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Biomedical subjects

A Feinstein

Publications and source records attributed to A Feinstein.

At least 19 recordsLinked to original sources

Volume measurement of multiple sclerosis lesions with magnetic resonance images. A preliminary study.

The ability to visualise multiple sclerosis lesions in vivo with magnetic resonance imaging suggests an important role in monitoring the course of the disease. In order to help the long-term assessment of prospective treatments, a semi-automated technique for measuring lesion volume has been developed to provide a quantitative index of disease progression. Results are presented from a preliminary study with a single patient and compared to measurements taken from lesion outlines traced by a neuroradiologist, two neurologists and a technician. The semi-automated technique achieved a precision of 6% compared to a range of 12-33% for the manual tracing method. It also reduced the human interaction time from at least 60 min to 15 min.

Brain

Acute optic neuritis. A cognitive and magnetic resonance imaging study.

Forty-two patients with acute optic neuritis (ON) (mean duration of symptoms 14.5 d) were compared with a matched, normal control group on a battery of tests of attention and information processing speed. Approximately half the sample (55%) had brain abnormalities shown by magnetic resonance imaging (MRI) and were more impaired across a variety of tests compared with those patients without brain lesions or normal controls. There was no difference in psychometric performance other than the pegboard task between the normal control group and those ON patients without brain involvement. Significant correlations were found between total lesion area in the brain and some tests of attention. Results from the Symbol Digit-Substitution Test were particularly sensitive in this regard and could correctly identify 70% of the sample with brain lesions.

Adult

Treatment of pyoderma gangrenosum with clofazimine.

We report a case of pyoderma gangrenosum in a 80-year-old woman suffering from ulcerative colitis and treated with clofazimine. Significant improvement was evident within 5 days following commencement of therapy, complete healing occurred after only 4 weeks of treatment.

Aged

Clinically isolated lesions of the type seen in multiple sclerosis: a cognitive, psychiatric, and MRI follow up study.

There is a dearth of longitudinal studies on psychometric and psychiatric change in multiple sclerosis (MS) particularly on the evolution of these abnormalities early in the disease process. A 4 1/2 year follow up study documenting magnetic resonance imaging (MRI), psychometric, and psychiatric abnormalities was undertaken in a group of 48 patients with clinically isolated lesions--for example, optic neuritis--which are frequently the harbinger of MS. At follow up about half the subjects had developed clinically definite MS, with memory deficits becoming apparent. Deficits in attention documented at initial assessment were present but unchanged in those subjects who still had a clinically isolated lesion status. However, after MS was categorised into a relapsing-remitting or chronic progressive course, patients with a chronic progressive course were found to have significantly deteriorated with regard to auditory attention tasks. T1 relaxation times in apparently normal white matter correlated with certain indices of cognitive impairment. In developing a model to explain the pathogenesis of intellectual and emotional change in MS, the interaction of organic, psychological, and social factors needs to be emphasised.

Adult

Psychotic illness in multiple sclerosis. A clinical and magnetic resonance imaging study.

Ten patients with multiple sclerosis (MS) and psychosis were assessed using the Present State Examination, and matched retrospectively with respect to age, disability, duration of symptoms, and disease type with 10 MS patients without psychosis. Both groups underwent MRI of the brain. There was a trend for the psychotic group to have a higher total lesion score, particularly around the periventricular areas. This reached statistical significance in the areas around the temporal horn. In all cases, neurological symptoms preceded the onset of psychosis. The psychotic group also had a later age of onset of psychosis than psychotic patients without brain disease. These results point to an aetiological association between the pathological process of MS and psychosis.

Adult

Solution structure of human and mouse immunoglobulin M by synchrotron X-ray scattering and molecular graphics modelling. A possible mechanism for complement activation.

The pentameric 71-domain structure of human and mouse immunoglobulin M (IgM) was investigated by synchrotron X-ray solution scattering and molecular graphics modelling. The radii of gyration RG of human IgM Quaife and its Fc5, IgM-S, Fab'2 and Fab fragments were determined as 12.2 nm, 6.1 nm, 6.1 nm, 4.9 nm and 2.9 nm in that order. The RG values were similar for mouse IgM P8 and its Fab'2 and Fab fragments, despite the presence of an additional carbohydrate site. The IgM scattering curves, to a nominal resolution of 5 nm, were compared with molecular graphics models based on published crystallographic alpha-carbon co-ordinates for the Fab and Fc structures of IgG. Good curve fits for Fab were obtained based on the crystal structure of Fab from IgG. A good curve fit was obtained for Fab'2, if the two Fab arms were positioned close together at their contact with the C mu 2 domains. The addition of the Fc fragment close to the C mu 2 domains of this Fab'2 model, to give a planar structure, accounted for the scattering curve of IgM-S. The Fc5 fragment was best modelled by a ring of five Fc monomers, constrained by packing considerations and disulphide bridge formation. A position for the J chain between two C mu 4 domains rather than at the centre of Fc5 was preferred. The intact IgM structure was best modelled using a planar arrangement of these Fab'2 and Fc5 models, with the side-to-side displacement of the Fab'2 arms in the plane of the IgM structure. All these models were consistent with hydrodynamic simulations of sedimentation data. The solution structure of IgM can therefore be reproduced quantitatively in terms of crystallographic structures for the fragments of IgG. Putative Clq binding sites have been identified on the C mu 3 domain. These would become accessible for interaction with Clq when the Fab'2 arms move out of the plane of the Fc5 disc in IgM, that is, a steric mechanism exposing pre-existing Clq sites. Comparison with a solution structure for Clq by neutron scattering shows that two or more of the six globular Clq heads in the hexameric head-and-stalk structure are readily able to make contacts with the putative Clq sites in the C mu 3 domains of free IgM if if the Clq arm-axis angle in solution is reduced from 40 degrees-45 degrees to 28 degrees. This could be the trigger for Cl activation.

Amino Acid Sequence

The conformational effects of N-glycosylation on the tailpiece from serum IgM.

1H-NMR spectroscopy has been used to study the conformation and dynamics of the isolated tailpiece from human serum immunoglobulin M, a 22-residue peptide containing a single asparagine glycosylation site. The peptide is isolated as a set of glycoforms, varying only in the sequence of the oligosaccharide attached at the glycosylation site. The oligosaccharides present have the general formula (Man)n(GlcNAc)2, with 45% having n = 6, 45% having n = 8 and 10% having n = 7 and/or 9. They have been identified and their NMR parameters compared to those found for the isolated oligosaccharides in free solution. The conformation and dynamics of the peptide component have also been studied, using NOE data and hydrogen-exchange experiments, and the results compared to those obtained from the aglycosyl peptide of the same sequence. The presence of the peptide is found to have no measurable effect on the conformation of the oligosaccharides. However, the presence of oligosaccharide causes a decrease in the conformational mobility of the backbone and sidechains of the peptide in the region of the glycosylation site. This is proposed to result from interactions between the oligosaccharide core and the amino acid side chains. Further, the conformation of the N-glycosidic linkage has been shown to be both rigid and planar. Thus, the conformational space available to an N-linked oligosaccharide in a glycoprotein relative to the protein may depend to a large extent upon the flexibility of the asparagine side chain. Various roles for the different glycoforms of the tail peptide are discussed.

Amino Acid Sequence

Predictors of post-traumatic stress disorder following physical trauma: an examination of the stressor criterion.

A prospective study documenting psychopathology was undertaken in 48 subjects exposed to a range of physical trauma, but whose injuries were of similar severity. No support was found for the DSM-III-R view correlating the severity of the stressor with the development of post-traumatic stress disorder (PTSD). Distress post injury (high scores on the impact of event scale), indicative of difficulty with cognitive assimilation of the traumatic event, was found to be highly predictive of psychiatric morbidity and PTSD at 6 months.

Accidents, Traffic

Pemphigus in families.

A family in which two sisters are affected by pemphigus is described. Literature research has revealed the presence of 25 families, comprising 53 patients, in which pemphigus existed in more than one member. The relationships between those affected were mainly parent-child or sibling-sibling. Pemphigus was found to be associated with specific HLA antigens: A26, Bw38, DRw4, and additionally occurred with a higher frequency in certain ethnic groups. The variety of etiologic factors in the pathogenesis of pemphigus is discussed and the significance of a genetic role elucidated.

Adult

Mask dermatitis.

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Adolescent

Psychosis associated with demonstrable brain disease.

Sixty-five psychotic patients with unequivocal evidence of brain pathology and a variety of neurological disorders were assessed with respect to phenomenology and outcome. No relationship was found between site of brain pathology and type of psychotic disorder. A majority of patients had a syndrome indistinguishable from schizophrenia without coarse brain involvement and shared similar variables predicting outcome of psychosis, thus raising important issues concerning their nosological status.

Adolescent