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Biomedical subjects

R D Nelson

Publications and source records attributed to R D Nelson.

At least 91 records · Page 5Linked to original sources
PubMed1983

Serology of Staphylococcus aureus infections using multiple antigens and serial serum samples.

The detection of antibody to S aureus in human serum can aid in the management of staphylococcal diseases [1]. RIAs and ELISAs can detect low levels of antibody and demonstrate increased antibody production during serious staphylococcal infections [2,3]. We compared four S aureus constituents--cell-wall peptidoglycan and teichoic acid, and extracellular alpha-toxin and nuclease--as antigens in a sensitive ELISA. The value of testing more than a single serum sample was also determined. Elevated IgG antibody to peptidoglycan, present in one or more serum samples of 13 (50%) of 26 patients with complicated bacteremia, was found to be the most sensitive test. All 26 patients had a significant IgG antibody response to peptidoglycan. Three (27%) of 11 patients with uncomplicated bacteremia had elevated levels of antibody to peptidoglycan in their serum, and seven (64%) showed a significant change in titer when serial serum samples were tested. Maximum detection rates for the other antigens in complicated and uncomplicated bacteremia were, respectively, 62% and 37% for teichoic acid, 38% and 37% for nuclease, and 54% and 13% for alpha-toxin. In single serum samples, the detection rate for all four antigens marginally improved the results, with detection rates of 62% and 36% for complicated and uncomplicated bacteremia, respectively. Cross-reactive antibody to peptidoglycan but not to the other three antigens was present in six (75%) of eight patients with long-standing subacute bacterial endocarditis due to either viridans streptococci or Staphylococcus epidermidis (data not shown).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial↗
PubMed1983

Stability of vitamin and mineral concentrations of a low-birth-weight infant formula during continuous enteral feeding.

The stability of several vitamins and minerals of a new formula for premature infants, Similac Special Care, was examined following passage through a simulated continuous infusion apparatus designed to duplicate that used for continuous enteral feeding in infants. The concentrations of calcium, iron, zinc, copper, magnesium, vitamin A, vitamin C, and vitamin E were measured before and after infusion at rates appropriate for delivering 120 calories/kg to infants weighing 733 and 1,000 g. Following passage through this apparatus, significant reductions were noted for calcium (44-54%), iron (23-34%), and zinc (18-32%). Concentrations of copper, magnesium, and vitamins A, C, and E remained stable. When another formula commonly used for premature infants, Similac 24LBW, was subjected to similar analysis, the concentrations of all vitamins and minerals studied remained stable. Our study demonstrates that infants fed Similac Special Care by continuous infusion may not receive the quantity of calcium, iron, and zinc implied by the product label.

Calcium↗
PubMed1983

Rifampin affects polymorphonuclear leukocyte interactions with bacterial and synthetic chemotaxins but not interactions with serum-derived chemotaxins.

Three independent experimental approaches support the hypothesis that rifampin competes for receptors on polymorphonuclear leukocytes (PMLs) with small peptide chemoattractants, e.g., N-formylmethionylleucylphenylalanine (FMLP), but not with serum-derived chemoattractants (C5a). First, rifampin inhibited chemotaxis induced with FMLP but reversed the immobilization of PMLs that occurred at high FMLP concentrations. Second, rifampin competed with radiolabeled FMLP for binding sites on PMLs and displaced already-bound radiolabeled FMLP. Third, rifampin blocked and reversed the bipolar shape changes induced in PMLs by FMLP. These effects occurred at concentrations attained during rifampin therapy and were not due to rifampin toxicity. In contrast, no effect of rifampin was observed on serum-derived chemoattractants (C5a) in any of the three systems. The evidence suggests, therefore, that rifampin is a ligand for FMLP-type receptors on PMLs.

Binding, Competitive↗
PubMed1983

Human neutrophil chemotactic response to group A streptococci: bacteria-mediated interference with complement-derived chemotactic factors.

The influence of M protein on the capacity of group A streptococci to generate neutrophil chemotactic activity in normal human serum was examined. Incubation of serum with M- bacteria for up to 10 min led to the production of chemotactic activity. In contrast, incubation of serum with M+ bacteria did not elicit serum chemotactic activity over a 1-h period, even though complement was activated to completion. Further experiments revealed that both M+ and M- bacteria could inhibit the chemotactic activity of serum preexposed to zymosan. However, the M+ bacteria possessed a 130-fold-greater inhibitory capacity in this regard than the M- bacteria. This antichemotactic property was not detectable in the fluid phase of serum incubated with bacteria, thereby ruling out neutrophil-directed effects. Treatment of the bacteria with trypsin resulted in the release of the inhibitory molecule, suggesting that proteins are involved in its maintenance at the cell surface. However, the resistance of the chemotactic factor inactivator to pepsin and trypsin indicated that the protease-sensitive M protein was not involved. These results demonstrate a heretofore uncharacterized activity of group A streptococci that may contribute to virulence through modulation of the host chemotactic response.

Antigens, Bacterial↗
PubMed1983

Candidacidal activity of myeloperoxidase: mechanisms of inhibitory influence of soluble cell wall mannan.

We have previously demonstrated the ability of human neutrophil myeloperoxidase to bind to mannan isolated from Candida albicans. Mannan may therefore be a primary component of the yeast cell wall which provides for binding of myeloperoxidase, a requirement potentially important for the candidacidal activity of the enzyme. In this report, we describe experiments to consider the relationship of the mannan-binding activity of myeloperoxidase to its candidacidal activity and the possibility that free mannan may inhibit myeloperoxidase-mediated candidacidal activity. We observed that binding of myeloperoxidase to the target yeasts was required for killing of C. albicans. We also observed that addition of soluble mannan significantly reduced myeloperoxidase-mediated killing of the yeasts in a dose-dependent manner by antagonizing binding of myeloperoxidase. Soluble mannan was demonstrated to have a similar dose-dependent inhibitory effect on neutrophil-mediated candidacidal activity without influencing phagocytosis of the organism. On the basis of these observations, we speculate that mannan solubilized in plasma and tissue fluid may interfere with neutrophil-mediated host defense against Candida infection.

Candida albicans↗
PubMed1983

Mechanisms of the adjuvant effect of hemoglobin in experimental peritonitis. VI. Effects of stroma-free hemoglobin and red blood cell stroma on mortality and neutrophil function.

Hemoglobin is known to increase the lethality of experimental E. coli peritonitis, but its mechanism of action has not been defined. Some evidence from this laboratory previously suggested that hemoglobin could interfere with local leukocyte function in the peritoneal cavity. In the present study we compared the effect of impure bovine hemoglobin, highly purified stroma-free hemoglobin, and red blood cell stroma on the mortality rate of rats with Escherichia coli peritonitis, as well as on human neutrophil function in vitro. Both hemoglobin preparations markedly increased the mortality rate at low bacterial concentrations. Red blood cell stromal elements increased the rate to a minimal degree and only at high bacterial concentrations. The character of the E. coli-induced peritoneal leukocytosis was not significantly affected by concomitant administration of either stroma-free hemoglobin or red blood cell stroma. Although crystalline bovine hemoglobin inhibited in vitro leukocyte chemotaxis, centrifugation of this preparation to remove debris abrogated this effect. Stroma-free hemoglobin had no effect on in vitro leukocyte chemotaxis. Red blood cell stromal elements in high concentration diminished phagocytosis and bacterial killing by human neutrophils, but stroma-free hemoglobin had no effect on these neutrophil functions. The results confirm that hemoglobin is a potent adjuvant in experimental E. coli peritonitis, but contrary to our previous conclusion does not owe this effect to direct interference either with neutrophil influx into the peritoneal cavity during bacterial peritonitis or with human leukocyte function in vitro. Such prior conclusions appear to have been based on insoluble material including stromal elements in the hemoglobin preparations used. Red cell stromal elements derived from as little as 1 ml of packed red cells can significantly interfere with the phagocytosis and killing of E. coli.

Animals↗
PubMed1983

Isolation of the turkey heterophil and measurement of its migratory functions under agarose.

A procedure for isolation of the turkey heterophil was developed. The procedure involves preliminary lysis of erythrocytes, using ammonium chloride and centrifugation of the leukocytes over a discontinuous gradient of 18% and 24% Ficoll. A minimum of 30% of the heterophils was consistently recovered from whole blood by application of this procedure. Spontaneous and chemotactic migratory responses of the isolated heterophils were assessed, using the migration under agarose technique. Supplementation of the agarose with 10% heat-inactivated turkey plasma and extension of the incubation period to 3 hours at 41 C in a 5% CO2-humidified atmosphere were required for optimal chemotaxis in response to zymosan-activated chicken serum. The heterophils did not respond chemotactically to the oligopeptide attractant, N-formyl-methionyl-leucyl-phenylalanine, and did not specifically bind a radiolabeled form of this ligand.

Animals↗
PubMed1982

Human neutrophil peptide receptors: mobilization mediated by phospholipase C.

Incubation of human neutrophils with phospholipase C from Clostridium perfringens caused an increase in the ability of the treated cells to bind the chemotactic peptide, F-Met-Leu-Phe. The increase in binding was related to an increase in specific binding of the ligand. The increase in specific binding was, in turn, related to an increased number of peptide receptors. The dissociation constant (KD) for the tripeptide was not altered, on the average, by enzyme treatment. The increase in peptide receptor number was related temporally, and possibly mechanistically, to enzyme-stimulated secretory function involving the secondary granules. Phospholipase C treatment did not similarly augment binding of the complement-derived attractant, C5a. Receptor numbers for different chemotactic ligands may therefore be controlled by different mechanisms. Supplementary experiments provided evidence that this phenomenon was attributable to phospholipase C activity and not to contaminating protease(s).

Complement C5↗
PubMed1982

Chemotactic requirements of bovine leukocytes.

A system was described for studying bovine leukotaxis. Chemotaxis was readily observed toward bovine serum activated by zymosan of agarose. However, bacterial culture filtrates and peptides, which were potent chemotaxins for leukocytes from other species, failed to affect bovine leukotaxis. Using conditions suitable for studying binding to leukocytes from other species, specific binding of a radiolabeled chemotactic peptide to bovine leukocytes was not apparent. These data indicate that bovine leukocytes have chemotactic requirements distinct from those of other species.

Animals↗
PubMed1981

Esterase dependence of human neutrophil functions: lysozyme secretion, spontaneous migration, and continuity of the respiratory burst.

To assess the esterase dependency of human neutrophil secretion of lysosomal enzyme, the influence of several aromatic amino acid esters on phorbol myristate acetate-induced release of lysozome was studied. This function was found to be esterase-dependent on the basis of the inhibitory influence of such esters. Of the esters tested, tryptophan octyl ester, tryptophan benzyl ester, benzoyl tyrosine ethyl ester, and tryosine methyl ester were the most potent inhibitors of this response, being effective in the order listed. All esters with inhibitory effects were active at concentrations of less than or equal to 100 muM. Other neutrophil functions found to be similarly sensitive to the presence of these esters were spontaneous and chemotactic migration an continuity of the respiratory burst. The common inhibition profile of these neutrophil activities by the esters used suggests the activity of a common enzyme in these various functions.

Amino Acids↗
PubMed1981

Neutrophils dysfunction during the course of intra-abdominal infection.

Twenty-four patients with intra-peritoneal infections were studied sequentially to evaluate neutrophil chemotaxis, spontaneous migration, and chemiluminescence. In six patients, infection was due to spontaneous disease processes and 18 others, infection was a sequel of intra-abdominal operation. In the patients studied prior to drainage, operation chemotaxis, spontaneous migration and chemiluminescence were all significantly depressed. Operation resulted in a further depression of these functions, and recovery of neutrophil migratory responses was delayed for two weeks. During the period of functional depression, 16 patients developed recurrent infections (nine episodes of intra-abdominal abscess, and 12 episodes of extra-abdominal infection). These infection were associated with a fall-off in neutrophil migratory and chemiluminescence responses prior to clinical evidence of infection. This study suggests that the delayed recovery of neutrophil function may be related to the recurrent infection seen in this patient population. Further, monitoring of neutrophil function in patients recovering from intra-abdominal infection may provide early evidence of recurrent infection.

Abdomen↗
PubMed1981

Migration of mouse lymphocytes in vitro. I. Normal lymph node lymphocytes.

Normal unstimulated mouse lymph node lymphocytes (LNLs) migrated into filters in a gradient of normal mouse serum (NMS), heat-inactivated mouse serum (HI-MS), or zymosan-activated mouse serum (ZAS). Blind well chemotaxis chambers with 5-micrometer pore size cellulose nitrate membranes were used. Migration was assessed both by the leading front technique and the mean aggregate number. A concentration of 2.5 x 10(6) LNLs/ml or greater was needed to detect migration. Migration of LNLs to 1% NMS was time dependent and was inhibited by cytochalasin B. Comparison of the migration patterns of LNLs, neutrophils, and macrophages revealed that all cell types were responsive to NMS. LNLs responded as well to HI-MS as they did to NMS, neutrophils responded less well to HI-MS than to MMS, and macrophages did not respond to HI-MS. The LNL response to ZAS was significantly greater than the response to NMS to HI-MS and neutrophils and macrophages also responded strongly to ZAS. The migration of LNLs from various mouse strains to NMS revealed that the LNLs from different mouse strains possess varying degree of motility. The factor in mouse serum which induced migration was not strain specific. The LNLs from peripheral (inguinal, axillary, and brachial) nodes demonstrated greater motility in response to NMS than mesenteric LNLs. Using the checkerboard assay to discriminate chemotaxis from chemokinesis, mouse serum appeared to be solely chemokinetic when the leading front technique was used. However, using the mean aggregate number technique, mouse serum was determined to be both chemokinetic acid chemotactic for LNLs. The results indicate that the method can be reliably used to study those factors which influence the motility of normal or altered populations of lymphocytes.

Animals↗
PubMed1981

Influence of yeast mannan on human neutrophil functions: inhibition of release of myeloperoxidase related to carbohydrate-binding property of the enzyme.

We investigated the possibility that dissolved mannan polysaccharide from Candida may have an inhibitory influence on the host defense mechanisms associated with neutrophils and thereby contribute to the pathogenesis of candidoses. We created a model for this hypothesis by using mannan derived from bakers' yeast (Saccharomyces cerevisiae) and mannan isolated from the serum of a patient with chronic mucocutaneous candidosis. We observed that these mannans inhibited the respiratory burst and release of myeloperoxidase stimulated by phagocytosis of serum-opsonized zymosan in vitro. Mannan did not inhibit release of three other lysosomal enzymes. The selective inhibition of release of myeloperoxidase was attributable to a carbohydrate-binding property of the enzyme, with the mannan causing co-sedimentation of the enzyme with the cellular fraction.

Candida↗
PubMed1981

Chemotactic deactivation of human neutrophils: protective influence of phenylbutazone.

The antiinflammatory drug, phenylbutazone (PBZ), has been studied in terms of its influence on chemotactic deactivation of human neutrophils. When PBZ was present during the time of preincubation of cells with N-formyl-methionyl-phenylalanine (F-Met-Phe), loss of subsequent spontaneous mobility and chemotactic responsivity to F-Met-Phe did not occur. The action of PBZ to protect neutrophils from peptide-mediated chemotactic deactivation was found to involve in part its inhibitory influence on hexose monophosphate shunt activity and in part its antagonistic effect on interaction of peptide receptors with N-formyl peptide. Phenylbutazone interfered with binding of N-formyl-methionyl-leucyl-[3H]phenylalanine but not [125I]C5a to the neutrophil, displaced labeled tripeptide bound in the absence of PBZ, increased the dissociation constant (KD) for labeled tripeptide, and limited down regulation of peptide receptor function. These results provide an example of drug-mediated modulation of the interaction of neutrophils with N-formyl peptide and strongly support the possibility that PBZ interacts directly and specifically with the human neutrophil peptide receptor as a competitive antagonist. They also provide an additional example of a compound outside of th N-formyl peptide series that interacts with the peptide receptor.

Anaphylatoxins↗
PubMed1981

Neutrophil dysfunction in sepsis. II. Evidence for the role of complement activation products in cellular deactivation.

Abnormalities in chemotactic and bactericidal activity have been identified in patients suffering from burn injury, trauma, and infection. Such abnormalities may lead to bacteremia or nosocomial infection. The mechanism for these abnormalities is unclear. We studied the role of chemotactic deactivation by complement component C5a in 47 patients with intra-abdominal infection and with disordered neutrophil function. Plasma C5a levels in such patients were elevated (102.1 +/- 8.3 versus 52.6 +/- 3.4 ng/ml for control subjects, P less than 0.01). There was a linear relationship between C5a and chemotaxis (r = 0.56, P less than 0.01). Examination of patients' neutrophils showed changes consistent with nonspecific deactivation. There were parallel losses of chemotaxis to N-formyl methionyl-leucyl-phenylalanine (FMLP) and activated serum (C5a) (r = 0.74, P less than 0.001), chemotaxis and intracellular beta-glucuronidase (r = 0.82, P less than 0.001), and C5a and FMLP chemotaxis and (r = 0.56, P less than 0.01). Receptor assays revealed specific loss of C5a binding but intact FMLP binding. Exposure of normal neutrophils to plasma from patients with depressed chemotaxis caused similar loss of C5a receptors and loss of FMLP and activated serum-induced chemotaxis at high plasma concentrations and selective loss of activated serum response at lower concentrations. These data support the concept that a major factor leading to neutrophil dysfunction during intra-abdominal infection is nonspecific chemotactic deactivation of neutrophils after in vivo exposure to high levels of chemoattractants such as C5a.

Adolescent↗
PubMed1980

Chemotactic deactivation of human neutrophils: role of stimulation of hexose monophosphate shunt activity in nonspecific deactivation.

We have investigated the mechanism of the nonspecific component of chemotactic deactivation of human neutrophils. This component of deactivation occurs on exposure of neutrophils to larger doses of cytotaxin and is expressed as depressed subsequent spontaneous migration and chemotaxis toward all cytotaxins tested. We demonstrate a possible mechanistic association between stimulation of hexose-monophosphate shunt activity and the nonspecific component of deactivation. This association is evidenced by failure to effect deactivation of 0 degrees C, by the ability of non-chemotactic stimulatory agents to mimic cytotaxin-induced deactivation, by the ability of agents which block shunt activity to protect against deactivation, and by the ability of methylene blue to deactivate neutrophils from individuals with chronic granulomatous disease. Thus, excessive stimulation of shunt activity, possibly through generation of products of oxygen metabolism, appears to have an inhibitory influence on nonspecific neutrophil migratory functions.

Carbon Dioxide↗
PubMed1979

Neutrophil function in lymphoreticular malignancy.

Neutrophil chemotaxis, phagocytosis, and metabolic stimulation were studied in 25 patients with untreated lymphoreticular malignancies, 8 patients with untreated carcinomas, and 8 patients undergoing therapy for lymphoreticular tumors. Phagocytic activity and metabolic stimulation during phagocytosis were comparable to controls in all patient groups. Slight, but significant, differences were found in chemotactic responsiveness of untreated patient groups when compared to controls. In almost all instances, chemotactic responsiveness reverted to normal in most patients studied after therapy for the malignant process. In patients with intact immunologic function these minor differences in chemotactic responsiveness are probably not sufficient to predispose to infection. However, this defect could be additive, and when present in combination with impaired immunity may contribute to compromised host defense.

Adolescent↗