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Biomedical subjects

T Ashcroft

Publications and source records attributed to T Ashcroft.

At least 19 recordsLinked to original sources

Mononuclear phagocyte populations in the transplanted human lung.

BACKGROUND: Dendritic cells (DC) are essential for the development of alloreactivity, however, little has been published regarding the distribution and phenotype of these and related mononuclear cells in human lung transplantation. METHODS: Lung frozen sections were examined for the presence of CD1a+ DC and for mononuclear cells and alveolar macrophages expressing CD11b and CD68. The effects of transplantation and immunosuppression were assessed by comparison of normal transplant transbronchial biopsy specimens to specimens from unused donor lungs; the normal transbronchial biopsy specimens also were compared with those showing rejection or obliterative bronchiolitis. RESULTS: All biopsy specimens, including those with obliterative bronchiolitis, showed a marked depletion of CD1a+ DC in lung allografts. This has not been described previously. In addition, transplantation and immunosuppression reduced alveolar macrophage coexpression of CD68 and CD11b, and this was reversed in acute rejection. CONCLUSION: The roles of pulmonary DC and other mononuclear phagocyte subpopulations need to be further defined, and data from animal models of lung transplantation should be interpreted with caution.

Antibodies, Monoclonal↗

Immunohistochemical expression of endothelial markers in left atrial myxomas: a study of six cases.

Vascular endothelial cells are antigenically heterogeneous and therefore it has been recommended that a range of immunohistochemical markers is employed to show the presence of cells of endothelial origin in surgical pathology. In this study we applied three monoclonal antibodies--to factor VIII-related antigen, JC70 (CD31), QBend 10 (CD34)--and Ulex europaeus agglutinin type 1 lectin (UEA-1), to six consecutive cases of left atrial myxoma. We found that JC70 and QBend 10 consistently stained myxoma cells in all their different growth patterns contrasting with factor VIII-related antigen expression and UEA-1 binding which were restricted to areas which showed morphological evidence of vascular differentiation. These findings suggest that the constituent cells of atrial myxomas show more widespread endothelial differentiation than has previously been recognized and that differences in immunohistochemical staining may reflect the maturation status of these cells.

Adult↗

Primary malignant melanoma of the bronchus.

A rare case of primary malignant melanoma of the bronchus is described. Before considering this diagnosis, metastasis from an occult primary must be convincingly excluded and the tumour should conform to certain guidelines. This patient presented with a solitary lung tumour for which she underwent left lower lobectomy and continues to be tumour free 54 months after surgery. Two possible mechanisms of aetiology are suggested.

Aged↗

Pregnant women and smoking.

One study estimates that smoking cessation programs for pregnant women could prevent several thousand low birthweight babies and save numerous lives each year. Cessation must be encouraged and supported at any point during pregnancy.

Canada↗

MHC class II and ICAM-1 expression and lymphocyte subsets in transbronchial biopsies from lung transplant recipients.

The expression of MHC class II antigens and ICAM-1 and the composition of lymphocyte infiltrates have been studied in frozen sections of transbronchial biopsies from lung transplant recipients. First, biopsies obtained from patients who showed acute rejection, OB, and normal features were compared. Second, we compared first-year biopsies from patients developing OB and patients with a good clinical outcome. HLA-DR was widely expressed on epithelia and vascular endothelium. Increased vascular HLA-DP expression was found in OB biopsies. In OB patients there was a significantly increased frequency of bronchial HLA-DP and vascular HLA-DQ expression. Expression of ICAM-1 by bronchial and bronchiolar basal cells, a phenomenon not reported previously in humans, was seen in a small number of biopsies. CD8 predominant lymphocytic infiltrates were present in all groups and were increased in OB biopsies and OB patients. Increased numbers of CD4-positive cells were found in rejection and OB when compared with normal biopsies. These findings support an immunological basis for the development of OB.

Antigens, CD↗

Organizing pneumonia following pulmonary transplantation and the development of obliterative bronchiolitis.

Twelve patients receiving lung transplants between 1988 and 1992 who developed clinical and histological features of obliterative bronchiolitis (OB) were compared with a group of 13 patients with good stable lung function (FEV1 more than 80% of predicted). Histological features of 180 biopsies were studied from the first postoperative year in order to assess whether any were associated with the development of OB. Clinically and histologically defined pulmonary rejection occurring after the first month was more frequent in OB patients (P = 0.03). Organizing pneumonia that was associated with acute rejection but not with nonviral infection was also seen more frequently in OB patients (P = 0.003). When all available lung transplant recipients surviving beyond 18 months were included in analyses, organizing pneumonia in the first year was associated with an increased relative risk of developing OB of 2.26 (95% CL 1.19-4.29), and the occurrence of coexistent organizing pneumonia and pulmonary rejection gave a relative risk for OB of 6.33 (95% CL 1.61-24.94). An increased incidence of histologically defined organizing pneumonia in OB patients has not been described previously. Furthermore the coexistence of organizing pneumonia with pulmonary rejection in the first year posttransplantation is a strong predictive factor for the development of OB.

Adult↗

Development of immunological assays to monitor pulmonary allograft rejection.

BACKGROUND: At present the diagnosis of pulmonary allograft rejection is made after examination of transbronchial biopsy specimens; this method is highly invasive. A study was performed to determine whether immunological parameters measured in peripheral blood or bronchoalveolar lavage samples correlate with the histological diagnosis of rejection. METHODS: Left unilateral pulmonary allotransplantation was performed between dogs. The animals were immunosuppressed with cyclosporin A after transplantation but the dose of this drug was gradually reduced to allow controlled rejection to take place. Rejection was diagnosed histologically. Four immunological parameters were investigated: measurement of lavage derived T cell proliferation in response to limited culture with interleukin 2; measurement of changes in the frequency of donor reactive cytotoxic T lymphocytes; assay of the level of donor cell binding IgG antibody in recipient plasma; and measurement of the antibody dependent cell mediated cytotoxic response to donor cells after labelling with recipient plasma. RESULTS: Assays based on measurement of the function of T cells produced significant results at a time later than the histological diagnosis of severe rejection. The level of donor reactive IgG antibody increased at a time that corresponded closely with the diagnosis of severe rejection. This IgG did not activate the antibody dependent cell mediated cytotoxic effector mechanism to a significant extent. CONCLUSIONS: Measurement of parameters of donor specific immunoreactivity can yield data which are indicative of severe pulmonary allograft rejection. These methods make use of samples which can be obtained by minimally invasive methods. Measurement of the plasma level of donor reactive IgG antibody appears to be the most useful assay. However, each of the in vitro assays used during this series of experiments was less sensitive to the onset of rejection than was routine histological examination.

Animals↗

The family's cancer journey: a literature review.

Cancer is recognized by health professionals as a phenomenon experienced by the entire family, not just by the individual member diagnosed with the disease. This article is based on an examination of approximately 200 clinical papers and research studies written between 1970 and 1991. Four major dimensions of the family cancer experience were identified from the literature: developmental stage of the family, cancer illness trajectory, family responses to cancer, and health care provider behaviors. The most developed body of literature documents the family responses to cancer and health-care provider behaviors directed at these responses. Gaps in research knowledge are identified and directions and recommendations for future research are outlined.

Adaptation, Psychological↗

Distribution of gamma delta T-cells in the bronchial tree of smokers and non-smokers.

AIMS: To assess the distribution of gamma delta T-cells in the human bronchial tree; and to compare quantitatively the differences between gamma delta T-cell numbers in different parts of the airway wall in smokers and non-smokers. METHODS: Full thickness bronchial wall sections were taken from 10 whole lung specimens from both smokers and non-smokers. Serial cryostat sections stained with the monoclonal antibodies CD3 and TCR delta-1 were examined with the aid of interactive image analysis to assess gamma delta T-cell numbers both in absolute terms and as a proportion of total T lymphocyte numbers. RESULTS: In all cases gamma delta T-cells were demonstrable throughout the airway wall. Although in absolute terms they tend to occur predominantly in the bronchial epithelium, this seems to reflect higher numbers of T lymphocytes in the epithelium in general compared with the submucosa. No genuine epitheliotropism is evident. Comparison by smoking status shows a significant increase in gamma delta T-cell numbers in the bronchial glands of smokers compared with non-smokers. CONCLUSIONS: gamma delta T-cells form an integral though variable component of the immunocompetent cell population of the human airway in both smokers and non-smokers. Although epitheliotropism does not exist in the bronchial tree, gamma delta T-cells seem to form a significant part of the bronchial gland inflammation associated with smoking.

Adolescent↗

Variability in ciliary beat frequency in normal subjects and in patients with bronchiectasis.

BACKGROUND: There is a wide variation in tracheobronchial clearance of inhaled aerosol in normal subjects and in patients with bronchiectasis, but little information is available on the variability in ciliary beat frequency (CBF). METHODS: The variability in CBF was measured in 10 nasal mucosal samples from each of 19 normal controls and 23 stable bronchiectatic subjects. RESULTS: The CBF varied at different mucosal sites in both normal subjects and bronchiectatic patients. Although the CBF of the fastest beating cilia was similar in both groups, the CBF of the slowest beating cilia was, on average, lower and showed greater within subject variation in bronchiectatic than in normal subjects. CONCLUSIONS: There is a wide variation in CBF in nasal mucosal samples and this is significantly wider in bronchiectatic subjects with some cilia beating slowly. This may be a consequence of chronic inflammation or infection.

Adult↗

Bronchus associated lymphoid tissue (BALT) in human lung: its distribution in smokers and non-smokers.

BACKGROUND: Bronchus associated lymphoid tissue (BALT) is a normal component of the lung's immune system in many animals and may be analogous to gut associated lymphoid tissue (GALT). This study aimed at assessing the nature and extent of BALT in human lung and determining whether its expression is induced within the human airway in response to smoking. METHODS: Paraffin embedded, formalin fixed full thickness bronchial wall sections were examined from 31 whole lung specimens derived from both smokers and non-smokers. Samples were taken from throughout the bronchial tree to include main stem bronchi, lobar bronchi and segmental bronchi, as well as first to third generation carinae. Standard 4 microns step sections were stained by haematoxylin and eosin and immunocytochemical methods to show foci of BALT. RESULTS: Examination of 256 airway sites detected 46 foci of BALT. These differed from those described in other mammals in being distributed throughout the bronchial tree, in being found in relation to bronchial glandular epithelium as well as luminal bronchial epithelium, and in lacking any accompanying M cells. Analysis by smoking status showed that the expression of BALT was significantly more common in smokers than non-smokers (82% (14/17) v 14% (2/14) respectively). CONCLUSIONS: The findings support the view that BALT in humans is an integral feature in a comparatively small proportion of lungs from non-smokers while being significantly more prominent in lungs from smokers. The tissue shows several important differences from that described in other mammals.

Adolescent↗

How reliable is the diagnosis of lung cancer using small biopsy specimens? Report of a UKCCCR Lung Cancer Working Party.

BACKGROUND: A study was undertaken to investigate the accuracy of typing of a series of bronchial carcinomas by experienced pathologists with an interest in lung cancer from the examination of bronchoscopic biopsy specimens. METHODS: Eighty bronchial biopsy specimens showing positive results for bronchial carcinoma were circulated to five pathologists, who recorded diagnostic criteria and diagnosis for each. Diagnoses were then compared with the diagnosis agreed from the resection specimen corresponding to each biopsy specimen. A "non-small cell carcinoma, not further specified" classification group was introduced for small biopsy specimens. RESULTS: A diagnostic accuracy of 75% was achieved for squamous cell carcinomas, 66% for small cell carcinomas, and 50% for adenocarcinomas. There was diagnostic confusion between small cell and non-small cell carcinoma in less than 10% of cases. The introduction of a non-specific non-small cell classification improved diagnostic accuracy by 10-15% for each non-small cell tumour group. CONCLUSIONS: There are appreciable inaccuracies in applying the World Health Organisation's 1981 classification of lung cancer to the diagnosis of bronchial carcinoma from small biopsy specimens and these inaccuracies have been measured. They can be diminished by introducing a less specific "non-small cell" category for use with this sort of biopsy material. Care should be taken not to overinterpret small biopsy specimens in lung cancer.

Biopsy↗

Pleuropulmonary abnormalities in primary Sjögren's syndrome.

Sixteen patients with primary Sjögren's syndrome (1 degree SS) who complained of dyspnea were investigated with high resolution computerized tomography of the thorax, bronchoalveolar lavage, and transbronchial biopsy. Six patients had evidence of interstitial fibrosis, 5 had a peribronchiolar lymphocytic infiltration and 3 had pleural thickening. We conclude that significant pulmonary disease is not uncommon in patients with 1 degree SS.

Adult↗