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Biomedical subjects

M Frieri

Publications and source records attributed to M Frieri.

At least 37 records · Page 2Linked to original sources

Preliminary investigation on humoral and cellular immune responses to selected food proteins in patients with Crohn's disease.

Crohn's disease is a chronic inflammatory disorder for which an immunologic etiology has been proposed. Food hypersensitivity may contribute to part of the pathogenesis of this disorder. In preliminary studies, we evaluated 11 Crohn's patients by history, skin testing (ST), total and specific(s) IgE and sIgE/sIgG4 levels to five food proteins [egg (E), milk (M), wheat (W), soy (S), and corn (C)] using a sensitive enzyme monoclonal antibody assay. Skin testing was also performed using grass and mold allergens. Lymphocyte concanavalin (Con A) mitogenic and antigenic responses to food proteins were also determined by tritiated thymidine incorporation. Mean sIgG4 values for four food proteins are listed below: (Table: see text). No patient reacted with elevated sIgE or sIgG4 to corn. All patients had low to negative sIgE levels to all foods and only three had increased total IgE. Three of eight were history and ST positive to M, E, and W. Six of eight had at least one positive ST to M, E, W, and S. All patients had negative sIgG4 to tested inhalants and two had elevated sIgE to grass pollen. Although mean lymphocyte Con A mitogenesis was significantly decreased in eight patients compared with controls (P less than .05), an increased food stimulatory response to milk protein was observed (P less than .05). Perhaps, decreased sIgE and cell-mediated mitogenic responsiveness may lead to an enhanced humoral IgG response. The increased sIgG4 humoral response to egg protein and cellular sensitivity to milk protein may indicate mucosal antigenic stimulation or leakage in patients with Crohn's disease in spite of negative sIgE levels.

Adolescent↗

Analysis of plasma histamine levels in patients with mast cell disorders.

PURPOSE: The use of plasma histamine determinations as a screening tool to distinguish patients with recurrent unexplained anaphylaxis, flushing, or both from those with mastocytosis has never been evaluated. This retrospective study was designed to determine if plasma histamine levels can be used as a screening test. PATIENTS AND METHODS: Values of plasma histamine levels, measured using a sensitive radioenzymatic assay, from 41 patients with mastocytosis, 26 patients with recurrent unexplained anaphylaxis, and 76 normal subjects were statistically analyzed to determine diagnostic usefulness and accuracy. Patients with mastocytosis were subdivided into four smaller groups on the basis of clinical and histopathologic findings: (1) isolated urticaria pigmentosa, (2) indolent systemic mastocytosis, (3) mastocytosis with dysmyelopoiesis, and (4) lymphadenopathic mastocytosis with eosinophilia. RESULTS: The distribution of plasma histamine values among patients with unexplained anaphylaxis strongly resembled that among the normal subjects (p greater than 0.50, Smirnov test), whereas patients with mastocytosis tended to show moderate to marked elevations above the upper limit of normal (617 pg/mL). The geometric mean plasma histamine levels in mastocytosis subgroups 2, 3, and 4 were found to be quite similar (1,085, 1,976, and 1,433 pg/mL; p greater than 0.50, F-test); moreover, each mean level was significantly greater than those of the normal subjects and of patients with unexplained anaphylaxis (p less than 0.01, Scheffé multiple comparison test). Analysis of the 27 sets of plasma histamine values collected on patients with indolent systemic mastocytosis revealed that the earliest value observed fell below 617 pg/mL in eight patients (30%). A similar analysis applied to the two earlier values indicated that both values would fall below 617 pg/mL in 9% of the patients. Data in four patients with mastocytosis demonstrated a diurnal variation in plasma histamine, with the highest values observed in the early morning (approximately 2:00 A.M.) and the lowest values in the afternoon (approximately 2:00 P.M.). CONCLUSIONS: We conclude that, on average, patients with mastocytosis have elevated plasma histamine levels, whereas patients with unexplained anaphylaxis have plasma histamine levels within the normal range during asymptomatic periods; that plasma histamine levels in patients with mastocytosis exhibit a diurnal variation; and that plasma histamine determinations alone are not useful to screen patients for mastocytosis.

Adult↗

Comparison of the therapeutic efficacy of cromolyn sodium with that of combined chlorpheniramine and cimetidine in systemic mastocytosis. Results of a double-blind clinical trial.

Both antihistamines and cromolyn sodium have been suggested for the treatment of systemic mastocytosis. To determine if one drug regimen was superior to the other, eight patients with systemic mastocytosis were admitted to a double-blind, double-crossover study in which the therapeutic efficacy of cromolyn sodium was compared with that of a combination of chlorpheniramine and cimetidine. Response to therapy was assessed by the patients using symptom scores and by the attending physicians during clinic examinations in addition to sequential plasma and urinary histamine determinations. In the six patients who completed the trial, the patient symptom scores and the physician evaluations indicated that there was no advantage of one drug regimen over the other. Plasma and urinary histamine levels, markedly elevated in most of the patients, were not consistently altered by administration of either cromolyn sodium or the combined antihistamines. Thus, cromolyn sodium and the combined antihistamines were indistinguishable when used for the symptomatic treatment of systemic mastocytosis, and neither regimen altered systemic histamine levels.

Adult↗

The presence of immunoglobulin D in endocrine disorders and diseases of immunoregulation, including the acquired immunodeficiency syndrome.

Immunoglobulin D (IgD) was determined by double diffusion in the serum from 26 patients with endocrine disorders and diseases of immune imbalance along with controls. IgD was detected in the serum of nine patients that included two with primary parathyroidism, one with insulin-resistant diabetes, four with immunodeficiencies, and two with Hodgkin's disease. IgD was absent in the serum of seven patients with the same diagnoses after treatment. IgD was present in the serum of the majority of acquired immune deficiency syndrome patients (in eight of ten cases). The presence of IgD in the serum of these patients suggests that it plays a role in receptor-mediated events.

Acquired Immunodeficiency Syndrome↗

Patterns of skeletal scintigraphy and their relationship to plasma and urinary histamine levels in systemic mastocytosis.

Scintigraphic findings in ten cases of systemic mastocytosis are described. Four radionuclide bone patterns were noted: normal, unifocal, multifocal, and diffuse. Compared with radiographic surveys, bone images were better able to show the widespread skeletal involvement in patients with diffuse disease, and to detect a greater number of focal lesions. Serum calcium, phosphorus, and bone-derived alkaline phosphatase, as well as urinary calcium, phosphorus, and hydroxyproline levels, were usually within normal limits even when the bone scintigrams were clearly abnormal. Plasma and urinary histamine levels were highest in patients whose bone images detected widespread skeletal involvement. In systemic mastocytosis, not only does scintigraphy document active bone disease more effectively than laboratory studies of bone metabolism and radiographs of bone, but it also appears to reflect the general severity of the disease process.

Adult↗

Analysis of the effect of mast cell granules on lymphocyte blastogenesis in the absence and presence of mitogens: identification of heparin as a granule-associated suppressor factor.

To explore the effect of mast cell products on lymphocytes, the blastogenic response of lymphocytes to mast cell granules in the absence and presence of mitogens was determined. Membrane-free granules (MFG) and dialyzed, washed histamine-free granules (DWG) in the absence of mitogens did not induce significant blastogenesis in peripheral blood mononuclear cells (PBMC) before or after partial depletion of macrophages (5 to 10%). In contrast, concanavalin A- (Con A) (5 micrograms/ml), pokeweed mitogen- (PWM) (1/200 dilution), tetanus toxoid-, and Candida-, but not phytohemagglutinin-, induced blastogenesis in macrophage-depleted PBMC were inhibited by both MFG and DWG. Fractionation of solubilized DWG by anion exchange Dowex chromatography into protein- and heparin-rich fractions revealed the inhibitory activity resided in the heparin-containing fractions. The ability of commercial porcine heparin glycosaminoglycan as well as native rat heparin proteoglycan to inhibit lectin-induced blastogenesis in a dose-response fashion confirmed the previous data with the use of fractionated DWG. Histamine and commercial porcine heparin glycosaminoglycan were not additive in inhibiting lectin-induced lymphocyte blastogenesis. The inhibitory effect of heparin on Con A-induced blastogenesis could be overcome by adding excess Con A to macrophage-depleted mononuclear cell preparations and could be reproduced by using over-sulfated chondroitin 6-sulfate. This is the first examination of the ability of mast cell granules to influence lymphocyte function and the first demonstration of the ability of native heparin proteoglycan to modulate lymphocyte blastogenesis.

Animals↗

Nitric oxide production and apoptosis by GP120.

Nitric oxide (NO) is increased by gp120 in astrocytes and in monocyte-derived macrophages. Of the gp120 fragments (F1: amino acid 254-274, F2: amino acid 315-329, F3: amino acid 421-438), F1 has been shown to increase NO in astrocytes and gp120 also primes CD4+ T cells for apoptosis. Peripheral blood mononuclear cells (PBMCs) at 10(6)/ml (N = 10) were incubated at 24 and 72 hours in RPMI, 10% CO2 with low doses (100 nM) gp120 and high doses (400 nM) of the smaller fragments. Supernatants were collected and assayed for the relative contribution of gp120 and its fragments on NO production at both time points. Apoptosis was detected by in situ hybridization with and without 1 microgram/ml LPS as superantigen at 72 hours. The major contribution to apoptosis and NO production was from F1. At 24 hours F1 had a 1.9-fold increase from control, whereas F2 and F3 had 1.25- and 1.35-fold increases. At 72 hours both F1 and F2 had a 1.5-fold increase and F3 had a 1.33 increase. Thus, F1 contributed significantly to NO production at 24 hours. Both F1 and F2 had significant contributions to NO production at 72 hours. F1 had the most contribution to apoptosis both with and without lipopolysaccharide (LPS). These findings may contribute to further understanding the mechanism of HIV-induced apoptosis.

Apoptosis↗

Treatment update for allergic rhinitis.

This manuscript addresses the pathogenesis of allergic rhinitis, use of nasal provocation as a method to assess inflammatory mediators and the role of cytokines, and topical glucocorticosteroids. Immunologic changes of allergen immunotherapy, pharmacotherapy with a focus on non-sedating, and topical antihistamines are discussed. The antiinflammatory potential of fexofenadine, azelastine, and newer therapeutic modalities with anti-IgE are addressed.

Anti-Inflammatory Agents↗

Clinical and basic science research on allergic rhinitis and asthma from Nassau University Medical Center.

Allergic inflammatory disorders involved with the upper and lower airway are related to allergic rhinitis and asthma. The role of nasal provocation and airway epithelium as models to evaluate allergic rhinitis and asthma are illustrated in studies from our research center. New concepts related to the anti-inflammatory effect of nasal steroids, antihistamines, isomers of beta 2 agonists, cromolyn sodium, and enoxaparin sodium related to airway remodeling are addressed in this article.

Adrenal Cortex Hormones↗

Late phase response during nasal challenge: effect of astemizole on leukotriene B4 levels.

Nasal provocation (NP) in allergic rhinitis patients can elicit a late phase inflammatory response in which interleukins (IL), leukotrienes (LT), and neutrophils have been implicated. Certain antihistamines have been shown to have anti-inflammatory properties. The objective was to determine whether astemizole at 10 mgs/day has any anti-inflammatory characteristics. We clinically evaluated 20 patients with allergic rhinitis and measured nasal IL-8 and LTB4 during NP with increasing doses of grass and ragweed antigen in a double-blind placebo-controlled fashion after a 4-week course of treatment. Clinical symptom scores for sneezing, pruritus, and rhinorrhea were evaluated. Nasal fluid was examined by ELISA and RIA for IL-8 and LTB4 levels along with neutrophil assessment before NP and at 3, 6, and 8 hours. Symptom scores for nasal sneezing, pruritus, rhinorrhea, and nasal LTB4 levels at 6 and 8 hours and IL-8 at 3, 6, and 8 hours were generally lower in astemizole-treated patients compared to those on placebo. Nasal IL-8 levels corresponded to LTB4 levels at diluent and at 6 hours in the placebo group (P = 0.01). The percentage of neutrophils correlated with LTB4 levels at baseline, coefficient = 0.76, P = 0.02 and at 6 hours, coefficient = 0.62, P = 0.035 in the placebo group. This study is the first to demonstrate an effect of astemizole during NP on IL-8 and LTB4 levels with a significant correlation of neutrophil numbers in untreated patients during the nasal late phase response.

Adult↗

Nitric oxide in allergic rhinitis and asthma.

Nitric oxide is a free radical molecule that can have both homeostatic and proinflammatory roles in the nasal mucosa, sinuses and airway. We have demonstrated elevated levels of nitric oxide in either nasal fluid, serum and spontaneous, or antigen-stimulated mononuclear cells from patients with allergic rhinitis, sinusitis, and asthma. We also showed that various therapeutic agents such as glucocorticoids, theophylline and macrolides can decrease nitric oxide levels in these patients. Thus determination of nasal, serum, mononuclear cell or airway production of nitric oxide may be an important biomarker of inflammation for monitoring newer anti-inflammatory therapy.

Asthma↗

New frontiers in immunotherapy.

Traditional allergen immunotherapy has been shown to be effective in numerous studies and can affect the natural course of allergic diseases. However, knowledge gained from cytokine regulation and vaccines as immuno-modifiers have shed new insight into other forms of immunotherapy. Novel routes, the role of allergen vaccines, and humanized anti-IgE and DNA-based immunization are the new frontiers of immunotherapy. This review considers both humoral and cellular response, mechanisms, and investigations at our center and the role of anti-IgE-based immunization as other strategies.

Antibody Formation↗