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Biomedical subjects

G Currie

Publications and source records attributed to G Currie.

33 records · Page 2Linked to original sources

The Microphthalmia gene product interacts with the retinoblastoma protein in vitro and is a target for deregulation of melanocyte-specific transcription.

Little is known of the molecular mechanisms underlying the differentiation of the melanocyte from the melanoblast or the progression from the melanocyte to a malignant melanoma. Since the adenovirus E1A products have proved a useful tool for understanding control of differentiation in other systems, we explored the possibility of using E1A as a probe for factors controlling melanocyte-specific gene expression and differentiation. The results obtained show that the adenovirus E1A 13S, but not the 12S, product can transform the highly pigmented and TPA-dependent melanocyte cell line melan-a. Transformation is characterised by a morphological change, loss of TPA-dependence, the ability to grow in soft agar and strikingly, loss of pigmentation which correlates with loss of expression of the melanocyte-specific TRP-1 and tyrosinase genes. Cotransfection assays demonstrated that repression of TRP-1 by E1A correlated with E1A binding to p105Rb and p300, with the target in the TRP-1 promoter being the M-box, and 11 bp basic-Helix-loop-Helix (bHLH) factor-binding motif conserved between melanocyte-specific promoters. Consistent with the M-box acting as a target for E1a-mediated transcription repression, we also show that the basic-helix-loop-helix-leucine zipper (bHLH-LZ) protein (Mi) encoded by the microphthalmia gene (mi), which is required for pigment cell differentiation, is a positive acting transcription factor which can interact with the retinoblastoma product in vitro and activate the TRP-1 promoter. Moreover, expression of the mi gene was reduced around 50-fold in the non-pigmented E1a-transformed melan-a cells compared to the nontransformed melan-a cell line, with ectopic expression of Mi able to prevent repression of the tyrosinase and TRP-1 promoters in the presence of E1A. Mi therefore appears to play a crucial role in melanocyte-specific gene expression. The parallels between repression of myogenesis and muscle cell bHLH factors, and Mi and melanocyte differentiation are discussed.

Adenovirus E1A Proteins↗

Learning theory and the design of training in a health authority.

Gives an explanation of the salient factors which affected the design of a training intervention aimed at clinicians in West Birmingham Health Authority. Discusses the theoretical considerations relevant to learning in an organization, using a case study to illustrate.

Allied Health Personnel↗

Matrix-assisted laser desorption of peptides and proteins on a quadrupole ion trap mass spectrometer.

The use of ultraviolet matrix-assisted laser desorption (MALD) to ionize peptides and proteins for analysis in a quadrupole ion trap is described. An ion source was modified to accommodate a fiber optic to transmit laser radiation from a nitrogen laser (337 nm) to the tip of the sample probe containing peptide or protein samples in a matrix of 2,5-dihydroxybenzoic acid (DHB) or 3,4-dimethoxy-4-hydroxy-cinnamic acid. Detection limits are demonstrated with 10 fmol of sperm-whale myoglobin. The dimer of sperm-whale myoglobin was also observed at m/z 34,430. A comparison is made of the tandem mass spectrum of (MS/MS) of human angiotensin I desorbed by MALD to that of the peptide desorbed by liquid secondary-ion mass spectrometry. Both spectra were found to contain abundant structural information.

Angiotensin I↗

Prognostic significance of serum lysozyme in adult acute myelogenous leukaemia.

Pre-treatment sera from 88 adult patients with acute myelogenous leukaemia have been assayed for their lysozyme content. All 19 patients who presented with a serum-lysozyme level below 15 mug/ml failed to acheive haematological remission from intensive chemotherapy. Serum-lysozyme levels above 85 mug/ml were found in 10 patients, all of whom went into remission. Remissions in this group were, however, shortlived. Of the 59 patients with lysozyme levels between 15 and 85 mug/ml, 39 achieved haematological remission and 12 survived longer than 60 weeks. These findings suggest that estimation of serum-lysozyme may help to identify those patients who are unlikely to respond to the intensive-chemotherapy protocols currently advocated and who could therefore be spared exposure to them.

Adult↗

Medical and social screening of patients aged 70 to 72 by an Urban General Practice Health Team.

A medico-social survey of 259 elderly patients aged 70-72 was carried out by three doctors, a health visitor and a nurse in an urban general practice. Seven hundred and ninety diseases or disabilities were identified-an average of 3.2 per patient-of which 20.5% were unknown to the doctors. Using a simple check list for symptom inquiry, the health visitor or nurse missed very little of the physical or psychological disease. In some respects their symptom inquiry was more revealing than that of the doctors but they had difficulty in eliciting evidence of malnutrition, masked depression, and incipient dementia. Initial health screening of the elderly for unreported disease in general practice can easily be done by a health visitor with training in geriatric problems and the recognition of psychiatric illness.Initial health screening can also be done by a nurse with community-nursing experience but she will require additional training in the techniques of social assessment. The doctor must examine those patients found to be suffering from alerting symptoms. A general practice of three or four doctors requires one health visitor for routine work and one additional health visitor or nurse for screening of the elderly. Unreported disease in the elderly indicates failure to make contact and failure to ask the right questions. Unknown disease may be due to inadequate records.

Aged↗