMed1996

Induction of antibodies reactive with GM2 ganglioside after immunization with lipopolysaccharides from Camplyobacter jejuni.

Ganglioside GM2, expressed on the surface of some human cancers, is a promising target for immune therapy, since GM2 antibodies are cytotoxic, can be induced in humans by vaccination, and the presence of GM2 antibodies is associated with a better prognosis in melanoma patients. In our efforts to induce long-lived, cytotoxic GM2 antibodies, we investigated lipopolysaccharides (LPS) containing "GM2-like" oligosaccharides. LPS were prepared from Campylobacter jejuni serotypes O:1, O:23, or O:36 (all sharing the oligosaccharide structure GalNAcbeta1-4Gal(113NeuAc)-Hex with ganglioside GM2), and tested for their ability to induce GM2-reactive antibodies. Immunization of NZW rabbits (2 animals per vaccine) with LPS from C. jejuni serotype O:1 in Freund's adjuvant resulted in production of high-titer IgG antibodies reactive with purified bovine brain GM2 in ELISA, dot-blot immune strains and immune thin-layer chromatography, and with GM2 derived from various human tumors by immune thin-layer chromatography. These rabbit antibodies bound to cancer cell lines expressing GM2 on their cell surface, as determined by mixed hemadsorption assays, mediating strong antibody-dependent cellular cytotoxicity (ADCC) with tumor cells expressing cell-surface GM2. Antibodies induced by vaccination with C. jejuni serotype O:1 were higher-titer (IgG ELISA titer > 1:60,000) than antibodies induced by immunization with purified GM2 (IgG ELISA titer > 1:200). Immunization with LPS from C. jejuni serotype O:36 resulted in production of moderately high-titer IgM and low-titer IgG GM2 antibodies. Immunization with LPS from C. jejuni serotype O:23 did not elicit GM2-reactive antibodies. No clinical symptoms were observed in animals immunized with these LPS preparations, with purified GM2 ganglioside, or with LPS derived from C. jejuni serotype O:19 (containing a GM1-like oligosaccharide). Our results indicate that lipopolysaccharides sharing carbohydrate epitopes with gangliosides may be useful immunogens for inducing antibodies to ganglioside antigens.

Animals↗
PubMed1996

Quality of life in multiple sclerosis: the disability and impact profile (DIP).

Seventy-three Dutch and Flemish patients with definite multiple sclerosis (MS) were assessed by means of the Disability and Impact Profile (DIP), which is a 2 x 39 item, self-administered questionnaire with parallel questions about disabilities and their importance for or impact on the patient, resulting in a profile of weighted scores. It was designed as a tool for clinical assessment of quality of life (QoL) domains in MS patients. Group data showed more than 50% loss on weighted scores for "walk", "clean home", "work" and "worry about deterioration". In individual patients a median of 7 (range 0-23) major disruptions of quality of life (MD-QoL: loss on weighted score more than 50%) was found. Prevalence of MD-QoL in more than 10% of the patients was found for as many as 31 disabilities and > 50% for 3 ("clean home", "work" and "worry about deterioration"). Results in the MS group were compared with available data from 25 patients with rheumatoid arthritis (RA) and 25 patients with a spinal cord lesion (SCl). Weighted scores of "read", "memory" and "concentration" were significantly lower in the MS group than in the RA and SCl groups. Significantly lower weighted scores in both the MS and RA groups were found for "worry about deterioration", "physical endurance", "clean home", "work", "see" and "write". In conclusion, major disruptions in many domains of QoL were found in MS patients. Weighted score profiles for MS were in accordance with clinical manifestations. Unlike Kurtzke's Extended Disability Status Scale, DIP assesses a wide range of potentially MS-affected human activities, and also takes into account the subjective perception of disabilities.

Adult↗
PubMed1996

Cerebral activations during number multiplication and comparison: a PET study.

Positron emission tomography was used to examine the cerebral networks underlying number comparison and multiplication in eight normal volunteers. Cerebral blood flow was measured within anatomical regions of interest defined in each subject using magnetic resonance imaging. Three conditions were used: rest with eyes closed, mental multiplication of pairs of arabic digits and larger-smaller comparison of the same pairs. Both multiplication and comparison activated the left and right lateral occipital cortices, the left precentral gyrus, and the supplementary motor area. Beyond these common activations, multiplication activated also the left and right inferior parietal gyri, the left fusiform and lingual gyri, and the right cuneus. Relative to comparison, multiplication also yielded superior activity in the left lenticular nucleus and in Brodmann's area 8, and induced a hemispheric asymmetry in the activation of the precentral and inferior frontal gyri. Conversely, relative to multiplication, comparison yielded superior activity in the right superior temporal gyrus, the left and right middle temporal gyri, the right superior frontal gyrus, and the right inferior frontal gyrus. These results underline the role of bilateral inferior parietal regions in number processing and suggest that multiplication and comparison may rest on partially distinct networks.

Adult↗
PubMed1996

Slowly progressive anarthria with late anterior opercular syndrome: a variant form of frontal cortical atrophy syndromes.

We describe eight patients with slowly progressive speech production deficit combining speech apraxia, dysarthria, dysprosody and orofacial apraxia, and initially no other deficit in other language and non-language neuropsychological domains. Long-term follow-up (6-10 years) in 4 cases showed an evolution to muteness, bilateral suprabulbar paresis with automatic-voluntary dissociation and frontal lobe cognitive slowing without generalised intellectual deterioration. Most disabled patients presented with an anterior opercular syndrome (Foix-Chavany-Marie syndrome), and pyramidal or extrapyramidal signs. CT and MRI findings disclosed asymmetric (left > right) progressive cortical atrophy of the frontal lobes predominating in the posterior inferior frontal region, notably the operculum. SPECT and PET revealed a decreased cerebral blood flow and metabolism, prominent in the left posterior-inferior frontal gyrus and premotor cortex, extending bilaterally in the most advanced cases. Pathological study of two cases showed non-specific neuronal loss, gliosis, and spongiosis of superficial cortical layers, mainly confined to the frontal lobes, with no significant abnormalities in the basal ganglia, thalamus, cerebellum, brain stem (except severe neuronal loss in the substantia nigra in one case), and spinal cord. We propose to call this peculiar syndrome Slowly Progressive Anarthria (SPA), based on its specific clinical presentation, and its metabolic and pathological correlates. SPA represents another clinical expression of focal cortical degeneration syndromes, that may overlap with other similar syndromes, specially primary progressive aphasia and the various frontal lobe dementias.

Aged↗
PubMed1996

Ability of serum prostate-specific antigen levels to predict normal bone scans in patients with newly diagnosed prostate cancer.

OBJECTIVES: To determine whether pretreatment serum prostate-specific antigen (PSA) levels in newly diagnosed prostate cancer patients can identify a group with a low probability of osseous metastasis and safely eliminate the need for a bone scan as a routine part of the staging evaluation. METHODS: We retrospectively reviewed 683 patients with prostate cancer between 1990 and 1993. Patients with prior therapy or serum PSA levels obtained longer than 3 months prior to bone scan were excluded. Bone scans were reviewed by two nuclear medicine physicians with a third deciding equivocal cases. RESULTS: Only 6% of 490 evaluable patients had a positive bone scan on initial evaluation. Scans were positive in 0 of 290 (0%) with PSA levels below 10 micrograms/L, 4 of 88 (4.5%) with PSA levels between 10 and 20 micrograms/L, and 24 of 112 (21%) with PSA levels above 20 micrograms/L. Although the risk of a positive bone scan increased with increasing PSA levels, PSA is a poor positive predictor of positive bone scans. The risk of a positive bone scan was 8% (5 of 64 patients) when PSA was between 20 and 50 micrograms/L, and increased to 40% (19 of 48 patients) for PSA levels greater than 50 micrograms/L. In contrast, serum PSA levels below 10 micrograms/L are strong negative predictors of positive bone scans, with no positive scans in 290 patients with PSA levels below 10 micrograms/L. Although the risk of a positive bone scan increased with increasing stage and grade, tumor stage and grade were poor negative predictors of positive bone scans. Up to 4% of patients with clinically confined or well-differentiated to moderately differentiated tumors had positive scans. Scans were positive in 12% of poorly differentiated tumors, but all these patients had PSA levels above 10 micrograms/L. CONCLUSIONS: Our data support the elimination of routine bone scintigraphy in patients with newly diagnosed prostate cancer and PSA levels below 10 micrograms/L. Bone scans are indicated when PSA levels are above 10 micrograms/L, or with T3 or poorly differentiated disease.

Adult↗
PubMed1996

Self as subject: a formulation and an assessment strategy.

IN James' view the self has two components, the self as subject, the I-self, or the self as knower; and the self as object, the me-self, or the self as known (James 1968). They are the dynamic and imagistic aspects of the self, respectively. Until recently, as Harter emphasizes in her comprehensive review (Harter 1983), quantitative studies of the self have focused almost exclusively on the self as object. They have explored such aspects of self-concepts as the self as independent, likable, or competent; contrasts between real and ideal images of the self; and developmental changes in self-concepts.

Adolescent↗
PubMed1996

Perceptions of stigma in women infected with HIV.

This qualitative focus group study explored perceptions of stigma in HIV-seropositive women. The sample included 19 HIV-positive women who participated in one of four focus group sessions. Participants were asked to talk about and describe their perceptions of how others think about and respond to them and other HIV-infected individuals. Content analysis was used to code the data and identify participant perceptions. Four themes representing distinctly different perceptions of stigma were identified: distancing, overgeneralizing stereotypes, social discomfort, and pity. The implications of the findings for intervention and future research are discussed.

Adult↗
PubMed1996

Evaluation of enzyme immunoassay for detection of salivary antibody to Helicobacter pylori.

The Helisal test is a quantitative enzyme immunoassay for the measurement of Helicobacter pylori-specific immunoglobulin G antibodies in saliva. This test was evaluated in comparison with culture and histopathologic examination of gastric biopsy specimens obtained from 195 patients who underwent 200 endoscopic procedures for the investigation of gastrointestinal symptoms. Forty-one (21%) patients were found to have peptic ulcer disease, and one other patient had a gastric carcinoma. H. pylori was detected in gastric biopsy specimens obtained from 98 (49%) of the procedures. The sensitivity, specificity, and positive and negative predictive values of the Helisal test were 81, 75, 76, and 80%, respectively. The test was negative for 16 (38%) of the 42 patients with peptic ulcer disease or a gastric malignancy diagnosed at endoscopy. These results suggest that the Helisal assay is only moderately accurate for the detection of H. pylori infection in symptomatic patients.

Adolescent↗