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Biomedical subjects

S D Rogers

Publications and source records attributed to S D Rogers.

48 records · Page 3Linked to original sources

The response to particulate debris.

The most common cause of failure of total hip and other arthroplasties is aseptic loosening of the prosthesis. Substantial evidence suggests that the adverse tissue response to prosthesis wear particles is an important contributor to bone loss around implants. The results may be an increased risk of loosening and severe bone loss, which makes revision surgery more difficult. Studies in humans have demonstrated that the appearances of the periprosthetic tissues are related to the type, number, and size of wear particles. The appearance and tissue response around any given prosthesis is related to the balance among the rate of production of wear particles, the ability of the tissues to deal with the particles, and the rate of clearance of the particles from the joint. Prosthesis wear particles may be produced by wear at the articulating surface, particularly if there is three-body wear, by abrasion due to movement at the prosthesis-bone interface of uncemented prostheses, by abrasion at the prosthesis-cement and cement-bone interfaces of cemented prostheses, or at any articulation of the components of modular prostheses. Future in vivo and in vitro studies of the effects of wear particles should focus on quantitative measurement of the effects of particles and on the use of particles of comparable size and in concentrations similar to those found in the tissues surrounding failed prostheses.

Animals↗

Interleukin-8 and neutrophil leucocytes: adhesion, spreading, polarisation, random motility, chemotaxis and deactivation in assays using 'sparse-pore' polycarbonate (nuclepore) membranes in the Boyden chamber.

Adhesion, spreading, chemotaxis and deactivation of chemotactic responses of separated human peripheral blood neutrophil leucocytes under the influence of interleukin-8 (IL-8) were tested using a previously described Boyden chamber-type method involving 'sparse-pore' polycarbonate (Nuclepore) filtration membrane. The random motilities of neutrophils in similar concentrations of IL-8 were tested using corresponding chambers with polycarbonate membranes of standard pore densities. In addition, polarisation of neutrophils in suspension in various concentrations of IL-8, and the possibility of deactivation of this polarisation response by IL-8 itself or by N-formyl-methionyl-leucyl-phenylalanine (FMLP) were examined. Neutrophils exhibited maximum chemotaxis to IL-8 in a concentration of 100 ng/ml, and to a degree which was similar to the maximum response to FMLP (10(-7) M). This chemotactic response to IL-8 was markedly reduced by pretreatment of the cells with either 100 ng/ml IL-8 (deactivation) or 10(-7) M FMLP (cross-deactivation). On the other hand, the chemotactic response of the neutrophils to FMLP was reduced by pretreatment with FMLP but was not deactivated by pretreatment with IL-8 (i.e. deactivation but not cross-deactivation). Neutrophils in suspension were maximally polarised by 100 ng/ml IL-8, and to lesser degrees by 1, 10 and 1,000 ng/ml IL-8. The detailed morphology of the polar cells was not distinguishable from that induced by 10(-8) M FMLP. Pretreatment of the cells with either IL-8 or FMLP resulted in no reduction of polarisation in response to subsequent exposure to either agent (i.e. neither deactivation nor cross-deactivation).(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Adhesion↗

Inhibition of chemotaxis of neutrophil leukocytes to interleukin-8 by endotoxins of various bacteria.

The effects of endotoxins from various bacteria (Escherichia coli, Klebsiella pneumoniae, Vibrio cholerae, Shigella flexneri, Salmonella typhosa, and Pseudomonas aeruginosa) on chemotaxis of neutrophil leukocytes to formyl peptide and interleukin-8 were tested in an improved chemotaxis assay involving a "sparse-pore" polycarbonate (Nuclepore) membrane in a Boyden-type chamber. The possible chemotactic activity of the endotoxins themselves were tested by the same technique. In addition, the effects of these substances on random motility of neutrophils were tested with a corresponding assay involving similar chambers fitted with membranes of standard pore density. Possible activation of the complement system of serum by each endotoxin was tested with sheep erythrocyte assays and the maximum endotoxin concentration (100 micrograms/ml) used in the chemotaxis and motility assays. All endotoxins inhibited chemotaxis of neutrophils to interleukin-8. No endotoxin affected chemotaxis to formyl peptide or was itself chemotactic for neutrophils. Endotoxin of S. flexneri inhibited random motility of neutrophils, while the others had no such effect. Endotoxins of K. pneumoniae and of P. aeruginosa produced moderate and marked inhibition, respectively, of total complement, as measured by hemolysis of sheep erythrocytes, without affecting the levels of C3c and C4 in these assays. Endotoxins of the other bacteria had no demonstrable effect in any of these assays of complement activation. These results suggest that chemotaxis to interleukin-8 may be mediated by cellular mechanisms different from those involved in chemotaxis to formyl peptide. Furthermore, the presence of these endotoxins could be significant for the suppression of neutrophil accumulation in inflammatory lesions mediated by interleukin-8.

Bacterial Toxins↗

Cloning and characterization of cutE, a gene involved in copper transport in Escherichia coli.

The copper-sensitive/temperature-sensitive phenotype of the Escherichia coli cutE mutant has been complemented by cloning wild-type genomic DNA into the plasmid vector pACYC184 and selecting transformants on medium containing 4 mM copper sulfate and chloramphenicol. One of these complementing clones, designated pCUT1, contained a 5.6-kb BamHI fragment. This recombinant plasmid transformed cutE, allowing wild-type growth of transformants on medium containing copper sulfate. Complementation of copper sensitivity was assessed by comparing both cell survival at increased copper levels and the results of 64Cu accumulation assays. An EcoRI subclone, 2.3 kb in size, was also shown to complement cutE when cloned in both medium- and high-copy-number vectors and was completely sequenced. This clone was mapped on the E. coli physical map at 705.70 to 707.80 kb. A series of subclones was constructed from pCUT1 and used to show that the large open reading frame of the translated sequence was essential for complementation. This open reading frame has a potential upstream promoter region, ribosome-binding site, and transcriptional terminator and encodes a putative protein of 512 amino acids that contains a region showing some homology to a putative copper-binding site.

Acetyltransferases↗

Effects of plasma proteins on the adhesion, spreading, polarization in suspension, random motility and chemotaxis of neutrophil leukocytes on polycarbonate (Nuclepore) filtration membrane.

The effects on adhesion, spreading, polarization in suspension, random motility and chemotaxis to N-formyl-methionyl-leucyl-phenyl-alanine (FMLP) of neutrophil leukocytes on polycarbonate (Nuclepore) membrane in the Boyden chamber of purified serum albumin, gamma globulin and fibrinogen, as well as of the Hanks'-soluble components of Cohn fractions III (beta and gamma globulins) and IV (albumin, alpha globulins and transferrin) of plasma proteins were tested in comparison to the corresponding effects of dilute fresh heparinized plasma. Serum albumin, fibrinogen and fibronectin inhibited adhesion of neutrophils, so that the spreading, random motility and chemotaxis of these cells could not be assessed in the presence of these proteins alone. These plasma proteins induced little or no polarization of the cells in suspension. Of the remaining preparations, gamma globulin promoted adhesion and excessive spreading and caused corresponding reduction of random motility and chemotaxis to FMLP of these cells. This plasma protein, even in low concentration, induced marked polarization of neutrophils in suspension. Both Cohn fractions III and IV supported adhesion and permitted random motility and chemotaxis to FMLP approximating that which occurs in dilute plasma. These fractions induced moderate polarization of cells in suspension. Addition of serum albumin or fibronection to the preparations of gamma globulin, or Cohn fractions III or IV did not alter the adhesion, random motility or chemotaxis of the neutrophils in these preparations. These results suggest that alpha and beta globulins, as well as gamma globulins are factors in plasma affecting adhesiveness and polarization of neutrophils and which provide for optimal motility and chemotaxis of these cells on solid substrata.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗

Acral erythema secondary to high-dose cytosine arabinoside with pain worsened by cyclosporine infusions.

Acral erythema after high-dose cytosine arabinoside (Ara-C) has been described as a painful, sharply demarcated, and intense erythema of the palms and soles. This phenomenon occurred and is described in three out of three allogeneic bone marrow transplant (BMT) recipients who received high-dose Ara-C and total-body irradiation for conditioning therapy via the same protocol. These patients also received cyclosporine and methotrexate as prophylaxis for acute graft-versus-host disease. Two of the three patients experienced an increase in the pain associated with acral erythema during cyclosporine infusions and required large doses of narcotic analgesics. Since alcohol intensifies the pain of stomatitis and cyclosporine is manufactured in an alcohol base, the high alcohol content is suspect as the causative factor for this adverse reaction/drug interaction.

Adolescent↗

Tissue plasminogen activator: an evaluation of clinical efficacy in acute myocardial infarction.

Recombinant tissue plasminogen activator (t-PA) is a synthetic fibrinolytic protein which activates plasminogen or converts plasminogen to plasmin specifically in the presence of fibrin. With its "clot-selectivity", t-PA is capable of lysing clots without having a significant effect on circulating plasminogen. In contrast, activation by streptokinase and urokinase is non-specific and affects circulating as well as thrombus plasminogen. These agents, therefore, have a greater potential to induce bleeding than does t-PA. Plasma levels of t-PA following intravenous administration are generally proportional to the dose, but there can be significant interpatient variation. The drug is eliminated primarily by hepatic metabolism and is then excreted in the urine. Half-life of circulating t-PA ranges from 2-8 minutes. Most clinical trials of t-PA have evaluated its use in acute myocardial infarction. Indeed, its current indication is for thrombolysis in evolving MI. Short-term benefits of t-PA administration include a prompt reperfusion and restoration of coronary artery patency in patients with total coronary artery occlusion. The degree to which the heart benefits from thrombolysis is unknown, but electrocardiographic changes, changes in cardiac enzymes and alterations in the pattern of chest pain indicate that rapid reperfusion may limit the size of the infarct. Overall, t-PA appears to be a relatively safe thrombolytic agent. Bleeding is the most significant adverse effect reported with t-PA administration. In most cases, however, bleeding has been minor. Other reported adverse effects include reperfusion arrhythmias, bradycardia, and chest pain. Allergic reactions were not observed in clinical trials.

Animals↗

Isolation of mutants sensitive to 2-aminopurine and alkylating agents and evidence for the role of DNA methylation in Penicillium chrysogenum.

Using high performance liquid chromatography, the presence of N6-methyladenine has been found at a level of 0.1 mol percent in DNA extracted from Penicillium chrysogenum. No 5-methylcytosine was detected. A mutant strain HP547, which is sensitive to the lethal effects of N-methyl-N'-nitro-N-nitrosoguanidine, methylmethane sulphonate and the base analogue 2-aminopurine shows an increased spontaneous mutation rate and no detectable DNA methylation. Comparison of restriction enzyme digests of wild type and undermethylated strains indicated that methylation was occurring at a different sequence to that of the Dam methylase system of E. coli.

2-Aminopurine↗

Direct evidence for myogenic autoregulation of the renal microcirculation in the hamster.

We transplanted neonatal hamster renal tissue into a hamster check pouch chamber and subjected the renal tissue to increases and decreases in extravascular pressure. A decrease in extra-vascular pressure decreased, and an increase in extravascular pressure increased, the diameter of preglomerular arterioles. Thus, the change in preglomerular arteriolar diameter was directly related to alterations in extravascular pressure. Neither saralasin nor indomethacin affected these changes, whereas papaverin prevented them. The efferen arterioles responded passively to changes in extravascular pressure; i.e., the changes in their diameter were inversely related to changes in extravascular myogenic autoregulation of preglomerular vessels.

Afferent Pathways↗