PubMed Health⌕ Search

Biomedical subjects

B K English

Publications and source records attributed to B K English.

36 records · Page 2Linked to original sources
PubMed1996

Serious infections due to penicillin-resistant Streptococcus peneumoniae in two children with nephrotic syndrome.

Children with nephrotic syndrome are susceptible to the development of invasive bacterial infections, particularly those caused by Streptococcus peneumoniae. Recently, penicillin-resistant pneumococcal infections in children have occurred in increased frequency in some regions. We have seen two children with nephrotic syndrome who developed penicillin-resistant pneumococcal bacteremia and/or peritonitis. A change in the initial therapy from penicillin in the usual dose in these patients must be considered.

Female↗
PubMed1996

Differential effects of tyrosine kinase inhibitors on tumor necrosis factor and nitric oxide production by murine macrophages.

The temporal requirements for tyrosine phosphorylation in the induction of tumor necrosis factor (TNF) and inducible nitric oxide synthase (NOS) were compared in the routine macrophage cell line RAW 264.7. Preincubation of RAW 264.7 cells with herbimycin A or genistein (but not with either of three tyrphostins tested) significantly blocked TNF and NOS production on exposure of these cells to combinations of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). The addition of either genistein or herbimycin A to RAW 264.7 cell cultures 1-6 It after stimulation with LPS and IFN-gamma had little or no effect on TNF production but markedly inhibited NOS protein accumulation. Together these data indicate that tyrosine kinase inhibitors block NOS production at a point well downstream of the initial wave of LPS- and IFN-gamma-mediated protein tyrosine phosphorylation.

Animals↗
PubMed1996

Lipoteichoic acid from viridans streptococci induces the production of tumor necrosis factor and nitric oxide by murine macrophages.

Bacterial endotoxin or lipopolysaccharide is the major proinflammatory component of gram-negative bacteria, but the components of gram-positive bacteria that trigger the inflammatory cascade are poorly understood. Lipoteichoic acid (LTA) purified from 2 strains of viridans streptococci induced the accumulation of tumor necrosis factor (TNF) mRNA and protein by the murine macrophage cell line RAW 264.7 in a dose- and time-dependent manner. Furthermore, in the presence of recombinant interferon-gamma, LTA from both strains of viridans streptococci provoked the accumulation of inducible nitric oxide (NO) synthase mRNA and the production of NO. Together these observations indicate that LTA can trigger macrophage activation and the production of TNF and NO and suggest that LTA may be an important determinant of the host inflammatory response to gram-positive infection.

Animals↗
PubMed1996

Acquired hyporesponsiveness to bacterial lipopolysaccharide and interferon-gamma in RAW 264.7 macrophages.

Bacterial lipopolysaccharide (LPS) can induce hyporesponsiveness to its own toxic effects, as reflected by the diminished production of tumor necrosis factor (TNF) and other inflammatory mediators by animals (and by purified macrophages) upon re-challenge with LPS. We have examined the regulation of TNF and inducible nitric oxide synthase (iNOS) production in the murine macrophage cell line RAW 264.7. These cells accumulated TNF mRNA and secreted TNF protein in a dose-dependent fashion after exposure to either LPS or recombinant murine interferon-gamma (riFN-gamma). Pre-exposure of RAW 264.7 cells to relatively high concentrations of LPS (> 10 ng/mL) resulted in diminished production of TNF in response to subsequent challenge with either LPS or riFN-gamma. In contrast, production of iNOS mRNA was either unaffected or augmented by pre-exposure of these cells to LPS. Our findings indicate that the hyporesponsive state of RAW 264.7 macrophages preincubated with LPS is not specific for LPS and that the production of TNF and nitric oxide (NO) by macrophages are differentially regulated.

Animals↗
PubMed1993

Hck tyrosine kinase activity modulates tumor necrosis factor production by murine macrophages.

The hematopoietic cell kinase (hck) is a member of the src family of tyrosine kinases, and is primarily expressed in myeloid cells. Hck expression increases with terminal differentiation in both monocyte/macrophages and granulocytes and is further augmented during macrophage activation. Recent evidence has implicated src-related tyrosine kinases in critical signaling pathways in other hematopoietic lineages. Herein we demonstrate that manipulation of the level of hck expression in the murine macrophage cell line BAC1.2F5 alters the responsiveness of these cells to activation by bacterial lipopolysaccharide (LPS) but does not affect survival or proliferation. Overexpression of an activated mutant of hck in BAC1.2F5 cells augments tumor necrosis factor (TNF) production in response to LPS, whereas inhibition of endogenous hck expression, by antisense oligonucleotides, interferes with LPS-mediated TNF synthesis. Together, these observations suggest that hck is an important component of the signal transduction pathways in activated macrophages.

Base Sequence↗
PubMed1993

The provision and use of medical services during the 1991 World Student Games in Sheffield.

This paper describes the provision and use of medical services organized by Sheffield during the World Student Games in 1991. A descriptive study of medical and physio-therapy records, together with minor incident logs and hospital referrals, was carried out. It was found that 571 medical records and 357 physiotherapy records were completed, of which 83 per cent were generated at the Games Village. The majority of patients were competitors, although team officials accounted for a disproportionate number. Most physiotherapy requests were for sports injuries, whereas this was not so for medical cases. Twenty-five per cent of medical records and 40 per cent of physiotherapy records were for recurrent conditions which had started before arrival. Athletics and football accounted for the greatest number of records per competitor. During the Games, 82 patients were referred to hospital, of whom only 12 were admitted. The largest group of hospital referrals was for dental treatment, and the next largest was for minor trauma. A total of 1089 minor incidents were recorded, mainly at the competition venues and in the Physiotherapy Room at the Games Village. In addition, the Red Cross and the St John Ambulance Association attended to 330 people during the Games. The smallest national teams tended to make most demands on services, probably because the larger teams were accompanied by their own medical and physiotherapy staff. It is concluded that the main demands for medical services at the World Student Games were for general practice and physiotherapy at the Games Village, and for first aid at competition venues.(ABSTRACT TRUNCATED AT 250 WORDS)

Athletic Injuries↗
PubMed1992

Decreased granulocyte-macrophage colony-stimulating factor production by human neonatal blood mononuclear cells and T cells.

Impaired production and delivery of neutrophils to the site of infection have been implicated in the increased susceptibility of the neonate to infection. Because granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) play critical roles in the production of neutrophils from marrow precursors, we assessed the ability of leukocytes from neonates and adults to produce GM-CSF, G-CSF, and, for comparison, macrophage colony-stimulating factor (M-CSF) after stimulation with concanavalin A +/- phorbol myristate acetate [blood mononuclear cells (MC) and T lymphocytes] or lipopolysaccharide (monocytes). MC and monocytes from adult and neonatal subjects produced mRNA for GM-CSF, G-CSF, and M-CSF, whereas T cells produced only GM-CSF mRNA. Neonatal MC and T cells accumulated only approximately 30% as much GM-CSF mRNA as did adult MC and T cells. In contrast, the accumulation of GM-CSF mRNA by neonatal and adult monocytes was similar. Neonatal MC also accumulated similar amounts of G-CSF mRNA and somewhat more M-CSF mRNA than did adult MC; results with monocytes were similar to those with MC. Results of colony-stimulating activity bioassays on supernatants from neonatal and adult MC stimulated with concanavalin A paralleled the mRNA results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Differential regulation of lymphotoxin and tumor necrosis factor genes in human T lymphocytes.

Lymphotoxin (LT) and tumor necrosis factor (TNF) are related cytokines that share many biological effects. The genes for LT and TNF are adjacent to each other on chromosome 6 in man, but previous data indicate that the kinetics of their production differ markedly. To explain the mechanisms for this difference, we compared the regulation of these two genes in human T lymphocytes, isolated from peripheral blood, after stimulation with the mitogens concanavalin A and phorbol myristate acetate. Differences in the kinetics of protein secretion were paralleled by differences in cognate mRNA accumulation. TNF mRNA accumulated rapidly after stimulation, peaked by 6 h, and returned to unstimulated (base-line) levels by 24 h. In contrast, LT mRNA accumulated slowly after stimulation, usually peaked at approximately 18 h, and remained increased above base-line levels at 48-72 h. By nuclear transcription run-on assays, increased transcription of TNF mRNA and LT mRNA was demonstrated after stimulation. However, TNF transcription peaked earlier and appeared to be 4-10 times greater than that of the LT gene. In contrast, the half-life of LT mRNA was 8-10-fold longer than that of TNF mRNA as demonstrated by actinomycin D pulse-chase experiments. Cycloheximide did not block LT or TNF mRNA accumulation, indicating that new protein synthesis was not required for induction of either gene. These results suggest strongly that the LT and TNF genes are regulated differently in human T lymphocytes after mitogen stimulation. TNF mRNA accumulates rapidly primarily because of increased transcription and decreases rapidly related to its brief half-life. In contrast, LT mRNA accumulates more slowly but persists much longer; the accumulation of this mRNA appears to be controlled largely by post-transcriptional mechanisms.

Adult↗
PubMed1991

Cellular and molecular mechanisms for reduced interleukin 4 and interferon-gamma production by neonatal T cells.

The mechanisms by which T lymphocytes acquire the capacity to produce interleukin 4 (IL-4) and other lymphokines during intrathymic and extrathymic development are poorly understood. To gain insight into this process, we determined the capacity of human neonatal and adult T lineage cell populations to produce IL-4 after polyclonal activation. IL-2 and interferon-gamma (IFN-gamma) production were studied in parallel, since their production by neonatal T cells is known to be similar or diminished, respectively, compared to adult T cells. Production of IL-4 by neonatal CD4+ T cells and IFN-gamma by neonatal CD4+ and CD8+ T cells was markedly lower compared with analogous adult cell populations, whereas IL-2 production was similar. Transcription of IL-4, as determined by nuclear run-on assays, and IL-4 mRNA-containing cells, as determined by in situ hybridization, were undetectable in neonatal T cells, whereas both were detectable in adult T cells. IFN-gamma transcription and IFN-gamma mRNA-containing cells were reduced in neonatal T cells compared with adult T cells. Reduced lymphokine production by neonatal T cells correlated with their lack of a CD45R- (putative memory T cell) population; cells with this surface phenotype comprised 30-40% of the adult CD4+ T cells and were highly enriched for IL-4 and IFN-gamma, but not IL-2 production. IL-4, IFN-gamma, and IL-2 mRNA expression by neonatal CD4+CD8- thymocytes was similar to that found in circulating neonatal CD4+ T cells. Taken together, these findings suggest that the extrathymic generation of memory T cells during postnatal life may result in an increased capacity for IL-4 and IFN-gamma gene expression. In addition, IFN-gamma and IL-2 mRNA were significantly more abundant than IL-4 mRNA in activated neonatal CD4+CD8- thymocytes and CD4+ T cells, as well as adult CD4+ CD45R- T cells. Therefore, the capacity of T lineage cells to express the IL-4 gene may be more restricted compared to other lymphokine genes beginning in intrathymic development. This restricted capacity appears to persist during postnatal extrathymic maturation of T cells.

Adult↗
PubMed1988

Production of lymphotoxin and tumor necrosis factor by human neonatal mononuclear cells.

Lymphotoxin (LT) and tumor necrosis factor (TNF) are cytokines with many common biologic effects including antiviral activity and induction of fever and the acute phase response; despite common effects, they are molecularly distinct. Because neonates are unduly susceptible to viral infection and frequently fail to mount a febrile response to infection, we hypothesized that neonatal cells would produce less LT and TNF than adult cells. We analyzed LT and TNF production by blood mononuclear cells and purified T cells using Northern blot analysis to detect specific messenger ribonucleic acid and specific assays to detect LT and TNF protein in culture supernatants. Compared to LT, TNF messenger ribonucleic acid and protein were produced more rapidly both by total mononuclear cells and by T cells in response to mitogen stimulation. Although there was intersubject variability, adult and neonatal mononuclear cells and T cells (n = 6) produced similar amounts of LT and TNF messenger ribonucleic acid and protein with similar kinetics. In experiments with phytohemagglutinin-stimulated mononuclear cells from ten additional subjects, supernatant LT was somewhat greater in neonatal cultures (neonatal = 62.8 +/- 60.5, adult = 13.2 +/- 10.7 units/ml, p less than 0.05), and TNF was somewhat greater in adult cultures (neonatal = 708 +/- 429, adult = 1987 +/- 392 pg/ml, p less than 0.01) at 24 h; results at 48 h and 72 h were similar. Thus, neonatal MC produced as much or more LT than did adult MC. Although the decreased production of TNF by neonatal MC was statistically significant, these cells did produce substantial amounts of this cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗