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Biomedical subjects

M A Kaliner

Publications and source records attributed to M A Kaliner.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effects of ipratropium bromide on bradykinin nasal provocation in chronic allergic rhinitis.

Bradykinin (BK) induces albumin exudation and glandular secretion in chronic allergic rhinitis subjects. Since bradykinin may stimulate nociceptive sensory nerves, neural reflex arcs could contribute to the secretion process. Six chronic allergic rhinitis subjects received 1000 nM bradykinin by unilateral nasal provocation using the method of Raphael et al. This dose induces optimal contralateral glandular secretion. Ipratropium bromide (80 micrograms) or saline were applied topically before the challenges. Total protein, albumin, glycoconjugate, and lysozyme were measured in lavage fluids. On the ipsilateral side, bradykinin induced significant total protein, glycoconjugate, and albumin secretion. None of these were affected by ipratropium. On the contralateral side, total protein and glycoconjugates were increased by bradykinin, while albumin and lysozyme were not significantly affected. Ipratropium bromide completely ablated total protein and glycoconjugate secretion on the contralateral side indicating that cholinergic reflexes mediated the glandular secretion. In chronic allergic rhinitis, bradykinin directly stimulated albumin secretion, but also stimulates nociceptive neuron--parasympathetic nerve reflexes to induce glandular secretion. The reflex loop was apparent on the contralateral side to the unilateral bradykinin challenge. This loop induced mucoglycoconjugate, but not serous cell, secretion in chronic allergic rhinitis subjects and can be inhibited by iptratropium bromide.

Adult↗
PubMed1994

Hydrogen peroxide effects on rat mast cell function.

Oxidant exposure of the airway mucosa may play a significant role in the pathophysiology of asthma and allergic rhinitis. Mast cells play an important role in asthma, and oxidant exposure has been reported to cause direct mast cell degranulation as well as augment immunoglobulin E (IgE)-mediated responses in vivo. H2O2 is an oxidant generated by inflammatory cells and by the interaction of ozone with lipids or aqueous solutions. In this study, the RBL-2H3 mast cell line was used to investigate the ability of H2O2 to induce mast cell responses as well as to effect mast cell responses to IgE and the calcium ionophore A23187. Although cytotoxicity of RBL-2H3 cells at the membrane level was not observed with any concentration of H2O2, DNA damage resulted from exposure to 0.2 and 2.0 mM H2O2, and cell proliferation was inhibited by 0.075-0.2 mM H2O2. RBL cell prostaglandin D2 generation was enhanced after 60- and 120-min exposure to 0.2-20 mM H2O2. Direct serotonin release required 120-min exposures to 2.0 mM and 60-min exposures to 20 mM H2O2. However, degranulation responses induced by either IgE or A23178 were diminished after exposure to 0.2-2.0 mM H2O2. Lesser amounts (0.005-0.02 mM) had no effect on mast cell function. In summary, H2O2-induced responses of RBL cells, as well as modification of responses to IgE and A23187, occurred only at high concentrations of H2O2, which also induced both intracellular damage and inhibition of cell proliferation. Concentrations of H2O2 more likely to be physiologically relevant had no effect on mast cell responses or cytotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Perennial rhinitis subjects have altered vascular, glandular, and neural responses to bradykinin nasal provocation.

BACKGROUND: Bradykinin (BK) is known to stimulate vascular permeability by direct actions on vascular B2 receptors, and may stimulate nociceptive sensory nerves that recruit parasympathetic reflexes which induces glandular secretion. Differences in these responses may occur in allergic rhinitis. METHODS: The effects of bradykinin (BK) on nasal secretion in vivo were studied by unilateral BK nasal challenge in 8 normal subjects and 6 subjects with severe perennial allergic rhinitis. BK (0, 100, 1,000 nmol) were applied to one nostril (ipsilateral, IL) and saline lavage fluids collected separately from the IL and contralateral (CL) nostrils for analysis of total protein, albumin, glycoconjugates, and lysozyme. RESULTS: In both groups, BK induced significant dose-dependent IL total protein and albumin secretion, but significantly more total protein and albumin were stimulated in normal than rhinitis subjects after 1,000 nmol BK. Glycoconjugate and lysozyme secretion was not significantly stimulated on either the IL or CL sides in normal subjects. However, in perennial allergic subjects, BK stimulated significant, dose-dependent glycoconjugate and lysozyme secretion on the IL side. Reflex effects were studied on the CL side. Normal subjects did not have significant CL glandular secretion. In contrast, rhinitis subjects secreted significantly higher amounts of total protein and glycoconjugate on the CL side after 1,000 nmol BK. There was no reflex-mediated albumin exudation in either group. CONCLUSIONS: These results indicate that in normal subjects BK stimulates predominantly vascular permeability, and that cholinergic reflexes do not significantly contribute to their BK-induced nasal secretion. In rhinitis subjects, BK again induced albumin exudation, but with less vascular permeability and greater glandular secretion than normal subjects on the challenged side. Only rhinitis subjects demonstrated significant contralateral reflex-mediated glandular secretion, and this response required the highest dose of BK. This suggests that BK is more adept at directly inducing vascular effects than glandular secretion of nociceptive nerve-parasympathetic reflexes. Alterations in BK-induced vascular permeability, glandular secretion, and neural reflexes occur in patients with severe perennial allergic rhinitis, changes suggestive of 'nasal hyperresponsiveness' to BK.

Adult↗
PubMed1994

Angiotensin-converting enzyme in the human nasal mucosa.

Angiotensin-converting enzyme (ACE; EC 3.4.15.1) may participate in respiratory inflammatory diseases by regulating levels of inflammatory peptides such as bradykinin. The presence of ACE in the human nasal mucosa and in nasal secretions was determined by immunohistochemistry, measures of enzyme activity, and immunoblot. ACE activity was significantly more abundant in the membrane-rich fraction than in the soluble cytosolic fraction of nasal mucosal extracts (74.18 +/- 24.50 versus 3.99 +/- 1.83 pmol/min/mg protein, respectively, P < 0.01 by an enkephalin degradation assay; 89.16 +/- 16.17 versus 2.30 +/- 0.89 mU/mg protein, P < 0.01 by colorimetric assessment of Bz-Gly-Gly-Gly degradation). Topical application of histamine stimulated secretion of ACE activity into nasal lavage fluid (2.90 +/- 0.88 versus 1.53 +/- 0.45 U/liter after saline provocation, P < 0.05 by Bz-Gly-Gly-Gly assay). Allergen challenge also induced nasal secretion of ACE. In both histamine and allergen challenges, ACE release correlated closely with that of the vascular proteins IgG and albumin. Methacholine, a stimulant of glandular secretions, failed to augment ACE levels above baseline. ACE-immunoreactive material was localized by the immunogold technique with silver enhancement to the glycocalyx, between epithelial cells, and to interstitial, extracellular sites in the superficial lamina propria, with the highest intensity of staining immediately beneath the basement membrane. Some ACE was detectable in the mucus material of gland and duct lumens but not in gland cells themselves. Endothelial cells and some interstitial mononuclear cells also stained for ACE. ACE was identified by immunoblotting as a 150 kD band on SDS-PAGE.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Immunological localization of neuropeptide-degrading enzymes in the nasal mucosa.

Neutral endopeptidase (NEP, EC 3.4.24.11), angiotensin-converting enzyme (ACE, EC 3.4.15.1) and carboxypeptidase N (CPN, EC 3.4.17.3) are potentially important enzymes which regulate the degradation of neuropeptides, such as bradykinin (BK) and substance P (SP), in the respiratory mucosa. Some neuropeptides are also degraded by these enzymes in vitro and in vivo. We investigated the localization of these enzymes in the human nasal mucosa by an indirect immunohistochemical technique (immunogold silver staining). NEP-immunoreactive areas were present in the epithelium, the serous cells of the submucosal glands, and the endothelial cells of small vessels. The epithelium and the serous cells were the predominant areas of NEP immunoreactivity in the nasal mucosa. ACE-immunoreactive areas were seen in the outer layer of the epithelium, the endothelial cells of vessels, and widely distributed in the superficial lamina propria. The endothelial cells of the vessels showed maximum positive intensity to ACE. CPN-immunoreactive areas were observed in the epithelium, the endothelium of vessels and the superficial lamina propria, except for the gland cells. The superficial lamina propria exhibited maximum immunoreactivity for CPN. We observed that the enzymes were widely distributed in the nasal mucosa. The epithelium, including the epithelial cells and glycocalyx, contains all three enzymes. These enzymes play an important role in the mucosal immunity of the respiratory mucosa by degrading active neuropeptides. These results show that NEP secretion is regulated by a glandular, cholinergic control. On the other hand, ACE and CPN secretion are regulated by vascular permeability.

Humans↗
PubMed1993

Analysis of nasal secretions during experimental rhinovirus upper respiratory infections.

BACKGROUND: To determine the underlying mechanisms for rhinovirus-induced nasal secretions, nasal lavage fluids were analyzed during experimental rhinovirus infections. METHODS: Twenty patients with allergic rhinitis and 18 nonallergic control subjects were inoculated with rhinovirus type 39. Nasal lavage was performed before and on days 2 through 7 after viral inoculation, and the lavage fluids were assayed for proteins and mast cell mediators. RESULTS: The secretion of total protein and both plasma proteins (albumin and IgG) and glandular proteins (lactoferrin, lysozyme, and secretory IgA) increased after rhinovirus inoculation. Analysis of the specific protein constituents revealed that nasal secretions during the initial response to the rhinovirus infection were predominantly due to increased vascular permeability. Allergic subjects tended to have fewer symptoms and more vascular permeability than control subjects, and increased histamine secretion after rhinovirus inoculation was more frequently seen in the allergy group. CONCLUSION: Nasal secretions found early in the course of a viral upper respiratory infection are due to increased vascular permeability, whereas glandular secretions predominate later in the infection.

Adolescent↗
PubMed1993

Substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide increase in nasal secretions after allergen challenge in atopic patients.

BACKGROUND: There is suggestive evidence that neuropeptides participate in allergic reactions. Substance P (SP) and calcitonin gene-related peptide (CGRP) are released by sensory nerves, whereas vasoactive intestinal peptide (VIP) is released mainly by parasympathetic nerves. Both sets of nerves are thought to be stimulated by allergic inflammation. The aim of this study was to assess nasal secretions to determine whether SP, CGRP, and VIP were increased after allergen challenge. METHODS: Eight patients with allergic rhinitis were challenged nasally with 1 mg histamine or increasing doses of allergen. Nasal lavages were collected into a cocktail of protease inhibitors in order to restrict neuropeptide degradation. Radioimmunoassay for SP, CGRP, and VIP were performed on each sample. RESULTS: All patients had immediate clinical reactions to both histamine and allergen challenges, and seven patients experienced a later allergic reaction. After histamine challenge, SP and CGRP did not increase significantly above baseline in the nasal lavages, whereas VIP did (p < 0.02). In contrast, SP, CGRP, and VIP all significantly increased immediately after allergen challenge and returned to baseline within 2 hours. At the clinical peak of the late allergic reaction, SP, but not CGRP or VIP, was increased slightly but significantly (p < 0.01). CONCLUSIONS: Thus SP, CGRP, and VIP are found in nasal secretions after allergen challenge, which confirms that neuropeptides are released in human beings during allergic reactions. The selective stimulation of VIP secretion by histamine challenge suggests that histamine-induced cholinergic reflexes induce the release of VIP. These data support the suggestion that neuropeptides may be partly responsible for some of the nasal symptoms of allergy.

Adult↗
PubMed1993

How the current understanding of the pathophysiology of asthma influences our approach to therapy.

Asthma can no longer be equated with bronchospasm; instead, we know now that this disease is due to combinations of mucosal edema and inflammation, increased secretions, and muscle contraction. The appreciation of the contribution of these various causes of airflow obstruction and the role that inflammation plays in asthma dictates that we approach treatment using two parallel modalities: (1) symptomatic drugs that act to relieve the airflow obstruction but have no effects on the underlying causes of the disease (e.g., bronchodilators such as beta-adrenergic agonists, theophylline, and anticholinergic compounds) and (2) specific treatment aimed at preventing or reversing the underlying causes responsible for the disease. Four specific treatments are available today: allergen avoidance, immunotherapy, cromolyn sodium, and inhaled corticosteroids. Management of asthma in the 1990s requires that all patients receive specific treatments intended to reduce the disease processes and that symptomatic treatment be used only as necessary.

Allergens↗
PubMed1993

Estimation of nasal epithelial lining fluid using urea as a marker.

BACKGROUND: The luminal surface of respiratory mucous membranes is lined with an epithelial lining fluid (ELF) layer. Previous attempts to determine ELF volumes in airways have used dyes or freely diffusible molecules such as urea, yet have not led to a universally accepted method. The nasal mucous membrane provides an accessible area to examine whether urea is an appropriate marker of respiratory ELF volume. METHODS AND RESULTS: Collection of undiluted nasal secretions after either glandular stimulation or induction of vascular permeability confirmed that plasma urea and nasal urea concentrations are equivalent. Baseline ELF volume was calculated as 800 microliters/nostril. The calculated molar concentrations of urea in ELF did not vary with either methacholine or histamine challenge. CONCLUSIONS: These data indicate the plasma, interstitial, glandular, and ELF urea concentrations are equivalent and, therefore, that urea is a useful marker of ELF volume in the nasal mucosa.

Adult↗
PubMed1993

Quantification of resident inflammatory cells in the human nasal mucosa.

BACKGROUND: To define the normal resident inflammatory cell population in the nasal mucosa, surgical specimens of human nasal turbinates were immunohistologically stained for various cell markers. METHODS: Freeze-dried paraffin-embedded sections were stained for lymphocyte cell-surface markers, and Carnoy's fixed sections were stained for mast cells and immunoglobulins. The numbers of stained cells were microscopically counted. RESULTS: T cells (CD3+ cells) were abundant in the lamina propria, and the number of CD4+ cells and CD8+ cells accounted for two thirds and one third of CD3+ cell number, respectively. Cells that stained for the alpha-chain of the interleukin-2 receptor (activated cells, CD25+) were limited and accounted for only 0.6% of CD3+ cell number. B cells (CD22+ cells) and monocytes and macrophages (CD14+ cells) were observed less frequently than T cells. Many immunoglobulin-producing cells were found in close proximity to the submucosal glands, and those cells were predominantly IgA+. Mast cells were widely distributed in the nasal mucosa, and about one third of these cells were stained for IgE molecules. Nonmast cells bearing IgE were rarely observed. CONCLUSION: Thus the dominant cell in the nasal mucosa is a CD3+, CD4+, CD25-lymphocyte.

Animals↗
PubMed1993

Nasal secretions in response to acetylsalicylic acid.

BACKGROUND: Acetylsalicylic acid (ASA) induces rhinorrhea in a subset of patients with asthma or chronic rhinosinusitis or both and nasal polyps. The underlying mechanism of the reaction is obscure. METHODS: To assess the nasal response to ASA challenge, four groups of patients were challenged orally with ASA: group A (10 ASA-sensitive patients); group B (nine patients with nasal polyps and histories of tolerance to ASA); group C (nine ASA-tolerant patients with chronic allergic rhinitis); and group D (eight healthy nonatopic subjects). RESULTS: Nasal lavages obtained before and after ASA challenge were assayed for proteins (total protein, lactoferrin, lysozyme, albumin) and inflammatory mediators (histamine, prostaglandin D2, and leukotriene C4). ASA challenges induced severe rhinorrhea and congestion and significant increases in mean concentrations of all measured nasal proteins in group A. Histamine and prostaglandin D2 rose, but not significantly. In the two control groups with chronic rhinitis, ASA induced increases in the concentration of proteins and histamine. Leukotriene C4 concentrations were significantly elevated in nasal lavages after ASA challenge in groups A and C only. In group D no symptoms or changes in nasal proteins were observed after aspirin challenge. CONCLUSIONS: These observations suggest that production of lipoxygenase products of arachidonate may induce glandular secretions that may participate in the clinical changes associated with ASA sensitivity.

Adult↗
PubMed1993

Identification of neutral endopeptidase mRNA in human nasal mucosa.

Neutral endopeptidase (NEP) may regulate peptide-induced inflammation in the upper respiratory tract. NEP mRNA was detected by Northern blotting in poly(A)+ mRNA prepared from human turbinates. NEP mRNA bands were detected at 3.9 and 1.8 kb. In situ hybridization identified NEP mRNA in epithelial cells, serous cells of submucosal glands, and vessel walls. The vacuoles of goblet and mucous cells were not stained, but it is likely that the cytoplasm of these cells contained some NEP mRNA. Radioactive in situ hybridization with 35S-UTP appeared to be more sensitive than nonradioactive in situ hybridization with biotin-UTP and immunogold detection. The NEP mRNA-containing cells identified by in situ hybridization were the same as those identified by immunohistochemistry to contain immunoreactive NEP. These NEP-containing cells have been previously shown to possess peptide receptors. This is consistent with the hypothesis that NEP on cells bearing peptide receptors may regulate neuropeptide-induced inflammation in human nasal mucosa.

Biotin↗
PubMed1993

Effects of capsaicin desensitization on nasal mucosal secretion in guinea pigs in vivo.

Capsaicin-sensitive mechanisms may contribute to histamine's effects on guinea pig nasal mucosal secretion in vivo. Histamine nasal provocations were performed, secretions were collected, and the following variables were measured: total protein (marker of all secretory processes), alkaline phosphatase (marker of glandular secretion), and albumin (marker of vascular permeability, epithelial permeability, and glandular transport). By challenging only one nostril (ipsilateral), the contralateral responses to these challenges were examined and the nature of "nasonasal" reflexes was determined. Histamine increased albumin and alkaline phosphatase concentrations in lavage fluid on the ipsilateral and contralateral sides. The alkaline phosphatase secretion was reduced by atropine. Capsaicin induced dose-dependent albumin exudation. To determine the roles of capsaicin-sensitive sensory nerves, one nostril was desensitized by topical application of capsaicin to one nostril in increasing doses daily for 5 wk. This led to 1) ablation of all secretory responses to capsaicin, 2) ablation of histamine-induced alkaline phosphatase and total protein secretion, 3) blunted histamine-induced albumin exudation on the desensitized side, and 4) ablation of histamine-induced contralateral reflex-mediated protein secretion. These results indicate that capsaicin stimulates vascular responses, probably by stimulating nociceptive nerve axon responses. Histamine induces vascular responses and albumin exudation by both capsaicin-sensitive sensory neuron axon responses and direct effects on vessels. Histamine stimulates glandular secretion through a capsaicin-sensitive afferent/cholinergic efferent reflex.

Albumins↗
PubMed1993

Distribution of secretory leukoprotease inhibitor in the human nasal airway.

Secretory leukoprotease inhibitor (SLPI) is a secreted glandular protein thought to regulate elastase activity and, more recently, to inhibit both mast cell chymase activity and histamine release from mast cells. To begin to examine the possible role of SLPI in humans, we determined the distribution of SLPI in the human nasal mucosa and quantitated the functional activity of SLPI in nasal lavage fluid. Immunochemical staining of the nasal mucosa revealed intense, selective immunoreactivity in the serous cells of the submucosal glands. The level of SLPI in nasal secretions was measured by enzyme immunoassay. In control subjects (n = 8), the level of SLPI in nasal lavage fluid (NLF) after saline challenge (baseline level) was 2.5 +/- 0.5 micrograms/ml, accounting for 3.3 +/- 0.6% of total protein in nasal secretions. After methacholine (MCh) and histamine (HIST) challenge, the level of SLPI increased to 7.0 +/- 1.4 and 6.1 +/- 1.6 micrograms/ml, respectively (both p < 0.05). In atopic patients (n = 8), the level of SLPI after MCh and HIST challenge increased from a baseline level of 7.6 +/- 2.0 micrograms/ml to 22.1 +/- 6.4 and 25.2 +/- 10.5 micrograms/ml, respectively. After allergen challenge, the concentration of SLPI increased significantly in atopic patients, whereas there was no increase in the level of SLPI in control subjects. Western blot analysis of MCh-induced nasal secretions revealed a single band with a molecular weight of 12 kD, the same as recombinant SLPI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Nasal secretion of the ozone scavenger uric acid.

Uric acid, an important scavenger of ozone, has been identified as the major low molecular weight antioxidant in baseline and cholinergically induced nasal secretions. The purpose of this study was to determine the specific tissue source of uric acid in airway secretions. The secretion of uric acid is increased by cholinergic stimulation and correlates closely with the secretion of lactoferrin (a nasal glandular protein), suggesting that submucosal glands are involved. Indeed, nasal turbinate tissue was found to contain uric acid. However, careful analysis of nasal turbinate tissue failed to reveal the presence of xanthine oxidase, the enzyme responsible for uric acid synthesis. These data suggest that uric acid might be taken up secondarily by glands from plasma. This possibility was strengthened by the observation that lowering the plasma urate level with probenecid concomitantly lowered urate secretion. These findings are consistent with the hypotheses that the principal source of uric acid in nasal secretions is plasma and that uric acid is taken up, concentrated, and secreted by nasal glands.

Albumins↗