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Biomedical subjects

F P Winstanley

Publications and source records attributed to F P Winstanley.

At least 19 recordsLinked to original sources
PubMed1995

Effect of ibuprofen on the acute-phase response and protein metabolism in patients with cancer and weight loss.

The aim of this study was to determine whether administration of the non-steroidal anti-inflammatory agent ibuprofen might attenuate the acute-phase response in patients with colonic cancer. Cytokines and acute-phase proteins were measured before administration of ibuprofen and again 3 days later, when protein synthesis was measured using 15N-glycine. In patients with cancer, ibuprofen caused a significant reduction in the plasma concentration of all five acute-phase proteins studied. Although interleukin 6 levels were raised, they did not change following administration of ibuprofen. Unlike the situation in patients with cancer who did not receive ibuprofen, whole-body protein kinetics were similar to those of control subjects in patients with cancer who received ibuprofen. Whether or not ibuprofen had been administered, non-export hepatic protein synthesis rates were significantly lower in patients with than in those without cancer. These results suggest that short-term administration of ibuprofen can attenuate accelerated whole-body protein kinetics and the acute-phase response in patients with advanced cancer.

Acute-Phase Proteins↗
PubMed1992

Regulation of tumor necrosis factor production in healthy humans and in patients with cancer.

To study the factors that influence cytokine release, the effect of endotoxin on in vitro tumor necrosis factor production by monocytes from debilitated patients with cancer (n = 6) was compared with that from healthy controls (n = 5). Spontaneous and endotoxin-stimulated monocyte tumor necrosis factor production was similar in patients with cancer and controls. However, with total peripheral blood mononuclear cells, enhancement of tumor necrosis factor production by endotoxin in patients with cancer (46 +/- 12, mean +/- SEM) was greater than in controls (0% +/- 7%). This enhanced response correlated with reduced peripheral blood mononuclear cell blastogenesis in response to phytohemagglutinin (r = .66) and could be partially reversed in vitro by addition of exogenous interleukin 2. Thus, a component of total peripheral blood mononuclear cells (probably T cells) seems to influence monocyte cytokine production in response to endotoxin. Moreover, this regulatory component is decreased in patients with cancer, correlates with decreased peripheral blood mononuclear cell blastogenesis, and can stimulated with interleukin 2.

Adult↗
PubMed1992

Bioassay of interleukin 1 (IL-1) in human gingival crevicular fluid during experimental gingivitis.

The cytokine IL-1 was demonstrated in crevicular fluid during a 14- and 21-day experimental gingivitis in healthy human volunteers. A sensitive and specific bioassay allowed detection of biologically active IL-1 at levels ranging from 0.18 ng/microliters at baseline to 1.70 ng/microliters in inflamed gingiva. Levels of IL-1 increased rapidly with plaque accumulation and in advance of the subsequent gingival inflammation, peaking within 7 days of the start of gingivitis. As changes in IL-1 were detected before clinically recognizable gingival changes, IL-1 may have potential as an early marker of gingival inflammatory changes.

Adult↗
PubMed1992

Bioassay of bovine interleukin-1-like activity.

A bioassay for bovine interleukin-1 (IL1) activity is described. The assay is based on the IL1-stimulated proliferation of a mouse T-lymphocyte cell line, D10(N4)M. Bovine mononuclear cells stimulated with lipopolysaccharide produce an interleukin-1-like activity which stimulated the growth of the D10(N4)M cell line in a dose-dependent manner. The stimulatory activity was neutralised by a combination of both anti-human IL1 alpha and anti-human IL1 beta sera. The quantity of IL1-like activity released from the mononuclear cells increased asymptotically with increasing lipopolysaccharide dose.

Animals↗
PubMed1992

Detection of TNF alpha receptors on ovine leucocytes by flow cytofluorimetry.

Tumour necrosis factor receptor activity was detected on sheep leucocytes using flow cytofluorimetry and commercially available fluorescent human tumour necrosis factor. The density of receptors per cell and the proportion of cells expressing TNF receptor activity was found to be in the following rank order: monocytes greater than granulocytes greater than lymphocytes.

Animals↗
PubMed1991

Elevated circulating interleukin-6 is associated with an acute-phase response but reduced fixed hepatic protein synthesis in patients with cancer.

It has been suggested that, as part of the inflammatory response to the presence of a tumor, various cytokines are produced and these induce hepatic synthesis of acute-phase proteins (APP). Under these circumstances it is not known what changes occur in the fixed component of hepatic protein synthesis. The aim of this study was to compare circulating interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF) concentrations and fixed hepatic protein synthesis rates in a group of healthy controls (n = 6) with a group of patients with an established APP response secondary to hepatic metastasis from colorectal cancer (n = 6). Fixed hepatic protein synthesis rates were measured following a primed, constant 20-hour infusion of 15N-glycine. The liver was biopsied at laparotomy. The APP response was assessed by serum C-reactive protein concentration and cytokines were assayed by a combination of immunoassay and bioassay. The patients with advanced cancer and an on-going APP response had elevated circulating IL-6 concentrations (p less than 0.01). Rates of fixed hepatic protein synthesis were 30% lower than those observed in controls (p less than 0.01). These findings demonstrate that in patients with hepatic metastasis, although the synthesis of certain acute-phase export proteins can be increased, fixed protein synthesis is reduced. Whether these changes in the distribution of hepatic protein synthesis are mediated by IL-6 will require further investigation.

Acute-Phase Reaction↗
PubMed1990

Synaptic membrane complex carbohydrates in experimental hepatic encephalopathy.

To evaluate further the status of synaptic plasma membranes (SPMs) in the brain in the syndrome of hepatic encephalopathy (HE) lipid- and protein-bound sialic acid and ganglioside and protein composition were investigated in SPMs from the brains of six rabbits with galactosamine-induced fulminant hepatic failure and five normal rabbits. HE was associated with no appreciable changes in the chromatographic pattern of gangliosides or the concentration of protein-bound sialic acid, but the syndrome was associated with a 20% increase in lipid-bound sialic acid and, as assessed electrophoretically, an increase in the concentration of a protein with a molecular weight of about 70 kDa. Thus, changes in the composition of complex carbohydrates and protein in SPMs occur in a model of HE. The findings raise the possibility that nonhumoral factors, such as increased sialylation of glycolipids, contribute to the generation of abnormal neurotransmission in HE.

Animals↗
PubMed1989

The serum interleukin 6 response to elective surgery.

We have investigated changes in serum interleukin 6 (IL-6) in patients undergoing elective cholecystectomy. Serum IL-6 increased in all patients within 1.5 hour of incision, reaching a maximum between 1.5-4 hours after incision (median 50 U/ml; range 22-79 U/ml). The maximum serum IL-6 correlated with the length of the operation (r = 0.95). Serum C-reactive protein was not detectable until 8-12 hours post-incision, but maximum serum C-reactive protein did not correlate with maximum serum IL-6 concentration or length of operation. There was no consistent increase in plasma interleukin 1 or tumour necrosis factor following surgery. Serum IL-6 is an early marker of tissue damage and may be of value in the study of the metabolic response to injury.

C-Reactive Protein↗
PubMed1987

Lipopolysaccharide structure and serum sensitivity of non-serogroupable Neisseria meningitidis.

Bactericidal activities of normal human serum for non-serogroupable strains of Neisseria meningitidis were determined. In similar experiments with isolates of Neisseria gonorrhoeae from localized infections, strains with group I lipopolysaccharide (LPS) were uniformly serum resistant and those with group II were serum sensitive. We found no similar association between serum sensitivity of the meningococcal strains and their lipopolysaccharide groups determined by the same pyocin typing system used to classify the gonococcal isolates. Immune mouse sera raised against non-serogroupable meningococci of either LPS group I or II were bactericidal for non-serogroupable strains of the same LPS group and also cross-reactive for strains of the opposite group. They were not bactericidal for the majority (13/17) of the serogroupable strains tested. These findings suggest there are antigens, in addition to the LPS and capsules, that elicit some of the "natural" bactericidal antibodies to pathogenic meningococci.

Animals↗
PubMed1985

Factors influencing host susceptibility to meningococcal disease.

Host-parasite interactions influencing the development of the protective humoral immune response to Neisseria meningitidis are briefly reviewed. Possible consequences of the observed decreased titres of bactericidal activity specific for meningococcal serogroups A, B and C among patients with gonorrhoea are discussed with reference to: the epidemiology of the two diseases, the protective role of "natural" antibodies to the Neisseria species and the carriage rate of serogroupable strains of N. meningitidis among patients with gonorrhoea and a control population.

ABO Blood-Group System↗
PubMed1984

Alteration of pyocin-sensitivity pattern of Neisseria gonorrhoeae is associated with induced resistance to killing by human serum.

A laboratory-grown strain of Neisseria gonorrhoeae, selected in vivo, BS4 (agar), is susceptible to complement-mediated killing by fresh human serum but is relatively resistant to killing by human phagocytes. It can be induced to serum resistance by incubation with a small molecular weight fraction of guinea pig serum. The serum-susceptible and induced-resistant forms show differences in pyocin sensitivity tests. This indicates either differences in the structure of their lipopolysaccharides or masking of some determinant(s). The pyocin sensitivity pattern of BS4 (agar) is only slightly different from that of a closely related strain, BSSH, which is more susceptible to killing by human phagocytes.

Bacteriocins↗
PubMed1984

Absence of bactericidal antibodies against Group-I lipopolysaccharide determinants of Neisseria gonorrhoeae during human infection.

None of 34 sera from patients with gonorrhoea contained antibodies bactericidal for strains of Neisseria gonorrhoeae with Group-I lipopolysaccharide (LPS). All contained antibodies against a strain with Group-II LPS, as do sera from uninfected controls. The absence of Group I-LPS antibodies in infected humans contrasts with previous findings that mice immunised with strains from either of the LPS groups produced bactericidal antibody to Group I. Our hope that detection of antibodies to Group-I strains would provide a screening test for gonorrhoea was, therefore, not realised.

Antibodies, Bacterial↗
PubMed1984

Binding of Neisseria gonorrhoeae by lectin-like receptors on human phagocytes.

The adherence of gonococci to phagocytes was examined for the presence of "lectin-like" receptors capable of binding these bacteria. The data suggests such "lectin-like" receptors are present on PMN and monocytes that recognize sugars present in the gonococcal cell wall and that there are quantitative and qualitative differences in expression of these receptors. These findings may have importance in investigation of the interaction of gonococci with phagocytes and with the subsequent induction of immunity in the disease.

Binding Sites↗
PubMed1984

Host-parasite interactions influencing establishment of gonococcal infection--a paradox resolved?

This study indicates that the gonococcal strains of lipopolysaccharide group (II) most frequently isolated from localized infections have a growth advantage over strains of group I. Their increased association with neutrophil polymorphs and their susceptibility to lysis by normal human serum would seem to act to the disadvantage of the bacteria. Our findings taken together with the cytotoxic effect of gonococci on neutrophil polymorphs offer an explanation for this apparent paradox.

Cytotoxins↗
PubMed1983

Blood group, secretor status, and susceptibility to infection by Neisseria gonorrhoeae.

To determine whether the presence or absence of anti-B isohaemagglutinin in individuals of blood group B increases their susceptibility to gonococcal infections 567 new patients attending a sexually transmitted disease clinic were screened for blood group and secretor status. Of the patients with blood group B, 20.1% had gonorrhoea and 12% had not. A higher percentage (20.9%) of patients with no anti-B isohaemagglutinin had gonorrhoea compared with those without (12.1%). There was, however, no synergy between the absence of anti-B isohaemagglutin and nonsecretion of water-soluble blood group B antigen. Further research is needed to determine the underlying host-parasite interactions responsible for the increased susceptibility to gonorrhoea in these individuals.

ABO Blood-Group System↗
PubMed1983

ABO blood group and susceptibility to gonococcal infection. I. Factors affecting phagocytosis of Neisseria gonorrhoeae.

The effect of opsonization of Neisseria gonorrhoeae by isohaemagglutinins from normal serum on attachment to human polymorphonuclear leukocytes (PMN) was investigated. No significant differences between sera from blood groups O, A, B or AB were found. Differences in attachment of gonococci were related to differences in lipopolysaccharide detected by sensitivity to R-type pyocines of Pseudomonas aeruginosa. Non-pilate variants of each test strain markedly stimulated nitroblue tetrazolium (NBT) reduction in PMN, but their pilate variants were essentially inactive in the NBT test.

ABO Blood-Group System↗