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Biomedical subjects

J Brostoff

Publications and source records attributed to J Brostoff.

At least 37 records · Page 2Linked to original sources
PubMed1993

T cell epitopes of the major fraction of rye grass Lolium perenne (Lol p I) defined using overlapping peptides in vitro and in vivo. I. Isoallergen clone1A.

One hundred and fifteen overlapping synthetic peptides spanning the entire sequence of the iso-allergen clone1A of Lol p I from rye grass Lolium perenne were synthesized by the multi-pin technique. The peptides were overlapping 12mers, offset by two residues and overlapping by 10 residues. Sets of six adjacent overlapping peptides (except pool-1, 15, 20) were pooled and were used in vitro and in vivo to map the T cell epitopes on Lol p I. Six atopics who were skin test and RAST positive to rye grass showed T cell responses to L. perenne extract (LPE) and its major fraction (Lol p I). Five out of six showed T cell responses in vitro to peptide pool-17, while five non-atopics did not respond to any of the peptide pools. By testing the individual peptides of pool-17, we have located the T cell epitope on Lol p I. Interestingly, when we tested pool-17 and its single peptides in vivo by intradermal skin testing we found in one patient a typical DTH after 24-48 h to pool-17 and its peptides (peptides 3 and 4) which exactly matched the in vitro responses. By defining the T cell epitopes in this way a greater understanding of the allergic response to pollen will be obtained, and a more effective and less dangerous vaccine may be possible for treating patients with hay fever.

Adult↗
PubMed1992

Efficacy of traditional Chinese herbal therapy in adult atopic dermatitis.

There has been considerable interest in traditional Chinese herbal therapy (TCHT) as a new treatment for atopic dermatitis. To establish the efficacy and safety of this treatment, a daily decoction of a formula containing ten herbs that has been found to be beneficial in open studies was tested in a double-blind placebo-controlled study. 40 adult patients with longstanding, refractory, widespread, atopic dermatitis were randomised into two groups to receive 2 months' treatment of either the active formulation of herbs (TCHT) or placebo herbs, followed by a crossover to the other treatment after a 4-week washout period. The main outcome measures were extent and severity of erythema and surface damage as judged by standardised body scores. The patients' own assessments of the overall response to treatment were also sought. The geometric mean score for erythema at the end of active treatment was 12.6 (95% confidence interval [CI] 5.9 to 22.0) and at the end of the placebo phase was 113 (65 to 180). The geometric mean score for surface damage was 11.3 (5.8 to 21.8) and 111.0 (68 to 182), respectively. The 95% CI for the mean geometric ratio for the two values with active treatment was 0.04 to 0.22 for erythema (p less than 0.0005) and 0.04 to 0.27 for surface damage (p less than 0.0005). Of the 31 patients who completed the study and expressed a preference, 20 preferred that phase of the trial in which they received TCHT whereas 4 patients preferred placebo (p less than 0.02). There was a subjective improvement in itching (p less than 0.001) and sleep (p less than 0.078) during the TCHT treatment phase. No side-effects were reported by the patients although many commented on the unpalatability of the decoction. TCHT seems to benefit patients with atopic dermatitis. Palatability of the treatment needs to be improved and its safety assured.

Administration, Oral↗
PubMed1992

Oilseed rape--a new allergen?

Oilseed rape (Brassica napus) is a commonly grown crop in Europe and it has been suggested that its pollen may be a potent new allergen. The prevalence of sensitization in a normal exposed population and an objective study of those patients found to be allergic to the rape pollen is described. The results show a low prevalence of allergy to oilseed rape pollen (less than 0.2%) unless the subjects were occupationally exposed. Those affected, with one exception, were already atopic and allergic to other pollens. The role of volatile materials given off by the plant remains to be elucidated.

Adult↗
PubMed1992

Specific inhibition of IgE antibody production by an antisense oligodeoxynucleotide oligomer (Oligostick).

We have investigated the ability of an antisense oligonucleotide (ASE-1) to specifically inhibit IgE synthesis by a human myeloma cell line, U266. ASE-1 inhibited IgE production in a concentration-dependent manner, as assessed by isotype-specific ELISA measurement of immunoglobulin in myeloma cell supernatants. Inhibition of IgE production was specific and not due to cytotoxicity since IgG1 and IgM production by human myeloma cell lines ARH-77 and RPMI-1788 respectively, was not significantly affected by up to 20 microM ASE-1 whereas IgE production was inhibited by approximately 70% at this concentration. These results indicate that antisense oligonucleotides represent a potential therapeutic approach to the treatment of IgE-mediated allergic diseases.

Antibodies, Neoplasm↗
PubMed1991

Children with atopic eczema. I: Clinical response to food elimination and subsequent double-blind food challenge.

The role of foods in the exacerbation of atopic eczema was studied by offering a food elimination diet and subsequent random order, double-blind food challenges to 91 eczematous patients, [49 males and 42 females, median age 4.5 years (range 0.5-15)]. Eczema improved in 49 of 66 (74 per cent) (skin score fall greater than or equal to 3) after stopping cows' milk, eggs and various other foods, with significant decreases in erythema, excoriation, lichenification and extent of eczema. One hundred and ninety-four food challenges were given to 64 patients who had shown objective or subjective improvement. Eczema and associated symptoms were significantly worse after cows' milk and tomato compared with placebo. Egg did not worsen eczema, but 48 per cent of 44 challenges were incomplete, mainly due to hypersensitivity reactions and challenge refusal. The longer a food had been avoided, the less likely was the chance of a positive food reaction. Clinical history did not predict response to dietary manipulation. A standard elimination diet avoiding cows' milk, egg, tomatoes and possibly colours and preservatives should help up to three-quarters of patients, and is easy to implement with the help of a dietician. This diet may be considered in all children with moderate or severe eczema.

Adolescent↗
PubMed1991

Children with atopic eczema. II: Immunological findings associated with dietary manipulations.

A group of 91 children with atopic eczema entered a study where clinical and immunological features were compared before and after a food elimination diet, and after double blind randomized food challenges in which a food was given for several days at a time. Eczema improved significantly during the diet and became worse on food challenges. The clinical outcome of food elimination could not be predicted by the initial skin prick test results, serum immunoglobulins, total or food-specific IgE, or complexed IgG or IgE. There was a tendency for patients whose eczema did not improve after food elimination to have higher initial serum IgG levels, without a corresponding increase in skin infections. The radioallergosorbent test to soy gave a higher result in those who improved on diet. No significant changes in serum or complexed immunoglobulins occurred over the period of food elimination or subsequent food challenge. Results of food challenges could not be predicted by initial serum immunoglobulin levels. A history of spring/summer exacerbations of eczema correlated with positive skin prick tests to silver birch pollen, but not to grass pollen. Serological tests did not help in planning food diets in atopic eczema, and the immunological studies did not delineate any particular mechanism by which foods might exacerbate eczema.

Adolescent↗
PubMed1990

Lithium counteracts histamine suppression of human T cell mitogenesis.

Human T cell proliferative responses to concanavalin A (conA) were suppressed by approximately 50% by histamine (100 microM). In contrast, LiCl (1 or 3 mM) potentiated T cell responses by about 50%, but 10 mM LiCl had no significant effect on T cell proliferation. Histamine suppression was not significantly affected by the presence of potentiating concentrations of LiCl, whereas 10 mM LiCl completely abrogated histamine suppression.

Adult↗
PubMed1990

Depressed lymphocyte transformation and the role of prostaglandins in atopic dermatitis.

We have shown that peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis have a reduced in vitro proliferative responsiveness to concanavalin A when compared with non-atopic controls. Addition of the cyclo-oxygenase inhibitor indomethacin caused a significant enhancement of the mitogen response in the patients, indicating a suppressive effect of cyclooxygenase products. We have further demonstrated increased levels of prostaglandin E2 in the supernatants of the PBMC cultures and increased levels of IgE immune complexes in the sera of the atopic dermatitis patients and therefore hypothesize that IgE immune complexes may cause increased monocyte production of prostaglandins which in turn appears to be responsible for a reduced lymphocyte proliferation.

Adolescent↗
PubMed1989

Methionine-enkephalin stimulates in vitro proliferation of human peripheral lymphocytes via delta-opioid receptors.

The influence of methionine-enkephalin (Met-Enk) on in vitro proliferation of human peripheral lymphocytes was investigated. Met-Enk, in the concentration range 10(-12) to 10(-4) M enhanced the proliferative response to suboptimal concentrations of concanavalin A of human peripheral lymphocytes and to cells in the absence of mitogen. The response to Met-Enk in the absence of mitogen was not influenced by the presence of fetal calf serum: similar levels of enhancement were seen in cultures supplemented with 10% autologous serum. Enhancement of proliferation was blocked in a concentration-dependent manner by both naloxone and the delta specific antagonist ICI-174864. The sensitivity to the antagonistic influence of ICI-174864 suggests strongly that the stimulatory influence of Met-Enk on human lymphocyte proliferation in the absence of mitogen is mediated via the delta-opioid receptor.

Adult↗
PubMed1989

Nasal histamine release following hyperosmolar and allergen challenge.

Allergic rhinitis is characterised by symptoms of sneezing, itching of the nose with watery secretions, and nasal obstruction. We have previously shown that patients can have the diagnosis of allergic rhinitis confirmed by nasal provocation tests and assessment of nasal inspiratory peak flow (NIPF) after specific allergen or hyperosmolar challenge. We now show that histamine is released into the nasal lavage fluid in response to such challenges. Saline lavage alone results in detectable histamine levels in the order of 5 ng/ml, but in the presence of allergen (HDM) there is a significant increase in histamine release in atopics but not in control subjects. With hyperosmolar challenge, atopics showed a biphasic response in that histamine release was increased with 1.8% and 3.6% saline but returned to baseline with 5.4% and 7.2% saline, then showing a further increase with 9.0% saline. This raises the possibility of two populations of responsive mast cells. Hyperosmolar challenge leads to symptoms of nasal itch and sneezing as well as histamine release in atopics but not in controls. This suggests that hyperosmolar challenge can be used as a simple diagnostic test for allergic rhinitis and may provide a model for nasal hyper-reactivity.

Adolescent↗