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Biomedical subjects

A McMaster

Publications and source records attributed to A McMaster.

8 recordsLinked to original sources
PubMed2005

Glucocorticoids suppress macrophage migration inhibitory factor (MIF) expression in a cell-type-specific manner.

MIF is a potent proinflammatory cytokine involved in inflammatory arthritis. Glucocorticoids (GC) have been reported to induce secretion of MIF in rodent cells, and as MIF counteracts the anti-inflammatory effects of GC, this has implications for human inflammatory disease. Transient transfection studies showed that the MIF promoter was repressed by dexamethasone (Dex) (10 nM) in CEM C7A cells, with up to 50% suppression by 100 nM. However, there was no regulation of the promoter by GC in A549 cells. We also found that subnanomolar concentrations of Dex suppressed MIF secretion, measured by ELISA, by 80% in both human T lymphoblasts (CEM C7A) and human lung epithelial cells (A549). Endogenous MIF mRNA was also repressed by GC in CEM C7A cells, measured both by Northern blot and quantitative RT-PCR assays, but there was no such regulation in A549 cells. This suggests that GC affects translation rather than transcription of MIF in A549 cells. These results contradict earlier results with the rat cell line RAW 264.7. Therefore, we analysed MIF secretion from RAW 264.7 cells but found no GC effect on secretion. Understanding how GC regulates MIF in a cell-type-dependent manner may give insights into GC-refractory human inflammatory diseases.

Animals↗
PubMed1999

Significance of Epstein-Barr virus status and post-transplant lymphoproliferative disease in pediatric thoracic transplantation.

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) is a serious complication of organ and bone marrow transplantation. The importance of EBV matching between recipient and donor remains unclear. Between October 1987 and December 1997, 64 pediatric cardio-pulmonary transplants were performed at this center (58 hearts, two heart/lungs, four sequential single lungs). The EBV viral capsid antigen (VCA) immunoglobulin G (IgG) status of both donor and recipient was determined at the time of transplant. Of 56 patients from whom paired sera was available for analysis, 27 (50%) were recipient and donor EBV IgG positive, four (7%) were recipient EBV IgG positive and donor EBV IgG negative, and 12 (20%) were recipient EBV IgG negative and donor EBV IgG negative. The remaining 13 (23%) patients were EBV IgG negative but received organs from EBV IgG-positive donors. The EBV immunoglobulin M (IgM) status was determined from 6 weeks post-transplant in the 11 mismatches who survived for longer than 28 d. Seven became EBV IgM positive, two remained EBV IgM negative; the status of the remaining two remains unknown. The EBV IgM status was also determined retrospectively in patients who were EBV IgG negative pretransplant and received organs from EBV IgG-negative donors. Nine became EBV IgM positive; the rest remained negative. PTLD was diagnosed in two of 56 patients from whom paired sera was available; one was donor and recipient EBV IgG negative; the other was donor and recipient EBV IgG positive. No cases of PTLD were diagnosed in the remaining eight patients from whom paired sera was not available. Our experience suggests that PTLD does not occur with any greater frequency in the 'mismatch' group, and does not justify EBV matching in pediatric thoracic transplantation where there is a higher proportion of EBV-negative recipients than in adults.

Adolescent↗
PubMed1991

Discrepant results with a latex agglutination test in the assessment of cytomegalovirus antibody status of cardiac transplant donors.

The cytomegalovirus (CMV) antibody status of 79 cardiac transplant recipients and their respective donors was determined by a latex-agglutination technique and by a CMV IgG ELISA technique on the same samples. Although good agreement between the two methods was found in recipient samples the latex method produced significantly more positive results in donor samples than did the ELISA test. Clinical and serological follow-up of the patients concerned over the first 6 months after transplantation suggested that the ELISA results were correctly predictive of donor transmitted primary CMV infection and that, therefore, the latex test was producing false positive readings. Further investigation is needed to discover the reason for these discrepancies. The use of donor samples taken at the time of organ retrieval may have prejudiced the latex test results. Until these problems are resolved it is suggested that the latex agglutination technique should not be the sole method adopted to assess donor CMV antibody status.

Antibodies, Viral↗
PubMed1990

Management of cytomegalovirus antibody negative patients undergoing heart transplantation.

In a series of 61 consecutive patients undergoing heart, heart and lung, and lung transplantation, 24 patients were known to be cytomegalovirus (CMV) antibody negative on the day of transplantation. Enzyme linked immunosorbent assays (ELISA) for CMV IgG were performed on donor samples on the day of operation. In 16 of the 24 susceptible patients the test was negative and the only preventive measure taken was the use of blood and blood products from CMV-antibody negative blood donors. None of these patients acquired primary infection with CMV. In another six patients the donor serum was found to contain CMV specific IgG, and in these patients, including one heart and lung transplant recipient, prophylaxis with CMV specific hyperimmune globulin was given. All six patients developed CMV IgM antibodies and in five there was an associated but clinically mild illness. None of these patients required treatment. In the remaining two patients ELISA tests on the donor sera gave equivocal results and hyperimmune globulin was withheld. Both patients developed primary CMV infection of greater severity than those given hyperimmune globulin and one required treatment. Reference tests confirmed that the donor sera contained CMV antibodies. Primary CMV infection in susceptible patients after heart transplantation can be avoided by the use of screened blood and blood products where the organ donor is seronegative to CMV and it can be improved by the use of prophylactic hyperimmune globulin where the donor is CMV antibody positive.

Antibodies, Viral↗
PubMed1986

High dose intravenous streptokinase in acute myocardial infarction--short and long term prognosis.

Streptokinase (1 million international units) was given intravenously over 30 or 60 minutes to 50 patients four hours or less after the onset of acute myocardial infarction. All were aged less than or equal to 70 years and had 4 mm or greater ST segment elevation in anterior or inferior leads. Rapid (mean 95 min) ST segment resolution, which was taken to indicate reperfusion of the myocardium, occurred in 36 (72%) patients. In these 36 the average time from onset of symptoms to peak creatine kinase, creatine kinase MB, and myoglobin was 9.45 hours, whereas it was 17 hours in the 14 patients in whom indirect criteria did not indicate reperfusion. Reperfusion arrhythmias were invariably present and ventricular tachycardia developed in five patients and ventricular fibrillation in two. The infarct related artery was seen to be open in 28 (70%) of the 40 patients who had delayed coronary arteriography. The frequency of patency in the infarct related artery was no different in patients given streptokinase less than 2 hours or between 2-4 hours from onset of symptoms nor did it differ when streptokinase was infused over 30 or 60 minutes. Mean left ventricular ejection fraction was 57% in those with a patient infarct related artery and 48% in those with an occluded vessel. Eight patients subsequently underwent elective percutaneous transluminal coronary angioplasty after successful thrombolysis and six had coronary artery bypass grafting. There were nine in-hospital reocclusions of the infarct related coronary arteries. Two bleeding episodes occurred; one required transfusion. Five of the 50 patients died in hospital. All of them had had an anterior myocardial infarction; four had bifascicular block and one had right bundle branch block. During follow up, four patients died, two suddenly and two from reinfarction. During follow up (mean 15 months) the frequency of reinfarction, dyspnoea, and angina was low and there was no difference in the proportions of patients returning to work between those with an open infarct related artery and those with a closed infarct related artery. Intravenous administration of high dose streptokinase to selected patients during the acute phase of myocardial infarction is a safe, effective, and practical method of thrombolysis. It must, however, be followed by coronary arteriography to select those patients in whom percutaneous transluminal coronary angioplasty or coronary artery bypass grafting will be helpful.

Adult↗