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Biomedical subjects

H F Davies

Publications and source records attributed to H F Davies.

16 recordsLinked to original sources
PubMed2001

Removal of bowel aerobic gram-negative bacteria is more effective than immunosuppression with cyclophosphamide and steroids to decrease natural alpha-galactosyl IgG antibodies.

Natural alpha-Galactosyl (Gal) antibodies play an important role in the rejection of pig xenografts by humans and Old World monkeys. In this study we investigate the efficacy of two different strategies to reduce the serum level of natural anti-Gal antibodies. On the one hand, removal of aerobic gram-negative bacteria from the intestinal flora, because anti-Gal antibodies appear to be produced as a result of the continuous sensitization by these microorganisms. On the other hand, we studied the effect on these antibodies of an immunosuppressive regimen of cyclophosphamide and steroids. Ten baboons were treated for three months with norfloxacin (Nor Group; n=6) or cyclophosphamide and steroids (CyP Group; n=4). A further four baboons did not receive any treatment (Control Group). Aerobic gram-negative bacteria became negative in stools of the Nor Group after two weeks of treatment, and remained undetectable until week 7. Thereafter, a gradual increase on the fecal concentration of aerobic gram-negative bacteria was observed despite the norfloxacin treatment. The mean anti-Gal IgG in the Nor Group gradually declined from week 4 to 9 to a mean of 62.7 +/- 18% of the baseline level, and during this period were significantly lower than in the CyP (P<0.02) and the Control (P<0.05) groups. No differences were observed between the three groups during the 16 weeks of follow-up in serum levels of anti-Gal IgM, hemolytic anti-pig antibodies, total IgG, IgM and IgA. In conclusion, removal of normal aerobic gram-negative bacteria from the intestinal flora is more effective than immunosuppression with CyP and steroids in reducing the level of natural anti-Gal antibodies, although there is no discernible effect on IgM antibodies.

Animals↗
PubMed1998

HLA-specific antibodies in highly sensitized patients can cause a positive crossmatch against pig lymphocytes.

BACKGROUND: The presence of IgG HLA-specific antibodies in the serum of patients awaiting transplantation indicates T- and B-cell priming and would result in acute rejection of a poorly matched human allograft. Recent advances in xenotransplantation, with the amelioration of hyperacute rejection using transgenic pig kidneys, may benefit such patients. However, accelerated cellular rejection might result from the primed T-cell recognition of antigenic epitopes shared between pig and human MHC molecules. METHODS: We have compared the reactivity of IgG antibodies from 8 nonsensitized (NS) and 13 highly sensitized (HS) patients with human and pig lymphocytes by flow cytometry. Xenoreactive natural antibodies (XNA) were absorbed with pig red blood cells, and HLA class I-specific antibodies were further absorbed with pooled human platelets. RESULTS: Before XNA absorption, 20 of the 21 patients had a positive IgG crossmatch with pig lymphocytes, and there was no difference between NS and HS patients. In contrast, after XNA absorption, none of the 8 NS patients were positive, compared with 9 of the 13 HS patients (mean of the median channel fluorescence values of 7.7 and 86.5, respectively; P=<0.001). For XNA-absorbed HS patient sera, 20 of 30 (67%) pig lymphocyte crossmatch combinations were positive, with a mean median channel fluorescence value of 125 (range 31 to 294) compared with 9.5 (range 7 to 13) for the 10 crossmatch-negative combinations. Platelet absorption resulted in a concomitant reduction in antibody binding to pig lymphocytes in three of six HS patient sera, indicating that HLA class I-specific antibodies are responsible, at least in part, for the positive crossmatch. CONCLUSION: These results suggest that some IgG HLA-specific antibodies can bind to pig lymphocytes, analogous to a positive crossmatch with allogeneic donors.

Animals↗
PubMed1994

CD4 and CD8 monoclonal antibody therapy in canine renal allografts.

Therapy with CD4 and CD8 monoclonal antibodies was evaluated in dogs which received double-haplotype MHC-mismatched renal allografts. Neither CD4 nor CD8 monoclonal antibodies given alone prolonged allografts survival (creatinine > or = 300 micromol/l) beyond 7 days. However, combined therapy with CD4 and CD8 antibodies given up to day 10 did prolong allograft survival to a median of 14 days. A longer (21 day) course of CD4 and CD8 antibodies did not extend allograft survival further. The effect of prolonged antibody therapy was restricted by the occurrence of both an antiglobulin response and an anaphylactoid reaction to the monoclonal antibody preparation. When the CD4 and CD8 antibodies were combined with a pan-T-cell-depleting Thy-1 antibody, the survival of double-haplotype mismatched allografts was further prolonged (median 16 days). The median survival of single-haplotype mismatched renal allografts on this triple therapy was 21 days, with one surviving to day 36.

Anaphylaxis↗
PubMed1981

Obstetric pain relief in a district hospital. The provision of a limited epidural service.

The effectiveness of the various methods used to provide obstetric pain relief in a District General Hospital was assessed. More than 70% of mothers were generally satisfied with the pain relief they received, but the majority would, in retrospect, have liked some additional analgesia at some stage. Seventeen per cent would have liked an epidural. Neither the social group of the mothers nor their duration of residence in the area of the hospital affected the demand for additional pain relief. The demand for epidurals was greater in social groups I and II. The effect of the obstetric pain relief service on the workload of available trained staff was assessed: most of the demands were made between the hours of 0900 and 2100 hours.

Anesthesia, Epidural↗
PubMed1979

Stimulation of lymphocyte proliferation by non-lymphoid porcine tissue cells.

Cultured porcine non-lymphoid cells, characterized by biochemical and morphological criteria, were derived from different tissues of individuals typed by serological and mixed lymphocyte culture methods for gene products of the major histocompatibility complex. These cultured cells have been used as stimulators in mixed lymphocyte-tissue cell cultures in order to investigate (1) the magnitude, kinetics and dose-dependence of lymphocyte transformation caused by tissue cells compared with that caused by lymphocytes as stimulators; (2) the relationship between the expression of serologically detected Ia-like antigens by tissue cells and their ability to cause lymphocyte transformation; (3) the genetic control of stimulation by tissue cells and by lymphocytes and (4) the expression and genetic control of lymphocyte stimulatory properties restricted to tissue cells and absent from lymphocytes. It has been shown that some but not all kinds of tissue cells can stimulate allogeneic lymphocytes strongly and that the characteristics of such stimulation are similar to those observed in mixed lymphocyte cultures. Strong stimulation by tissue cells does not always correlate with the expression of serologically detectable Ia-like antigens, but appears to be controlled by the major histocompatibility complex. There is evidence that certain tissue cells possess lymphocyte stimulatory properties not shared by lymphocytes. Preliminary data suggest that such tissue cell specific stimulation is not controlled by the major histocompatibility complex, though more detailed genetic analysis is required.

Animals↗