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Biomedical subjects

J Hawker

Publications and source records attributed to J Hawker.

At least 19 recordsLinked to original sources
PubMed2006

Farnesyltransferase and geranylgeranyltransferase I inhibitors upregulate RhoB expression by HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter.

Recently, we have shown that RhoB suppresses EGFR-, ErbB2-, Ras- and Akt-mediated malignant transformation and metastasis. In this paper, we demonstrate that the novel antitumor agents farnesyltransferase inhibitors (FTIs) and geranylgeranyltransferase I inhibitors (GGTIs) upregulate RhoB expression in a wide spectrum of human cancer cells including those from pancreatic, breast, lung, colon, bladder and brain cancers. RhoB induction by FTI-277 and GGTI-298 occurs at the transcriptional level and is blocked by actinomycin D. Reverse transcription-PCR experiments documented that the increase in RhoB protein levels is due to an increase in RhoB transcription. Furthermore, treatment with FTIs and GGTIs of cancer cells results in HDAC1 dissociation, HAT association and histone acetylation of the RhoB promoter. Thus, promoter acetylation is a novel mechanism by which RhoB expression levels are regulated following treatment with the anticancer agents FTIs and GGTIs.

Acetylation↗
PubMed2006

Are we prepared for a deliberate release of a biological agent?

OBJECTIVES: Following the events of 11 September 2001 in New York, planning for the deliberate release of chemical, biological, radiological and nuclear agents has intensified in the UK, with Department of Health recommendations for National Health Service and public health action. A consequence of this was to assess preparedness across the West Midlands region of England for mounting an effective response to a deliberate release of a biological agent. STUDY DESIGN: Descriptive study. SETTING: West Midlands, UK. This work involved key organizations and entailed obtaining information from those responsible for and likely to be involved in managing incidents via questionnaire surveys based around preparedness and planning arrangements. RESULTS: Findings revealed that plans delineating action to take during an incident do exist. However, staff training (40%) in acute trusts and testing of plans in primary care trusts (45%) could be improved. Communication arrangements in hospitals require support. CONCLUSION: Work is ongoing but there is more to do. Trusts should provide staff training and engage in exercises to test plans and communication arrangements.

Bioterrorism↗
PubMed2006

An outbreak of Escherichia coli O157 gastroenteritis in a care home for the elderly.

In the summer of 2001 an outbreak of Escherichia coli O157 gastroenteritis affected staff and residents of a care home for the elderly in the West Midlands, UK. E. coli O157 phage type 2 was isolated from faeces in eight patients and 12 staff members. Thirty-five staff and 40 residents met the case definition for clinical gastrointestinal infection. Serological testing identified a further 14 possible cases of infection amongst asymptomatic staff and residents. The outbreak was atypical, as the disease seemed to be milder than has been observed in past outbreaks in similar settings. The index case, a member of staff, developed bloody diarrhoea and haemolytic-uraemic syndrome (HUS), but only one resident developed bloody diarrhoea and required hospitalization. No deaths occurred, despite the high-risk nature of the affected population. The source of the outbreak could not be identified. The prolonged nature of the outbreak and observed lapses in infection control practices indicated that person-to-person spread was the likely route of transmission. This outbreak illustrates the importance of observing appropriate infection control measures in the institutions providing residential and nursing care to the elderly.

Aged↗
PubMed2000

Influence of cranberry juice on attachment of Escherichia coli to glass.

An extract from fresh cranberries was shown to decrease the strength of attachment of Escherichia coli to glass coverslips when incubated together for 2 h. Pre-conditioning of the surface prior to biofilm formation also significantly weakened the strength of attached cells.

Bacterial Adhesion↗
PubMed1999

Public health. Parity begins at home.

The NHS can make a considerable contribution to reducing social exclusion and inequalities. GPs' surgeries should play a greater role in giving information on social security benefits. Primary care should be targeted at those most in need. The NHS has many employees on low incomes and should provide them with an effective occupational health service.

Chronic Disease↗
PubMed1998

Tuberculosis mortality in notified cases from 1989-1995 in Birmingham.

This is a retrospective descriptive study examining medical records of notified cases of tuberculosis in Birmingham, UK, who died before completion of treatment, plus notified cases identified at postmortem. During the study period, 1989-1995, there were a total of 2088 notifications of tuberculosis of which 75 (3.6%) died. This case-fatality rate is lower than that reported from earlier studies, a finding which may be due to improved ascertainment, earlier diagnosis and improved treatment in recent years. Forty-five deaths (60%) were in males and 30 (40%) in females. The median age at death was 66 y. Forty-five deaths (60%) were among the white ethnic group, 21 (28%) among persons of Indian sub-continent origin, 4 (5.3%) among Black Caribbeans and 5 (6.6%) among the other ethnic groups. Case-fatality rates were significantly higher (P < 0.01) in caucasians (9.4%) than in Asians (1.5%) and only half of this difference was explained by the age of those affected. Twenty-two (29%) cases were confirmed by a positive sputum smear and a further 23 (31%) by a positive sputum culture. Eighteen (24%) cases also had histological confirmation. Twelve (16%) cases were identified on autopsy. The case fatality rate in respiratory disease was significantly higher (RR = 1.19, P > 0.05) than in non-respiratory disease. As delay in diagnosis is likely to be the main contributing factor leading to death, a high index of suspicion of tuberculosis is needed when investigating elderly patients with general chronic illness, especially if there are prolonged respiratory symptoms. Early diagnosis will reduce mortality as the disease rapidly responds to treatment.

Black or African American↗
PubMed1998

Tyrosine phosphorylation of paxillin/pp125FAK and microvascular endothelial barrier function.

The transendothelial movement of solutes is a dynamic process controlled by a complex interaction between the cytoskeleton and adhesion proteins. The aim of this study was to examine whether protein tyrosine phosphorylation is involved in the regulation of endothelial barrier function. The apparent permeability coefficient of albumin (Pa) was measured in isolated and perfused coronary venules. Tyrosine phosphatase inhibitors, including phenylarsine oxide and sodium orthovanadate, dose and time dependently increased basal Pa. Western blot analysis of cultured coronary venular endothelial cells revealed that inhibition of tyrosine phosphatase induced an increase in phosphotyrosine content in a number of proteins, including bands at 65-70 and 120-130 kDa, which were identified as paxillin and focal adhesion kinase (pp125FAK), respectively. The time course and dose responsiveness of protein tyrosine phosphorylation were tightly correlated with those of increases in Pa. Furthermore, stimulation of endothelial cells with histamine or phorbol myristate acetate (PMA) enhanced tyrosine phosphorylation of paxillin and pp125FAK, which was blocked by the tyrosine kinase inhibitor damnacanthal. Correspondingly, the increases in venular permeability elicited by histamine and PMA were abolished in damnacanthal-treated venules. Taken together, the data suggest a possible involvement of protein tyrosine phosphorylation in the control of endothelial barrier function. Paxillin and its associated focal adhesion proteins may play a specific role in agonist-induced hyperpermeability responses in the endothelium of exchange vessels.

Animals↗
PubMed1998

Efficient protein transfection of cultured coronary venular endothelial cells.

Although it is well recognized that microvascular endothelial cells play an important role in the local regulation of tissue perfusion and exchange processes, the precise effect of specific endothelial proteins on microvascular function remains to be elucidated. The lack of information is partially due to methodological limitations, because pharmacological approaches that are routinely used in conventional microcirculatory studies produce nonspecific information. The purpose of this study was to develop an efficient method of transfecting endothelial cells with proteins for functional analysis. TransIT, a polyamine reagent, proved very successful for beta-galactosidase (beta-Gal) protein transfection of bovine coronary venular endothelial cells, because time-course and dose-dependent experiments showed that a transfection efficiency of 88 +/- 7% was possible. In control studies, beta-Gal was detected in transfected cells that were trypsinized and washed, indicating that the protein was not merely adhering to the cell surface. Furthermore, transfection of a cell-impermeable peptide inhibitor of protein kinase C (PKC) resulted in a decrease in PKC activity in comparison with control cells. This approach provides a technical basis for further transfection of endothelial cell monolayers with antibodies and constitutively active or dominant-negative proteins to study the molecular control of microvascular function.

Animals↗