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S L Lewis

Publications and source records attributed to S L Lewis.

51 records · Page 3Linked to original sources
PubMed1988

Alterations in chemotactic factor-induced responses of neutrophils and monocytes from chronic dialysis patients.

Chronic renal failure patients on dialysis have an increased susceptibility to infection. Previous studies have demonstrated that these patients have a decreased in vitro neutrophil (PMN) chemotactic response and a reduction in C5a receptor availability on both PMN and monocytes. This study was designed to determine if other chemotactic factor-mediated responses of PMN and monocytes from hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients are abnormal. The responses investigated included in vitro chemotaxis, superoxide generation, H2O2 production, and myeloperoxidase (MPO) release. These studies showed that PMN from HD and CAPD patients are significantly decreased in their chemotactic response to both C5a and fMLP when compared to normal controls. The response of HD patient's PMN to C5a was decreased by an average of 55.1% (p less than 0.005) and for CAPD patients by 49.7% (p less than 0.01). Similarly, chemotactic responses to fMLP were decreased by an average of 44.7% (p less than 0.005) for HD patients and 36.3% (p less than 0.02) for CAPD patients. Superoxide anion production by PMN and monocytes from HD and CAPD patients in response to C5a and fMLP was also significantly decreased compared to controls. PMN superoxide production in response to C5a was decreased by an average of 36.5% (p less than 0.001) for HD patients and 32.0% (p less than 0.001) for CAPD patients. fMLP-stimulated production of superoxide was also decreased but to a lesser degree with a mean decrease of 18.0% (p less than 0.01) for HD patients and 24.1% decrease (p less than 0.01) for CAPD patients. This decreased responsiveness was restricted to C5a- and fMLP-stimulated superoxide production since phorbol myristate acetate (PMA)-stimulated responses were comparable to controls. A similar pattern of decreased superoxide production was found with monocytes from these patients. Comparable decreases in chemotactic factor-stimulated responses were also observed in a flow cytometric assay of H2O2 production in both PMN and monocytes and an in vitro assay of MPO release from PMN. Analysis of the binding of fluorescent C5a to PMN showed a direct correlation between decreased C5a binding and decreased O2- production and MPO release. Since all of these chemotactic factor-stimulated events are involved in the inflammatory process and the killing of microorganisms, alterations in these WBC functions in dialysis patients may contribute to their increased susceptibility to infection.

Chemotactic Factors↗
PubMed1987

Neutrophil and monocyte alterations in chronic dialysis patients.

Chronic renal failure patients maintained on dialysis have an increased risk for infection. This article summarizes research that has been done on the function of neutrophils (PMNs) and monocytes from chronic hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients. The studies involving the HD patients showed that there is a decreased PMN in vitro chemotactic response, decreased C5a receptors on both PMNs and monocytes, and decreased oxidative metabolic responses of PMNs and monocytes to the chemotactic stimuli C5a and formyl-met-leu-phe (fMLP), but not to nonchemotactic factors. The results of studies involving phagocytosis have been conflicting and are discussed in this paper. Due to the basic principles of peritoneal dialysis, this treatment approach depletes the peritoneum of phagocytic cells, adversely affects the function of peritoneal WBCs, dilutes the existing opsonins, and alters the physiologic environment of the peritoneal cavity. Studies of peripheral PMN and monocyte function in CAPD patients have shown that, similar to HD patients, they also have decreased C5a receptors and decreased oxidative metabolic responses to the chemotactic factors C5a and fMLP. Although the factors contributing to the risk of infection in chronic dialysis patients are multifaceted, there are definitely alterations in PMN and monocyte function.

Disease Susceptibility↗
PubMed1987

Leukocyte C5a receptor modulation during hemodialysis.

Exposure of blood to hemodialysis (HD) membranes results in the activation of the complement system. In this study, flow cytometry was used to analyze the binding of fluoresceinated chemotactic factors (C5a, f-Met-Leu-Phe-Lys [fMLPL], and casein) and aggregated IgG to PMN and monocytes isolated from normal whole blood following passage through a hemodialyzer. Analysis of ligand binding by these PMN and monocytes showed no difference in the binding of casein, fMLPL, or aggregated IgG throughout the 45 minute procedure. In contrast, a progressive decrease in the binding of C5a by PMN and monocytes occurred. By 45 minutes, the average percentage of PMN binding C5a had dropped from 95 to 61% and monocytes from 73 to 40%. In additional studies, blood samples were obtained from chronic renal failure patients undergoing hemodialysis at four different time intervals during dialysis. Total white blood cell (WBC) counts showed that the mean WBC count at 30 minutes dropped to 60.9% of the predialysis WBC count, and rebounded to 133.8% by two hours and 128.2% by four hours. Analysis of the binding of C5a, casein, fMLPL, or aggregated IgG by PMN or monocytes from HD patients indicated there were no significant differences at the four time intervals studied. When blood samples from normal subjects or chronic hemodialysis patients were incubated in vitro with dialysis membrane fibers, a loss of identifiable C5a receptors was observed on PMN from normal blood, while PMN from HD patients showed no significant change in the percentage of C5a-receptor-positive cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Complement C5↗
PubMed1987

Analysis of density changes and chemotactic receptors of leukocytes from chronic hemodialysis and peritoneal dialysis patients.

Analysis of standard Ficoll-Hypaque (density = 1.077 g/ml) separation profiles of peripheral white blood cells (WBC) from patients undergoing hemodialysis (HD) demonstrated that dialysis caused a marked decrease in the density of polymorphonuclear leukocytes (PMN) resulting in about 50% of these cells separating with the mononuclear cells. In vitro exposure of normal control peripheral blood to HD membranes as well as to the purified chemotactic factors C5a, C5ades-Arg, and formyl-Met-Leu-Phe (fMLP) also resulted in PMN density changes which altered the Ficoll-Hypaque separation profiles of WBC. Therefore, these results imply that C5a generation, resulting from complement activation by the HD membrane, induced the density changes in the PMN from HD patients. Further studies using flow cytometry and fluorescein-labeled chemotactic factors (C5a, formyl-Met-Leu-Phe-Lys [fMLPL] and casein) indicated that HD patients had a significant reduction in the ability of their PMN and monocytes to bind C5a. This contrasted with the findings of no significant difference in the percentage or fluorescence intensity of HD patients' PMN or monocytes binding casein or fMLPL. Functional studies to analyze chemotactic-factor-mediated responses indicated that there was a decreased ability of HD patients' PMN and monocytes to generate superoxide anion, produce H2O2 and release myeloperoxidase in response to both C5a and fMLP. Additional studies evaluated the binding of chemotactic factors to PMN and monocytes from normal blood following passage through a hemodialyzer and from patients undergoing HD. Analysis of receptor binding by control cells passed through the dialyzer showed that there was a progressive decrease in the percentage of C5a-receptor-positive PMN and monocytes but no change with casein or fMLPL. In contrast, peripheral PMN and monocytes from chronic renal failure patients on HD showed no difference in C5a, casein or fMLPL receptors during the course of HD as compared to the predialysis period. This appears to be attributable to a difference in the regulation of the C5a that is generated as a result of the dialysis-membrane-induced activation of the complement system. Although C5a has been shown to be continuously generated during the course of HD, these patients show no modulation of their C5a receptors during the course of HD or when their whole blood is exposed to dialysis membrane fibers. These findings suggest that there are mechanisms functioning in chronically dialyzed patients to protect them from the effects of excessive C5a generation during HD.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Separation↗
PubMed1987

Phenylalanine and tyrosine in serum and eluates from dried blood spots as determined by reversed-phase liquid chromatography.

We have developed a reversed-phase liquid-chromatographic procedure for simultaneously determining phenylalanine and tyrosine in serum and eluates of dried blood spots. Batch derivatization with phenylisothiocyanate and a 10-min linear gradient chromatographic assay with ultraviolet absorbance detection provide rapid sample throughput. Interrun precision (CV) is less than 12%; analytical recovery (from blood spot samples) exceeds 85%. Results for patients' samples correlate well with those from an amino acid analyzer and we encountered no apparent interferences. The speed and specificity of this assay facilitate the rapid diagnosis and monitoring of patients with phenylketonuria.

Chromatography, High Pressure Liquid↗
PubMed1986

Density changes in leukocytes following hemodialysis or exposure to chemotactic factors.

Analysis of standard Ficoll-Hypaque separation profiles of peripheral WBC from patients undergoing hemodialysis (HD) demonstrated that dialysis caused a marked alteration in the number of cells found at both the interface between the Ficoll-Hypaque and plasma which normally contains mononuclear cells and the cell pellet which normally contains granulocytes. By 30 min into dialysis, there was a 175% increase in white blood cells in the mononuclear band with a corresponding decrease in the number of cells obtained from the cell pellet. When peripheral blood samples from normal donors were pumped through various types of hemodialyzers, a shift in the cell separation profiles similar to that of patients undergoing HD was observed. Differential analysis of the cells obtained from both the interface between the Ficoll-Hypaque and plasma and the cell pellet showed that by 30 min into dialysis, the 'mononuclear' band contained 40-50% polymorphonuclear neutrophils (PMN). To ascertain whether the cell separation changes were possibly due to C5a generation resulting from complement activation by the HD membrane, whole blood was incubated with the purified chemotactic factors C5a, C5ades arg, and formyl-methionyl-leucyl-phenylalanine. This resulted in similar alterations in PMN densities. This study demonstrates that both in vivo and in vitro exposure of human peripheral blood to HD membranes as well as the chemotactic factors C5a, C5ades arg, and formyl-methionyl-leucyl-phenylalanine results in density changes in PMN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

C5a receptor modulation on neutrophils and monocytes from chronic hemodialysis and peritoneal dialysis patients.

Chronic renal failure patients have an increased risk for infection which may partially be due to altered chemotactic ability of their white blood cells. This study was designed to evaluate chemotactic factor and Fc receptor expression on neutrophils (PMN) and monocytes from chronic renal failure patients on hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Analysis of these receptors was performed using flow cytometry and fluorescent chemotactic factors (C5a, f-Met-Leu-Phe-Lys [fMLPL] and casein) and heat-aggregated human IgG. Peripheral blood PMN and monocytes obtained from 14 HD patients (in the predialysis period) and 14 CAPD patients were analyzed for their ability to bind each of the fluoresceinated ligands. PMN and monocytes from both patient groups had a significant reduction in their ability to bind C5a. The average percentage (+/- s.e.m.) of PMN that bound C5a was 93.9 +/- 1.1 for the controls, 72.9 +/- 3.8 for HD patients, and 79.3 +/- 4.0 for CAPD patients. Similar results were obtained with monocytes with 69.7 +/- 1.9% for controls, 54.6 +/- 4.5% for HD patients, and 31.0 +/- 4.5% for CAPD patients. These differences in C5a binding were also reflected in the average intensity of fluorescence. There was no significant difference in the percentage or fluorescence intensity of PMN or monocytes that bound casein or aggregated IgG when either group of dialysis patients was compared to the control values. Binding of fMLPL by PMN and monocytes from the HD patients and PMN from the CAPD patients were similar to control values but the binding of fMLPL by monocytes from CAPD patients was significantly suppressed (p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Complement C3↗
PubMed1984

Conservative surgery for vesicocolic fistula.

Vesicocolic fistula due to diverticular disease of the colon is conventionally treated by resection of the diseased bowel and closure of the vesical defect. Three cases are described in which separation of the viscera and simple suture of the vesical and colonic defects was carried out. A greater omental graft was interposed between the rectum and bladder. Two of the patients are well 12 and 26 months postoperatively. The third patient died a year postoperatively from a complication of her diverticular disease.

Aged↗
PubMed1983

Demonstration of specific receptors for fluoresceinated casein on human neutrophils and monocytes using flow cytometry.

Casein is chemotactic for human neutrophils (PMNs) and monocytes. The binding of fluorescein (FITC)-conjugated casein (mixture of alpha, beta, and kappa-casein) and purified alpha-casein to PMNs, monocytes, and lymphocytes was analyzed using flow cytometry. These studies demonstrate that 75-95% of PMNs and 46-85% of monocytes have membrane receptors for casein while lymphocytes lack these receptors. The binding of FITC-casein and FITC-alpha-casein was specific and was blocked only by unlabeled casein and alpha-casein, but not by ovalbumin, bovine or human serum albumin, beta-casomorphin, C5a, or formyl-methionyl-leucylphenylalanine (fMLP). The binding of FITC-casein was reversible when PMNs were stained with this fluorescent agent and subsequently incubated with unlabeled casein. Double-labeling studies of mononuclear cells using FITC-casein and the OKM1 monoclonal antibody in conjunction with a rhodamine conjugated anti-Ig second antibody demonstrate that mononuclear cells binding FITC-casein also stain with the OKM1 monoclonal antibody, indicating a specificity for monocytes.

Binding, Competitive↗
PubMedDate not supplied

Periodic elevation of complement activation products in peritoneal dialysis effluent.

Peripheral white blood cells (WBCs) of chronic ambulatory peritoneal dialysis (CAPD) patients show a reduced expression of chemotactic receptors and a desensitization to chemotactic factor induced events. Chronic complement activation has been suggested as a cause of such phenomena, resulting from either uremia, the indwelling peritoneal catheter, and/or dialysis fluid stimulation. The presence of complement activation products in peritoneal dialysis effluent was assessed by longitudinal measurement of C3bi in eight patients over a 6 to 8 month period, while peritoneal polymorphonuclear leukocyte (PMN) and monocyte CR3 and C5a receptor expression was quantitated by flow cytometry. In six of eight patients, C3bi levels were stable over time and usually measured less than 5 micrograms/ml. Two other patients showed periodic elevation of C3bi, which was not associated temporally with peritonitis. Further study is required to identify the origin of such activated complement components within the peritoneal cavity. However, no correlation was found between dialysate C3bi levels and peritoneal PMN or monocyte expression of CR3 or C5a receptors. Furthermore, the incidence of peritonitis for the two individuals with elevated C3bi was discordant (1 episode/8 patient months vs. 0 episodes/32 patient months), suggesting little or no relationship between these parameters.

Adult↗
PubMedDate not supplied

Contribution of noradrenergic and serotonergic neurons to the circulatory effects of centrally acting clonidine and alpha-methyldopa in rabbits.

The effects of intracisternal clonidine (0.04, 0.2, and 1.0 microgram/kg) and of alpha-methyldopa (alpha-MD; 400 micrograms/kg) on mean arterial pressure (MAP) and heart rate (HR) were studied in conscious rabbits before, and 7 and 14 days after, intracisternal injection of (a) vehicle, (b) 6-hydroxydopamine (6-OHDA; 600 micrograms/kg), or (c) 5,6-dihydroxytryptamine (5,6-DHT; 633 micrograms/kg) (n = 6 per group). In the initial control experiment clonidine and alpha-MD produced similar falls in MAP and HR in each group; there was also good reproducibility of responses in vehicle-treated rabbits on the 3 experimental days. But after 6-OHDA or 5,6-DHT administration the circulatory effects of clonidine and alpha-MD were markedly attenuated. On day 14 after injection of 6-OHDA, the clonidine-induced falls in MAP and HR averaged 38 and 18%, respectively, of the control responses (p less than 0.001). On day 14 after 5,6-DHT administration, the falls in MAP and HR after clonidine administration were reduced to 27 and 13% of control, respectively (p less than 0.01), while the corresponding responses after alpha-MD administration were 39 and 61% of control (p less than 0.05). Neurochemical findings suggest that 6-OHDA affected noradrenergic (NA), dopaminergic (DA), but not serotonergic (5HT) neurons, and that 5,6-DHT affected 5HT but not NA and DA neurons. We conclude that the circulatory effects of clonidine and alpha-MD are mediated through both central NA and 5HT neurons.

Animals↗
PubMedDate not supplied

Career hazards for the dancer.

Most dance injuries are of the overuse variety. Their gradual onset, coupled with the intense competition for professional positions, often results in injuries being ignored and thus seen late in their course. While treatment of the specific injury is of paramount concern, maintenance of the extremes of flexibility, strength, and conditioning necessary to dance professionally is an equally important treatment element.

Accidents, Occupational↗
PubMedDate not supplied

Phenotypic characterization of monocytes and macrophages from CAPD patients.

The purpose of this study was to phenotypically characterize and compare peripheral blood monocytes from CAPD patients with peritoneal macrophages isolated from their peritoneal dialysis effluents. Monocytes/macrophages were labeled with fluorescent ligands or monoclonal antibodies specific for 1) receptors for C5a, formyl-met-leu-phe (fMLP); Fc region of IgG; C3b (CR1); and C3bi (CR3), 2) Class II histocompatibility antigens HLA-DR and HLA-DQ; and 3) monocyte/macrophage surface antigen CD14. The cells were analyzed using flow cytometry. Results indicated that there were no differences between monocytes and peritoneal macrophages in their receptor expression for fMLP, CR1, or CR3. However, paired t-testing indicated that peritoneal macrophages had significantly increased expression of Fc and C5a receptors, as well as enhanced antigen expression of HLA-DR, HLA-DQ, and CD14. These results suggest that peritoneal macrophages from CAPD patients are activated with increased expression of receptors and antigens important in host defense.

Humans↗
PubMedDate not supplied

Calcium metabolism in blood and peritoneal lymphocytes from continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: Cellular immune function in peritoneal dialysis patients has been shown to be depressed, but the mechanism of this immunosuppression has not been ascertained. Because calcium is an important mediator of lymphocyte activation, this study was designed to investigate if there was an alteration of calcium metabolism in the lymphocytes of continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Sixteen CAPD patients were studied at the initiation of CAPD and after two months of treatment. Twenty-three normal controls were also enrolled in the study. Cytoplasmic calcium changes were investigated in response to the mitogen phytohemagglutinin (PHA) in peripheral blood and peritoneal lymphocytes, using the intracellular calcium probe indo-1 and flow cytometry. Baseline cytoplasmic calcium levels and changes in cytoplasmic calcium in response to PHA were assessed at the initiation of CAPD and after two months of therapy. RESULTS: Peripheral lymphocytes of patients and controls had similar calcium baseline levels, but the peritoneal lymphocytes had baseline cytoplasmic calcium levels averaging 81% higher than the corresponding calcium levels of the patients' peripheral blood lymphocytes. As compared to peripheral lymphocytes, the response to PHA stimulation was significantly less in the peritoneal lymphocytes, increasing an average of only 46.8% above baseline. Peripheral blood lymphocytes of the patients responded by an average increase of 78.9% over baseline. Control cells increased an average of 66.3% over baseline. Follow-up studies done two months after the initiation of CAPD indicated there were no significant changes (as compared to month 0) that occurred in baseline or stimulated intracellular calcium concentrations. CONCLUSIONS: While the peripheral lymphocytes of CAPD patients respond adequately to PHA, the high baseline calcium levels of the peritoneal lymphocytes suggest that these cells may be in a state of chronic activation and may respond minimally to an antigenic challenge.

Adult↗