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Biomedical subjects

J Brostoff

Publications and source records attributed to J Brostoff.

At least 73 records · Page 4Linked to original sources

Release in vivo of IL-1 like activity by human skin.

We have demonstrated the release in vivo by normal human skin of a factor which possesses IL-1-like activity in the mouse thymocyte amplification assay. Quantitatively similar amounts of this factor were released from involved and uninvolved skin of patients with cutaneous T cell lymphoma. The IL-1-like factor was associated with inhibitory activity in the mouse thymocyte amplification assay. High performance liquid chromatographic analysis showed that this inhibitory activity co-chromatographed with prostaglandin E2. These results provide further evidence for the role of the skin as an immunologically active organ and suggest that PGE2 may have an immunomodulatory role in human skin.

Animals↗

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↗

Low dose sublingual therapy in patients with allergic rhinitis due to house dust mite.

In a double-blind placebo-controlled cross-over trial, low dose sublingual therapy with house dust mite was effective in relieving symptoms in 72% of the group of patients with perennial rhinitis due to house dust mite (P less than 0.03). Following active treatment, there was a significant increase in morning peak nasal inspiratory flow rate (P less than 0.01) in those who improved (thirteen out of eighteen) and resistance to nasal provocation with house dust mite also increased, in some cases up to 1000-fold (P less than 0.05). Oral therapy is safe and avoids the side effects of desensitizing injections which can be serious. The potential for oral desensitization is great and further studies on this form of treatment are needed.

Administration, Oral↗

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↗

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↗

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↗

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↗

Lack of effect of LTB4 on human natural killer cell activity and T lymphocyte transformation.

Human natural killer (NK) cell activity was not significantly affected by leukotriene (LT) B4 over a wide concentration range (10(-6)-10(-14) M), whether added directly to the NK cell assay or after preincubation of effector cells for 2 h with the drug before addition of Cr labelled K562 target cells. In addition, LTB4 did not affect the kinetics of NK cell mediated cytotoxicity. Addition of LTB4 (10(-6)-10(-10) M) to concanavalin A (Con A) or phytohaemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) had no significant effect on proliferation measured by tritiated thymidine incorporation, using both optimal and sub-optimal mitogen concentrations. Whilst it is clear that LTB4 is an important mediator of inflammation involving polymorphonuclear (PMN) leukocytes in vivo, it does not affect NK cell or T cell function in vitro.

Humans↗

Human mast cells recovered by bronchoalveolar lavage: their morphology, histamine release and the effects of sodium cromoglycate.

Mast cells make up between 0.5 and 3% (mean 1.35%) of total cells recovered by bronchoalveolar lavage (BAL). The majority of these cells have the morphological characteristics of mucosal mast cells in that they fail to stain in the alcian blue-safranin reaction after fixation in formol-saline but stain well after fixation in Carnoy's solution. Cells staining with berberine sulphate were seen in only four of the 26 lavages. BAL cells released histamine in response to anti-human immunoglobulin E (IgE) in a dose-dependent manner that was optimal at a dilution of anti-IgE of 1:100. Maximum release was obtained by 2 min. Histamine release was completely inhibited by a combination of 2-deoxyglucose (5 mmol/l) and antimycin A (1 mumol/l). Disodium cromoglycate (DSCG) significantly inhibited this histamine release at 1 mmol/l (P less than 0.02), 100 mumol/l (P less than 0.002) and 10 mumol/l (P less than 0.003), with maximum inhibition of 50.1% at 10 mumol/l.

Adult↗

Decreased natural killer cell activity in atopic eczema.

We have studied NK cell activity in atopic and non-atopic subjects using a standard 51Cr-release assay and K562 target cells. In atopics (AT) with allergic rhinitis and/or asthma, NK cell activity was similar to that in non-atopic (N) subjects, whilst patients with severe atopic eczema (AE) had depressed NK cell activity compared to AT or N subjects. In addition, circulating T-cell numbers and Con A responsiveness was decreased in AE, although neither parameter was correlated with decreased NK cell activity. However, decreased NK cell activity in atopic eczema was positively correlated with decreased numbers of Fc gamma + lymphocytes (P = 0.01) and decreased effector: target cell binding (P = 0.05), and negatively correlated with increased monocytes in AE (P = 0.09). AE NK cell activity was equally or more sensitive to the inhibitory effects of drugs such as dibutyryl cyclic AMP, prostaglandins (PG) D2,E2 and histamine. The relative percentage increase in NK cell activity by the interferon inducer poly I:C was similar in AE patients and controls. The results suggest that reduced numbers of circulating NK cells and pre-NK cells account for the depressed level of NK cell activity in subjects with severe atopic eczema.

Adult↗

Migraine is a food-allergic disease.

Foods which provoked migraine in 9 patients with severe migraine refractory to drug therapy were identified. The patients were then given either sodium cromoglycate or placebo orally in a double-blind manner, with foods previously identified as provocants. Sodium cromoglycate exerted a protective effect, thus confirming that it can prevent a hypersensitivity mechanism as well as the symptoms of migraine. Immune complexes were not produced in those patients who were protected by sodium cromoglycate. These observations confirm that a food-allergic reaction is the cause of migraine in this group of patients.

Acute Disease↗

Toxic oil syndrome, clinical and immunological characteristics: a review.

In May 1981 a new disease, with epidemic characteristics, appeared in Spain. Initially it was thought that an infectious agent was responsible for the disease, a theory that was later discarded when the disease was found to be associated with the ingestion of adulterated olive oil contaminated with potentially toxic chemicals. More than 20 000 people have been affected, and whilst official reports put the death toll at 250, the true figure may exceed 300. The disease is multi-systemic in presentation, affecting several organs and systems of the body. The disease has a poor prognosis in its chronic stages, which affect approximately 10% of victims, and its ultimate natural history is still to be observed. The pathogenesis of the disease remains to be elucidated, despite considerable efforts already made in this direction.

Anilides↗