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Biomedical subjects

A Feinstein

Publications and source records attributed to A Feinstein.

At least 19 recordsLinked to original sources
PubMed1998

Types and characteristics of remote memory impairment in schizophrenia.

Remote memory, as the term is used in the present study, refers to semantic information or autobiographical information for events and facts that are thought to be stored in the neocortex. In schizophrenia, findings of abnormalities in remote memory have been reported. However, it is unclear whether these are due to retrieval factors or other factors (e.g. paucity of information, disorganized lexicosemantic representations). Furthermore, it is unclear whether there is a temporal gradient in remote memory. In the first study, we utilized a cueing procedure for semantic fluency in order to determine whether retrieval factors play a marked role in impairments. In comparing patients with schizophrenia to patients with affective disorder and normal controls, we found that cueing had an equivalent effect upon all groups, suggesting that marked retrieval deficits were not the primary determinant of poor performance in fluency. Furthermore, we found that semantic fluency was disproportionately impaired vis-a-vis phonologic fluency, suggesting that abnormalities may be greater in storage areas presumed to be in temporal parietal cortex rather than in prefrontal cortex (which has been associated with retrieval deficits). In the second study, we examined the temporal gradient of autobiographical memory in patients with schizophrenia and normal controls. Whereas normal controls exhibited high and equivalent performance across childhood, early adult, and recent memories, patients with schizophrenia exhibited a u-shaped profile perhaps unique in the neuropsychiatric literature. This may reflect a combination of secondary memory impairments which effect the acquisition of new information coupled to very mildly accelerated rate of forgetting, 'recency' effects, and/or inefficient encoding. Taken together, these studies provide further support for the notion that schizophrenia has a relatively unique pattern of neuropsychological deficit based on neocortical dysfunction that includes, though is not restricted to, temporoparietal regions.

Adult↗
PubMed1998

A longitudinal study of psychosis due to a general medical (neurological) condition: establishing predictive and construct validity.

A sample of 44 patients with a neurological disorder and a DSM-IV diagnosis of Psychosis due to a General Medical Condition were followed on average for 4 years and their response to treatment and clinical course noted. Outcome was more benign than in schizophrenia, with most patients having a brief duration of psychosis and good response to small doses of neuroleptics. One-fourth of patients suffered a single, brief psychotic episode with return to full premorbid function. None required maintenance neuroleptic treatment. The outcome and descriptive profile of the disorder also differed from late-onset schizophrenia. Thus, Psychosis due to a General Medical (Neurological) Condition does appear to have predictive validity. However, no temporal association was found between the neurological illness and psychosis. Possible reasons for this are discussed.

Adult↗
PubMed1997

Prevalence and neurobehavioral correlates of pathological laughing and crying in multiple sclerosis.

OBJECTIVES: To establish the point prevalence of pathological laughing and crying (PLC) in multiple sclerosis (MS). To define associated neurological, emotional, and cognitive correlates of PLC. DESIGN: A consecutive sample of 152 patients with clinically or laboratory definite MS were screened for PLC, defined as sudden, involuntary displays of laughing or crying or both, without associated subjective feelings of depression or euphoria. Thereafter, a case-control design was followed with patients with PLC matched to patients with MS without PLC on age, gender, physical disability (Expanded Disability Status Scale), duration of MS, and premorbid IQ. SETTING: An MS outpatient clinic, the population representative of a large urban catchment area. PATIENTS: Fifteen of 152 patients had PLC, 11 of whom (mean [SD] age, 43.7 [8.3] years, 7 women) agreed to further testing. Thirteen patients with MS without PLC acted as controls. MAIN OUTCOME MEASURES: Neurological examination, Pathological Laughter and Crying Scale, Hospital Anxiety and Depression Scale, 28-item General Health Questionnaire, and the Wechsler Adult Intelligence Scale-Revised. RESULTS: The point prevalence of PLC in MS was 10%. Patients had a mean Expanded Disability Status Scale score of 6.5, had had MS for a mean (SD) of 10 (5.8) years, and had entered a chronic-progressive phase of their illness. Pathological laughing and crying was not associated with disease exacerbations. Compared with controls, patients were not more depressed or anxious, but had a greater decline in IQ. CONCLUSIONS: Pathological laughing and crying as distinct from emotional lability affects 1 in 10 patients with MS. It occurs in severely physically disabled patients, generally with long-standing disease. The presence of cognitive deficits relative to controls implies more extensive brain involvement.

Adult↗
PubMed1997

Structure of human IgM rheumatoid factor Fab bound to its autoantigen IgG Fc reveals a novel topology of antibody-antigen interaction.

Rheumatoid factors are the characteristic autoantibodies of rheumatoid arthritis, which bind to the Fc regions of IgG molecules. Here we report the crystal structure of the Fab fragment of a patient-derived IgM rheumatoid factor (RF-AN) complexed with human IgG4 Fc, at 3.2 A resolution. This is the first structure of an autoantibody-autoantigen complex. The epitope recognised in IgG Fc includes the C gamma 2/C gamma 3 cleft region, and overlaps the binding sites of bacterial Fc-binding proteins. The antibody residues involved in autorecognition are all located at the edge of the conventional combining site surface, leaving much of the latter available, potentially, for recognition of a different antigen. Since an important contact residue is somatic mutation, the structure implicates antigen-driven selection, following somatic mutation of germline genes, in the production of pathogenic rheumatoid factors.

Antigen-Antibody Reactions↗
PubMed1996

Crystallization of a complex between the Fab fragment of a human immunoglobulin M (IgM) rheumatoid factor (RF-AN) and the Fc fragment of human IgG4.

Rheumatoid factors (RF) are the characteristic autoantibodies found in patients with rheumatoid arthritis. They recognize epitopes in the Fc region of immunoglobulin G (IgG) and are often of the IgM isotype. In order to analyse the nature of RF-Fc interactions, we have crystallized a complex between the Fab fragment of a human monoclonal IgM rheumatoid factor (RF-AN) and the Fc fragment of human IgG4. The stoichiometry of the complex within the crystals was found to be 2:1 Fab:Fc. The crystals diffracted X-rays to 0.3 nm resolution, and the space group was C2, with cell dimensions a = 16.03 nm, b = 8.19 nm, c = 6.42 nm, beta = 98.3 degrees. We have also determined the sequence of the variable region of the RF-AN light chain, not hitherto reported. This belongs to the V lambda III-a subgroup and is closely related to the germline gene Humlv318, from which it differs in three amino acid residues. This is the first reported crystallized complex between a human autoantibody and its autoantigen.

Amino Acid Sequence↗
PubMed1995

Proton magnetic resonance spectroscopy of systemic lupus erythematosus involving the central nervous system.

We examined 13 patients with neurological manifestations of systemic lupus erythematosus (SLE) based on previous and/or current neurological or psychotic episodes by magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) together with psychiatric and cognitive assessment. MRI was abnormal in 7 patients, showing high signal lesions in the white matter and/or cerebral atrophy. Proton MRS centred on white matter lesions in 5 patients showed a reduction in the N-acetyl aspartate creatine ratio compared with normal appearing white matter in the SLE group and in 10 healthy controls. This pattern of abnormality does not allow differentiation of SLE lesions from the chronic plaques occurring in multiple sclerosis. There was a very high incidence of current psychiatric morbidity in the SLE group, namely in 12 of the 13 patients. There was no correlation between the presence of current psychiatric involvement and/or cognitive dysfunction and abnormalities detected with MRI or MRS.

Adult↗
PubMed1995

Depression associated with multiple sclerosis: an etiological conundrum.

OBJECTIVE: Although depression frequently occurs in multiple sclerosis (MS), an association with cerebral pathology is unclear. This sets MS apart from other common neurological disorders. The reasons for this are explored. METHOD: The literature on depression and magnetic resonance imaging (MRI) is reviewed and methodological issues are critically evaluated. RESULTS: Failure to demonstrate cerebral correlates of depression is in part a function of poor study design. However, the diffuse nature of cerebral demyelination creates difficulties in image analysis peculiar to MS. CONCLUSIONS: More research using valid psychiatric assessment procedures, high field strength MRI and automated lesion detection is needed to resolve the issue. It is premature to reject psychosocial causes at this stage.

Brain↗
PubMed1994

Crystallization and preliminary X-ray analysis of the Fab fragment of a human monoclonal IgM rheumatoid factor (2A2).

Crystals of the Fab fragment of a human monoclonal IgM rheumatoid factor have been obtained and are suitable for X-ray structure determination. This molecule, derived from the synovial B cells of a patient with rheumatoid arthritis, is an autoantibody with specificity for IgG Fc. The crystals have space group P2(1), cell dimensions a = 69.0 A, b = 76.6 A, c = 98.8 A and beta = 90.6 degrees, and diffract to a resolution of at least 2.8 A.

Antibodies, Monoclonal↗
PubMed1994

Effects of practice of serial tests of attention in healthy subjects.

The effects of practice on the serial performance of auditory and visual attention tasks were investigated in 10 healthy volunteers tested at 2 to 4 weekly intervals over eight test sessions using a battery of psychometric tests. Subjects as a group showed an ability to significantly (p = .05) improve their performances over time on all tests except for the Simple Reaction Time and Symbol Digit Modalities Test, the latter demonstrating a trend towards improvement (p = .07). Improvement when it occurred was almost uniformly linear and on tests such as the Pegboard and Stroop, was still discernable at the eighth session. On tests such as Paced Visual Serial Addition Task, floor effects were noted after five sessions and no further improvement was possible. In general, younger subjects tended to make fewer errors, perform quicker and improve for longer periods than their older counterparts. The results indicate that on tests of attention, healthy subjects have the ability to significantly improve performance with practice and this may extend over as many as eight discrete test sessions. The implications for neuropsychological research are discussed.

Adult↗
PubMed1993

A serial study of psychometric and magnetic resonance imaging changes in multiple sclerosis.

Over a 6-month period, five patients with early relapsing--remitting multiple sclerosis and five with long-standing, benign multiple sclerosis underwent serial psychometric testing and contrast enhanced magnetic resonance imaging of the brain at 2-weekly or monthly intervals, respectively. All patients were individually matched with healthy controls who completed the same psychometric battery at the same time intervals. As a group, multiple sclerosis patients either made more errors or performed slower on all psychometric tasks than controls. In the control subjects and those patients with a stable brain lesion score, no consistent deterioration occurred in any test and the overall pattern was one of improvement over time commensurate with practice effects. However, patients with a deteriorating lesion score either showed a fall-off in performance on some psychometric tasks (patients 2, 3) or else an impaired ability to improve with practice on certain tests of attention and information-processing speed (patient 10).

Adult↗