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A Dewar

Publications and source records attributed to A Dewar.

At least 55 records · Page 3Linked to original sources
PubMed1994

Atypical carcinoid tumour of the thymus: a study of eight cases.

Atypical carcinoids of the thymus are rare neoplasms of uncertain prognosis. We have studied eight cases (six male, two female; age range 48-60 years, mean 55 years), none with evidence of a paraneoplastic neuroendocrine syndrome. Tumour size was large and ranged from 7.5 to 10 cm. Microscopically, all had a nesting/insular or trabecular pattern, eosinophilic cytoplasm, round nuclei with fine chromatin and small nucleoli. No small cell features were evident. Mitotic activity ranged from 2 to 21 per 1.52 mm2. Focal necrosis was seen in all cases. All were positive for cytokeratin (AE1/AE3, CAM 5.2) and the neuroendocrine markers NSE, synaptophysin and chromogranin; five cases were positive for calcitonin. On electronmicroscopy all contained dense core granules, often numerous. Three cases were stage I and five stage III (infiltrating lung or chest wall). Follow-up information was available in four cases (one stage I and three stage III): the stage I tumour had local recurrence and metastasis to the lung within a year whilst the three patients with stage III tumours died of liver, bone and brain metastases within 3 years.

Carcinoid Tumor↗
PubMed1994

Fertility in men with primary ciliary dyskinesia presenting with respiratory infection.

BACKGROUND: Primary ciliary dyskinesia is characterised by chronic rhinosinusitis, chronic bronchial sepsis (usually with bronchiectasis), dextrocardia in approximately 50% of cases, and male infertility. The latter, described in patients attending infertility clinics, results from immotile but viable spermatozoa. Experience in a respiratory clinic suggests that infertility in men is not invariable. METHODS: The seminal fluid of 12 men with primary ciliary dyskinesia, six with dextrocardia, who presented consecutively with upper and lower respiratory tract sepsis was examined. Nasal ciliary beating was dyskinetic or absent in all cases, and nasal ciliary ultrastructure was abnormal in those 11 patients examined. RESULTS: Viable but immotile spermatozoa with abnormal tail ultrastructure were found in the ejaculate of only two patients. Two other patients had apparently fathered children; seminology in both these cases showed a normal spermatozoa count, one with normal spermatozoal motility and normal ultrastructure, the other with moderately reduced spermatozoal motility and abnormal ultrastructure (dynein arm deficiency on the peripheral microtubule doublets). A further two patients had normal spermatozoa counts, normal spermatozoa tail ultrastructure, and normal or only moderately reduced motility of spermatozoa. The spermatozoa of one patient were normally motile but there was severe oligozoospermia, and five patients were azoospermic. CONCLUSIONS: Not all men with primary ciliary dyskinesia have immotile spermatozoa. Seminal analysis is recommended in men with primary ciliary dyskinesia so that accurate counselling about reproductive capability may be given.

Adolescent↗
PubMed1994

Interaction of Pseudomonas aeruginosa with human respiratory mucosa in vitro.

Pseudomonas aeruginosa commonly infects the airways of patients with cystic fibrosis and bronchiectasis. It produces several toxins that slow ciliary beat, stimulate mucus production and damage epithelium. It adheres to epithelial cells, damaged mucosa (in animal models), and mucus. However, little is known of the interaction of P. aeruginosa with intact human respiratory mucosa. We have studied the interactions of a nonmucoid clinical isolate of P. aeruginosa with adenoid tissue in a novel organ culture model with an air-mucosal interphase P. aeruginosa (5.9 +/- 0.9 x 10(6) colony-forming units (cfu)) was pipetted onto the organ culture surface, and incubated for 15 min, 1, 2, 4, 8, 12, 16, and 24 h, at 37 degrees C in 5% CO2 in a humidified atmosphere. Assessment has been made by transmission and scanning electron microscopy. Transmission electron microscopy (TEM) showed that uninfected organ cultures had normal ultrastructure. TEM of infected organ cultures at 8 h showed significant epithelial damage: 43.9 +/- 10% of cells extruding from the epithelial surface, 17.7 +/- 3% of cells with loss of cilia, 32.9 +/- 10.2% of cells with mitochondrial damage, and 11.6 +/- 3% of cells with cytoplasmic blebbing. P. aeruginosa only infrequently adhered to normal epithelium, but adhered to areas of epithelial damage and to basement membrane. Scanning electron microscopy (SEM) of organ cultures up to 2 h found P. aeruginosa only infrequently associated with mucus. SEM at 4 h revealed P. aeruginosa predominantly associated with mucus and extruded damaged epithelial cells, but also occasionally associated with cilia, and very occasionally with unciliated cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoids↗
PubMed1993

Ultrastructural characterization of platelet-activating factor-stimulated human eosinophils from patients with asthma.

1. Purified human eosinophils from asthmatic patients were stimulated with platelet-activating factor in vitro and examined for morphological changes by transmission electron and light microscopy. Changes were also evaluated by morphometric analysis and were related to the platelet-activating factor-stimulated release of granular eosinophil cationic protein. 2. Stimulation of eosinophils with platelet-activating factor induced a dose-dependent shape change, including the elongation of cells, loss of microvilli and the formation of lamellipodia. This effect was maximal at 25 min and was reversible. 3. Stimulation with platelet-activating factor also induced granule movement to the cell periphery and fusion of adjacent granules. Granules became swollen and vesiculated, whereas both the matrix and core showed evidence of solubilization. 4. There was a time-dependent secretion of eosinophilic cationic protein from human eosinophils upon stimulation with platelet-activating factor which occurred without significant lactate dehydrogenase release. 5. Morphometric analysis of the transmission electron micrographs indicated a significant reduction in cytoplasmic area after 10 min of incubation with platelet-activating factor from 39.0 +/- 1.7 microns 2 for untreated eosinophils to 33.2 +/- 2.3 microns 2 (P < 0.02) for platelet-activating factor-treated cells, underscoring the observation that the cells change from spherical to ellipsoidal. No significant increase in the perimeter of the cells was found. 6. The number of granule-profiles in platelet-activating factor-stimulated eosinophils was slightly reduced when compared with control, and an increase in granule area was observed 10 min after platelet-activating factor challenge (0.215 +/- 0.011 microns 2 versus 0.246 +/- 0.016 microns 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Identification of serous-like cells in the surface epithelium of human bronchioles.

The conductive airways of the mammalian lung are lined by several morphologically distinct cell types, both ciliated and non-ciliated. Of the non-ciliated secretory cells, mucous (goblet), Clara and neuroendocrine cells have been identified in adult human bronchiolar epithelium but, thus far, the serous cell has not. We have examined human membranous and respiratory bronchioles from macroscopically normal peripheral lung (n = 5 cases). For ultrastructural studies, a minimum of five nucleated, non-ciliated cell profiles, containing electron-dense secretory granules, were selected at random from both bronchiolar levels in each case, such that a total of 60 cells was examined. Data from the computer-aided image analysis of the cells indicated that two populations existed, differing in both granule area and granule number per cell p < 0.0005 by discriminant analysis. By visual inspection, the cells fell neatly into two groups: those which, were predominantly serous-like in type, and those which were "Clara". In the membranous bronchioles, serous-like cells had a mean(SEM) granule area per cell of 3.67(0.62) microns 2 and Clara cells 0.47(0.07) microns 2 (p < 0.001). Also, in the membranous bronchiole, the mean(SEM) number of granules in serous-like cells was 40(4.7) and in Clara cells 10(1.1) (p < 0.001). At the respiratory bronchiolar level, the corresponding means were similar to those of the membranous bronchioles and, likewise, serous and Clara cells were significantly different. Thus, our data, indicate that serous cells are present in the adult human bronchiole.

Aged↗
PubMed1992

Apposition of fibroblasts to mast cells and lymphocytes in normal human lung and in cryptogenic fibrosing alveolitis. Ultrastructure and cell perimeter measurements.

The perimeters of mast cells and lymphocytes in human lungs were measured in electron micrographs by digitizer to determine the percentage of perimeter apposed to fibroblast (PPAF). Fibroblasts were apposed to the majority of mast cells. The median PPAF for mast cells in normal lung was 50.3 per cent, and in cryptogenic fibrosing alveolitis (CFA), 35.7 per cent. Although the value in CFA was lower, the difference was not statistically significant (median difference 11.8; 95 per cent confidence interval (-19.6, 25.1); P = 0.65). The PPAF range overall was 3.8-94.1 per cent. There was similar apposition of fibroblasts to lymphocytes, and no statistical differences were found when median PPAF results for mast cells and lymphocytes were compared for normal and CFA lung. The high degree of percentage apposition, accurately quantified in this study, shows that fibroblasts, mast cells, and lymphocytes are ideally arranged structurally in normal alveolar walls, to facilitate the many physiological interactions which are currently being uncovered. The present study also shows that apposition persists in pathological states, e.g., CFA lung, but because all these cells are increased in number in CFA lung, apposition is easier to identify here than in normal lung.

Adult↗
PubMed1992

Effect of tumor necrosis factor on hypoxic pulmonary vasoconstriction.

The effects of tumor necrosis factor (TNF) on hypoxic pulmonary vasoconstriction (HPV) and endothelium-dependent relaxation were examined in a blood-perfused rat lung preparation. Lungs from TNF-treated rats (0.26 mg/kg iv 12 h before experimentation) had a significantly greater HPV and a reduced vasorelaxant response to the endothelium-dependent vasodilator acetylcholine (ACh) but a similar vasorelaxant response to the endothelium-independent vasodilator nitroprusside compared with lungs from control rats (pretreated with 0.1 ml saline iv). Pentoxifylline (20 mg/kg iv and ip 20 min before administration of TNF) had no detectable effect on either HPV or ACh-induced relaxation but completely negated the augmentation on HPV and the inhibiting action on ACh-induced relaxation caused by TNF. The TNF effect on ACh relaxation was unaffected by pretreatment with L-arginine. These results indicate that TNF induces endothelial dysfunction and enhances HPV, effects that are inhibited by pentoxifylline.

Acetylcholine↗
PubMed1991

Biochemical and structural adaptation of autologous skeletal muscle used for counterpulsation.

We have studied in a normal animal model (sheep), the biochemical and morphological adaptation of electrically stimulated skeletal muscle used for extra aortic counterpulsation. Immunocytochemical analysis of latissimus dorsi, using monoclonal antibodies to slow and fast myosin heavy chains, indicated an increase in the population of mixed fibres after stimulation for one week. By one month, up to 70% of fibres expressed both slow and fast myosin heavy chains in addition to the 15% of fibres expressing only slow myosin heavy chains. After 4 months, the population of mixed fibres was further transformed towards purely slow fibres to give values of 40 and 67% of fibres expressing only slow myosin heavy chain at 4 and 6 months, respectively. Increased staining, both in intensity and area, for NADH tetrazolium reductase activity (an enzyme of the oxidative metabolic pathway) was detected by 28 days. An increase in mitochondrial number was observed also by 28 days, further indicating a shift towards an oxidative metabolism. The molecular adaptation of latissimus dorsi was achieved by stimulation every fourth cardiac cycle at 35 Hz, 3 V, initiated 48 hours after the operation; this being a marked reduction in the delay from operation prior to stimulation. Evaluation of other regimes indicated that more frequent modes, or an increase in voltage or frequency, caused damage to the muscle during the early phase of molecular adaptation. A thorough understanding of the time sequence of the different adaptive processes is required to determine the ideal regime of stimulation initiated promptly after mobilisation of the muscle; aimed at harvesting the maximum amount of energy from the autologous muscle.

Adaptation, Physiological↗
PubMed1991

Structural features of interstitial lung disease in systemic sclerosis.

Most studies of lung histology in systemic sclerosis have been based on autopsy specimens and consequently emphasize end-stage fibrotic disease. Although occasional pathologic descriptions of open-lung biopsies have recognized the presence of inflammatory cells, suggesting a similarity to "lone" cryptogenic fibrosing alveolitis, the two conditions have never been formally compared. In this study we describe the morphologic features of 49 open-lung biopsies from 34 systemic sclerosis patients with interstitial lung disease, many of whom had their lung disease diagnosed at an early stage. None had pulmonary hypertension. Examination of lung tissue by light microscopy showed the earliest changes to include patchy lymphocyte and plasma cell infiltration of the alveolar walls, interstitial fibrosis, and increased macrophages but only occasional polymorphonuclear cells and lymphocytes in the alveolar spaces. Alveolitis was not observed without fibrosis. Comparison of 22 biopsies with a similar number from patients with lone cryptogenic fibrosing alveolitis, matched for age and sex, revealed no qualitative or quantitative differences, other than a higher prevalence of focal lymphoid hyperplasia (follicular bronchiolitis) in the systemic sclerosis patients than in the lone cryptogenic fibrosing alveolitis controls (23 and 5%, respectively). There was an inverse correlation between the extent of interstitial inflammation and patients' age (p less than 0.05), disease duration (p less than 0.05), and age at onset of systemic sclerosis (p less than 0.01). There was also an inverse correlation between DLCO and interstitial fibrosis (p less than 0.01) and loss of lung architecture (p less than 0.05). Ultrastructural studies of eight systemic sclerosis biopsies showed evidence of endothelial and epithelial injury together with interstitial edema and excess collagen deposition. Occasional mast cells were observed, often in close contact with interstitial fibroblasts, but there were no tubuloreticular structures or evidence of immune complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Expression of gastrin-releasing peptide (human bombesin) gene in large cell undifferentiated carcinoma of the lung.

Production of the growth factor gastrin-releasing peptide (GRP) or human bombesin has been shown to be a feature of neuroendocrine tumours of the lung, particularly small cell carcinoma, and is possibly responsible for the characteristically rapid growth of this tumour. Large cell undifferentiated carcinoma of the lung (LCC) is also characterized by rapid growth and there is increasing evidence that some LCCs exhibit neuroendocrine differentiation. We therefore investigated GRP/bombesin immunoreactivity and the expression of GRP gene in ten LCCs. Histologically, all were composed of large cells with abundant cytoplasm, open nuclei, and prominent nucleoli, and there was no evidence of squamous, glandular, or neuroendocrine differentiation. At the ultrastructural level, most showed squamous or glandular differentiation but none contained neuroendocrine granules. None of the tumours showed immunoreactivity for GRP/bombesin but seven of the ten showed a focal hybridization signal when treated with 32P-labelled GRP cRNA probes, indicating the presence of GRP mRNA. This was confirmed by northern blot analysis. This study shows for the first time that GRP gene is expressed in LCC. The production of GRP may contribute to the aggressive behaviour of LCC.

Bombesin↗
PubMed1990

Neural control of airway mucus secretion.

Neural mechanisms contribute to the control of secretion of mucus in the airways of a number of animal species including humans. The nerves involved are adrenergic, cholinergic and non-adrenergic, non cholinergic (NANC) and contribute to greater or lesser degrees, depending upon the species, to secretion from submucosal glands and epithelial goblet cells. Experimental studies implicate abnormalities in neural control in the pathophysiology of certain bronchial diseases in humans which are associated with mucus hypersecretion. New observations indicate a number of novel interventions with therapeutic potential for control of mucus in chronic bronchitis and asthma.

Bronchial Diseases↗
PubMed1990

Effect of platelet activating factor on formation and composition of airway fluid in the guinea-pig trachea.

1. We studied the effect of platelet activating factor (PAF) on leakage of albumin, and secretion of fucose (a marker for mucus glycoprotein) and protein into the tracheal lumen of the guinea-pig isolated in situ, and on bioelectric properties and fluxes of mannitol in vitro. We also studied the effect of PAF on mucus secretion in human bronchi in vitro. 2. In guinea-pig, intravenous PAF markedly increased the luminal concentration of protein but did not significantly increase fucose concentrations. Increased albumin leakage (274% above controls at a dose of 50 ng/kg PAF) was associated with the increased luminal content of protein (248% above controls at the same dose of PAF). 3. Leakage of albumin was maximal 10 min after PAF, was significantly reduced by 20 min and had returned to baseline by 30 min. This pattern of leakage could be repeated with successive administrations of PAF. 4. PAF induced small but significant biphasic changes in bioelectric properties in vitro. The initial response was rapid in onset and characterized by maximal increases in short-circuit current (Isc) of 6.5% above controls at 7.5 min and in conductance (G) of 7% at 20 min. Both responses were blocked by the PAF receptor antagonist WEB 2086. Amiloride blocked the increase in Isc. Permeability of the tissue to mannitol (Pmann) was unaltered. The delayed response was characterized by maximal increases in Isc and G of 10% above controls at 60-90 min which were not significantly affected by WEB 2086 or amiloride. Pmann was increased by 38% at 90 min. 5. PAF increased fucose secretion in human bronchi in vitro. 6. Lyso-PAF in vitro caused changes similar to those induced by PAF on bioelectric properties and mucus secretion, but had no significant effects in vivo. 7. Light microscopy showed no evidence of epithelial disruption in animals given intravenous PAF at a dose causing significant albumin transudation. 8. We conclude that PAF increases the protein content of guinea-pig tracheal fluid principally by inducing plasma leakage rather than mucus secretion and that the small changes in ion transport and epithelial conductance may reduce the tendency to epithelial disruption during plasma leakage.

Action Potentials↗
PubMed1990

Heterogeneous ultrastructure of human bronchial mast cells: morphometric subdivision of cell types and evidence for a degranulation gradient.

Structural heterogeneity of mast cells in human bronchial mucosa was investigated by examining 100 cells by electron microscopy and morphometry. Differential counts of secretory granules allowed subdivision of mast cells into three groups: (1) 49 cells with greater than 65% mixed granules; (2) 30 cells with greater than 30% scrolled granules; (3) 12 cells with greater than 30% particulate granules. Nine cells showed borderline characteristics. Records of depths of cells in the mucosa showed that most mixed-granule cells occupied middle levels, whereas most scrolled granule cells lay higher up, near the basement membrane. This raised the possibility that scrolled-granule cells may represent partly degranulated mixed-granule cells. Nineteen mast cells were filled with very dense mixed granules, and appeared to correspond to those staining with safranin in paraffin sections. However, morphometry did not produce any criteria for distinguishing these cells sharply from paler mixed-granule cells, which were therefore regarded as degranulating forms of the same type of cell. Evidence was found of a gradient of mast cell degranulation which appeared to increase in magnitude upward from deep submucosa to superficial mucosa. This evidence included finding a significant upward reduction in total granule area per cell, total granule numbers, numbers of mixed granules, and numbers of dense-cored granules. It was concluded that although bronchial mucosal mast cells could be subdivided ultrastructurally into three apparently heterogeneous groups, degranulation was found to produce a wide range of different cell appearances, and could, conceivably, even be responsible for the above grouping, rather than intrinsic mast cell heterogeneity.

Bronchi↗
PubMed1989

The ultrastructural features of developing Kveim test granulomas.

The Kveim test provides a useful model for the ultrastructural study of developing epithelioid cell granulomas in man. We present a controlled prospective study in which 140 patients with possible sarcoidosis had two simultaneous Kveim tests, one being biopsed at a varying interval and the other at the usual 28 days: 52 patients showed a positive test. Controls were provided by the 88 negative tests, Kveim biopsis from 12 healthy subjects, and biopsies of normal spleen injection sites in a further 12 sarcoid patients. In all three groups the initial response (3 to 5 days) was macrophage influx. From 8 to 10 days, in developing positive tests only, mononuclear cells with abundant rough endoplasmic reticulum appeared. Mature epithelioid cells were seen at 12 to 14 days, when lymphocyte numbers and lymphocyte-histiocyte interactions were at a maximum. Epithelioid cells showed marked secretory activity; the ultrastructural features of the developing epithelioid cell vacuoles are identical to those seen in exocrine cells. Mast cells are not involved in the development of granulomas.

Granuloma↗
PubMed1988

Giant cell carcinoma of the lung--immunohistochemical and ultrastructural evidence of dedifferentiation.

Ten examples of giant cell carcinoma of the lung were examined by immunohistochemistry for expression of keratin and vimentin intermediate filaments and for epithelial membrane antigen (EMA). Six cases were also examined electron microscopically. Keratin expression and, to a lesser extent, EMA immunoreactivity were reduced in comparison with better differentiated forms of lung carcinoma. Vimentin expression was increased, often taking the form of strong paranuclear staining. This may correspond to dense paranuclear aggregates of intermediate filaments seen ultrastructurally. Desmosomes were absent or sparse in most tumours. We propose that giant cell carcinoma arises by a process of dedifferentiation. The resulting loss of epithelial features gives rise to neoplastic cells which have features in common with some forms of sarcoma.

Adenocarcinoma↗
PubMed1988

Non-small cell lung carcinomas with neuroendocrine features. A light microscopic, immunohistochemical and ultrastructural study of 11 cases.

Eleven resected primary lung carcinomas classified as large cell carcinomas or squamous cell carcinomas, but showing some microscopic resemblances to bronchial carcinoid and small cell carcinoma, were studied. All cases were neurone-specific enolase and protein gene product 9.5 positive, indicating neuroendocrine differentiation. Staining for bombesin, C-terminal peptide of human pro-bombesin and chromogranin was positive in some cases. Electron microscopy showed dense-core granules in six of seven cases investigated, the remaining case showing small granules of uncertain nature. All but one patient died within 15 months after operation. These data indicate that neuroendocrine differentiation in non-small cell carcinomas of the lung may in some cases be suspected on routine histology. The follow-up data suggest that the identification of these cases might have implications for prognosis and therapy, and consequently for diagnostic lung tumour classification.

Adult↗