Unsuccessful outpatient counselling to help patients with peripheral vascular disease to stop smoking.
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Biomedical subjects
Publications and source records attributed to J Morris.
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We describe a whole mount in situ hybridization procedure to detect and localize low abundance transcripts (qmf1) and myosin heavy chain proteins in quail embryos. The critical factor in transcript detection was the extent of proteinase K digestion. Optimal digestion increased probe accessibility and reduced background. The use of digoxigenin-labeled probes and immunological detection with anti-digoxigenin-alkaline phosphatase conjugated antibody allowed signal development in 6-10 h, unlike the 7 days required using 35S-labeled probes. Myosin heavy chain proteins were detected using immunofluorescence and confocal laser scanning microscopy to allow precise localization of signal within developing embryos.
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Tumor cell progression and parenchymal infiltration play important roles in the pathogenesis of gliomas. Using retrovirally marked rat 9L gliosarcoma cells, which when injected in the CDF rat brain form noninfiltrating tumors which grow only surrounding existing blood vessels, we were able to investigate elements of tumor growth and progression within the substance of the brain. Transfection of 9L by oncogenes associated with tumor progression and expressed in gliomas resulted in alterations in the in vivo phenotype of these cells, with the production of faster growing, well-vascularized, large solid tumors. However, diffuse infiltration was not seen. Moreover, coinjection of 9L or its transfectants together with the infiltrative C6 cell line resulted in a mixed tumor of noninfiltrating 9L cells in an environment of infiltrating C6 cells, suggesting that the infiltrative ability of C6 cells is controlled on the individual cell level.
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A cDNA encoding a receptor antagonist of interleukin 1 (IL-1ra), secreted from human monocytes, has recently been isolated and sequenced [Eisenberg, S. P., Evans, R. J., Arend, W. P., Verderber, E., Brewer, M. T., Hannum, C. H. & Thompson, R. C. (1990) Nature (London) 343, 341-346]. We have identified another version of this IL-1ra, which is predominantly expressed in epithelial cells. This IL-1ra lacks a leader sequence and, thus, is probably intracellular. Both proteins are derived from the same gene through use of an alternative transcriptional start site and internal splice-acceptor site. Expression of intracellular IL-1ra cDNA in COS cells demonstrated that the intracellular product specifically inhibited exogenous interleukin 1-dependent responses. Keratinocytes were shown to contain significant amounts of nonsecreted IL-1ra protein. Constitutive expression of the intracellular IL-1ra may be an intracellular defensive mechanism in exposed epithelial cells and/or may serve to regulate autocrine interleukin 1-mediated pathways of differentiation.
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A "late phase" antigen-induced bronchoalveolar eosinophilia has been demonstrated in ovalbumin sensitized guinea pigs (1,2). This in vivo response to antigen inhalation can be inhibited by a 2,6-disubstituted pyridine analog of LTB4, U-75,302(2) (3). In the present study, the mechanism of the drug action was studied by assessing the activity of U-75,302 and a second analog, U-75,485 to displace [3H]-leukotriene B4 binding at the guinea pig eosinophil membrane, as well as their action as chemoattractants or inhibitors of the directional migration of guinea pig eosinophils in vitro. Radioligand competition experiments demonstrated that both analogs interacted strongly with the high affinity LTB4 binding sites on guinea pig eosinophil membrane. Both analogs are powerful chemoattractants for guinea pig eosinophils since they induced directional migration of guinea pig eosinophils when administered alone. In addition, when the cells were treated with either analog and their chemotaxis response was measured in response to a natural chemoattractant, both U-75,302 and U-75,485 at concentrations of 0.1 to 100 microM dose dependently inhibited the LTB4 induced chemotaxis response. The EC50s obtained for U-75,302 and U-75,485 as inhibitors of LTB4 induced guinea pig eosinophil chemotaxis were estimated to be 11.5 +/- 5.5 microM and 5.4 +/- 2.5 microM respectively. Under the same conditions, they had no significant effect upon eosinophil migration induced by zymosan activated plasma at concentrations below 100 microM. We suggest that the inhibition of antigen-induced eosinophil infiltration in guinea pig airway in vivo by U-75,302 or U-75,485 may be a result of partial antagonism or desensitization at the LTB4 receptor level of guinea pig eosinophils.
A significant proportion of women who undergo coronary arteriography for investigation of angina have normal coronary angiograms. We wanted to test the hypothesis that screening women with risk factors for coronary arterial disease would reduce the need for subjecting them to this invasive procedure. Comparisons were made between 100 women with normal coronary angiograms and 100 women with angiographic evidence of coronary arterial disease. Both groups had presented with angina and had undergone coronary angiography in 1985 or 1986. Women with angina and normal coronary angiograms had fewer risk factors than those with coronary arterial disease. They were younger (mean 49.0 and 55.9 years, respectively), had less severe angina on presentation (atypical or mild angina: 35% vs 16%), were less likely to have a family history of myocardial infarction (12% vs 53%), were more likely to have never smoked cigarettes (64% vs 13%), and fewer of them had a serum cholesterol in excess of 6 mmol/l (36% vs 64%). Five independent predictors of coronary arterial disease were identified; family history, myocardial infarction, age, hypertension and smoking habit. No women with angina and abnormal coronary angiograms were found to be free of risk factors, whereas 42% of women with angina and normal coronary angiogram were free of risk factors. The data suggests that coronary angiography will probably be normal in women with angina who are free of risk factors.
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We investigated 117 patients undergoing percutaneous nephrolithotomy, percutaneous nephrostomy, ureterorenoscopy, the push-back or push-bang procedure for ureteral stones, Double-J* ureteral stenting plus extracorporeal shock wave lithotripsy (ESWL), ESWL alone or cystoscopy. Blood samples obtained before, during and 1 hour after the procedure were cultured and assayed for endotoxin and tumor necrosis factor. Also, culture was done of the urine preoperatively and postoperatively, and the stones when they could be retrieved. There was a temporal relationship among bacteremia, endotoxemia and elevation of tumor necrosis factor. An unexpected finding was peroperative endotoxemia in a significant number of patients with stones. Risk factors noted for postoperative bacteremia, endotoxemia and/or elevation of tumor necrosis factor included preoperative endotoxin level, type of procedure, presence of preoperative bacteriuria and pyuria. With respect to the procedure the risk was greatest after the push-back method and least after cystoscopy (push-back method greater than percutaneous nephrolithotomy/percutaneous nephrostomy greater than Double-J stenting plus ESWL greater than ureterorenoscopy greater than ESWL greater than cystoscopy). If the risk factors are measured preoperatively it may be possible to identify the risk of postoperative bacteremia/endotoxemia and, therefore, septic shock postoperatively. Our patients appear to be a good clinical model to investigate the problems related to septicemia.
Aspergillus infection involving the central nervous system are unusual, but should be included in the differential diagnosis in patients with the acquired immunodeficiency syndrome and neurologic signs and symptoms. Of the few reported AIDS cases with central nervous system aspergillosis, the majority have had focal brain abscesses. We report an atypical case that presented as a basal meningitis with pontine infarction secondary to invasive Aspergillus sinusitis.
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In an investigation of risk behaviour among injecting drug users in the North-West of England, information was obtained concerning the sharing of injecting equipment, respondent's sexual partners and the use of condoms. Between six and nine months after the initial contact, 169 respondents (56%) were contacted again. The emphasis in the second phase of the project was on changes, if any, in risk behaviour that had occurred in the intervening period. Significant reductions were found in sharing, mostly in the more indiscriminate use of others' injecting equipment. No reduction was observed in sharing between injecting partners and little in sharing between close friends. The number of sexual partners had decreased and the use of condoms, although it increased among those involved in temporary relationships, remained low. Impediments to further progress in risk reduction are discussed.
Transcription of the prolactin (PRL) gene has been analyzed in wild-type D6, PRL-deficient B3, and revertant r16 GH3 cells. Levels of processed nuclear transcripts from the PRL gene were substantially reduced in the deficient line compared to wild-type cells and returned to greater than wild-type levels in the revertant line. Rare PRL transcripts in the deficient line contained the same 5' end found on transcripts in wild-type and revertant cells as judged by primer extension and S1 nuclease protection assays, implying that the cells are deficient in utilization of the normal wild-type promoter. Deficient cells also contained wild-type levels of the PRL- and growth hormone-specific transcription factor pit-1/GHF-1, and no difference was found in the ability of extracts from wild-type and deficient cells to retard various restriction fragments from both the proximal and the distal PRL promoter regions. The deficient and wild-type cells were equally competent in initiating transcription from a transfected rat PRL promoter containing both the distal and proximal promoter elements. These observations imply that PRL-deficient cells are not defective in a trans-activating factor functioning on these PRL promoter fragments (trans model). Rather, inefficient use of the PRL promoter in the variant cells may reflect an increased methylation state of the PRL gene itself (cis model).