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Biomedical subjects

C A Michie

Publications and source records attributed to C A Michie.

At least 19 recordsLinked to original sources

Effect of lamivudine on human T-cell leukemia virus type 1 (HTLV-1) DNA copy number, T-cell phenotype, and anti-tax cytotoxic T-cell frequency in patients with HTLV-1-associated myelopathy.

Patients with human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) typically have a high HTLV-1 proviral load in peripheral blood mononuclear cells and abundant, activated HTLV-1-specific cytotoxic T lymphocytes (CTLs). No effective treatment for HAM/TSP has been described so far. We report a 10-fold reduction in viral DNA for five patients with HAM/TSP during treatment with the reverse transcriptase inhibitor lamivudine. In one patient with recent-onset HAM/TSP, the reduction in viral DNA was associated with a fall in the frequency of CTLs specific to two peptides in the immunodominant viral antigen Tax. The half-life of peripheral blood mononuclear cell populations was estimated from changes in viral DNA copy number, CTL frequency, reduction in CD25 expression, and the loss of dicentric chromosomes following radiation-induced damage. Each of these four different techniques indicated a cellular half-life of approximately 3 days consistent with continuous lymphocyte replication and destruction. These results indicate that viral replication through reverse transcription significantly contributes to the maintenance of HTLV-1 viral DNA load. The relative contribution of proliferation versus replication may vary between infected people.

Adult↗

The clinical significance of T-cell superantigens.

Superantigens are a diverse collection of molecules that share the ability to activate specific lymphocyte subsets. In animal models, many of these molecules delete T-cell populations or render them anergic. The clinical impact of superantigens is significant, but much of their pathophysiology remains unclear.

Animals↗

Physiological secretion of chemokines in human breast milk.

Human breast milk has been observed to contain high concentrations of the chemotactic cytokines (chemokines) interleukin-8 (IL-8) and RANTES. Concentrations are greatest in colostrum, but are measurable in milk after several months of lactation. These chemokines are also found in the secretions of patients with galactorrhoea and in the "witch's milk" of the newborn. Chemokine levels show good correlation with the sodium levels but not with cell counts or the creamatocrit of the secreted milk. Mothers with pre-term deliveries show no statistical difference in chemokine secretion in comparison with those with term deliveries. Immunohistochemisty demonstrates IL-8 and RANTES immunoreactivity in the acinary epithelial cells of normal mammary tissue and IL-8 and RANTES were shown to be produced by cultured, human mammary epithelial cells (HMEC) after stimulation with different cytokines. These results suggest that mammary epithelial cells are the source of chemokines in human milk and that the recruitment of leukocytes in human milk is likely to be chemokine-driven.

CD4 Antigens↗

Modeling the lifespan of human T lymphocyte subsets.

T lymphocytes may be classified as naive or memory cells, depending on whether they possess immunological memory. The central tenet of this work is that memory lymphocytes revert to naive lymphocytes in vivo. This phenomenon is modeled by a mechanism qualitatively similar to Demoivre's law of human mortality. Additionally, both lymphocyte subsets undergo decay. Model parameters and their standard errors are estimated by maximizing a likelihood function constructed by Kalman filtering of the experimental data on the assumption that it is contaminated by measurement noise of constant relative error.

Cell Death↗

Lymphocyte dynamics, apoptosis and HIV infection.

Death of HIV-infected CD4+ cells and HIV-induced death of uninfected CD4+ cells by apoptosis have been suggested to be important factors in causing the gradual progressive decline of CD4+ cells in the blood of HIV-positive patients. Recent advances in our knowledge of the dynamics of infection and the mechanism of apoptosis are reviewed with the aid of a mathematical model.

Apoptosis↗