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Biomedical subjects

M Turner

Publications and source records attributed to M Turner.

At least 235 records · Page 13Linked to original sources

Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis.

High levels of interleukin 6 (IL 6/B cell stimulatory factor-2) were detected in synovial fluids from the joints of patients with active rheumatoid arthritis (RA). The cells found in freshly isolated synovial fluid constitutively expressed IL 6 mRNA. The synovial tissues obtained by joint biopsy were also found to produce IL 6 in vitro. Immunohistochemical analysis demonstrated that CD2+ T cells as well as CD20+ blastoid B cells in the synovial tissues produce IL 6. The data indicate that IL 6 is generated constitutively in RA and its overproduction may explain the local as well as the generalized symptoms of RA, since IL 6 can function as B cell growth and differentiation factor as well as hepatocyte-stimulating factor.

Antigens, CD20↗

Identification and characterization of cDNA clones encoding antigens of Eimeria tenella.

An Eimeria tenella cDNA library was constructed in the expression vector lambda gt11 from poly (A+) RNA extracted from sporulating oocysts. The library was screened with rabbit antiserum raised against antigens extracted from fully sporulated oocysts. All of the antigen-expressing plaque-purified clones were initially characterized by cross screening with antisera raised against different stages of the E. tenella life cycle, as well as with antiserum raised against sporozoites of a related species, namely E. acervulina. A selected number of clones were further characterized by antibody selection coupled with immunoblotting and DNA cross hybridization. Three different E. tenella antigens were identified. All three appear to be constitutively expressed at the protein level during sporogony.

Animals↗

Microbial contamination and growth in total parenteral nutrition solutions.

TPN bags (196) and giving sets were subjected to microbiological examination following administration within a busy nutrition ward. Of these, five (2.6%) were found to be contaminated with coagulase-negative Gram-positive cocci. In all but one instance the contamination was restricted to the terminal ends of the giving sets rather than to the nutrition bag itself. Isolation of micro-organisms from the ward environment suggested that the contamination had arisen extrinsically during the setting up of the infusions. Isolates from the contaminated products, together with type species of Escherichia coli and Candida albicans, were examined with respect to their growth requirements and used to challenge four TPN formulations. Growth and survival of the organisms was monitored for up to 21 days. In all instances significant numbers of organisms were recovered after 72 h. Significant growth of the Staphylococcal isolate and C. albicans occurred over the initial 48-72 h incubation, this appeared to be greater in extent for the lipid-containing formulations. The temperature of storage of the formulation was the major determining factor for microbial growth and survival. No survivors were recovered, however, from any formulation after 21 days.

Candida albicans↗

Dopamine receptor modulation of corticosterone secretion in neonatal and adult rats.

The effects of the dopamine agonist, pergolide, upon plasma corticosterone levels have been studied in 30 day old neonatal and adult rats. Dose-related elevations in corticosterone were observed at both ages and these elevations were blocked by the dopamine (D2) receptor antagonist spiperone. These studies demonstrate that dopaminergic neurochemical control of the hypothalamus-pituitary-adrenal axis exists in four week old rats in contrast to our previous studies which have shown opioid control to be absent at this age. It appears that neurochemical control of corticosterone is dissimilar in the neonate.

Aging↗

Role of HLA class II and cytokine expression in rheumatoid arthritis.

HLA class II expression is notable in rheumatoid arthritis. We have investigated the mechanism of HLA class II regulation in the joints and found local synthesis, as judged by mRNA levels to be high. The role of antigen presentation in maintaining class II mRNA was explored, and blocking presentation by using monoclonal antibodies to HLA class II inhibited synthesis of mRNA for HLA-DR alpha chain. HLA class II expression is maintained by cytokines and so cytokine production in rheumatoid joints was investigated. It was chosen to use mRNA analysis by slot blotting as a screening assay, and the expression of many cytokines was detected. Levels of these were maintained in culture in the absence of extrinsic stimulation.

Antibody Formation↗

Does the maternal kidney contribute to the increased circulating 1,25-dihydroxyvitamin D concentrations during pregnancy?

The observation that during pregnancy the circulating 1,25-dihydroxyvitamin D, 1,25(OH)2D, concentrations are higher than in the nonpregnant state as well as recent evidence showing that, in vitro, the placenta and/or decidua are sites of 1,25(OH)2D synthesis has led to the general belief that the increased circulating 1,25(OH)2D concentrations originate from the placenta and/or decidua during pregnancy. The observation of a patient with end-stage renal disease who became pregnant after 10 years of chronic hemodialysis treatment has revealed that, despite delivery of a viable infant who had a normal development for gestational age and of normal serum 25-hydroxyvitamin D levels, her serum 1,25(OH)2D3 concentrations were only 10-15 pg/ml following 25 weeks of gestation. These 1,25(OH)2D3 concentrations are far lower than those usually encountered in normal women at the end of the 2nd trimester of pregnancy. It is felt that an important contribution of the placenta and/or of the decidua to the synthesis of the hormone should have led to higher 1,25(OH)2D3 concentrations than those observed in this patient. These observations, along with evidence from the literature, prompted us to reappraise the hypothesis on the origin of the circulating maternal 1,25(OH)2D3 during pregnancy and to postulate that the kidney might be more important than previously thought to the synthesis of the hormone during pregnancy.

Alkaline Phosphatase↗

Interleukin-1 and tumour necrosis factor mRNA expression in rheumatoid arthritis: prolonged production of IL-1 alpha.

In rheumatoid arthritis there is a chronic immune and inflammatory reaction which can lead to the destruction of the diseased joint. Cytokine gene expression was studied in synovial cells using cDNA probes specific for human interleukin 1 (IL-1), -alpha and IL-1 beta, tumour necrosis factor (TNF), -alpha and TNF beta (lymphotoxin); protein molecules which induce cartilage degradation and bone resorption. In all cases studied, IL-1 mRNA was present in freshly isolated synovial cells from fluid or membrane. Compared to levels of IL-1 mRNA found in optimally activated normal blood mononuclear cells, the levels of IL-1 alpha mRNA were high in seven of the nine patients studied, whereas IL-1 beta mRNA, the dominant form in blood, was relatively lower. TNF alpha and TNF beta mRNA were also detected. Rheumatoid synovial cells, cultured without any stimulus, continued to express high levels of IL-1 alpha mRNA for up to 5 days, compared to the 24 h response of activated blood cells; IL-1 beta mRNA in culture was also prolonged. Cultures of rheumatoid joint cells produced IL-1 bioactivity, with roughly equal amounts of IL-1 alpha and beta, as assessed using neutralizing antibodies. TNF bioactivity was also detected which may be of importance as TNF induces the production of IL-1. The finding of these mediators produced in large amounts in active rheumatoid synovial cells suggests that mutually stimulatory cell interactions, mediated by these molecules, may be important in the chronic inflammation and tissue destruction in rheumatoid arthritis.

Arthritis, Rheumatoid↗

Effects of tumour necrosis factor and alpha interferon on chronic B cell malignancies.

Tumour necrosis factor (TNF) induces the lysis of many malignant cells in vitro and regression of some tumours in vivo. However, TNF is also a growth factor for normal fibroblasts, T cells and B cells and we have recently shown that TNF can also act as a growth factor for chronic B cell neoplasms, including hairy cell leukaemia and B-CLL. In these cells it promotes proto-oncogene expression, RNA and DNA synthesis and increases overall cell survival. Stimulation appears to be autocrine in nature since exposure of the neoplastic cells to recombinant TNF protein induces the corresponding messenger RNA and synthesis of the protein itself. TNF induced proto-oncogene expression and DNA synthesis occur over a substantially longer time period than when the cells are stimulated with agents such as TPA and Calcium ionophore (2), but we have no evidence that the delay represents the time taken to generate TNF dependent secondary cytokines such as IL-1 and IL6. Alpha interferon opposes TNF mediated activation and our recent data indicate that this effect is independent of alpha interferon down regulation of TNF receptors. It appears to be related instead to a decreased accumulation of TNF mRNA which occurs contemporaneously with an alpha interferon induced rise in 2-5 A synthetase. If TNF dependent growth is important for the survival of B-CLL cells, then agents which mimic alpha interferon or which block TNF induced autocrine growth would be predicted to be of therapeutic benefit.

B-Lymphocytes↗

Human T cells from autoimmune and normal individuals can produce tumor necrosis factor.

T cell clones derived from patients with autoimmune diseases were found to be capable of producing tumor necrosis factor (TNF). This was demonstrated by stimulating the clones, in the absence of accessory cells, with antibodies against the Ti/T3 complex and with recombinant interleukin 2 (IL2). Analysis of RNA extracted from these clones showed that TNF mRNA was more abundant than lymphotoxin (LT) mRNA. We also found that TNF protein in the supernatants of these clones was generally more abundant than LT as assessed by using the murine L929 cell assay. TNF production was not limited to T cells from autoimmune individuals, since the T cell tumor HUT78 and T cells purified from the peripheral blood of healthy individuals also made TNF. Unlike the T cell clones, HUT78 produced greater amounts of LT mRNA than TNF mRNA. Induction of TNF mRNA in T cells from healthy individuals displayed a two-signal requirement (phorbol myristate 13-acetate and phytohemagglutinin or OKT3 and phorbol myristate 13-acetate), similar to that described for the induction of the T cell lymphokines IL 2 and interferon-gamma (IFN-gamma). Additionally we found that IL2 alone was sufficient to induce TNF in these cells when they had been precultured with phytohemagglutinin for 7 days to express IL 2 receptors. The cloned T cells we have characterized also produce IFN-gamma which was detected in the supernatants of the clones using a radioimmunoassay. The evidence suggests that T cells can produce TNF and have the potential to deliver by themselves the dual and synergistic signals of TNF/LT and IFN-gamma to target cells, a process which may be of importance in the pathogenesis of human autoimmunity.

Antigens, Differentiation, T-Lymphocyte↗

A comparison of the responses of staphylococci and streptococci to teicoplanin and vancomycin.

Continuous turbidimetric monitoring of cultures of staphylococci and streptococci exposed to teicoplanin or vancomycin revealed considerable inhibitory activity at concentrations below the conventionally-determined minimum inhibitory concentration. Teicoplanin was more active than vancomycin against low inocula, but exhibited a larger inoculum effect. A modest decline in susceptibility to teicoplanin and vancomycin could be induced by sequential exposure to the drugs. Such variants gradually reverted to susceptibility on passage in antibiotic-free broth. The morphological consequences of exposure to the two antibiotics were similar as judged by scanning electron microscopy.

Anti-Bacterial Agents↗

Community outbreak of adenovirus type 7a infections associated with a swimming pool.

In July 1982, an outbreak of pharyngitis caused by adenovirus type 7a occurred among children in a small town in western Oklahoma. Predominant symptoms were fever and sore throat (by case definition), headache (83%), abdominal pain (64%), and conjunctivitis (51%). At least 77 persons were identified whose symptoms met the case definition for illness. Onsets of illness peaked during the week of July 5 to 12, and the outbreak resolved within three weeks. A systematic telephone survey of the town revealed that persons who had swum at the community swimming pool were more likely to be ill than those who had not (P less than .001). A second survey of families with season passes to the pool showed that among swimmers, illness was directly related to average number of hours of exposure to the pool each week (P less than .001 by chi-square for trend). In addition, swimmers who reported swallowing pool water were more likely to be ill (29 of 56, 52%) than persons who did not (ten of 41, 24%) (P = .01). Throat-swab specimens from five of seven ill persons (71%) grew adenovirus 7a compared with one of 12 well persons (8%) (P = .01). The pool chlorinator had reportedly malfunctioned during early July. The outbreak resolved with proper operation of the chlorination system. Swimming pools continue to be a potential source of community-wide outbreaks of adenovirus infections.

Adenoviridae Infections↗

Nutritional management of pregnancy in patients on home parenteral nutrition.

Three pregnancies are reported in two patients on home parenteral nutrition for intestinal failure. The nutritional regimen, 2300 kcal (9.63 MJ) (18% as lipid emulsion), 14 g amino acid nitrogen and electrolytes supplied daily in a 'big bag', was based on the measured resting energy expenditure and urinary nitrogen excretion during the third trimester in a 30-year-old woman on home parenteral nutrition. Commercial preparations of trace elements were added to the infusion as dictated by serum levels. Iron, iodine and fluoride were given orally, and vitamin B12 by monthly intramuscular injection. There were no serious deficiencies in trace elements and maternal weight-gain and fetal growth were satisfactory in all three pregnancies. The two pregnancies in one patient went to term and both infants had birthweights at the 50th centile for gestational age. The second patient who had had two spontaneous abortions went into premature labour at 30 weeks and gave birth to a baby with a minor facial deformity who subsequently developed the idiopathic respiratory distress syndrome. All three placentas were histologically normal. The growth and development of all three babies has been satisfactory. This nutritional regimen should be adequate for most pregnant patients who have attained a normal nutritional status on parenteral nutrition.

Adult↗