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Biomedical subjects

W H Inman

Publications and source records attributed to W H Inman.

At least 37 records · Page 2Linked to original sources
PubMed1988

Modulation of the mitogenic response of an epidermal growth factor-dependent keratinocyte cell line by dexamethasone, insulin, and transforming growth factor-beta.

The stimulation of DNA synthesis by epidermal growth factor (EGF) has been studied for a cell line having properties useful for investigating the mechanism of action of EGF in epithelial cell populations. These studies employ a mouse keratinocyte cell line (MK), isolated by Weissman and Aaronson (1983), which is stringently dependent on exogenous EGF for growth in serum containing medium. The studies reported here characterize the compliment of EGR receptors present on the surface of MK cells and demonstrate the regulatory influence of other hormones on the capacity of EGF to stimulate DNA synthesis. Up-regulated MK cells contain approximately 22,000 EGF receptors per cell, but when the cells are grown in the presence of EGF the receptor number is reduced to about 4,000. It is estimated that only a small number of high-affinity receptors (less than 500) are required for EGF-dependent cell proliferation. In contrast to its action in fibroblastic cells, dexamethasone is a strong inhibitor of EGF-stimulated DNA synthesis of MK cells. Insulin at high concentrations, or insulin-like growth factors I or II (IGF-I, IGF-II) at physiological concentrations, synergistically enhance the EGF response. Interestingly, insulin or IGF-I or II are also able to reverse most of the dexamethasone inhibition of DNA synthesis. Transforming growth factor-beta (TGF-beta) inhibits, in reversible manner, the EGF stimulation of DNA synthesis and this inhibition is not overcome by insulin. TGF-beta receptors have been measured in MK cells and Scatchard analysis indicates approximately 20,000 receptors per cell. None of the modulatory hormones (insulin, dexamethasone, TGF-beta) significantly altered 125I-EGF binding characteristics in MK cells, suggesting a point of action distal to 125I-EGF binding.

Animals↗
PubMed1987

Non-steroidal anti-inflammatory drugs: assessment of risks.

The prescription-event monitoring procedure developed at the University of Southampton was used to evaluate five different non-steroidal anti-inflammatory drugs (NSAIDs), including piroxicam, in approximately 55,000 patients. The overall incidence of side effects was what would be expected. The risks of gastrointestinal haemorrhage and peptic ulceration were spread uniformly across the five drugs under study. No real difference was seen in the incidence of these conditions when patients discontinued the medication or switched to another NSAID. Overall, serious side effects were extremely rare. One provocative finding was the possibility that drugs of this class may exert a cardioprotective effect. There appeared to be a deficit of cases of myocardial infarction while the patients were taking an NSAID. Responsibility for the efficacy and safety of all drugs resides with many people and organizations: the manufacturers, national health departments, licensing departments, and physicians. The press, which has contributed to many unwarranted panics concerning drug safety, also must refrain from using power without responsibility.

Adult↗
PubMed1986

Prescription-Event Monitoring. Recent experience with 5 NSAIDs.

The principles and methods of Prescription-Event Monitoring (PEM) are presented and illustrated by a study of general practice notes of 55,642 patients, who were prescribed one of five non-steroidal anti-inflammatory drugs (NSAIDs). PEM showed the expected side effects and a low incidence of serious adverse reactions. The general pattern of events during and following treatment was, with few exceptions, very similar. The incidence of side effects that have led to the withdrawal of three of the drugs from the market was extremely low. Complications of peptic ulcer were uncommon and deaths from this cause were rare. No difference was apparent in the incidence of serious gastrointestinal complications during or after stopping treatment or changing to another NSAID.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1985

Stimulation of glucose uptake by transforming growth factor beta: evidence for the requirement of epidermal growth factor-receptor activation.

Transforming growth factor beta (TGF-beta), derived from human platelets, stimulates the uptake of 2-deoxy-glucose by cultured cell monolayers 2- to 4-fold. Stimulation can be detected as early as 30 min with as little as 0.1 ng of TGF-beta per ml and maximal effects can be obtained at 2 hr with 1 ng of the growth factor per ml. TGF-beta-induced stimulation of sugar uptake is enhanced by the co-addition of platelet-derived growth factor (10 ng/ml) or epidermal growth factor (EGF, 1 ng/ml). The NR-6 variant of mouse 3T3 cells, which lack EGF receptors, is not stimulated by TGF-beta. Antisera to EGF receptors that block 125I-labeled EGF binding also inhibit TGF-beta stimulation of 2-deoxyglucose uptake, although 125I-labeled TGF-beta binding remains unimpaired. In contrast, anti-sera to the EGF receptor, which do not block EGF binding, have no measurable effect on the TGF-beta-stimulated uptake of 2-deoxyglucose. We confirm that the receptor for TGF-beta is distinct from the receptor for EGF and we conclude that TGF-beta stimulation of 2-deoxyglucose uptake requires the co-activation of the EGF receptor kinase system.

Animals↗
PubMed1984

Prescription-event monitoring. A preliminary study of benoxaprofen and fenbufen.

Prescription-Event Monitoring (PEM) has been established at the Drug Surveillance Research Unit of the University of Southampton as a low-cost technique for ascertaining the pattern of events, whether drug-related or not, in large general practice cohorts. The reporting of "events" without the need for an opinion about the probability that they may be adverse drug reactions (ADRs) removes much of the uncertainty inherent in voluntary ADR reporting systems. Numerators (adverse events) and denominators (the number of prescriptions), enable estimates of incidence to be derived from the data. Where related drugs are studied concurrently, differences in the pattern of events may signal important differences in their safety or efficacy . A successful large-scale preliminary exercise involving nearly 9 000 doctors and 16 000 patients is described.

Anti-Inflammatory Agents, Non-Steroidal↗