Biomedical subjects
L Homer
Publications and source records attributed to L Homer.
Production and kinetics of interleukin-1 in hemodialysis. In vivo and in vitro study.
Interleukin-1-beta (IL-1-beta) was measured in the plasma and peripheral blood mononuclear cell lysates of uremic patients undergoing maintenance hemodialysis by means of either cuprophane or polysulfone membranes. Basal plasma levels of IL-1-beta in hemodialyzed patients were strikingly higher than those of uremic patients on conservative treatment or of healthy subjects. Plasma levels of IL-1-beta in uremic patients increased significantly after 3 and 6 months of hemodialysis. The study of the kinetics of IL-1-beta concentration during a single hemodialysis session revealed that the concentration of IL-1-beta fell to 21 and 22% of the predialysis level with cuprophane and polysulfone, respectively. Hemodialysis patients also had a significantly higher intracellular IL-1-beta level than normal controls. During the hemodialysis session, an increase in cell-associated IL-1-beta was seen regardless of the membrane employed. In a parallel study, normal mononuclear cells were subjected to closed-loop in vitro dialysis with either cuprophane or polysulfone membranes, with or without acetate buffer. After 120 min of recirculation, an increase in cell-associated IL-1-beta was detected, but no changes were seen in the circulating medium. IL-1-beta production was not significantly influenced by either membrane or the dialysate composition. Hemodialysis has been associated with high plasma- and cell-associated IL-1 levels. The kinetics of intradialytic changes of IL-1-beta levels make IL-1 an unlikely cause of acute complications in hemodialysis. On the other hand, a chronic elevation of IL-1 in plasma of patients on maintenance hemodialysis may contribute to the development of some of the long-term complications of this treatment.
Immune deficiency in uremia: interleukin-2 production and responsiveness and interleukin-2 receptor expression and release.
We have studied the role of interleukin-2 (IL-2) and its receptors in the impaired in vitro lymphocyte response characteristic of hemodialysis patients treated by means of cuprophane membranes. The proliferative response of T lymphocytes as well as T-cell-dependent B cell proliferation after stimulation with mitogens was significantly reduced in hemodialysis patients. The in vitro production of IL-2 after such stimulation in parallel cultures was found to be similar in patients and in controls. The expression of IL-2 receptor on the lymphocyte cellular membrane in the hemodialysis group was also similar to controls. The in vitro proliferative response of uremic lymphocytes to exogenous IL-2, however, was significantly depressed suggesting a reduced availability of biologically active IL-2 receptor. The release of soluble IL-2 receptor by lectin-stimulated lymphocytes in culture was also significantly lower in the patient group; yet, hemodialysis patients has a strikingly elevated level of plasma soluble IL-2 receptor, and similar high levels were also found in three other groups of end-stage renal disease patients dialyzed by means of cellulose acetate, polysulfone and polyacrylonitrile membranes, as well as in a group of uremic patients on conservative treatment. In the hemodialysis patient group a significant positive correlation between levels of soluble IL-2 receptor and the duration of hemodialysis was found. Since soluble IL-2 receptor has been reported to down-regulate lymphocyte responses, the elevation in plasma levels of soluble IL-2 receptor in hemodialysis patients may be a pathogenetic factor in the progressive development of impaired immunity associated with end-stage renal disease.
Normal T lymphocyte function in patients with end-stage renal disease hemodialyzed with 'high-flux' polysulfone membranes.
T lymphocyte function was analyzed in patients hemodialyzed with 'high-flux' polysulfone membranes, which have been reported to improve the patients' overall clinical condition and well-being. For comparison purposes, patients treated by the use of 'low-flux' cuprophane membranes were also studied. Peripheral blood white cell counts, numbers of lymphocytes as well as the numbers of T cells and their CD4 and CD8 subsets were within normal range in both patient groups. The absolute number of B cells was slightly decreased in cuprophane-membrane- but not polysulfone-membrane-treated patients. The proliferative response of T lymphocytes after stimulation with optimal concentration of phytohemagglutinin (PHA) was normal in patients treated with 'high-flux' membrane dialysis but significantly reduced in those treated with cuprophane membranes. The generation of interleukin-2 (IL-2) receptor on T lymphocytes after PHA stimulation was normal in the polysulfone-membrane-treated group and slightly impaired in the cuprophane-membrane-dialyzed patients. Production of both IL-2 and interleukin-1, as well as the natural killer cell activity, in patients treated by 'high-flux' membrane dialysis were also comparable to controls. The levels of serum beta 2-microglobulin were significantly elevated in patients-maintained on 'high-flux' dialysis membranes but did not reach the levels seen in patients dialyzed by cuprophane membranes. The beta 2-microglobulin at levels seen in patients on cuprophane dialysis had no effects on activation and proliferation of control lymphocytes in vitro. These results suggest that impaired functional responses of T lymphocytes seen in end-stage disease patients on prolonged hemodialysis with cuprophane membranes are not seen in similar patients hemodialyzed with polysulfone membranes.
High-risk factors for cervical cancer. An epidemiological study in SWA/Namibia.
In an epidemiological study conducted in SWA/Namibia to document the prevalence of high-risk factors for cervical cancer 754 women belonging to a number of ethnic groups were examined. The prevalence of cervical intra-epithelial neoplasia and human papillomavirus infection was among the highest reported in the world. There was also an alarming incidence of other sexually transmitted diseases and disturbingly low usage of contraceptive methods. There is an urgent need for a comprehensive, well-organised cytological screening programme if an 'epidemic' of cervical cancer is to be prevented in SWA/Namibia. There was good evidence to suggest that an identical situation exists in the RSA.
T cell subsets and cellular immunity in end-stage renal disease.
The T lymphocyte population was studied by immunofluorescent staining with monoclonal antibodies and laser flow cytometry in the blood of 50 patients with end-stage renal disease undergoing long-term maintenance intermittent hemodialysis. The absolute number of T cells was lower in patients receiving dialysis for more than one year (p less than 0.001), as was the absolute count of helper T cells (p less than 0.005). In patients under 30 years of age, the absolute number of helper T cells was markedly reduced, whereas the number of suppressor/cytotoxic T lymphocytes was not changed. In patients between the ages of 30 and 60 years, both helper and suppressor cells were significantly reduced. In patients over 60 years of age, only the number of helper T cells was reduced. The in vitro response of patients' lymphocytes was reduced both in the mixed lymphocyte reaction (p less than 0.01) and after phytohemagglutinin stimulation (p less than 0.001). Natural killer cytotoxicity of patients' peripheral blood mononuclear cells, however, was unaffected.
Effect of endotoxin on oxygen consumption by a flow-controlled canine hind-limb preparation.
The effect of endotoxin upon oxygen consumption in a peripheral vascular bed was assessed in a canine hind-limb preparation. The left iliac vessels in 12 adult male mongrel dogs were isolated, the artery cannulated proximally and distally such that arterial inflow could be routed through a roller pump, and a nonocclusive catheter placed in the vein. Oxygen consumption was then calculated as the product of flow rate and and arteriovenous oxygen content difference at a series of flow rates before and after the systemic administration of endotoxin (3 mg/kg) or saline solution. At each flow rate, oxygen consumption by the extremities of endotoxic animals was significantly greater (P < 0.01) than that measured in control animals. This finding mitigates the hypothesis that endotoxin has a direct effect on cells reducing tissue oxygen consumption.
Blood clearance of the BAI strain A virus of avian myeloblastosis in newly hatched chicks.
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Interleukin-1 kinetics in hemodialysis.
Interleukin-1 (IL-1) was measured in the plasma and in mononuclear cell (MC) lysates from patients on maintenance hemodialysis (HD) using either cuprophan (CU) or polysulfone (PS) membranes. Basal plasma levels of IL-1 in HD patients were significantly higher than those of uremic patients on conservative treatment or of healthy subjects. In 10 patients on conservative treatment, plasma levels of IL-1 increased significantly after 3 and 6 months of HD. During a single HD session, plasma IL-1 fell to 21% (CU) and 22% (PS) of pre-HD levels. Hemodialysis patients had a significantly higher intracellular IL-1 content than normal controls. During HD, a further increase was seen regardless of the membrane employed. A parallel in vitro study showed that IL-1 produced during HD requires at least 24 hours to be released, and that both CU and PS are able to bind and clear IL-1.