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Biomedical subjects

D Lamb

Publications and source records attributed to D Lamb.

At least 19 recordsLinked to original sources
PubMed1995

Tenascin immunoreactivity in cryptogenic fibrosing alveolitis.

Tenascin is a hexameric extracellular matrix (ECM) glycoprotein which has been demonstrated to have a temporal relationship with active scar formation in adult tissues. We hypothesized that this ECM protein might therefore serve to identify areas of active scarring in lung biopsies from patients with cryptogenic fibrosing alveolitis (CFA). The distribution of tenascin was examined in open lung biopsies from ten patients with CFA, six patients with sarcoidosis, and six pulmonary resection specimens from patients with no evidence of interstitial lung disease, using an immunohistochemical technique. Immunoreactive tenascin was not identified in histologically normal control lung parenchyma and was only focally found around large aggregates of granulomas in sarcoidosis. In the CFA, tenascin production was demonstrated in minimally damaged alveolar walls and areas of active disease but not in end-stage scarred lung. There was considerable local heterogeneity of staining within cases, which did not appear to relate to the density of the local inflammatory infiltrate. Large plaques of tenascin were noted to be particularly associated with hyperplastic type II alveolar epithelial lining cells, which are recognized to produce fibrogenic cytokines. The examination of tenascin expression in open lung biopsies from patients with CFA may be useful in assessing fibrogenic activity and may thus provide additional prognostic information.

Biomarkers↗
PubMed1995

A novel model for human interstitial lung disease: hapten-driven lung fibrosis in rodents.

A novel model is described of chronic pulmonary fibrosis in rodents. The condition is induced by a single intratracheal instillation of a well-characterized fluorescent haptenic antigen, fluorescein isothiocyanate (FITC), into non-immune animals. This results in an acute inflammatory response involving a granulocytic infiltrate, which disappears over a week and is replaced by a chronic mononuclear infiltrate in which T lymphocytes predominate. Over several months, a chronic patchy fibrosis is accompanied by a sustained mononuclear interstitial infiltrate localized at sites of persistent FITC deposition. Where no FITC is present, the lung tissues are apparently normal. An immune response is mounted, as measured by the appearance of specific anti-FITC serum antibodies. This model has relevance to the pathogenesis of some forms of human interstitial lung disease.

Animals↗
PubMed1995

Lung disease in the cystic fibrosis mouse exposed to bacterial pathogens.

Lung disease is the major cause of death in cystic fibrosis (CF), but there is no evidence for overt lung involvement at birth. We show here that the same is true for the gene targeted cftrm1HGU mutant mouse. Furthermore, this CF mouse model demonstrates an impaired capacity to clear Staphylococcus aureus and Burkholderia (Pseudomonas) cepacia, two opportunistic lung pathogens closely associated with lung disease in CF subjects. The cftrm1HGU homozygotes display mucus retention and frank lung disease in response to repeated microbial exposure. Thus, lung disease in the cftrm1HGU mouse develops in response to bacterial infection, establishing a model to dissect the pathogenesis of CF pulmonary disease and providing a clinically relevant end point to assess the efficacy of pharmacologic or genetic interventions.

Animals↗
PubMed1995

A type 2 (Th2-like) pattern of immune response predominates in the pulmonary interstitium of patients with cryptogenic fibrosing alveolitis (CFA).

CFA is an inflammatory condition of the lungs resulting in scarring, pulmonary failure and death. The etiology of the disease is unknown, but the pathogenesis is believed to involve a persistent immunological reaction to unidentified antigen in the lung resulting in tissue damage. Recent advances in our understanding of the immune system have shown that different patterns of stimulatory cytokines are produced at sites of inflammation by a range of cell types. Patterns of cytokine reproduction by inflammatory cells are recognized to be associated with different patterns of immunological response, and these have been described as type 1 (or Th1-like) and type 2 (or Th2-like) on this basis. We have studied cytokine expression in the intestinal inflammatory cell infiltrate in lung tissue from patients with CFA using mRNA in situ hybridization and immunohistochemistry. Our results show that while there is evidence for both a type 1 (characterized by interferon-gamma (IFN-gamma) and type 2 (characterized by IL-4 and IL-5) response present in CFA, the type 2 (or Th2) pattern of cytokines appears to predominate. This would be consistent with a possible role for the humoral immune response in the pathogenesis of this condition. In addition, recent evidence suggests that IL-4 and IFN-gamma may be important regulatory factors for pulmonary fibroblasts. The relative paucity of IFN-gamma may contribute to the excessive fibroblast activation, deposition of collagen and scar formation that occurs in CFA.

Aged↗
PubMed1995

Interobserver variation in cell selection for DNA image cytometry.

AIMS: To describe a systematic investigation of interobserver differences in interpretation of nuclear morphology in preparations of small cell lung cancer (SCLC). METHODS: The screening/reviewing facility on the highly optimised microscope environment was used to individually tag 127 nuclei, chosen to reflect the spectrum of morphological appearances in nuclear preparations from three biopsy specimens of SCLC. Each nucleus was reviewed and labelled as control (lymphocyte), malignant or unsatisfactory by each of four observers. DNA histograms were plotted for each specimen using the nuclei identified as malignant by each participant. The histograms were compared in terms of identification of DNA stemlines and by calculation of a 5c exceeding rate (5cER). RESULTS: Interobserver variation in assessment of morphology was seen in 55.1% of nuclei. Disagreement occurred most frequently in the malignant/unsatisfactory category. Differences in morphological classification had little influence on histogram assessment by means of visual inspection but did show an effect on 5cER. CONCLUSIONS: There are significant interobserver differences in subjective assessment of nuclear morphology in cytometric preparations. This effect may seriously influence cytometric measurements.

Carcinoma, Small Cell↗
PubMed1992

Expression of proliferating cell nuclear antigen in lung cancer: a systematic study and correlation with DNA ploidy.

Heterogeneity of expression of the proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically in 156 tissue samples from 33 surgically resected pulmonary carcinomas using the monoclonal antibody 19A2. The DNA content of each of these samples was measured by flow cytometry. Mean PCNA expression was higher in squamous carcinomas than in adenocarcinomas but there was marked intra-tumour variation in PCNA index in almost all cases. Intra-tumour heterogeneity of DNA content was noted in 11 cases. The PCNA index of these cases (34.1) was higher than that of DNA homogeneous cases (19.4). The wide variation in PCNA expression between different samples within a tumour would indicate that systematic sampling and counting will be necessary in future immunohistochemical studies of cell proliferation in tumour material.

DNA, Neoplasm↗
PubMed1992

The prognosis of adenosquamous carcinomas of the uterine cervix.

OBJECTIVES: Firstly, to identify a cohort of women with invasive adenosquamous carcinomas of the uterine cervix, including mucin-producing squamous cell carcinomas. Secondly, to compare the biological characteristics and behaviour of a cohort of adenosquamous carcinomas with a cohort of non-mucin-producing squamous cell carcinomas. DESIGN: Histological review, retrospective survival analysis. SETTING: Regional multidisciplinary gynaecological oncology service. SUBJECTS: 161 cases of stage 1B and above invasive cervical carcinoma presenting between 1 January 1980 and 31 July 1987. Thirty nine women with adenosquamous carcinomas were compared with 103 women with non-mucin-producing squamous cell tumours. RESULTS: Inclusion of routine stains for mucin in the assessment of histological material resulted in the reclassification of 38 (24%) of the cases, including the identification of 31 mucin-producing squamous cell carcinomas. The survival with adenosquamous tumours was significantly worse than with squamous cell cancers (P = 0.006), 5-year survival rates being 52% and 75% respectively. Multivariate analysis showed that this effect was explained by differences in clinical stage, pelvic lymph node metastasis and vascular invasion by tumour. CONCLUSIONS: The application of routine mucin stains to cervical tumours identifies a group of previously unrecognized adenosquamous cancers. Tumours so identified are likely to pursue a more aggressive clinical course associated with a poorer survival when compared to non-mucin-producing squamous carcinomas.

Adenocarcinoma↗
PubMed1992

Death and reductionism: a reply to John F Catherwood.

This reply to John F Catherwood's criticism of brain-related criteria for death argues that brainstem criteria are neither reductionist nor do they presuppose a materialist theory of mind. Furthermore, it is argued that brain-related criteria are compatible with the majority of religious views concerning death.

Brain Death↗
PubMed1992

B lymphocyte accumulations in human pulmonary sarcoidosis.

BACKGROUND: Although cell mediated immunity is primarily thought to mediate the pathogenesis of sarcoidosis, the presence of immunoglobulins, immune complexes and complement suggests that processes of humoral immunity may contribute to immunopathology in sarcoid lesions. To test this hypothesis, the distribution of B lymphocytes in paraffin embedded sarcoid lesions in mediastinal lymph nodes and open lung biopsy specimens was investigated. METHODS: Paraffin sections from eight open lung and 21 lymph node biopsies from sarcoid patients and five normal and five tuberculous lymph nodes from patients with tuberculosis were stained with a panel of monoclonal antibodies by means of avidin/biotin enhanced immunocytochemistry. RESULTS: Immunohistochemical analysis of the 29 biopsy specimens from the sarcoid patients revealed large numbers of B cells in the intergranulomatous regions. Further investigations in the open lung biopsy specimens indicated that these B cells were often organised into discrete circular or oval shaped aggregates with no germinal centre morphology, in which a few CD45RO memory T lymphocytes were scattered. The B cells were polyclonal, and a few plasma cells (IgM+, IgA+, IgG+) were identified. CONCLUSIONS: The finding of large numbers of B lymphocytes in sarcoid pulmonary lesions is in contrast to bronchoalveolar lavage studies, which have demonstrated proportions of 5% or less of B cells as a total of all immune cells, and therefore indicates that bronchoalveolar lavage may not correctly sample the immune cells of lung interstitial tissue in pulmonary sarcoidosis. The B cells at these sites are the possible origin of some of the humoral changes in the serum and lesions of sarcoid patients. They may also influence the pathogenesis of the disorder by presenting antigen(s) and forming immune complexes at sites of disease activity.

Antigen-Antibody Complex↗
PubMed1992

Alveolar atypical hyperplasia in association with primary pulmonary adenocarcinoma: a clinicopathological study of 10 cases.

BACKGROUND: A distinctive cytologically atypical lesion has been found in patients with primary adenocarcinoma of the lung. The aim of this study was to characterise the lesion and assess its role in tumour pathogenesis. METHODS: Lung parenchyma from 175 consecutive resection specimens for primary pulmonary adenocarcinoma were examined. Foci of atypical hyperplasia were identified. Cell proliferation state and expression of S100 and carcinoembryonic antigens were evaluated by immunohistochemistry. Clinical data on cigarette smoking and occupational exposure to carcinogens were abstracted from inpatient case notes. RESULTS: Ten cases (5.7%) with these distinctive cytologically atypical lesions were identified. The lesions showed immunohistochemical evidence of increased cell proliferation and focal carcinoembryonic antigen expression. The associated adenocarcinomas were of peripheral (parenchymal) type. There was an association with cigarette smoking and two of the 10 patients had synchronous carcinomas elsewhere in the lung. CONCLUSION: The clinical and pathological associations of these lesions suggest that they may be important in the histogenesis of primary pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed1992

Microscopic and macroscopic measurements of emphysema: relation to carbon monoxide gas transfer.

BACKGROUND: Studies of the relation between the severity of structural change in emphysema and physiological abnormality have been based on macroscopic assessments, which have not been truly quantitative or sensitive enough to detect early changes. With a highly reproducible method for measuring emphysema using histological sections and a semiautomatic image analysis system, this quantitative assessment of emphysema was compared with a semiquantitative macroscopic assessment of emphysema and measurements of carbon monoxide gas transfer. METHODS: Microscopic and macroscopic measurements of emphysema on 44 thoracotomy specimens were compared; only two were from non-smokers. Airspace wall surface area per unit volume was measured microscopically with an automatic image analyser and expressed as both the mean airspace wall surface area per unit volume and the mean value of the five fields with the lowest values. Macroscopic emphysema was measured directly on a tracing of the midsagittal slice using a digitising tablet attached to a microcomputer and expressed as a percentage of the total area of lung. In cases with centriacinar emphysema the number of discrete lesions was counted. RESULTS: The area of macroscopic emphysema ranged from 0 to 78% of the total area of lung examined, but most patients had less than 1% involvement so that the distribution was highly skewed. Both mean airspace wall surface area per unit volume and the mean of five fields with the lowest airspace wall surface area per unit volume were normally distributed, with mean airspace areas ranging from 8.8 to 25.4 mm2/mm3 (mean 18.1 mm2/mm3). In lobes with centriacinar emphysema the number of discrete lesions correlated with airspace wall surface area per unit volume and with preoperative carbon monoxide transfer factor (TLCO) per unit lung volume. However, other measurements of macroscopic emphysema did not correlate with loss of alveolar wall surface area, and there was considerable overlap between subjects with no or minimal macroscopic emphysema and those with more severe disease. TLCO correlated with both mean airspace wall surface area per unit volume and the mean of five fields with the lowest airspace wall surface area per unit volume but not with the severity of macroscopic emphysema. CONCLUSION: If emphysema is to be quantified it must be measured microscopically; macroscopic measurements do not, in general, reflect the microscopic loss of airspace wall.

Aged↗
PubMed1992

Pathological assessment of mediastinal lymph nodes in lung cancer: implications for non-invasive mediastinal staging.

BACKGROUND: The use of computed tomography in mediastinal staging of lung cancer relies on the premiss that malignant lymph nodes are larger than benign ones. This hypothesis was tested by linking node size and presence or absence of malignancy and looking at factors possibly influencing the size of benign nodes. METHODS: All accessible mediastinal lymph nodes were taken from 56 consecutive patients with lung cancer who underwent thoracotomy. Nodes were measured and histologically examined. Resected cancer bearing lung from 44 of these patients was assessed for degree of acute and chronic inflammation. RESULTS: Lymph node size was not significantly related to the presence of metastatic disease, 58% of malignant and 43% of benign lymph nodes measuring over 15 mm. Similarly, there was no statistically significant relation between size of lymph nodes and the likelihood of malignancy, 20% of lymph nodes of 10 mm or more but also 15% of those less than 10 mm being malignant. Thresholds of 15 and 20 mm showed similar results. The maximum size of benign lymph nodes was significantly greater in those patients with histological evidence of acute pulmonary inflammation than in those without. CONCLUSIONS: The study shows that in patients with lung cancer (1) malignant mediastinal lymph nodes are not larger than benign nodes; (2) small mediastinal lymph nodes are not infrequently malignant; and (3) benign adenopathy is more common in patients with acute pulmonary inflammation.

Adenocarcinoma↗
PubMed1992

Intra-alveolar macrophage numbers in current smokers and non-smokers: a morphometric study of tissue sections.

BACKGROUND: The alveolar macrophage is believed to be important in the defence of the lung and possibly in the pathogenesis of lung disease. Cell counts in bronchoalveolar lavage fluid have suggested that smokers have an increased number of alveolar macrophages but have not enabled the number to be related to a measure of lung structure. METHODS: The number of alveolar macrophages was counted in histological sections from lung resection specimens from a group of smokers and non-smokers. The results were related to a measurement of lung structure obtained by means of an automated morphometric technique and expressed in terms of units of lung volume or of lung surface area. RESULTS: The smokers had a significantly increased number of alveolar macrophages per unit lung volume and per unit surface area, through the relative increase was less than has appeared from bronchoalveolar lavage studies. When smokers and non-smokers with similar lung structure were compared the smokers had more alveolar macrophages, indicating that smoking and not loss of lung structure is responsible for the increase. CONCLUSIONS: Smokers had more alveolar macrophages than non-smokers when the number was expressed quantitatively with respect to the underlying architecture. Changes in cell populations postulated to be important in the pathogenesis of disease within the lung should be related to lung architecture because this may vary considerably between individuals.

Adult↗
PubMed1992

Clinicopathological correlations in cor pulmonale.

BACKGROUND: The relation between pulmonary disease and physiological abnormality in patients with hypoxic cor pulmonale is controversial and the association between arterial hypoxaemia and right ventricular hypertrophy has been challenged. To address these problems matched patients treated with and without domiciliary oxygen were studied. METHODS: Necropsy data were obtained on 19 patients (14 male), 10 of whom had been treated with domiciliary oxygen. Pulmonary artery pressure and total pulmonary vascular resistance as well as blood gas tensions during the breathing of air and oxygen were available for the six months before death. Formalin fixed lung slices were assessed for panacinar and centriacinar emphysema. Right and left ventricular weights were measured and their ratio (LV&S/RV) was used as an index of right ventricular hypertrophy. Carotid body weights were available in 14 cases. RESULTS: Fourteen patients died of respiratory failure and antemortem thrombus was found in the pulmonary arteries of eight cases. Physiological measurements were unrelated to the degree of macroscopic emphysema, pulmonary hypertension, or daytime blood gas tensions. When allowance was made for the higher "ambient" arterial oxygen tension (PaO2) of those who had oxygen, PaO2 was correlated with LV&S/RV (r = 0.79), absolute right ventricular weight (r = -0.53), and carotid body weight (r = 0.68). CONCLUSIONS: These data show that in hypoxic cor pulmonale in vivo physiological disturbances are poor indicators of the underlying disease process. The relation of "ambient" PaO2 to right ventricular hypertrophy and carotid body weight suggests that domiciliary oxygen therapy might lead to regression of such established disease.

Blood Pressure↗
PubMed1992

Prognostic significance of tumor deoxyribonucleic acid content in surgically resected small-cell carcinoma of lung.

The prognostic role of deoxyribonucleic acid flow cytometry was investigated in 53 cases of surgically resected small-cell lung cancer. Deoxyribonucleic acid aneuploidy was detected in 26 patients (49.1%), the remaining tumors being either diploid or tetraploid. Patients with aneuploid tumors had a significantly reduced 2-year survival (38.5%) when compared with patients with diploid or tetraploid tumors (70.3%; p less than 0.05). This finding was independent of tumor stage on multiple logistic regression analysis. Diploid or tetraploid deoxyribonucleic acid content was associated with a particularly good 2-year survival (85%) in N0 or N1 disease. Tumor deoxyribonucleic acid ploidy should be taken into account in planning of management and assessment of prognosis in small-cell lung cancer.

Carcinoma, Small Cell↗
PubMed1992

Changes in neutrophil morphology and morphometry following exposure to cigarette smoke.

Acute cigarette smoking delays neutrophils within the pulmonary circulation in some smokers. Evidence from an in-vitro Micropore filter model of the pulmonary capillaries indicates that this may be due to a smoke induced decrease in cell deformability. In order to determine whether changes in cell shape are associated with the observed decrease in neutrophil deformability following smoke exposure, cell morphology, using scanning electron microscopy, and morphometric measurements, made using transmission electron microscopy, were performed on aliquots of neutrophils harvested from whole blood in non-smoking subjects before and after exposure in vitro to cigarette smoke. Smoke exposure increased the maximum diameter and circumference of neutrophils, without changing their area. There was also a change in the maximum to minimum cell diameter ratio, which indicated that the cells had become less spherical. Scanning electron microscopy showed that smoke exposed cells had developed blebbing of their surface membranes, suggestive of an oxidative injury to the cell membrane rather than the shape changes associated with cell activation. These changes in the morphology and morphometry of smoke exposed neutrophils may contribute to the reduction in cell deformability induced by cigarette smoke.

Anthropometry↗
PubMed1991

Preliminary results of left heart bypass in pigs using a heparin-coated centrifugal pump.

To assess the feasibility of left ventricular assist without systemic heparinization, we used a commercially available (Sarns 3M) centrifugal pump with tubing set and cannulas, all internally precoated for the purpose of this study with heparin, to bypass the left ventricle in 12 pigs for periods of either 1 or 3 hours. There was no significant activation of clotting and there was no sign of generalized embolization. However, on postmortem studies, 5 kidneys out of 22 examined showed signs of minimal thromboembolism. This experiment shows that artificial left ventricular assist, free of systemic heparinization but using heparin precoating, is feasible and safe, at least for a short period of time.

Animals↗