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S Sur

Publications and source records attributed to S Sur.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cytokine production at the site of disease in chronic eosinophilic pneumonitis.

Chronic eosinophilic pneumonitis (CEP) is characterized by longstanding respiratory symptoms accompanied by a massive pulmonary eosinophil infiltration. We hypothesized that cytokine(s) produced in the disease sites are implicated in the pathophysiology of CEP. We studied peripheral blood and bronchoalveolar lavage fluids (BALF) obtained from two lung segments of a patient with CEP. Seventy times more eosinophils were found in the BALF from an involved lung segment (showing patchy opacification on a chest roentgenogram) than from an uninvolved segment. The eosinophil-active cytokines interleukin-5 (IL-5), IL-6, and IL-10 were strikingly elevated in the BALF from the involved lung segment, whereas no or minimal levels of these cytokines were detectable in the BALF from the uninvolved segment or serum, respectively. Leukocytes in the involved lung segment, but not those in peripheral blood, expressed messenger ribonucleic acid (mRNA) for IL-5, IL-6, and IL-10. In contrast, IL-2, IL-3, IL-4, interferon-gamma (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha) were not detected in any sample. These findings suggest that increased production of several cytokines, such as IL-5, IL-6, and IL-10, in the involved lung segment, but not in the uninvolved lung segment or peripheral blood, is a critical pathophysiologic feature of CEP.

Adult↗
PubMed1995

Eosinophil major basic protein induces degranulation and IL-8 production by human eosinophils.

Eosinophil granule proteins, such as major basic protein (MBP), eosinophil peroxidase (EPO), and eosinophil cationic protein (ECP), possess a wide range of biologic activities including the ability to activate other cells, such as basophils, neutrophils, and platelets. Here we have analyzed the effects of these proteins on eosinophils themselves. MBP and EPO, at concentrations as low as 0.1 micrograms/ml, induced eosinophil degranulation as measured by release of eosinophil-derived neurotoxin (EDN); in contrast, ECP, at 1 micrograms/ml, was inactive. MBP (10 micrograms/ml) and EPO (0.1 micrograms/ml) induced EDN release comparable with one of the strongest agonists for eosinophils, secretory IgA. Pretreatment of cells with dibutyryl cAMP or cytochalasin B completely abolished the EDN release induced by MBP and EPO, suggesting that the effects of MBP and EPO are not due to cytotoxic lysis of the cells. Degranulation induced by MBP was only partially dependent on calcium, and no elevation of intracellular Ca2+ concentration ([Ca2+]i) was observed in eosinophils stimulated with MBP. MBP stimulated the production, up to eightfold, of IL-8 by eosinophils in a dose-dependent manner. The MBP-stimulated expression of IL-8 mRNA by eosinophils was confirmed by reverse transcription-PCR. The MBP-stimulated production of IL-8 was inhibited by actinomycin D, but not by cyclosporin A. Furthermore, MBP and calcium ionophore ionomycin synergistically induced production of leukotriene C4 from eosinophils. Thus, MBP and EPO may act as autocrine mediators in the pathogenesis of eosinophil-associated diseases, such as bronchial asthma.

Base Sequence↗
PubMed1995

Eosinophilic inflammation is associated with elevation of interleukin-5 in the airways of patients with spontaneous symptomatic asthma.

In vitro and in vivo studies have shown an important role for interleukin-5 (IL-5) in regulating eosinophil proliferation, survival, and effector function. Because eosinophilic inflammation is an important component of symptomatic episodes of asthma, we have investigated whether increased levels of IL-5 protein are present in bronchoalveolar lavage (BAL) fluid of patients with spontaneously symptomatic asthma (FEV1, l61% predicted; FEF25%-75%, 30% predicted) compared with patients with asymptomatic asthma (FEV1, 88% predicted; FEF25%-l75%, 76% predicted). The percent of BAL eosinophils (10.5% vs 0.6]) (p = 0.0001) and eosinophil-derived neurotoxin (386.0 ng/ml vs 6.3 ng/ml) (p = 0.0001) was greater in BAL fluids derived from patients with symptomatic asthma compared with patients with asymptomatic asthma. Levels of IL-5 measured with an immunoradiometric assay were significantly higher in patients with symptomatic asthma (n = 26) compared with those with asymptomatic asthma (n = 18) (274 pg/ml vs < pg/ml) (p = 0.02). The increased IL-5 levels were noted in a subset of patients with symptomatic asthma with BAL absolute eosinophil counts greater than 10(6) (IL-5, 664 pg/ml; n = 10) as opposed to patients with symptomatic asthma with BAL eosinophil counts less than 10(6) (IL-5, < 13 pg/ml; n = 16) (p = 0.005). This study suggests that IL-5 is not only induced in experimental models of allergen-induced asthma but can also be detected as asthma progresses from the asymptomatic to the clinically symptomatic state in subjects with significant BAL eosinophilia.

Adolescent↗
PubMed1995

Allergen challenge in asthma: association of eosinophils and lymphocytes with interleukin-5.

To test whether eosinophil recruitment after pulmonary allergen challenge is associated with interleukin (IL)-5 in patients with asthma, we performed segmental bronchoprovocation (SBP) with saline, and with low and high dosages of ragweed extract in six patients with allergic asthma. Bronchoalveolar lavage (BAL) of the challenged segments was performed 5 min after challenge (immediate BAL fluid) and repeated 24 h later (late BAL fluid). Allergen challenge resulted in recruitment of eosinophils, and increased levels of eosinophil-active cytokines. A bioassay showed the predominant eosinophil-active cytokine in the late BAL fluids to be IL-5. Analysis of the late BAL fluids revealed that IL-5 levels correlated with the numbers of eosinophils and lymphocytes. This study provides evidence that IL-5 is a critical cytokine associated with eosinophil and lymphocyte recruitment into the airways of patients with asthma following exposure to allergen.

Adolescent↗
PubMed1995

Chronic eosinophilic pneumonia and idiopathic bronchiolitis obliterans organizing pneumonia: comparison of eosinophil number and degranulation by immunofluorescence staining for eosinophil-derived major basic protein.

OBJECTIVE: To undertake additional assessment of the possible overlap between bronchiolitis obliterans organizing pneumonia (BOOP) and chronic eosinophilic pneumonia (CEP). DESIGN: We retrospectively reviewed open-lung biopsy specimens from six patients with CEP, five patients with idiopathic BOOP, and four patients with secondary BOOP, encountered during the 5-year period 1986 through 1991, for the presence of eosinophils and extent of eosinophil degranulation. MATERIAL AND METHODS: Using previously described immunofluorescence methods for detection of intact eosinophils and extracellular deposition of eosinophil-derived major basic protein, we counted the number of eosinophils per x160 microscopic field and evaluated the extent of eosinophil degranulation semiquantitatively. RESULTS: The median numbers of eosinophils were 221 (range, 26 to 343) in cases of CEP, 7 (range, 1 to 65) in cases of idiopathic BOOP, and 7.5 (range, 1 to 39) in cases of secondary BOOP. More eosinophils were found in CEP than in idiopathic BOOP or all cases of idiopathic and secondary BOOP. We found no differences in the extent of eosinophil degranulation among the three groups, although a tendency for more degranulation was noted in cases of CEP. CONCLUSION: Even though clinical and histologic overlap may exist between CEP and idiopathic BOOP, the exact relationship and the role of the eosinophil in idiopathic BOOP remain to be determined.

Adolescent↗
PubMed1994

Assessment of eosinophil and neutrophil participation in atopic dermatitis: comparison with the IgE-mediated late-phase reaction.

We hypothesized that repeated IgE-mediated late-phase reactions are critical in the pathogenesis of atopic dermatitis (AD). Prior studies have shown that extracellular deposition of eosinophil granule major basic protein (MBP) occurs in lesional AD skin, despite a paucity of infiltrating eosinophils, and that deposition of both neutrophil and eosinophil granule proteins occurs in the IgE-mediated late-phase reaction. We evaluated the participation of both eosinophil and neutrophil granule proteins in AD. Cutaneous biopsy specimens and serum and urine samples were obtained from 22 patients with AD. Lesional tissue was examined by means of immunofluorescence for neutrophil elastase and lactoferrin and for eosinophil granule MBP, eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP). Serum levels of elastase, MBP, EDN, and ECP and urine levels of MBP, EDN, and ECP were measured. Marked extracellular deposition of at least one of the eosinophil granule proteins was present in the dermis of 15 of the 22 AD skin specimens, but minimal or no extracellular neutrophil elastase or lactoferrin deposition was observed in any specimens. Serum and urine levels of MBP, EDN, and ECP in the patients were elevated when compared with those of normal controls, whereas serum levels of neutrophil elastase were not elevated. Serum MPB levels correlated with extent of body surface involvement. These results suggest that eosinophil degranulation occurs in AD but that neutrophil degranulation does not. Although eosinophil degranulation is prominent in both the late-phase reaction and in AD, the lack of neutrophil degranulation in AD demonstrates differences in the inflammatory reactions.

Adolescent↗
PubMed1994

Endotoxin contamination causes neutrophilia following pulmonary allergen challenge.

Segmental bronchoprovocation (SBP) with allergen was used in an attempt to study eosinophils recruited to the airway 24 h after challenge. Unexpectedly, in the first four patients, neutrophils (rather than eosinophils) were recruited in the bronchoalveolar lavage (BAL) fluids, and we hypothesized that the allergen extracts were contaminated with endotoxin. The extracts used for challenge in the first four patients tested positive for bacterial endotoxin in a limulus amebocyte lysate assay. Rechallenge of one patient from the first group with a comparable dose of an endotoxin-free extract and SBP with endotoxin-free extract in five additional patients resulted in preferential recruitment of eosinophils rather than neutrophils. The number of neutrophils recovered from the challenged segments in the patients challenged with endotoxin-free extract was significantly less than that observed in the first four patients. Taken together, these observations suggest that neutrophil recruitment in the 24-h BAL fluids from the first four patients was probably due to endotoxin contamination of the allergen extract. We caution investigators that endotoxin contamination of allergen extract may alter the cellular inflammation during the late airway response following allergen challenge.

Adolescent↗
PubMed1993

Eosinophil survival activity identified as interleukin-5 is associated with eosinophil recruitment and degranulation and lung injury twenty-four hours after segmental antigen lung challenge.

BACKGROUND: Segmental antigen challenge in allergic volunteer subjects leads to the recruitment of inflammatory cells, including eosinophils, to the lung and to lung injury as shown by albumin influx into the alveolar air space. The goal of this study was to determine whether eosinophil-active cytokines, including IL-3, IL-5, or granulocyte-macrophage colony-stimulating factor, are released into the lung 24 hours after segmental antigen challenge of ragweed allergic subjects with allergic rhinitis and to determine whether the presence of the cytokine or cytokines is correlated with markers of lung inflammation and lung injury. METHODS: Volunteers underwent challenge with a wide variety of antigen doses, which resulted in the recruitment of inflammatory cell mixtures both with and without eosinophils. RESULTS: Eosinophil survival activity (ESA), the ability of the cytokine to prolong blood eosinophil survival in culture, was found in 5 of 17 ragweed allergic subjects and only in subjects challenged with relatively high doses of ragweed antigen (0.2 ragweed antigen units/ml or more). No ESA was found in bronchoalveolar lavage (BAL) fluid in any of eight nonragweed allergic subjects. This activity could be almost completely neutralized by preincubating BAL fluid with specific antibody to IL-5, although a small contribution by granulocyte-macrophage colony-stimulating factor may also have been present. ESA correlated with eosinophil recruitment (r = 0.72, p < 0.001) and degranulation in the lung (r = 0.63 to 0.81, p < 0.01, for eosinophil granule constituents in BAL fluid) and lung injury as shown by albumin influx into the alveolar air spaces (r = 0.83, p < 0.001). ESA was unrelated to the presence of other inflammatory cells in the lung. Subjects who had IL-5 in BAL fluid appeared to undergo more severe initial reactions to antigen challenge. CONCLUSIONS: We conclude that IL-5 is the most important constituent in ESA in the lung 24 hours after antigen challenge and that it correlates with eosinophil recruitment, degranulation, and lung injury.

Allergens↗
PubMed1993

IL-5 is the predominant eosinophil-active cytokine in the antigen-induced pulmonary late-phase reaction.

The mechanism of airway eosinophilia during antigen-induced inflammation was investigated by measurement of eosinophil-active cytokines utilizing an eosinophil survival assay. In the first study, 4 patients with allergic rhinitis underwent segmental bronchoprovocation (SBP) with low, medium, and high doses of ragweed extract instilled into different bronchial subsegments; bronchoalveolar lavage (BAL) fluids were collected from each segment 12 min and 48 h after challenge. Eosinophil granule proteins and eosinophil survival activity were significantly elevated in the 48-h (late-phase) BAL fluids from these segments. Correlations were observed between the concentrations of eosinophil granule proteins and eosinophil survival activity (rs = 0.717 to 0.880, p < 0.001) in BAL fluids. Eosinophil survival activity was completely neutralized by anti-IL-5 monoclonal antibody in five of the seven 48-h samples tested representing three of the 4 patients. In the two remaining samples, eosinophil survival activity was only partially neutralized by either anti-IL-5 antibody or anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) but was completely neutralized by anti-IL-5 and anti-GM-CSF in combination. Subsequently, in the second study, 10 patients with allergic rhinitis were challenged by SBP with ragweed extract. Eosinophil survival activity was significantly elevated in the 48-h BAL fluids; this activity was partially neutralized by anti-IL-5 antibody about (48%) and completely neutralized by the combination of anti-IL-5 and anti-GM-CSF antibodies. These findings suggest that the eosinophil survival activity in the late inflammatory lesions following SBP with allergen is mainly associated with IL-5, with small contributions from GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Sudden-onset fatal asthma. A distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa?

To determine the histologic differences in the airways of patients who died from sudden-onset asthma and the more common slow-onset asthma, we studied seven cases of fatal asthma. The numbers of eosinophils and neutrophils, as well as extracellular deposition of their respective granule contents in the airway mucosa and submucosa, were determined and statistically analyzed. Four of the seven patients had slow-onset asthma attacks in which the time interval between onset of asthma and death was more than 2.5 h. In contrast, three patients had sudden-onset asthma in which the time interval between onset of asthma attack and death was less than 1 h. The four patients with slow-onset fatal asthma had more eosinophils (34.1 +/- 6.3 in slow-onset; 9.7 +/- 3.5 in sudden-onset; p = 0.002) and fewer neutrophils (4.8 +/- 2.0 in slow-onset; 16.8 +/- 5.4 in sudden-onset; p = 0.008) in the airway submucosa than did patients with sudden-onset fatal asthma. In addition, within the slow-onset fatal asthma group, eosinophils exceeded neutrophils in the airway submucosa (eosinophils > neutrophils, p = 0.002). By contrast, within the sudden-onset fatal asthma group, neutrophils exceeded eosinophils (neutrophils > eosinophils, p = 0.04). We suggest that sudden-onset fatal asthma is immunohistologically distinct from slow-onset fatal asthma and that it is characterized by a relative paucity of eosinophils in the face of an excess of neutrophils in the airway submucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

[Eosinophil and neutrophil degranulation in allergic inflammation: immunohistochemical localization of granule proteins in fatal asthma and stimulus-dependent degranulation in vitro].

Airway inflammation is a central feature of bronchial asthma. The eosinophil, a major infiltrating cell in the airway wall in asthma, expresses its effector function by degranulation of toxic granule proteins. The role of the neutrophil in allergic inflammation is still controversial. In order to clarify the possible involvement of degranulation in allergic inflammation, we studied the immunohistochemical localization of granule proteins of the eosinophil and the neutrophil, namely, major basic protein (MBP) and elastase, respectively, in the lungs from patients with fatal asthma. We found that extracellular deposition of MBP or elastase coexisted with epithelial damage in the airway and that more eosinophils were found in slow onset fatal asthma cases and more neutrophils in sudden onset fatal asthma. These results suggest that inflammatory cell degranulation may have induced tissue injury in cases of fatal asthma, and that there may be two pathologically distinct forms of fatal asthma in terms of involvement of eosinophils or neutrophils. Next we showed that IgA and IgG coupled to Sepharose beads induced eosinophil and neutrophil degranulation. IgA and secretory IgA (sIgA) for neutrophils and sIgA for eosinophils were the most potent stimulators of degranulation. Pretreatment of eosinophils with pertussis toxin (PTX) for 2 h irreversibly abolished sIgA-induced degranulation, whereas PTX treatment only transiently inhibited IgG-induced eosinophil degranulation. Activated PTX catalyzed the in vitro ADP ribosylation of 41- and 44-kDa proteins in eosinophils. A 2-h pretreatment of intact cells with PTX markedly reduced the pools of unmodified 41- and 44-kDa substrates available for subsequent ADP-ribosylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Double-blind trial of pyridoxine (vitamin B6) in the treatment of steroid-dependent asthma.

Pyridoxine has been reported to largely correct an abnormality of tryptophan metabolism present in patients with bronchial asthma and to reduce the symptoms of asthma in long-term studies. We enrolled 31 patients requiring steroids (oral or inhaled) for the treatment of their asthma in a double-blind, placebo-controlled assessment of 9 weeks' treatment with pyridoxine 300 mg per day (13) or placebo (18). Outcome variables included PEFR, FEV1, asthma symptom scores, 24 hour urinary 5-HIAA, skin test reactivity to histamine and compound 48/80 and blood serotonin levels. Plasma pyridoxine levels indicated overall patient compliance with a mean change from baseline to the end of the study of 82.5 +/- 27.7 ng/mL in patients on pyridoxine and -2.9 +/- 10.3 for those on placebo (P = .0001). Furthermore, patients routinely treated with theophylline had lower (10 +/- 8 ng/mL) plasma pyridoxine levels at baseline than those not on it (19 +/- 6 ng/mL; P = .01), suggesting that theophylline may lower plasma pyridoxine levels. There was no significant difference between the pyridoxine and placebo groups in the change from baseline to the last 2 weeks of treatment phase in any of the outcome variables. We conclude that under the conditions of the study, treatment with oral pyridoxine failed to improve the outcome variables in patients requiring steroids for the treatment of their asthma. The results of this study suggest that prescription or usage of oral pyridoxine for the treatment of asthma cannot be justified in such patients.

Administration, Inhalation↗
PubMed1992

Immunofluorescent staining for mast cells in idiopathic pulmonary fibrosis: quantification and evidence for extracellular release of mast cell tryptase.

In many diseases, retrospective analysis for determining the presence of mast cells has been difficult because of their loss of metachromatic staining properties once tissue has undergone formalin fixation. We quantified mast cells in peribronchiolar tissue of idiopathic pulmonary fibrosis (IPF) and in normal human lung by using rabbit antiserum to human mast cell tryptase. In lung biopsy specimens from 15 patients with IPF, the mean number of mast cells per high-power field in connective tissue directly adjacent to the lumen of small airways (0.5 to 2 mm in diameter) and other fibrotic foci was 29.9 +/- 10.8 in comparison with 13.7 +/- 3.5 in 16 normal controls (P < 0.001). In addition, mast cells in cases of IPF had an altered appearance--irregularity of the plasma membrane and release of extracellular tryptase. We conclude that the number of mast cells is increased in IPF and that the altered appearance of the mast cells suggests that they are activated and undergoing degranulation.

Biopsy↗
PubMed1991

Longitudinal study on distribution of Phlebotomus argentipes sandflies at different heights in cattleshed.

Distribution of Ph. argentipes at three levels (level I, 0-0.91 m; level II, 0.91-1.82 m; and level III 1.82-2.74 m) above the ground in 6 cattlesheds was studied during July 1989 to June 1990. Of the 8044 Ph. argentipes caught, 3151 (39.2%), 3936 (48.9%) and 957 (11.9%) were from levels I, II, and III respectively. Both male and fed, half-fed, gravid and unfed female sandflies were found at all the three levels and in all the three seasons viz., rainy, winter and summer, of the year. The maximum height of occurrence of sandflies was 2.51 m (8.3 ft) above the ground level.

Animals↗
PubMed1990

Efficacy of atropine methylnitrate alone and in combination with albuterol in children with asthma.

The bronchodilator effect of nebulized AMN, albuterol and their combination was evaluated in 16 steroid-dependent asthmatic children. In phase 1, maximal bronchodilation was determined by dose-response studies on separate days. Maximal bronchodilator dose of each drug was administered either alone or in combination during phase 2. In phase 1, 0.11 +/- 0.01 mg/kg of albuterol and 0.03 mg/kg of AMN produced maximum bronchodilation. In phase 2, the peak response to albuterol occurred within 30 min and to AMN, at 60 min. Maximal FEV1 achieved after AMN was 90 percent of the maximal achieved after albuterol. AMN FEV1 response was better than for placebo for 3 h; that for albuterol was better for 4 h. Combination therapy produced a peak response similar to that of albuterol but was better than albuterol by 6 h. Thus, the maximum bronchodilator effect of AMN is less than that of albuterol in asthmatic children, but the combination may extend the period of bronchodilatation.

Adolescent↗
PubMed1990

A random double-blind trial of the combination of nebulized atropine methylnitrate and albuterol in nocturnal asthma.

The combination of nebulized atropine methylnitrate (AMN) and a beta-agonist has been shown to produce greater and longer lasting bronchodilation than either drug alone. We examined the efficacy of the combination in diminishing the "morning dipping" in PEFR in eight hospitalized but stable asthmatics. The patients received nebulized albuterol along with either AMN (AMN + ALB) or placebo (ALB) in a random double-blind cross-over fashion at 10 PM on four nights. PEFR and FEV1 were recorded at 6 PM, 10 PM, and 6 AM before the administration of bronchodilators. There was no statistically significant difference between ALB and AMN + ALB in reducing the morning dipping in these patients.

Administration, Inhalation↗