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Biomedical subjects

J Westcott

Publications and source records attributed to J Westcott.

At least 19 recordsLinked to original sources
PubMed1999

A chain initiation factor common to both modular and aromatic polyketide synthases.

Antibiotic-producing polyketide synthases (PKSs) are enzymes responsible for the biosynthesis in Streptomyces and related filamentous bacteria of a remarkably broad range of bioactive metabolites, including antitumour aromatic compounds such as mithramycin and macrolide antibiotics such as erythromycin. The molecular basis for the selection of the starter unit on aromatic PKSs is unknown. Here we show that a component of aromatic PKS, previously named 'chain-length factor', is a factor required for polyketide chain initiation and that this factor has decarboxylase activity towards malonyl-ACP (acyl carrier protein). We have re-examined the mechanism of initiation on modular PKSs and have identified as a specific initiation factor a domain of previously unknown function named KSQ, which operates like chain-length factor. Both KSQ and chain-length factor are similar to the ketosynthase domains that catalyse polyketide chain extension in modular multifunctional PKSs and in aromatic PKSs, respectively, except that the ketosynthase domain active-site cysteine residue is replaced by a highly conserved glutamine in KSQ and in chain-length factor. The glutamine residue is important both for decarboxylase activity and for polyketide synthesis.

Acyl Carrier Protein↗
PubMed1998

The effects of upper respiratory infection on T-cell proliferation and steroid sensitivity of asthmatics.

BACKGROUND: The common cold is a potent trigger for asthma symptoms. Although the mechanisms are not completely understood, inflammatory events may play an important role. OBJECTIVE: We tested the hypothesis that changes in steroid responsiveness are implicated in the relationship between asthma and the common cold. METHODS: We investigated the steroid sensitivity of T cells from 10 patients with asthma (not taking steroids) and 10 control subjects, during upper respiratory infection and at recovery (6 weeks later). We stimulated peripheral blood mononuclear cells with phytohemagglutinin to measure T-cell proliferation, sensitivity to the inhibitory effects of steroids, and cytokine production. RESULTS: During infection compared with recovery, the asthma group exhibited lower responsiveness to dexamethasone at 10(-10) and 10(-9)mol/L and to 10(-10)mol/L hydrocortisone (P <.05) and both groups had decreased T-cell proliferation (P <.05). During recovery, patients with asthma had greater T-cell proliferation than control subjects (P <.02); the values expressed as uptake of [3H]-thymidine were 60119+/-3944 cpm (asthma) and 39078+/-6459 cpm (control subjects). The asthma group had higher TNF-alpha and IFN-gamma production during infection (P <.05); changes in IL-8 and IL-10 levels were not significant, and IL-4 was not detected. CONCLUSION: During infection, asthmatic subjects exhibit decreased T-cell responsiveness to steroids. The T-cell proliferative response to phytohemagglutinin, higher in asthma, is decreased with a common cold. These findings are associated with changes in the cytokine profile. Thus viral-induced upper respiratory infections can produce an inflammatory milieu with altered steroid function and selective increases in cytokines.

Adult↗
PubMed1997

Primary care in the A & E department: meeting the challenge--a workshop series for A & E nurses.

Accident and emergency (A & E) departments lie at the interface between primary and secondary care. Patients who attend the accident and emergency department with primary care needs have traditionally been seen as 'inappropriate' and labelled in pejorative terms. Over the past few years, however, new models of care have emerged through research and practice development for meeting the needs of this group of patients in A & E. For effective service development there is a need to challenge and change the traditional A & E culture. This paper describes an educational approach towards changing clinical practice, by disseminating research and practice development initiatives through a workshop series. It aimed to disseminate research in a relevant manner to practitioners and to develop the primary care orientation of a number of A & E departments in England and Scotland. The workshop series sought to influence clinical practice by sharing the experience of researchers and practitioners in a supportive learning environment. The use of this approach offered a means of bridging the gap between research and practice development. The paper outlines the rationale for the workshop series, its structure, aims and objectives, and the reported progress in relation to change management and service provision identified by the participants. The workshop series proved to be an effective means of disseminating experience of research, practice development and change management.

Education↗