Quarterly communicable disease review. October to December 2000--from the PHLS Communicable Diseases Surveillance Centre.
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Biomedical subjects
Publications and source records attributed to J Hawker.
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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.
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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.
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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.
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.
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.
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OBJECTIVES: To describe the epidemiology of tuberculosis (TB) in Birmingham, UK, by ethnic group and to assess the implications of the findings for future trends in TB in the UK. METHODS: Retrospective review of records of all patients notified with TB in Birmingham during 1989-1994. RESULTS: The decline in TB notifications in Birmingham halted and then reversed in 1987-1992. Trends in overall notifications were mainly influenced by trends in cases of Asian origin. Crude notification rates in 1989-1994 are 17 times higher in Asian than Caucasian residents (p < 0.01). Rates in African Caribbean residents are also statistically significantly higher than in Caucasians (p < 0.01) but significantly lower than in Asians. Crude rates for Asian people born abroad are 4.1 times higher than for Asians born in the UK (p < 0.01) but only 3.8% of Asian patients had been resident in the UK for less than 1 year. The group accounting for the highest number of cases were female Asians aged 20-29, followed by male Asians of the same age. Age-specific rates show that incidence increases with age in both Asian and white groups, with a small peak in 20-29-year-old Asians. TB is uncommon in all Caucasian age-groups under 50 years of age (less than 1 per 10,000) but is relatively common in all Asian age-groups over 15 years of age (over 10 per 10,000). CONCLUSIONS: The different epidemiology of TB in the Caucasian and Asian populations in the UK suggests that from about the second decade of the next century, TB in the UK will almost be entirely a problem of ethnic minorities and that even if new infection was eliminated now in Asian people, cases due to reactivation would continue to occur until the third quarter of the next century.
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The FK506-binding protein, FKBP12, is a putative target of type I receptors for transforming growth factor-beta (TbetaR-I). As the FK506 motif that competes with TbetaR-I for FKBP12 resembles an invariant Leu-Pro dipeptide in TbetaR-I, we replaced Leu193 and Pro194 with Ala, along with mutations across the Gly/Ser box. L193A, P194A, and L193A/P194A do not alter TbetaR-I function; T204D partially activates, independent of ligand; L193A/P194A/T204D was an even more potent constitutive mutation. Association with FKBP12 in a yeast two-hybrid assay was disrupted by P194A, L193A/P194A, and L193A/P194A/T204D, but not L193A or T204D alone. Thus, FKBP12 recognition is dispensable for TGFbeta signaling.