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M Boguniewicz

Publications and source records attributed to M Boguniewicz.

29 records · Page 2Linked to original sources
PubMed1995

Granulocyte macrophage colony-stimulating factor contributes to enhanced monocyte survival in chronic atopic dermatitis.

Evidence suggesting that prolonged effector cell survival may contribute to perpetuation of inflammation prompted us to ask whether monocyte macrophages, the predominate inflammatory cell in the lesion of chronic atopic dermatitis (AD), exhibit enhanced survival in AD. Cultures of peripheral blood monocytes from patients with chronic AD, psoriasis, and from normal (NL) donors were examined for morphologic features and DNA fragmentation characteristic of cells undergoing the process of apoptosis (programmed cell death). Cultures of AD monocytes exhibited a significantly lower incidence of apoptosis than did cultures of NL monocytes (45 vs 68%, P < 0.01), or psoriatic monocytes (45 vs 80%, P < 0.01). Furthermore, AD monocytes were unresponsive to both IL-1, an inhibitor of apoptosis, and IL-4, an enhancer of apoptosis, in comparison to cultured NL monocytes. Of note, GM-CSF in a concentration-dependent fashion, decreased the incidence of apoptosis in NL monocyte cultures and rendered them unresponsive to these cytokines. These findings suggested that GM-CSF may enhance monocyte survival in AD. In support of this hypothesis, AD monocyte cultures produced fivefold more GM-CSF than did cultures of NL monocytes or psoriatic monocytes (P < 0.05). Additionally, there was a significantly greater number of GM-CSF mRNA expressing cells detected by in situ hybridization in biopsies of lesions of chronic AD than in acute AD or NL skin (P < 0.05). Finally, NL monocytes incubated with supernatants obtained from monocytes of AD patients exhibited significant inhibition of apoptosis, an effect that could be ablated by a neutralizing antibody to GM-CSF. Taken together, these data strongly suggest that increased production of GM-CSF by cells from patients with AD inhibits monocyte apoptosis and may contribute to the chronicity of this inflammatory disease.

Acute Disease↗
PubMed1995

Adverse reactions to antibiotics: is the patient really allergic?

Many patients who believe themselves allergic to an antibiotic could in fact be given the suspected drug or a related agent safely. A systematic approach incorporating knowledge of immunopathogenic mechanisms, availability and limitations of diagnostic tests and therapeutic options will lead to successful management of these challenging patients.

Anti-Bacterial Agents↗
PubMed1994

Legionella and Pneumocystis pneumonias in asthmatic children on high doses of systemic steroids.

Asthma is increasingly treated as an inflammatory disease with inhaled and/or systemic corticosteroids. We report 3 cases of unusual pneumonias associated with high doses of oral steroids. Two patients contracted Legionella pneumonia and one patient contracted Pneumocystis carinii pneumonia. With increasing usage, it is important for physicians to be aware of the possible infectious complications of high dose steroids. This report highlights the risk of corticosteroid treatment in asthma in predisposing to opportunistic infections that have not heretofore been readily associated with asthma.

Asthma↗
PubMed1994

Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis.

The mechanisms involved in the initiation and maintenance of skin inflammation in atopic dermatitis (AD) are poorly understood. Recent data suggest that the pattern of cytokines expressed locally plays a critical role in modulating the nature of tissue inflammation. In this study, we used in situ hybridization to investigate the expression of interleukin 4 (IL-4), IL-5, and interferon-gamma (IFN-gamma) messenger RNA (mRNA) in skin biopsies from acute and chronic skin lesions of patients with AD. As compared with normal control skin or uninvolved skin of patients with AD, acute and chronic skin lesions had significantly greater numbers of cells that were positive for mRNA, IL-4 (P < 0.01), and IL-5 (P < 0.01), but not for IFN-gamma mRNA expressing cells. However, as compared with acute AD skin lesions, chronic AD skin lesions had significantly fewer IL-4 mRNA-expressing cells (P < 0.01), but significantly greater IL-5 mRNA (P < 0.01). T cells constituted the majority of IL-5-expressing cells in acute and chronic AD lesions. Chronic lesions also expressed significantly greater numbers of activated EG2+ eosinophils than acute lesions (P < 0.01). These data indicate that although acute and chronic AD lesions are associated with increased activation of IL-4 and IL-5 genes, initiation of acute skin inflammation in AD is associated with a predominance of IL-4 expression whereas maintenance of chronic inflammation is predominantly associated with increased IL-5 expression and eosinophil infiltration.

Acute Disease↗
PubMed1994

Conjugates or dsDNA linked to human gammaglobulin inhibit anti-dsDNA antibodies in vitro.

Previous studies have shown that both nucleosides and oligonucleotides linked to isologous gammaglobulin suppress anti-nucleic acid antibody production both in vivo and in vitro. The aim of this study was to determine whether one can make a DNA-human gammaglobulin (HGG) conjugate which can inhibit anti-double stranded DNA (dsDNA) antibodies obtained from a heterogeneous population of systemic lupus erythematosus (SLE) sera. To do so, we constructed conjugates of sonicated dsDNA fragments of 100-400 base pairs covalently linked to HGG with varying degrees of substitution of DNA:HGG. An ELISA inhibition assay was used to determine which conjugate best inhibits the binding of anti-dsDNA antibodies. Conjugate 2, prepared with monomeric HGG (150 kD) with a high degree of substitution (3.72 DNA:HGG) inhibited the binding of anti-dsDNA antibodies from 27 of 31 SLE sera. In addition, this conjugate inhibited the spontaneous formation of anti-dsDNA in vitro by cultured lymphoid cells from selected SLE patients. Together, this data suggests that a 'generic' tolerogen may provide an antigen specific therapy for SLE.

Antibodies, Antinuclear↗
PubMed1993

Treatment of steroid-dependent asthma with recombinant interferon-gamma.

We have recently reported that treatment of patients with severe atopic dermatitis with recombinant interferon-gamma (rIFN-gamma) resulted in clinical improvement as well as a reduction of circulating eosinophils. Since IgE-dependent late phase allergic reactions and eosinophilic infiltration are thought to play an important role in the pathogenesis of asthma, we conducted a two centre randomized double-blind placebo-controlled trial of rIFN-gamma in the treatment of steroid-dependent asthma. Patients were treated with daily subcutaneous injections of either 0.05 mg/m2 rIFN-gamma (n = 9) or placebo (n = 11) for 90 days. All patients completed the study without significant drug toxicity noted. Oral prednisone dose, forced expiratory volume in 1 second (FEV1), peak expiratory flow rates (PEFR) and circulating eosinophil counts were monitored throughout the trial. There was no significant difference between the two treatment groups in per cent reduction from baseline of daily prednisone (P = 0.51). There was also no significant difference between the two treatment groups in per cent change from baseline in FEV1 (P = 0.54) or in PEFR (P = 0.75). Total circulating eosinophil counts decreased by 31% in the rIFN-gamma group and increased by 8.5% in the placebo group (P = 0.09). We conclude that this treatment regimen was not effective in patients with steroid-dependent asthma.

Adolescent↗
PubMed1993

The effects of inhaled interferon gamma in normal human airways.

Recent studies suggest that cytokines such as recombinant interferon-gamma (rIFN-gamma) may play a role in the treatment of certain respiratory conditions associated with infection and inflammation. This study was designed to determine if rIFN-gamma could be delivered effectively in a group of normal human volunteers. The effectiveness of the inhaled delivery system was demonstrated by the recovery of free IFN-gamma in bronchoalveolar lavage (BAL) fluid and macrophage (M phi) expression of IP-10, an IFN-gamma-inducible molecule, after therapy but not at baseline. IL-1 beta, but not IL-8, gene transcripts also showed evidence for up-regulation after rIFN-gamma therapy. Compared with baseline, inhaled rIFN-gamma did not significantly alter clinical symptom scores, spirometry, morning peak expiratory flow rate (PEFR), or the response to methacholine. Of interest, the evening PEFR increased significantly (p = 0.02), from 568 +/- 36 L/min at baseline to 584 +/- 33 L/min after inhaled rIFN-gamma. Although there was no significant change in total white cell count in BAL fluid, the cellular composition did demonstrate a significant decrease in percentage of alveolar M phi (p = 0.02) and an increase in percentage of lymphocytes (p = 0.02) after rIFN-gamma. There were no histologic differences seen in bronchial biopsy specimens, and there was no evidence for up-regulation of ICAM-1 or HLA-DR expression after rIFN-gamma. We conclude that, in normal persons, rIFN-gamma can be effectively delivered by inhalation. Future trials using inhaled rIFN-gamma appear to be warranted for certain pulmonary diseases.

Administration, Inhalation↗
PubMed1991

Treatment with intravenously administered gamma globulin of chronic relapsing colitis induced by Clostridium difficile toxin.

We tested the hypothesis that children with chronic relapsing colitis induced by Clostridium difficile toxin have defective antibody responses to C. difficile toxins as a cause of their underlying illness. Six such children were tested for serum IgG and IgA antibody to C. difficile toxin A. These six children had lower IgG anti-toxin A levels than 24 healthy children (p = 0.026) and 18 healthy adults (p = 0.0008). Five patients treated with 400 mg intravenously administered gamma-globulin per kilogram every 3 weeks had significant increases in IgG (p = 0.01) but not IgA anti-toxin A (p = 0.406) levels, and all five had clinical resolution of their gastrointestinal symptoms as well as clearing of C. difficile cytotoxin B from their stools. These observations suggest that a deficiency of IgG anti-toxin A may predispose children to the development of chronic relapsing C. difficile-induced colitis. In such cases, intravenous gamma-globulin therapy may be effective in producing clinical remission.

Antibodies, Bacterial↗
PubMed1990

Recombinant gamma interferon in treatment of patients with atopic dermatitis and elevated IgE levels.

PURPOSE: Recombinant gamma interferon (rIFN-gamma) inhibits IgE synthesis in vitro by human peripheral blood mononuclear cells (PBMC). These data suggest a role for rIFN-gamma in the treatment of patients with severe atopic dermatitis (AD) and elevated IgE levels. The purpose of this study was to determine the effect of rIFN-gamma treatment on IgE production in patients with AD. PATIENTS AND METHODS: Twenty-two patients with chronic severe AD were treated with rIFN-gamma. In part I of the study, 14 patients were treated with daily subcutaneous injections at three successive dose levels (0.01 mg/m2, 0.05 mg/m2, and 0.1 mg/m2) for 5 days with 2 days off between each dose level. In part II, eight patients received rIFN-gamma at 0.05 mg/m2, daily for 6 weeks. One patient from part I and eight patients from part II of the study received three times per week maintenance thereby for up to 14 months. Prior to and at selected times during and after treatment, the clinical and immunologic status of the patients was assessed. RESULTS: In part I, spontaneous de novo IgE synthesis by PBMC was inhibited in 10 patients receiving rIFN-gamma at 0.01 mg/m2 (p = 0.038) and in nine at 0.1 mg/m2 (p = 0.066). There was no reduction of serum IgE levels at any of the three dose levels. Total clinical severity showed improvement at each dose level (p less than 0.04) with worsening 3 days after discontinuation of treatment. In part II, there was no significant inhibition of spontaneous IgE synthesis by PBMC nor was there any reduction of serum IgE. Nevertheless, there was a progressive and significant reduction (p less than 0.01) in total clinical severity over the 6 weeks of daily rIFN-gamma with a sustained improvement during maintenance therapy. CONCLUSION: The results of this pilot study suggest that rIFN-gamma may be efficacious in the treatment of AD and that further clinical trials are warranted.

Adolescent↗
PubMed1989

Role of the thymus in natural tolerance to an autologous protein antigen.

C5-deficient mice grafted with thymus from C5-sufficient donors and immunized with C5 failed to make humoral antibody to C5, suggesting that the transfer of thymus had induced tolerance. Irradiated C5-deficient hosts repopulated with lymphoid cells from thymectomized C5-deficient mice grafted with C5-sufficient thymus also failed to respond to immunization with C5, thus showing that the state of tolerance can be adoptively transferred. These results demonstrate that natural tolerance to self-protein antigen is "learned" in the thymus.

Animals↗