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Biomedical subjects

N M Johnson

Publications and source records attributed to N M Johnson.

At least 37 records · Page 2Linked to original sources
PubMed1989

Bronchoalveolar lavage cell counts as a predictor of short term outcome in pulmonary sarcoidosis.

Sixty seven patients with biopsy proven pulmonary sarcoidosis were prospectively studied to determine whether single point bronchoalveolar lavage cell counts were a useful indicator of functional outcome and whether repeated lavage helped in management. The mean follow up period was 25 (range 13-37) months. No patient was having corticosteroid treatment at the time of initial bronchoalveolar lavage. "High intensity alveolitis" (lymphocyte count greater than or equal to 28%) was present at the initial lavage in 42 patients. These patients showed a significant improvement in their pulmonary function and chest radiographs over the follow up period whereas patients with "low intensity alveolitis" did not. Of the 42 patients with high intensity alveolitis, 31 had chronic sarcoidosis (duration over two years, mean 80 months). These patients showed a significant improvement in FVC but not in TLCO. Corticosteroids resulted in greater functional and radiological improvement in the patients with high intensity alveolitis than in those with low intensity alveolitis. Repeat bronchoalveolar lavage in 34 patients, mean 8.4 months after the original lavage, showed a weak inverse relation between a reduced lymphocyte count and change in forced vital capacity and isotope uptake on a gallium scan. These correlations were too weak to make repeated cell counts useful in management. Our results suggest that high intensity alveolitis may be a favourable prognostic factor for lung function in pulmonary sarcoidosis, even in patients with chronic disease, but that repeat lavage adds little to the management of the individual patient.

Adrenal Cortex Hormones↗
PubMed1989

Effects of sodium cromoglycate and nedocromil sodium on histamine secretion from mast cells from various locations.

Nedocromil sodium and sodium cromoglycate inhibited histamine release from rat peritoneal mast cells. Tachyphylaxis was observed with both drugs. The 2 compounds were extremely selective in their action, being less active against peritoneal mast cells from the hamster and completely ineffective against mast cells from the mouse. Human basophil leucocytes, tissue mast cells of the guinea-pig and rat intestinal mast cells were also unresponsive. Both drugs inhibited immunological histamine release from human pulmonary mast cells obtained by bronchoalveolar lavage (BAL) and, less effectively, from lung parenchyma. Nedocromil sodium was about 1 order of magnitude more potent than sodium cromoglycate in each case. Tachyphylaxis was observed with the dispersed lung, but not with the cells obtained by BAL, and the degree of inhibition varied inversely with the magnitude of the secretory response. The possible clinical significance of these observations is discussed.

Animals↗
PubMed1988

Anomalous systemic venous drainage occurring in association with the hypogenetic lung syndrome.

A case in which anomalous systemic venous drainage occurred in association with the hypogenetic lung syndrome (scimitar syndrome) is described. The chest radiograph appearances of the anomalous systemic vein mimicked an anomalous pulmonary or scimitar vein. Angiography demonstrated that the patient also had a small anomalous pulmonary vein draining and a systemic artery supplying, the right lung. As the right lung was hypoplastic, all three features of the hypogenetic lung syndrome were present, in addition to partial anomalous systemic venous drainage.

Abnormalities, Multiple↗
PubMed1988

Effects of sodium cromoglycate and nedocromil sodium on histamine secretion from human lung mast cells.

Sodium cromoglycate and nedocromil sodium produced a dose dependent inhibition of histamine secretion from human pulmonary mast cells obtained by bronchoalveolar lavage and by enzymatic dissociation of lung parenchyma. Both compounds were significantly more active against the lavage cells than against the dispersed lung cells, and nedocromil sodium was an order of magnitude more effective than sodium cromoglycate against both cell types. Tachyphylaxis was observed with the parenchymal cells but not with the lavage cells. Nedocromil sodium and sodium cromoglycate also inhibited histamine release from the lavage cells of patients with sarcoidosis and extrinsic asthma.

Asthma↗
PubMed1987

Some further properties of human pulmonary mast cells recovered by bronchoalveolar lavage and enzymic dispersion of lung tissue.

The properties of human pulmonary mast cells obtained by bronchoalveolar lavage (BAL) and enzymic dispersion of lung tissue have been compared with those of basophil leucocytes. On challenge with anti-human IgE, the pulmonary cells released both histamine and the newly generated mediators prostaglandin D2 (PGD2) and leukotriene C4 (LTC4). In contrast, the blood leucocytes released histamine but very little leukotriene and no prostanoid. Interestingly, both basophil leucocytes and BAL cells released histamine spontaneously in a hyperosmolar environment whereas dispersed lung (DL) cells showed limited reactivity under these conditions. The possible clinical significance of these findings in human bronchial asthma is discussed.

Adult↗
PubMed1987

Lack of immune deficiency in sarcoidosis: compartmentalisation of the immune response.

The original findings of peripheral anergy in sarcoidosis led to the conclusion that sarcoidosis was a disease associated with immune deficiency, but patients with sarcoidosis do not appear to suffer from repeated infections suggestive of immune suppression. With the technique of bronchoalveolar lavage it is now possible to examine the local immune response within the lung, the most commonly affected organ in sarcoidosis. In this study three different indices of cell mediated immunity (lymphocyte transformation, interleukin-2 production, and interleukin-1 production) have been examined by comparison of cells recovered by lavage with those collected from peripheral blood. It was found that in vitro anergy was confined to peripheral blood cells, where all three markers of the immune response used in this study was impaired in the 12 patients with sarcoidosis group when compared with results in the 12 controls, with the most depressed responses seen in those patients classified as having active disease (lymphocyte proliferation 45% (SD 17%); interleukin-2 production 44% (13%), and interleukin-1 production 31% (10%) of control levels). By contrast, T lymphocytes recovered from the lungs of patients with sarcoidosis showed a greater response than did those from controls in terms of lymphocyte transformation and interleukin-2 production; these differences were greatest in those with active disease (lymphocyte proliferation 209% (27%) and interleukin-2 production 202% (19%) of control levels). Interleukin-1 production by cells of the monocyte lineage recovered from the lung gave similar results to those of the control and sarcoid groups. It is concluded that the anergy seen in the peripheral blood compartment possibly reflects redistribution of T lymphocytes rather than a generalised immune deficiency.

Adult↗
PubMed1987

Serum C-reactive protein concentrations in patients with pulmonary sarcoidosis.

In a prospective study serum C-reactive protein concentrations were measured in nine patients with "active" pulmonary sarcoidosis (as assessed by bronchoalveolar lavage lymphocyte counts, gallium-67 lung scanning, and serial pulmonary function testing), and in five patients with "inactive" disease. Active pulmonary sarcoidosis was associated either with no rise or with only a modest rise in serum C-reactive protein concentrations. In contrast, serum C-reactive protein concentrations in 12 patients with sputum positive pulmonary tuberculosis were considerably raised. Serum C-reactive protein may thus provide a valuable test in the differentiation of sarcoidosis from conditions which it may mimic and which are known to induce an acute phase response.

Adult↗
PubMed1987

Some studies on human pulmonary mast cells obtained by bronchoalveolar lavage and by enzymic dissociation of whole lung tissue.

Human pulmonary mast cells were obtained by bronchoalveolar lavage (BAL) and by enzymic dissociation of whole lung. The cells released histamine on immunological stimulation or on exposure to a hyperosmolar environment. Cell suspensions similarly released newly generated products of arachidonic acid metabolism. Increased numbers of mast cells were recovered by BAL of asthmatic subjects and patients suffering from sarcoidosis and these cells were hyperresponsive to immunological challenge. Mast cells recovered by BAL and enzymic dissociation were differentially inhibited by antiasthmatic drugs. These data emphasize the potential role of BAL mast cells in pulmonary diseases of diverse origin.

Adolescent↗
PubMed1987

Increased natural killer cell activity in sarcoidosis.

We have studied NK cell activity in 32 patients with sarcoidosis and in 29 control subjects. Cytotoxicity was increased in both active and inactive sarcoids, the lytic activity of sarcoid peripheral blood mononuclear cells (PBMC) being approximately 50% higher than that of control subjects. The number of lymphocytes bearing Fc receptors for IgG (FcR-IgG) was correlated with NK cell activity, both parameters being increased in the sarcoid group. Sarcoid NK cell activity was reduced to control levels after depletion of plastic adherent cells, whilst inhibition of cytotoxicity by PGE2 was increased using non-adherent sarcoid PBMC. Plastic depletion had no effect on NK cell activity or its inhibition by PGE2 using PBMC from control subjects. The results demonstrate the presence of a weakly adherent, PGE2 insensitive NK cell in sarcoid PBMC preparations.

Adult↗
PubMed1986

Clinical and bronchoscopic diagnosis of suspected pneumonia related to AIDS.

In a series of 25 patients with suspected pneumonia related to the acquired immune deficiency syndrome (AIDS) the first 12 underwent routine fibreoptic bronchoscopy and bronchoalveolar lavage with or without transbronchial biopsy before treatment. Eight were found to have Pneumocystis carinii pneumonia and had typical clinical presentations with a prolonged history of symptoms, including a dry cough, and bilateral diffuse alveolar or interstitial shadowing in chest radiographs. Among the subsequent 13 cases, 11 had similar clinical presentations and were treated with high doses of intravenous co-trimoxazole without bronchoscopy first. Bronchoscopy was performed in those who deteriorated at any stage or failed to improve by the fifth day of treatment. Nine patients recovered and were discharged. In two patients who died P carinii pneumonia was confirmed in one but no diagnosis was made in the other. The early and late survival in both groups of patients was similar. In patients at high risk for AIDS who have clinical features suggestive of P carinii pneumonia starting treatment with intravenous co-trimoxazole is justified. The few patients who deteriorate or fail to respond should undergo bronchoscopy with bronchoalveolar lavage and transbronchial biopsy.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Some properties of mast cells obtained by human bronchoalveolar lavage.

The properties of human pulmonary mast cells obtained by enzymic dispersion of whole lung and by bronchoalveolar lavage (BAL) have been compared with those of the basophil leucocyte. The latter cell types responded with release of histamine to challenge with anti-human IgE but the dispersed cells reacted only after passive sensitisation with serum from an atopic donor. Disodium cromoglycate inhibited the release of histamine from both types of pulmonary mast cell although the characteristics of the inhibition were different in the two cases. The drug was ineffective against the basophil. Increased numbers of mast cells were recovered by lavage of asthmatic subjects and these cells responded to immunological challenge with an enhanced release of histamine. The possible clinical significance of these findings in human bronchial asthma is discussed.

Adult↗
PubMed1986

Bronchoalveolar mast cells in sarcoidosis: increased numbers and accentuation of mediator release.

Bronchoalveolar lavage was carried out in 36 subjects with sarcoidosis and 20 control subjects undergoing bronchoscopy for routine diagnostic purposes. The proportion of mast cells in the lavage fluid of subjects with sarcoidosis (mean (SE) 0.84% 0.09%; p less than 0.01) when compared with that of controls (mean 0.32% (0.05%); p less than 0.01). This increase was greatest in subjects with positive gallium scans but was not correlated with the percentage recovery of lymphocytes or radiographic stage. Anti-IgE induced histamine release from the bronchoalveolar cells of 15 subjects with sarcoidosis was significantly increased at all effective doses of anti-IgE. This accentuation of histamine release was significantly greater in patients with positive gallium scans and correlated directly with the percentage recovery of lymphocytes (r = 0.7, p less than 0.005). The dose-response curve of anti-IgE induced histamine release from bronchoalveolar cells of subjects with more than 20% of lymphocytes in the lavage cell population was significantly greater than the dose-response curves of subjects with fewer than 20% of lymphocytes and of controls.

Adolescent↗
PubMed1986

The function and properties of human lung mast cells.

Mast cells may be recovered from human subjects by bronchoalveolar lavage. Such bronchoalveolar mast cells will release histamine in response to IgE-dependent challenge in a reaction that is dose-, time- and energy-dependent. They possess functional characteristics distinct from dispersed human lung mast cells. The percentage of mast cells within the bronchoalveolar cell population is critically dependent upon the underlying pathology. Greater numbers of mast cells may be recovered from the bronchoalveolar compartment of extrinsic asthmatics than from controls. In addition, bronchoalveolar mast cells from asthmatic subjects show an increased releasability of histamine in response to anti-IgE. Antigen challenge also leads to the release of histamine in vitro, demonstrating the potential for the antigen-specific initiation of bronchoconstriction in these subjects. Spontaneous release of histamine from bronchoalveolar mast cells of asthmatic subjects was also greater than in controls (up to 46%), a feature which may be related to non-immunological mechanisms of bronchoconstriction. Such non-immunological mechanisms have been further investigated utilising mannitol as a model of hyperosmolar histamine release. Mannitol induced a dose-dependent release of histamine from bronchoalveolar mast cells of normal subjects, and this release was significantly inhibited by sodium cromoglycate. The leukotrienes are putative major mediators of human asthma. After challenge with anti-IgE in vitro, dose-dependent release of leukotriene C4 and prostaglandin D2 occurs from the bronchoalveolar cells of normal subjects. The release of PGD2 shows significant correlation with histamine release. Lying superficially, bronchoalveolar mast cells would be readily accessible to inhaled antigen. Mediator release from such cells may be relevant to the pathogenesis of asthma.

Animals↗
PubMed1986

A comparison of nedocromil sodium and sodium cromoglycate on human lung mast cells obtained by bronchoalveolar lavage and by dispersion of lung fragments.

Bronchoalveolar lavage (BAL) mast cells provide a useful tool with which to screen potential therapeutic agents for human airway diseases. This study was therefore designed to compare the activity of nedocromil sodium and sodium cromoglycate in inhibiting anti-IgE induced histamine release from human mast cells obtained by BAL and from dispersed lung (DL) fragments. After 10 min pre-incubation with the mast cell preparations, both drugs displayed greater inhibition of histamine release from BAL than from DL mast cells. Under optimal conditions of 10 min pre-incubation with BAL and none with DL mast cells, nedocromil sodium showed significantly more activity than sodium cromoglycate on both BAL and DL mast cells.

Adult↗
PubMed1986

Left recurrent laryngeal nerve palsy as the presenting feature of sarcoidosis.

We report a case of sarcoidosis in which the presenting features were hoarseness of voice, hilar lymphadenopathy and paralysis of the left recurrent laryngeal nerve. Sarcoidosis does not usually enter into the differential diagnosis in this situation, which almost invariably implies the presence of malignant disease, particularly either lymphoma or bronchial carcinoma.

Adult↗
PubMed1985

Bronchoalveolar mast cells in extrinsic asthma: a mechanism for the initiation of antigen specific bronchoconstriction.

Bronchoalveolar lavage performed in 10 patients with extrinsic asthma and 14 controls yielded similar recoveries of fluid and cells. Mast cells and eosinophils, however, formed a greater proportion of the cells recovered from the asthmatic subjects (p less than 0.001 for mast cells; p less than 0.01 for eosinophils), the histamine content of the lavage cells being correspondingly increased (p less than 0.01). Both the percentage of mast cells and the histamine content of lavage cells were significantly inversely correlated with the forced expiratory volume in one second (FEV1; expressed as percentage of predicted) and with the ratio of FEV1 to forced vital capacity before lavage. There was also a significant inverse correlation between the concentration of histamine required to produce a 20% fall in FEV1 and the percentage of mast cells recovered (p less than 0.05). When incubated with antihuman IgE bronchoalveolar mast cells from asthmatic subjects released a significantly increased proportion of total cellular histamine than cells from control subjects at all effective doses of anti-IgE. By contrast, dose response curves for IgE dependent histamine release from peripheral blood leucocytes were similar in asthmatics and controls. Specific antigen led to release of histamine from bronchoalveolar cells and peripheral blood leucocytes of asthmatic subjects but not controls. Lying superficially within the airways, bronchoalveolar mast cells would be readily exposed to inhaled antigen and would release mediators directly on to the airway surface. Their immunological response suggests that they are likely to be important in the pathogenesis of airflow obstruction in asthma.

Adult↗