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Biomedical subjects

J Brostoff

Publications and source records attributed to J Brostoff.

At least 55 records · Page 3Linked to original sources

Intestinal permeability to 51Cr-labelled ethylenediaminetetraacetate in food-intolerant subjects.

Intestinal permeation of 51Cr-labelled ethylenediaminetetraacetate (51Cr-EDTA) was normal in 8 food-intolerant patients. Following ingestion of the offending food stuff there was a significant (p less than 0.003) decrease in the permeation of 51Cr-EDTA but the same phenomenon was observed in control subjects (n = 5) following cereal. Eight patients were tested following ingestion of lentil puree and subsequently with lentil puree containing the food to which they were sensitive. In these patients there was a significant increase in the permeation of 51Cr-EDTA following the 2nd test (p less than 0.01), but this was of insufficient magnitude to be of diagnostic use. These results show that food intolerance does involve some, but not gross changes in intestinal permeability to 51Cr-EDTA.

Adult↗

Postviral syndrome--how can a diagnosis be made? A study of patients undergoing a Monospot test.

Eighty-nine of 150 patients having a Monospot test filled out a questionnaire about their illness, and the General Health Questionnaire. They completed a follow-up questionnaire 6 months later. Twelve (8%) had a positive Monospot. Twenty-eight of 83 serum samples tested (34%) were positive for VP1 enteroviral antigen. Forty of the patients had a self limiting illness, 13 had a definite diagnosis (excepting glandular fever), 14 had a possible postviral syndrome, 10 had recurrent sore throats/flu, and 12 had a chronic non-specific illness. Patients with a specific diagnosis were less likely to complain of aching muscles/joints, sore throat, tiredness or loss of concentration. Their GHQ scores were lower, although this just failed to reach significance (P = 0.08), and they scored significantly lower on the somatic symptoms subscale (P = 0.022). Overall 72% scored above the GHQ threshold for 'psychological caseness' which is higher than in other studies. Sixty-five per cent of the sample questioned at 6 months felt that their illness started with a viral infection. The methodological problems involved in making a diagnosis of postviral syndrome are discussed.

Adolescent↗

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↗

Local increase in interleukin-1-like activity following UVB irradiation of human skin in vivo.

Using an in vivo skin chamber method, we demonstrated increased release of interleukin-1 (IL-1)-like activity at the site of irradiation with 3 times the minimal erythema dose of ultraviolet B (UVB). IL-1-like activity was estimated using the mouse thymocyte amplification assay. UVB-augmented release of IL-1-like activity peaked 1 h after irradiation and levels returned to baseline by 2 h. Release of IL-1-like activity from human skin after exposure to UV radiation may account for some of the local and systemic features of the sunburn response.

Adult↗

Poor sulphoxidation ability in patients with food sensitivity.

Patients with well defined reactions to foods were examined for their ability to carry out both sulphur and carbon oxidation reactions by using carbocisteine and debrisoquine as probe compounds. The proportion of poor sulphoxidisers (58 of 74) was significantly greater than that of a previously determined normal control population (67 of 200; p less than 0.005). The proportion of poor carbon oxidisers was not significantly different from the controls. Metabolic defects may play a part in the pathogenesis of adverse reactions to foods.

Adult↗

Effect of cardiopulmonary bypass on circulating concentrations of leucocyte elastase and free radical activity.

Circulating concentrations of leucocyte elastase and free radical activity were measured in 11 adults undergoing cardiopulmonary bypass. In all patients the bypass procedure was associated with pronounced changes in plasma elastase concentrations, and peak enzyme concentrations correlated closely with the duration of bypass (r = 0.91, p less than 0.001). Serial measurement of octadeca-9, 11-dienoic acid, a non-peroxide marker of free radical activity, showed significant changes only in the plasma free fatty acid fraction, suggesting a direct relation to the action of heparin rather than to the bypass procedure as such. These studies support the hypothesis that neutrophil activation plays a central role in the organ dysfunction that may complicate cardiopulmonary bypass and suggest that elastase release rather than free radical generation may be the appropriate marker of the event.

Aged↗

Nasal response to allergen and hyperosmolar challenge.

Rhinitis causes both clinical and social discomfort to patients, and in clinical practice is often underdiagnosed. We have examined a simple method for the assessment of a positive nasal provocation test to help in the diagnosis of rhinitis. In patients with histories suggestive of house dust mite (HDM) sensitivity and positive skin-prick tests or specific IgE to Dermatophagoides pteronyssinus, there was a fall in nasal inspiratory peak flow (NIPF) following nasal challenge with allergen. This was not seen in control subjects or in pollen-sensitive patients when challenged with house dust mite. Frequency of sneezing and degree of rhinorrhoea increased in these patients following challenge, and based on these findings we propose a simplified scoring system for the diagnosis of allergic rhinitis. We examined non-specific nasal reactivity using hyperosmolar solutions as a challenge system and found that allergic subjects responded with a fall in NIPF, although the clinical response was not identical to that seen with allergen. Control subjects did not respond to hyperosmolar challenge.

Adolescent↗

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↗

Circulating human leucocyte elastase levels in patients with pulmonary sarcoidosis.

In a pilot study plasma elastase concentrations were measured in 28 outpatients with pulmonary sarcoidosis. These were compared with the conventional criteria used in assessment of disease activity, namely lung function abnormalities, chest radiography changes and serum angiotensin converting enzyme (ACE) levels. An elevated plasma elastase concentration was found in 21/28 patients (mean 554 micrograms/l, range 192-1678). Of these, six had evidence of active pulmonary or cutaneous sarcoidosis and the plasma elastase level fell towards normal as the disease improved; another three had evidence of a coexistent acute phase response which might explain the raised level. Six of the remaining 12 patients had longstanding, fibrotic chest radiographic abnormalities with no apparent change during the short study period. Six of the seven patients with normal plasma elastase levels also had longstanding, apparently quiescent sarcoidosis. No correlation was found between the plasma elastase concentration and either chest radiographic score, lung function abnormalities, or serum ACE level. These findings suggest that patients with active pulmonary or cutaneous sarcoidosis have evidence of in vivo neutrophil activation. The additional finding of raised plasma elastase levels in some patients with fibrotic radiological changes implies the presence of ongoing chronic neutrophil activation, perhaps in the lung interstitium, for which further treatment might be indicated.

Adult↗

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↗

Sjögren's syndrome and fibrosing alveolitis complicated by pulmonary lymphoma.

The case of a middle aged woman who presented with fibrosing alveolitis, in her mid-forties, followed by a sicca syndrome and who subsequently developed a pulmonary lymphoma (B cell) while receiving azathioprine therapy is recorded. Of interest was the absence of polyclonal B cell activation, e.g., production of rheumatoid factor, hypergammaglobulinaemia, high titre antinuclear antibodies or antibodies to extractable nuclear antigens (ENA) during most of her illness. Persistently raised IgM levels and low IgA levels were demonstrated. The relevance of azathioprine to development of the lymphoma is discussed.

Female↗

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↗

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↗

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↗

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↗

IgE complexes in food allergy.

We have studied patients with the diagnoses of asthma, eczema, and arthralgia by monitoring the formation of immune complexes containing IgE after antigen egress from the gut before and after challenge with food. Following challenge, immune complexes containing IgE, IgG, and antigen are detectable in the circulation. Their appearance correlates with the production of symptoms. The effect of sodium cromoglycate was to prevent the appearance of complexes. This was associated with absence of symptoms. It is suggested that a local IgE-mediated mechanism acts as a "trigger" for the entry of antigen and the formation of immune complexes by altering the permeability of the gut mucosa. The resulting delayed onset symptoms could be viewed as a form of serum sickness with few or many target organs affected.

Adolescent↗