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Biomedical subjects

P Trinder

Publications and source records attributed to P Trinder.

17 recordsLinked to original sources
PubMed2003

Prophylactic aspirin use in the adult general population.

BACKGROUND: The aim of the study was to establish the prevalence and patterns of aspirin use in people with vascular problems. METHODS: A cross-sectional population survey was carried out on a stratified random sample of 10,000 adults aged 35 and over in North Staffordshire. RESULTS: A total of 6322 adults replied to the questionnaire (adjusted response 67 percent). The prevalence of vascular problems was 12.9 percent, and 67.6 per cent of respondents were using aspirin. The main association with aspirin use was previous advice about aspirin: adults who recalled being given advice were more likely to be using aspirin. Increasing age, disease severity and level of deprivation were also associated with increased aspirin use. Of adults without vascular problems, 7.1 percent also reported using aspirin regularly. CONCLUSIONS: There is still potential to increase aspirin use in those with vascular problems. The extent and quality of health care professionals' advice may be an important area to target. The reasons why some people without vascular problems take regular aspirin is an area for further investigation.

Adult↗
PubMed2000

Interleukin-7 or interleukin-15 enhances survival of Mycobacterium tuberculosis-infected mice.

Both antigen-presenting cells and immune effector cells are required to effectively eradicate or contain Mycobacterium tuberculosis-infected cells. A variety of cytokines are involved to ensure productive "cross talk" between macrophages and T lymphocytes. For instance, infection of macrophages with mycobacteria leads to effective interleukin-7 (IL-7) and IL-15 secretion, and both cytokines are able to maintain strong cellular immune responses of alpha/beta and gamma/delta T cells. Here we show that either cytokine is able to enhance survival of M. tuberculosis-infected BALB/c mice significantly compared to application of IL-2, IL-4, or phosphate-buffered saline (as a control). Enhanced survival could be achieved only when IL-7 or IL-15 was delivered as a treatment (i.e., 3 weeks postinfection), not when it was administered at the time of infection. Increased survival of M. tuberculosis-infected animals was observed following passive transfer of spleen cells harvested from M. tuberculosis-infected, IL-7- or IL-15-treated animals, but not after transfer of spleen cells obtained from mice which received either cytokine alone. Histological examination revealed that IL-7 and IL-15 failed to significantly impact on the number and composition of granulomas formed or the bacterial load. Our data indicated that administration of IL-7 or IL-15 to M. tuberculosis-treated animals resulted in a qualitatively different cellular immune response in spleen cells as reflected by increased tumor necrosis factor alpha and decreased gamma interferon secretion in response to M. tuberculosis-infected antigen-presenting cells.

Adoptive Transfer↗
PubMed1999

Interleukin-15 in mycobacterial infection of antigen-presenting cells.

Interleukin-15 (IL-15) shares many biological functions with IL-2 but also exhibits unique effects. Some of these represent the potent chemoattractant activity and expansion of distinct T-cell subsets, particularly memory T cells. IL-15 may therefore modulate the quality and quantity of cellular immune responses directed against intracellular pathogens. Immunohistochemical examination of skin lesions obtained from patients with the lepromatous or the tuberculoid form of Hansen's disease revealed intralesional IL-15 protein in both forms of the disease. In addition to Mycobacterium leprae, a number of different mycobacterial species are capable of effectively inducing IL-15 secretion in infected macrophages. In this work, increased IL-15 secretion was observed in IL-4/granulocyte-macrophage colony-stimulating factor (GM-CSF)-activated antigen-presenting cells (APC) compared with unstimulated macrophages. Immunocytological detection of intracellular IL-15 revealed that infection with different mycobacterial species resulted in different staining patterns of anti-IL-15 immunoreactive material in APC. In contrast to IL-2 or IL-7, IL-15 enhanced the cytolytic potential of immune effector cells in vitro and favoured the expansion of CD1b-restricted immune cells recognizing mycobacterial-associated antigens presented by autologous APC. IL-15 produced by infected cells in situ may represent one of the key cytokines involved in granuloma formation and may aid the augmentation of cellular immune responses directed against mycobacterial-infected cells.

Antigen-Presenting Cells↗
PubMed1999

Constitutive and IFN-gamma regulated expression of IL-7 and IL-15 in human renal cell cancer.

Although not structurally related, the pleiotropic cytokines interleukin-7 (IL-7) and interleukin-15 (IL-15) share a variety of biological functions including stimulation and maintenance of cellular immune responses. Cytokines, such as IL-7 or IL-15, elaborated by cells in situ, e.g. cancer cells, may be involved in shaping the quality of anti-tumor directed immune responses. We have analysed the constitutive and IFN-gamma-inducible expression of IL-15 or IL-7 mRNA, protein expression, and protein secretion in human tumor cell lines of distinct origin. IL-15 mRNA expression was detected in renal cell carcinoma (RCC), small cell lung carcinoma (SCLC), glioblastoma, neuroblastoma, mesothelioma cells and in EBV-transformed B-lymphocytes. IL-7-specific transcripts could be detected in colorectal cancer and in renal cell cancer cell lines. Immunohistochemical analysis demonstrated cytosolic IL-15 protein expression in renal cell cancer cells without apparent IL-15 protein secretion in vitro. Time kinetic analyses revealed that IFN-gamma mediated increase of IL-15 mRNA expression was transcriptionally regulated and dependent on de novo protein synthesis. However, enhanced IL-15 mRNA expression did not lead to effective protein secretion. In contrast, IL-7 mRNA expression in renal cell cancer or in colorectal cancer was associated with effective protein secretion which could be augmented by IFNgamma-treatment. These data suggest that both IL-7 and IL-15 mRNA are expressed in renal cell cancer, but exclusively IL-7 may be elaborated by tumor cells in situ. IL-15 regulation appears to be tightly controlled both at the transciptional and post-transcriptional level. Appropriate stimuli leading to effective IL-15 secretion from tumor cells may aid in modulating cellular immune responses directed against cancer.

Carcinoma, Renal Cell↗
PubMed1997

C1 inhibitor-C1s complexes are internalized and degraded by the low density lipoprotein receptor-related protein.

Like other serpin-enzyme complexes (SECs), proteinase-complexed C1 inhibitor (C1-INH) is rapidly cleared from the circulation and thought to be a neutrophil chemoattractant, suggesting that complex formation causes structural rearrangements exposing a domain which is recognized by specific cell surface receptors. However, the cellular receptor(s) responsible for the catabolism and potential mediation of chemotaxis by C1-INH-protease complexes remained obscure. To determine whether the SEC receptor mediates the binding and potential chemotaxis of C1-INH.Cs, we performed binding assays with HepG2 cells, neutrophils, and monocytes, and the results show that C1-INH.Cs neither bind to these cells nor cause a chemotactic response of neutrophils and monocytes. Furthermore, C1-INH.Cs, the COOH-terminal C1 inhibitor peptide, or the tetrameric C1-INH.Cs.Cr. C1-INH complex were found to be significantly less effective in competing with the SEC receptor ligand 125I-peptide 105Y for the binding to HepG2 cells than unlabeled 105Y, indicating that the SEC receptor does not sufficiently recognize C1-INH-protease complexes. The asialoglycoprotein receptor was also ruled out to be responsible for the removal of the heavily glycosylated C1-INH.Cs complex, since asialoorosomucoid did not compete for the clearance of C1-INH. 125I-Cs and asialoglycoprotein receptor knockout mice showed no alterations in the C1-INH.125I-Cs clearance rate. We found that C1-INH.125I-Cs complexes were efficiently degraded by normal murine fibroblasts expressing the low density lipoprotein receptor-related protein (LRP) and cellular degradation was significantly reduced by chloroquine and the receptor-associated protein, which is a potent inhibitor of the binding of all known ligands to LRP. Moreover, receptor-associated protein inhibited the in vivo clearance of C1-INH.125I-Cs and murine fibroblasts genetically deficient for LRP did not degrade C1-INH.125I-Cs. Our results demonstrate that C1-INH. Cs complexes do not stimulate neutrophil or monocytic chemotaxis but are removed by LRP, further underscoring its role as a serpin-enzyme complex clearance receptor.

Animals↗
PubMed1984

Determination of HDL-cholesterol using 2,4,6-tribromo-3-hydroxybenzoic acid with a commercial CHOD-PAP reagent.

The Boehringer one-component high-performance cholesterol oxidase reagent has been modified by the inclusion of 2,4,6-tribromo-3-hydroxybenzoic acid (TBHBA) to give a fourfold increase in sensitivity to a molar absorbance of approximately equal to 29,000 with respect to cholesterol. The resulting reagent system is particularly suitable for the determination of plasma HDL-cholesterol for which a reagent of high sensitivity is required. A simple method of bromination avoiding the use of elemental bromine is used to prepare TBHBA. The modified reagent system has been found to have good within- and between-batch precision and has shown itself to be reliable and trouble-free.

Bromobenzoates↗
PubMed1981

Oxidase determination of plasma cholesterol as cholest-4-en-3-one using iso-octane extraction.

Cholesterol esters in 20 microliter of plasma are hydrolysed with hot ethanolic KOH. Preformed cholesterol and cholesterol released by hydrolysis is reacted with cholesterol oxidase to form hydrogen peroxide and cholest-4-en-3-one, which is extracted from alkaline 50% v/v ethanolic solution with iso-octane. The absorbance of the ketone in iso-octane at the 232 nm peak is used to measure the cholesterol originally present. Plasma blanks obtained by omitting the cholesterol oxidase from the reagent shown negligible absorbance even when samples are grossly icteric, lipaemic, or haemolysed. The test is carried out in a single glass screw-capped tube, and the absorbance given by a sample containing 6.25 mmol/1 cholesterol is approximately 0.44, corresponding to a molar absorbance of approximately 17 500. The conversion of cholesterol to cholest-4-en-3-one is stoichiometric, and the absorbance of the iso-octane layer is stable for at least 48 hours. A single determination occupies 30 minutes, 30 samples can be analysed in 1 1/2 hours.

3-Hydroxysteroid Dehydrogenases↗
PubMed1980

A new method for the determination of plasma phenylalanine.

Two hundred microlitres of plasma is deproteinised, and chloride is removed with TCA/silver iodate. After centrifugation of the phenylalanine in the protein-free extract is oxidised to benzaldehyde with buffered sodium metaperiodate. The benzaldehyde is extracted into iso-octane, and the absorbance of the organic layer is measured at 240 nm. The method gives good agreement with a paper chromatographic method at normal and elevated levels of phenylalanine. All the reagents are stable indefinitely, and a single determination can be completed in 15 minutes.

Benzaldehydes↗
PubMed1969

Determination of blood glucose using an oxidase-peroxidase system with a non-carcinogenic chromogen.

Manual and automated methods for the determination of blood glucose have been devised using an oxidase/peroxidase system, with dl adrenaline, a non-carcinogen, as oxygen acceptor. The manual technique employs a stable single solution protein precipitant and the other reagents used are also stable. The automated methods are operated at 40/hr sample speed and washover between samples, over a very wide concentration range, is negligible.

Adrenochrome↗