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Biomedical subjects

R C Burton

Publications and source records attributed to R C Burton.

At least 55 records · Page 3Linked to original sources

The effect of immunosuppressive agents on lymphocyte subsets in rat peripheral blood.

A method for monitoring circulating lymphocytes subsets in the rat on an automated flow cytometer with monoclonal antibodies was used to ascertain in vivo effects of various doses of immunosuppressive agents. The agents tested were anti-lymphocyte serum (ALS), azathioprine (AZA), cyclophosphamide (CTX), cyclosporin A (CsA) and methylprednisolone (MP). Each immunosuppressive agent varied in its capacity to induce changes in T cell subsets and B cell numbers. The rapidity of onset of action of the agents varied considerably; with ALS and MP maximal effects were seen within hours whilst the effects with CsA, cyclophosphamide (CTX) and azathioprine (AZA) took several days to develop. ALS had marked anti-T cell activity but did not selectively affect the T cell subsets. AZA and CTX both exerted their major effect upon the B cell (OX4+) subpopulation. CsA administration was associated with the appearance of many circulating lymphocytes which expressed the pan-T marker (W3/13) but neither of the T cell subset markers (W3/25, OX8). With CsA there was no significant alteration in the W3/25:OX8 ratio, although a persistent decrease in the number of all T lymphocytes was observed after administration of this drug at a dose of 45 mg/kg had ceased. MP was the only drug which had a marked selective effect on a T cell subset. The numbers of circulating Class II major histocompatibility complex (MHC) reactive lymphocytes (W3/25+) were significantly more depressed than the Class I MHC reactive subset (OX8+). This effect persisted for up to 31 days after the single injection of a depot preparation of this drug, and was found to be associated with prolonged survival of precultured endocrine xenografts.

Animals↗

Effects of captopril on circulating T lymphocyte subsets.

Six patients treated with captopril for severe essential hypertension were studied to determine whether the drug significantly altered circulating peripheral blood T (Thymus derived) lymphocytes and T lymphocyte subsets. OKT3+ (functionally mature T lymphocytes), OKT4+ (class II major histocompatibility complex [MHC] reactive T lymphocytes) and OKT8+ (class I MHC reactive T lymphocytes) T lymphocytes were monitored using monoclonal antibodies and flow cytometry before commencement of treatment and then at intervals during 14 months of captopril administration. Results showed a significant increase in the absolute numbers of OKT4+ cells at 2 h (p less than 0.05) and a decrease at 12 weeks (p less than 0.01) during captopril treatment. These findings indicate that captopril has an effect on cellular immunity in vivo.

Aged↗

Sequential monitoring of peripheral blood lymphocyte subsets in rats.

The methodology of enumeration of T cell subsets in humans is well established and has widespread clinical application. Sequential monitoring of lymphocyte subsets in small animals requires a consistent and reliable methodology for staining and enumerating lymphocyte populations. The optimal conditions for enumerating subclasses of rat peripheral blood lymphocytes with the Spectrum III flow cytometer are described. The sources of biological variation and technical error that were considered in optimizing the techniques and the limitations in applying them are discussed.

Animals↗

Frequency of murine cytotoxic T cell precursors reactive to plasma cell tumour-associated antigens as compared to major histocompatibility antigens.

The frequency of cytotoxic T lymphocyte precursors (CTL-P) reactive to plasmacytoma (PCT) tumour-associated antigens (TAA) was studied in BALB/c mouse spleen. Progressively decreasing numbers of responder BALB/c spleen cells were cultured with mitomycin C-treated stimulator MPC-11 BALB/c PCT cells, and a Poisson analysis was performed of the wells scored positive in a 51Cr release assay with PCT target cells. It was found that approximately 2 per million BALB/c spleen cells were CTL-P reactive to TAA of MPC-11, and about one in three of these precursors responded to a TAA expressed by MPC-11 which was shared with the C3H PCT C1.18. The frequency of CTL-P reactive to TAA was shown to be 30 to 500 fold lower than that for CTL reactive to various major histocompatibility complex alloantigens, and the addition of exogenous Interleukin-2 only resulted in a 2-3 fold increase in this CTL-P frequency. These results suggest that the weak levels of tumour immunity induced in vivo by immunisation of BALB/c mice with MPC-11 are, at least in part, due to a very low frequency of CTL-P reactive to TAA of that PCT.

Animals↗

Flow cytometric enumeration of absolute lymphocyte number in peripheral blood using two parameters of light scatter.

A method was developed to measure the absolute lymphocyte count (ALC) of whole blood using the Spectrum III automated flow cytometer. Ninety-nine samples of human peripheral blood were analysed on the Spectrum and the Coulter Counter S Plus II, to allow for comparison of the two machines. Regression analysis was used to test the extent of agreement between the sets of measurements on the two machines. The results demonstrated that the slope of the regression line was not significantly different from one, indicating a high level of correlation between Spectrum and Coulter ALC's. However, the mean difference between Coulter and Spectrum ALC's was not equal to zero, with the Spectrum giving counts approximately 10% lower than those of the Coulter machine. This is attributed to the different ways by which the two machines define a lymphocyte, the Spectrum III by two parameters of light scatter and the Coulter S Plus II by the single parameter of cell volume.

Flow Cytometry↗

Association of herpesvirus infections with T-lymphocyte-subset alterations, glomerulopathy, and opportunistic infections after renal transplantation.

We studied the interrelation among herpes-virus infections, T-lymphocyte subsets, opportunistic infections, and renal histopathology in 28 recipients of renal allografts. All primary or reactivated herpesvirus infections occurring in the first three months after transplantation in recipients of cadaveric grafts accompanied persistent inversions in the ratio of OKT4 (helper/inducer) to OKT8 (cytotoxic/suppressor) lymphocytes. In the less heavily immunosuppressed recipients of organs of living related donors, these inversions were seen only in association with clinically apparent cytomegalovirus infections. Five of seven opportunistic infections occurred in patients with OKT4/OKT8 ratios of less than 1.0. Biopsy specimens from patients with renal dysfunction occurring in association with a low OKT4/OKT8 ratio frequently revealed glomerular damage rather than acute cellular rejection. Monitoring of T-lymphocyte subsets provides early evidence of herpesvirus infections and identifies patients at increased risk for opportunistic infection after renal transplantation.

Biopsy↗

Effects of prophylactic antibiotics on wound infection after elective colon and rectal surgery: 1960 to 1980.

Wound infection continues to be a common complication of elective colon and rectal surgery. During the period from 1960 to 1980, 42 prospective, controlled prophylactic antibiotic trials were undertaken which addressed this problem. In this report we have analyzed these trials and compared them to all noncontrolled, prospective wound infection surveys and a representative sample of the retrospective surveys of the same period. From this analysis several conclusions have become apparent: (1) wound infection remains a common complication for which prophylactic antibiotics are generally effective, (2) the most effective agents are those with activity against anaerobic bacteria, (3) orally administered nonabsorbable antibiotics have little effect on reducing wound infection following these procedures, and (4) the optimal antibiotic regimen is yet to be found. The data do suggest, however, the more preferred regimens currently available as well as those worthy of further investigation.

Anti-Bacterial Agents↗