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Biomedical subjects

A Fyfe

Publications and source records attributed to A Fyfe.

8 recordsLinked to original sources
PubMed1998

Complementary medicine.

The widespread use of complementary and alternative medicine techniques, often explored by patients without discussion with their primary care physician, is seen as a request from patients for care as well as cure. In this article, we discuss the reasons for the growth of and interest in complementary and alternative medicine in an era of rapidly advancing medical technology. There is, for instance, evidence of the efficacy of supportive techniques such as group psychotherapy in improving adjustment and increasing survival time of cancer patients. We describe current and developing complementary medicine programs as well as opportunities for integration of some complementary techniques into standard medical care.

Breast Neoplasms↗
PubMed1995

Direct gene transfer into donor hearts at the time of harvest.

Access to the donor heart at the time of harvest provides a unique opportunity for genetic manipulation of this organ before transplantation. We sought to determine (1) if donor mouse hearts express a foreign gene administered at harvest and, (2) if so, what route of gene delivery is most effective. At harvest, 30 micrograms of promoter cytomegalovirus-luciferase deoxyribonucleic plasmid in cationic liposomes was injected directly into the myocardial apex (group I), into the right atrium (group II), or into the coronary arteries (group III). The donor hearts were then transplanted into the abdomen of recipient mice of the same strain. The transplanted hearts were removed in 4 days and luciferase expression was assayed by immunohistochemistry. In group I, luciferase activity was localized to the apex. In group II, where plasmid was delivered into the right atrium, luciferase expression was detected in the right ventricle and sparsely in the coronary perivascular area. In group III, where plasmid was injected into the coronary arteries, the transplanted hearts demonstrated luciferase expression in (1) perivascular areas surrounding coronary arteries and veins, (2) coronary capillaries, and (3) the endocardia of both ventricles. This study suggests that (1) donor mouse hearts can be genetically modified at the time of harvest and (2) intracoronary infusion of plasmid yields the most effective method of delivery. Administration of plasmid in the coronary arteries localizes the expression to the endocardium and the coronary vasculature, both sites of immunologic interactions after heart transplantation.

Animals↗
PubMed1993

Coronary sinus sampling of cytokines after heart transplantation: evidence for macrophage activation and interleukin-4 production within the graft.

OBJECTIVES: This study was undertaken to evaluate the organ-specific release of cytokines after heart transplantation and to assess any correlation with transplant rejection. This cytokine profile should document the relative activation of mononuclear cell subsets within the graft. BACKGROUND: Up to 60% of mononuclear cells infiltrating the cardiac allograft during rejection are macrophages, but their role is undetermined. The T lymphocytes are activated, but the activity of specific T cell subsets is not known. We sought to assess for the first time in humans the in vivo activation of mononuclear cell subsets by measuring coronary sinus cytokine levels after heart transplantation. METHODS: Paired superior vena cava and coronary sinus serum samples were assayed for interleukin (IL)-2, IL-4 and IL-6, soluble IL-2 receptors, tumor necrosis factor-alpha and neopterin in 10 patients at the time of 40 routine endomyocardial biopsy procedures. All cytokine measurements were made by using enzyme-linked immunosorbent assay; neopterin was measured by using radioimmunoassay. RESULTS: Interleukin-2 levels were not detectable (< 0.8 U/ml) in either the superior vena cava or the coronary sinus in the presence or absence of rejection. Interleukin-2 receptor levels were uniformly elevated to 1,283 U/ml in the superior vena cava and to 1,232 U/ml in the coronary sinus, with no correlation with rejection severity. Interleukin-4 levels were consistently higher in coronary sinus serum than in peripheral blood (229 vs. 61 pg/ml, p < 0.0005), but there was no relation with rejection. Interleukin-6 levels were higher in the coronary sinus than in the superior vena cava (200 vs. 120 pg/ml, p < 0.05). Tumor necrosis factor-alpha showed consistently elevated levels in coronary sinus serum (68 vs. 17 pg/ml, p < 0.0005), with no relation with rejection. Neopterin, which is produced only by activated macrophages, was also consistently elevated in the coronary sinus (2.5 vs. 2.2 nmol, p = 0.08). CONCLUSIONS: The cardiac allograft is a major source of cytokines after heart transplantation. The cytokine profile allows the activity of subsets of the mononuclear cell infiltrate to be investigated. Elevated coronary sinus activity of the macrophage-specific metabolite neopterin suggests macrophage activation within the allograft. This possibility is supported by elevated coronary sinus levels of tumor necrosis factor-alpha and IL-6. The T lymphocytes are activated, as evidenced by high soluble IL-2 receptor levels, but IL-2 production was suppressed by conventional immunosuppressive therapy. Coronary sinus IL-4 levels represent T helper-2 cell activation within the graft despite immunosuppression. We could find no temporal relation between the coronary sinus or superior vena cava cytokine concentration or profile and severity of rejection on concurrent biopsy studies.

Analysis of Variance↗
PubMed1987

C3b receptor (CR1) expression on the polymorphonuclear leukocytes from patients with systemic lupus erythematosus.

Polymorphonuclear leukocytes (PMN) C3b receptor (CR1) numbers have been measured in 14 normal individuals and 15 patients with SLE. The results in the normals showed that PMN possess three distinct pools of CR1. CR1 expression was lowest at 0 degrees C (mean 86,000 +/- s.e.m. 7,000), but increased when the cells were incubated at 37 degrees C (125,000 +/- 16,000) or when the cells were exposed to the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP, 10(-5) mol 1) at 37 degrees C (207,000 +/- 21,000). The increased expression at 37 degrees C was not dependent upon protein synthesis, an intact cytoskeleton or energy. Although the response to FMLP did not require de novo protein synthesis, increased CR1 expression was dependent upon an intact cytoskeleton and energy. All three PMN CR1 pools were reduced in patients with active SLE, but were normal in those in whom the disease was inactive. Serial studies performed on three SLE patients showed that PMN CR1 numbers were low during periods of disease activity and increased during remission. These data suggest that low PMN CR1 numbers in SLE are a consequence of the disease.

Blood Proteins↗
PubMed1987

The relative roles of genetic and environmental factors in the regulation of erythrocyte C3b receptor (ECR1) numbers in normal individuals.

Erythrocyte C3b receptors (ECR1) have been measured in 122 pairs of twins (60 monozygotic, 62 dizygotic) using an [125I]-labelled monoclonal antibody (E11). The range of ECR1 numbers was wide, 99-4179 sites/cell, with a log-normal distribution around a geometric mean of 837 sites/cell. The intra-pair variance in dizygotic twins was no greater than that in monozygotic twins. These data indicate that ECR1 numerical expression is governed by environmental rather than genetic factors.

Adolescent↗
PubMed1986

Decreased C3b receptors (CR1) on erythrocytes from patients with systemic lupus erythematosus.

Using 125I-F(ab')2 anti-CR1 we have measured C3b receptors (CR1) on the erythrocytes of 56 normal individuals 26 patients with systemic lupus erythematosus (SLE) and 24 with rheumatoid arthritis (RA). The mean number of CR1 sites in SLE (1150/cell) but not RA (1460/cell) was significantly lower (P less than 0.01) than normal (2200/cell). Although the cumulative frequency curve for normals showed minor inflections at frequencies of 18% and 64%, these were not sufficiently marked to permit us to conclude that they distinguished subpopulations of different CR1 phenotypes. Measurement of CR1 numbers of two normal families and four families of SLE patients indicated that low CR1 numbers aggregated in families as did high CR1 numbers, a finding which suggests that CR1 numbers are under genetic control. However, certain observations in SLE patients indicated that low CR1 numbers could be an acquired abnormality. These included, (a) absent CR1 phenotype in a patient whose family had moderate and high CR1 numbers, (b) increasing CR1 numbers as SLE patients went into remission, (c) CR1 numbers were lower in patients with active compared with inactive disease and (d) CR1 numbers were different in each of two sets of identical twins (Fig. 4A). Our conclusions are that, (a) genetic factors probably influence CR1 numbers in normal individuals, (b) that our findings were not inconsistent with the two codominant allele models (Wilson et al., 1982), and (c) the low CR1 phenotype of SLE patients may be secondary to the disease process.

Arthritis, Rheumatoid↗