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Biomedical subjects

Bruce D Mazer

Publications and source records attributed to Bruce D Mazer.

7 recordsLinked to original sources

Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology.

Human immunoglobulin prepared for intravenous administration (IGIV) has a number of important uses in the treatment of disease. Some of these are in diseases for which acceptable treatment alternatives do not exist. In this review we have evaluated the evidence underlying a wide variety of IGIV uses and make specific recommendations on the basis of these data. Given the potential risks and inherent scarcity of IGIV, careful consideration of the indications for and administration of IGIV is warranted.

Asthma↗

Immune function in autistic children.

BACKGROUND: There have been reports that some children with autistic spectrum disorders have abnormal immune function. However, data in this area remain scarce and conflicting. OBJECTIVE: To evaluate the immune function of a series of autistic children in the context of this proposed association. METHODS: We prospectively collected data on 24 autistic children who, between January 1, 1996, and September 30, 1998, were referred unsolicited to an immunology clinic. We examined the clinical history and evaluated immunoglobulin levels; specific antibody titers to diphtheria, tetanus, and Haemophilus influenzae; T- + B-cell numbers; T-cell proliferation; and complement studies. RESULTS: Seven of the 24 children had a history of recurrent infections. Only 2 patients had immunoglobulin levels that were outside the age-adjusted reference ranges, 1 of whom was subsequently diagnosed as having common variable immune deficiency. All the patients had normal in vitro T-cell function and complement study results, and only 2 of 24 patients had subtle derangements in T-cell numbers. Elevated levels of IgE were found in 5 patients, which correlated with a clinical history of atopy. Low diphtheria or tetanus antibody levels were found in 12 patients, but in 11 of these, vaccination status was not up-to-date. CONCLUSIONS: Most of the autistic children studied had normal immune function, suggesting that routine immunologic investigation is unlikely to be of benefit in most autistic children and should be considered only when there is a history suggestive of recurrent infections.

Adolescent↗

Synthesis of IL-13 by human B lymphocytes: regulation and role in IgE production.

BACKGROUND: Our laboratory has demonstrated previously that human tonsillar B lymphocytes express IL-13 mRNA OBJECTIVE: We sought to investigate IL-13 production by human B cells and the association between B cell-derived IL-13 and IgE secretion. METHODS: Human B lymphocytes were isolated from tonsils and purified by means of rosetting with sheep RBCs or positive or negative selection with magnetic beads. They were stimulated with anti-CD40 antibodies with or without recombinant IL-4. Total mRNA was extracted, and IL-13 mRNA was measured by means of standard RT-PCR or by means of real-time PCR with commercially available primers. B cells were cultured with or without IL-13 neutralizing antibodies, and C epsilon transcripts and supernatant IgE levels were measured. RESULTS: IL-13 mRNA was detected in human B lymphocytes stimulated with anti-CD40 antibodies and IL-4 or IL-2 but not in unstimulated B cells. Real-time PCR demonstrated a 10- to 15-fold increase in IL-13 mRNA, maximizing at 36 hours. IL-13 protein was detected from B lymphocytes on day 3 and accumulated through day 7. The synthesis of IL-13 required both CD40 and IL-4 stimulation. The presence of IL-13 was confirmed by means of intracellular staining of cultured B lymphocytes and antigen-stimulated nasal biopsy specimens from atopic individuals. Addition of IL-13 neutralizing antibodies to purified B-cell cultures inhibited IgE production by up to 80% and diminished IgE (C epsilon) transcripts by 50%. CONCLUSION: Human B lymphocytes express IL-13 mRNA after ligation of CD40 and the addition of cytokines. Human B lymphocytes produce significant IL-13, and neutralization of IL-13 impairs IgE synthesis. IL-13 might be an important autocrine growth factor for IgE-producing B lymphocytes.

B-Lymphocytes↗

Similar allergic inflammation in the middle ear and the upper airway: evidence linking otitis media with effusion to the united airways concept.

BACKGROUND: Otitis media with effusion (OME) is a chronic inflammatory disease of the middle ear space characterized by the accumulation of fluid. Previous investigations have suggested that the immunopathologic mechanism underlying the development of middle ear effusion in patients with allergy is largely due to the effects of T(H)2 mediators. The composition of the inflammatory substrate in the effusions of allergic otitis media is similar to the late-phase allergic response seen elsewhere in the respiratory tract, such as in asthma and in allergic rhinitis. OBJECTIVE: To determine whether the middle ear compartment may be a component of the united airways in allergic disease by comparing the inflammatory profiles of the middle ear to the upper airway. METHODS: Middle ear effusions, torus tubaris (Eustachian tube mucosa at the nasopharyngeal orifice), and adenoidal tissue biopsies were obtained from 45 patients undergoing simultaneous tympanostomy tube placement for OME and adenoidectomy for adenoid hypertrophy. The cellular and cytokine profiles of each site were investigated by using immunocytochemistry (elastase, CD3, major basic protein) and in situ hybridization (IL-4, IL-5, IFN-gamma mRNA). Atopic status was determined for each patient by using skin prick testing. RESULTS: Eleven of the 45 patients with OME (24%) were atopic. The middle ear effusions of atopic patients had significantly higher levels of eosinophils, T lymphocytes, and IL-4 mRNA + cells ( P < .01) and significantly lower levels of neutrophils and IFN-gamma mRNA + cells ( P < .01) compared with nonatopic patients. The nasopharyngeal tissue biopsies revealed similar cellular and cytokine profiles. CONCLUSION: In atopic patients with OME, the allergic inflammation occurs on both sides of the Eustachian tube, both in the middle ear and in the nasopharynx. The results of this study support the concept that the middle ear may be part of the united airway in atopic individuals.

Adenoids↗

Evidence of allergic inflammation in the middle ear and nasopharynx in atopic children with otitis media with effusion.

BACKGROUND: Otitis media with effusion (OME) occurs in the setting of eustachian tube (ET) dysfunction. Previous studies have demonstrated a predominance of T helper 2 (Th2) mediators in the middle ear effusions (MEEs) of atopic children, suggesting that allergy plays a role in the pathogenesis of OME. Given that the middle ear is contiguous with the upper airway, the allergic inflammation seen in the middle ear of atopic patients with OME may also have been observed in the nasopharynx. OBJECTIVE: We hypothesize that atopic children have different cellular and cytokine profiles in MEE compared with nonatopic patients and that this allergic inflammation occurs in both the middle ear and the nasopharynx. METHODS: Forty-five patients undergoing both ventilation tube placement for OME and adenoidectomy for adenoid hypertrophy were recruited. The atopic status was determined for each patient using standard skin testing. The cellular and cytokine profiles of the MEEs and the torus tubarius and adenoid tissues were investigated using immunocytochemistry and in situ hybridization. RESULTS: Our results indicate that, within the atopic patient, there is a similar cellular and cytokine profile within the three regions sampled, with a predominant expression of interleukin-4 (a Th2 cytokine) and an increased infiltration of eosinophils compared with the nonatopic patient. CONCLUSION: These findings confirm the association of allergy with MEE and support the hypothesis that the middle ear may be an integral part of the United Airway Concept.

Adenoidectomy↗

T(H)2 cytokine expression in atopic children with otitis media with effusion.

BACKGROUND: Otitis media with effusion (OME) is more common in atopic children. Few studies have looked for the presence of inflammatory mediators in the middle-ear effusions of this population. OBJECTIVE: We hypothesize that atopic children with OME have a different inflammatory cell and cytokine profile than nonatopic patients with the disease. METHODS: Twenty-six patients with OME undergoing myringotomy and ventilation tube placement were recruited at the McGill University Hospital Center. The atopic status was determined for each patient by using standard skin testing. By means of immunocytochemistry, fluid specimens were assessed for T lymphocytes (CD3), eosinophils (major basic protein), neutrophils (elastase), mast cells (tryptase), and basophils (BB1). By using in situ hybridization, the expression of IL-4, IL-5, and IFN-gamma was assessed. RESULTS: There is a higher percentage of eosinophils and T lymphocytes in atopic patients with OME (n = 8) compared with that seen in nonatopic patients (n = 18, P <.01). There is a higher percentage of neutrophils in nonatopic patients with OME compared with that seen in atopic patients (P <.01). In examining cytokine profiles, there is a higher percentage of cells expressing IL-4 and IL-5 in atopic patients with OME compared with that seen in nonatopic patients (P <.01). CONCLUSION: The predominance of eosinophils, T lymphocytes, and T(H)2 mediators in the middle-ear effusions of atopic children provides evidence that allergy might play a role in the pathogenesis of OME.

Basophils↗