Biomedical subjects

P J Townsend

Publications and source records attributed to P J Townsend.

9 recordsLinked to original sources

PubMed1992

Enhancement of the antigen-presenting function of monocytes by cholesterol: possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis.

Extrinsic allergic alveolitis (EAA) (synonym: hypersensitivity pneumonitis) is a hypersensitivity lung disease characterized by lymphocytic infiltrates in the pulmonary interstitial tissues. We have previously reported that the numbers of lymphocytes in bronchoalveolar lavage (BAL) samples in this disease correlate with levels of cholesterol and neutral lipid-laden 'foamy' macrophages. We have also reported that the macrophages express an increased density of MHC class II antigens (in particular HLA-DQ) which are known to be essential for antigen recognition by T lymphocytes. The aim of the present study was to explore whether cholesterol is capable of enhancing the antigen-presenting function of mononuclear phagocytes by modulating the expression of HLA-D region products. Incubation of purified monocytes from healthy volunteers with cholesterol in serum-free medium induced a significant increase in both the percentages of monocytes expressing HLA-DQ (P less than 0.02) and in the intensity of expression of the three HLA-D sub-region products, HLA-DQ, -DP and -DR (P less than 0.02, less than 0.01, less than 0.05, respectively). The cholesterol pre-incubated monocytes also exhibited enhanced antigen-presenting function (P less than 0.05), compared with controls pre-incubated without cholesterol. These findings indicate that increases in cholesterol in the extracellular milieu may augment antigen presentation by modulating the expression of HLA-D region products on antigen-presenting cells. Apart from EAA, this observation may also have relevance to inflammatory mechanisms in atherosclerosis, where 'foamy' macrophages also occur in association with hypercholesterolaemia.

Alveolitis, Extrinsic Allergic↗

PubMed1992

Induction of lymphocyte proliferation by antigen-pulsed human neutrophils.

We have investigated whether purified antigen-pulsed human neutrophils can induce a proliferative response in purified resting blood lymphocytes. Neutrophils were pulsed with soluble tetanus toxoid (dose range 25-250 Lf/ml) and co-cultured with autologous lymphocytes that had been depleted of MHC class II expressing cells. The antigen-pulsed neutrophils induced an increase of lymphocyte proliferation which was dependent on the antigen dose and the neutrophil/lymphocyte ratios. Neutrophils were less potent than autologous monocytes in stimulating lymphocyte proliferation. Blocking with a monoclonal antibody to a common determinant of the human MHC class II complex failed to reduce the lymphoproliferative effects and allogenic antigen-pulsed neutrophils were also able to elicit lymphocyte proliferation similar to autologous neutrophils. We conclude that antigen-pulsed neutrophils are able to induce lymphocyte proliferation in a non-MHC-restricted fashion.

Antigen-Presenting Cells↗

PubMed1992

Gene expression during cardiac development.

The vertebrate heart forms as two concentric epithelial cylinders of myocardium and endocardium separated by an extended basement membrane matrix commonly referred to as cardiac jelly. Subsequent maturation involves a complex series of events including asymmetric changes in cell shape and division which contribute to bending and the formation of the bulboventricular loop, the formation of specialised tissues including endocardial cushion tissue of the atrioventricular (AV) and outflow tract regions, the development of conductive tissue and myocyte maturation leading to the overall pattern of expression characteristic of mature heart muscle. These processes depend on a precise spatial and temporal control of gene expression both of genes encoding regulatory molecules and those encoding structural components of the heart. In this chapter we address three aspects of cardiac development, namely, the determination of cell fate during formation of endocardial cushion tissue in the embryonic heart, transitions in troponin gene expression during fetal myocyte maturation, and the use of cloning techniques based on the polymerase chain reaction for identifying transcription factors present in the heart.

Animals↗

PubMed1990

Increases in HLA-DQ, DP, DR, and transferrin receptors on alveolar macrophages in sarcoidosis and allergic alveolitis compared with fibrosing alveolitis.

We have used flow cytometric methods to detect and quantify HLA-DR, DQ, and DP antigens and transferrin receptors on alveolar macrophages in lavage samples from 36 patients with granulomatous lung diseases (extrinsic allergic alveolitis [EAA], n = 13; sarcoidosis, n = 23), and 12 patients having fibrosing alveolitis (FA) (cryptogenic fibrosing alveolitis, n = 3; FA and scleroderma, n = 8; FA and primary biliary cirrhosis, n = 1). HLA-DR, DQ, and DP antigens were expressed on the majority of alveolar macrophages in all the patients, and the percentages of positive cells were similar to those in control subjects without lung disease. However, the amounts expressed were higher in those with EAA and sarcoidosis than in the FA group or control subjects, the most significant differences being in HLA-DQ and HLA-DP expression. Transferrin receptor expression was also higher in the granulomatous lung diseases. In sarcoidosis, higher levels of HLA-DQ correlated with lower lung function measurements (Dco p less than 0.025, FVC p less than 0.025, FEV1 p less than 0.005), suggesting this may be a marker of disease activity. HLA-DP levels also showed a trend (p less than 0.1) of inverse correlation with lung function. Levels of HLA-DQ (p less than 0.005) and HLA-DP (p less than 0.001) correlated more closely than HLA-DR with numbers of lymphocytes in the lavage fluids, and HLA-DQ levels correlated with increasing proportions of lymphocytes in proliferation (p less than 0.05). We suggest that high levels of HLA-DQ and DP on alveolar macrophages may be more relevant than HLA-DR to the enhanced antigen-presenting function of these cells in sarcoidosis, and possibly also in EAA.

Adult↗

PubMed1990

Lavage versus serum measurements of lysozyme, angiotensin converting enzyme and other inflammatory markers in pulmonary sarcoidosis.

The aim of this study was to explore whether amounts of angiotensin converting enzyme (ACE) and lysozyme produced within the lungs correlate more closely than serum levels of these enzymes, or other inflammatory markers, with chest radiographic profusion scores, lung function and therapy response in patients with pulmonary sarcoidosis. We have studied 25 patients, and levels in bronchoalveolar lavage (BAL) were used to determine "local" enzyme production by reference to serum and lavage albumin. Before treatment, serum lysozyme levels were elevated in more patients (80%) than serum ACE levels (40%). They also gave the best overall correlation with clinical measurements prior to treatment and falls in serum lysozyme closely parallelled improvement in lung function (transfer factor for carbon monoxide (DLCO)) on therapy. The only other markers showing significant correlations with disease severity were lavage neutrophil counts per ml and "local" ACE measurements prior to treatment. The value of pre-treatment levels of the different inflammatory markers in predicting response to corticosteroid therapy was explored and the only significant finding was that BAL lymphocyte percentages and numbers.ml-1 were initially higher in patients with lower post-treatment chest X-ray scores (p less than 0.01 and p less than 0.05, respectively). We conclude that serum lysozyme levels appear to be a more useful marker of overall disease activity in sarcoidosis than measurements of other inflammatory markers. However, BAL lymphocyte counts were the best predictive marker of radiographic response to corticosteroids.

Adult↗

PubMed1986

Bronchoalveolar lavage in patients with interstitial lung diseases: side effects and factors affecting fluid recovery.

One hundred and seventy patients with interstitial lung diseases undergoing bronchoalveolar lavage (BAL), were contrasted with 51 patients undergoing fibreoptic bronchoscopy alone to define the factors which predispose to post-lavage side-effects. Transient post-bronchoscopy fall in the peak expired flow (PEF) greater than or equal to 20% occurred in both groups (24% and 23% respectively), and thus was probably related to the bronchoscopy procedure. Post-lavage pyrexia (greater than or equal to 1 degree C) occurred only in the patients undergoing BAL (26%), p less than 0.001. Only 4% with pyrexia required antibiotics, and only 2% with falls in PEF needed bronchodilator therapy. The only significant clinical association was more frequent pyrexia in patients on treatment with prednisolone, particularly in women (p less than 0.01). Pyrexia was also associated with higher lavage fluid introduction volumes (greater than 240 ml). Side effects did not relate to the percentages of lavage fluid recovered, although smokers had lower recoveries and, recoveries tended to be higher in sarcoidosis than cryptogenic fibrosing alveolitis. Serial lavages in 25 patients caused no significant increase in side effects.

Adult↗

PubMed1985

Numerical and functional alterations in circulatory lymphocytes in cigarette smokers.

Simultaneous numerical and functional studies of circulatory lymphocytes were undertaken in healthy non-smoking and cigarette-smoking volunteers. The smokers all had light to moderate histories of less than 50 pack years. By contrast with non-smokers (n = 32), the smokers (n = 14) had a significant increase in the total number of lymphocytes, surface immunoglobulin bearing (sIg+) cells, total T-cells (T3+) and T helper-inducer cells (T4+), and a trend of increase in T suppressor-cytotoxic cells (8+). These changes differ from those in heavy smokers who have been reported to show significantly increased T suppressor-cytotoxic but significantly decreased T helper-inducer cells. Although the proportions of T-cell subsets did not differ significantly in the light to moderate smokers compared with non-smokers, in vitro T-suppressor function against the Ig-secreting response of allogeneic B-cells to pokeweed mitogen (PWM) stimulation was significantly impaired. The proliferative response of T-cells to phytohaemagglutinin (PHA) was, however, similar in both groups. This suggests that smoking may exert a selective influence upon a subset of T suppressor cells. In cytotoxicity assays, smokers showed a significant decrease in natural killer cell (NK) activity but not in antibody dependent cellular cytotoxicity (ADCC). It appears that these alterations are reversible since a group of ex-smokers (n = 10) were indistinguishable from our non-smoking group in all studies. The implications regarding the link between smoking and increased susceptibility to infection and malignancy are discussed; and these findings should be borne in mind in basic studies of lymphocytes.

Adult↗

PubMed1979

Circulating immune complexes in patients with cryptogenic fibrosing alveolitis.

Increased Clq binding levels have been obtained in serum from twenty-one (50%) of forty-two patients with cryptogenic fibrosing alveolitis (CFA) suggesting the presence of circulating immune complexes. There was a low frequency of positive results using a number of other tests for circulating immune complexes. The increased Clq binding levels were observed in six (35%) out of seventeen patients with lone lung involvement and in fifteen (60%) out of twenty-five patients with extrapulmonary connective tissue disorders. There was an especially close correlation between arthritis and elevated Clq binding. A strong correlation between Clq binding levels and levels of circulating rheumatoid factor (RF) and IgG, and enhancement in macrophage radiobioassay tests using RF-containing sera, suggested that RF might be involved in the circulating immune complexes in these patients. DNAase pre-treatment of sera did not influence the findings, and there was no correlation between Clq binding and levels of immunofluorescent ANA, C-reactive protein levels, or platelet counts. A weak correlation between Clq binding and erythrocyte sedimentation rates, and slightly lower binding levels in treated than untreated patients with 'lone' CFA suggested that binding levels may give some indication of disease activity and may in some instances be influenced by treatment.

Adult↗

PubMed1969

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Nursing, Practical↗