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Biomedical subjects

A Ford

Publications and source records attributed to A Ford.

11 recordsLinked to original sources

The gene for erythropoietin receptor is expressed in multipotential hematopoietic and embryonal stem cells: evidence for differentiation stage-specific regulation.

The principal regulator of erythropoiesis is the glycoprotein erythropoietin, which interacts with a specific cell surface receptor (EpoR). A study aimed at analyzing EpoR gene regulation has shown that both pluripotent embryonal stem cells and early multipotent hematopoietic cells express EpoR transcripts. Commitment to nonerythroid lineages (e.g., macrophage or lymphocytic) results in the shutdown of EpoR gene expression, whereas commitment to the erythroid lineage is concurrent with or followed by dramatic increases in EpoR transcription. To determine whether gene activity could be correlated with chromatin alterations, DNase-hypersensitive sites (HSS) were mapped. Two major HSS located in the promoter region and within the first intron of the EpoR gene are present in all embryonal stem and hematopoietic cells tested, the intensities of which correlate well with EpoR expression levels. In addition, a third major HSS also located within the first intron of the EpoR gene is uniquely present in erythroid cells that express high levels of EpoR. Transfection assays show that sequences surrounding this major HSS impart erythroid cell-specific enhancer activity to a heterologous promoter and that this activity is at least in part mediated by GATA-1. These data, together with concordant expression levels of GATA-1 and EpoR in both early multipotent hematopoietic and committed erythroid cells, support a regulatory role of the erythroid cell-specific transcription factor GATA-1 in EpoR transcription in these cells. However, the lack of significant levels of GATA-1 expression in embryonal stem cells implies an alternative regulatory mechanism of EpoR transcription in cells not committed to the hematopoietic lineage.

Animals

Management of acute asthma attacks in general practice.

A prospective study was carried out in a semirural group practice between June 1988 and December 1989 to investigate acute asthmatic attacks treated with nebulized salbutamol. Questionnaires were completed by the attending doctor and by the patient (or his or her parent). Sixty nine episodes, occurring in 52 patients, were recorded during the 18 month study period. The majority of the attacks were managed exclusively in the community, with hospital admission occurring on only three occasions, one patient being admitted twice. A large proportion of the patients had a severe attack of asthma as judged by their previous history. Oral steroids were prescribed in 62.3% of attacks, oral theophyllines in 31.9% and antibiotics in 37.7%; the salbutamol nebulizer was used on more than one occasion during 41.2% of attacks. Significant morbidity was experienced by the patients during the studied attack, with 85% suffering sleep disturbance and two thirds being unable to attend work or school. Only 52.5% of patients were on prophylactic treatment and 37.5% of the patients had discontinued some aspect of their asthma therapy in the three months prior to the attack. Patients' and doctors' views about the cause of the attacks differed widely: patients most commonly cited infection (26/41) and allergy (8/41) with only two patients citing poor compliance or inadequate treatment. Although doctors also attributed the cause of many attacks to infection (33/64), they cited poor compliance or inadequate treatment in 28 of 64 responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Evaluating an RN/co-worker model.

In 1988 the University of Kentucky Hospital implemented a nurse extender model to cope with diminishing RN resources. After a year and a half of operation the model was evaluated in terms of training costs, retention, personnel costs, RN and co-worker satisfaction, and impact on quality of care. The authors conclude that although it has some limitations, the Co-worker Model allowed patient beds to remain open while minimally affecting quality.

Evaluation Studies as Topic

The international collaborative study on the first international standard of birch (Betula verrucosa)-pollen extract.

A selected candidate international standard preparation of birch (Betula verrucosa)-pollen extract was studied together with other birch-pollen extracts in a multinational study involving 20 laboratories in 11 countries. The biologic activity of the extract had previously been demonstrated in quantitative skin prick testing. The study methods comprised RAST inhibition, histamine release, quantitative immunoelectrophoresis, isoelectric focusing, and other methods. The results from RAST inhibition were calculated as parallel-line assays with statistical tests for linearity and parallelism. Analysis of variance was applied to test the significance of differences between potency estimates. In all assay methods, the candidate standard could be used to assign relative potencies to other birch-pollen extracts. The candidate standard was adequately stable during 36 months of storage at or below 5 degrees C. On the basis of this study, the World Health Organization has established the preparation as the International Standard for birch-pollen extract with assigned units of 100,000 IU per ampule.

Binding, Competitive

Clinical applications of immunocytochemistry in the monitoring of the bone marrow in small cell lung cancer (SCLC).

A panel of monoclonal antibodies (MAbs) has been identified which may be useful in detecting SCLC tumour cells and which does not cross-react significantly with normal marrow elements. Compared with conventional techniques this MAb panel markedly increases detection of micrometastases in the bone marrow especially in limited disease and post-chemotherapy in responding patients. There is a close correlation between immunological positivity and the ability to grow SCLC-like cells for variable periods in serum-free culture. In 4 cases SCLC-like cells have been characterized by electron microscopy or by the establishment of SCLC cell lines in continuous culture. The prognostic importance of pre-treatment detection of marrow involvement is unknown. The implications of post-chemotherapy detection of micrometastases are also uncertain but there may be an association with early systemic relapse which may occur regardless of intervention, including high dose intensification with autologous marrow rescue with primary site and CNS prophylactic irradiation.

Antibodies, Monoclonal

The collaborative study of the international standard of dog, Canis domesticus, hair/dander extract.

A collaborative study was carried out to assess the suitability of a chosen preparation to serve as the international standard (IS) for dog (Canis domesticus) hair/dander extract. Sets of five coded preparations of dog extract, including the proposed IS, were delivered to each participating laboratory in glass-sealed ampules. Fifteen laboratories in nine different countries examined the preparations by RAST inhibition, crossed immunoelectrophoresis/crossed radioimmunoelectrophoresis, histamine release, and by other methods. In spite of the use of different versions of methods and different reagents, quite consistent results were obtained, and the proposed IS was found to have a satisfactory activity in all assays and to be useful as a calibrator when allergenic potency of similar dog allergenic extracts was estimated. Four laboratories estimated the specific content of allergens Ag 3, Ag 13, and albumin and found the proposed IS to be a suitable standard for these assays. On the basis of the results from this study, the World Health Organization established the preparation as the international standard for dog hair/dander extract with an assigned unitage of 100,000 IU per ampule. The units refer to both the total allergenic activity of the ampule and to that of individual allergens.

Allergens

BW A575C: pharmacological profile in vivo of a novel angiotensin converting enzyme inhibitor and beta-blocker.

The novel compound BW A575C, N-(1-(S)-carboxy-5-[4-(3-isopropylamino-2-(R,S)-hydroxypropoxy)-indole-2 - carboxamido]pentyl)-(R,S)-alanyl-(S)-proline, is a potent angiotensin converting enzyme (ACE) inhibitor and beta-blocker in vitro. It was therefore of considerable interest to establish whether this novel pharmacological profile was maintained in vivo. In conscious instrumented normotensive rats and dogs, intravenous and oral administration of BW A575C causes a dose-dependent rightward displacement of the pressor dose-response curve to angiotensin I (dose ratio of 29.5 and 16.1 in rats and dogs, respectively, at 1.0 mg/kg i.v.) and the tachycardia dose-response curve to isoprenaline (dose ratio of 3.1 and 8.0 in rats and dogs, respectively, at 1.0 mg/kg i.v.). In these experiments BW A575C is approximately 2-10 times more active as an ACE inhibitor than as a beta-blocker. In conscious instrumented acute renovascular hypertensive dogs, where plasma renin activity is elevated 10-fold, BW A575C (1.0 mg/kg i.v.) causes a reduction in blood pressure of 35% within 10 min of injection, which is sustained for up to 4 h. This reduction in blood pressure is accompanied by a consistent, but nonsignificant, reduction in heart rate. These results confirm the novel pharmacological profile of BW A575C in vivo and demonstrate that this compound is an effective antihypertensive agent in a renin-dependent model of hypertension.

Adrenergic beta-Antagonists

Patients are worms.

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Empathy