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Biomedical subjects

J E Fish

Publications and source records attributed to J E Fish.

At least 55 records · Page 3Linked to original sources
PubMed1995

Effects of colchicine on IgE-mediated early and late airway reactions.

BACKGROUND: The pathogenesis of bronchial asthma is thought to involve elements of both acute and chronic inflammation. Hence, there is growing interest in the potential of immunomodulatory drugs in asthma therapy. This study examines the effects of the anti-inflammatory compound colchicine on early and late allergen-induced, IgE-mediated airway reactions. METHODS: Nine mildly allergic asthmatic subjects were evaluated in a single-blind, two-way crossover study designed to examine the effects of colchicine and placebo on early and late airway reactions to ragweed allergen and related changes in nonspecific responsiveness to methacholine. RESULTS: Compared with placebo, colchicine provided 19% (p = 0.036) and 40% (p = 0.004) inhibition of early and late airway reactions to allergen, respectively. Allergen-induced increases in methacholine responsiveness were observed with both types of treatment, although there was a trend toward a smaller increase after administration of colchicine (p = 0.13). We also found that methacholine responsiveness per se was not directly altered by colchicine (n = 7). In 6 subjects, we found suppression of neutrophil leukotriene B4 generation after colchicine treatment, suggesting that the colchicine dose (0.6 mg twice daily) was sufficient to produce an anti-inflammatory effect. Further in vitro studies using purified human lung tissue mast cells failed to demonstrate inhibition of mediator release at concentrations corresponding to achievable tissue or blood levels during the in vivo trial. CONCLUSION: Colchicine partially inhibits IgE-mediated early and late airway reactions at conventional clinical doses. This inhibitory effect may be mediated via suppression of some cell species other than the lung tissue mast cell. Controlled studies to examine the benefits of colchicine in clinically evidenced asthma are warranted.

Adult↗
PubMed1994

Pulmonary function and gastroesophageal reflux in systemic sclerosis.

OBJECTIVE: To determine the relations among esophageal dysfunction, gastroesophageal reflux, and lung involvement in patients with systemic sclerosis. DESIGN: Retrospective review of esophageal motility, esophageal pH, and pulmonary function data. SETTING: University hospital outpatient clinic and community. PATIENTS: 39 consecutively referred patients who were grouped according to the presence or absence of abnormal distal (pH < 4.0 for > 5% of the 24-hour monitoring period) or proximal (pH < 4.0 for > 1% of the 24-hour period) gastroesophageal acid reflux. Patients were also grouped according to the presence or absence of distal esophageal peristalsis. MEASUREMENTS: Esophageal manometry, dual-probe (distal and proximal) esophageal 24-hour pH measurements, and pulmonary function studies (forced vital capacity, forced expiratory volume at 1 second, total lung capacity, and single-breath carbon monoxide diffusing capacity [DLco]). RESULTS: The mean total lung capacity (values as percentage predicted) was 87.1% +/- 11.2% (SD) for patients with abnormal proximal reflux and 77.8% +/- 21.6% for patients with normal proximal reflux (difference, 9.3%; 95% CI, -1.4% to 20.0%). The mean forced vital capacity for these patients was 91.1% +/- 12.4% and 85.4% +/- 25.6%, respectively (difference, 5.7%; CI, -6.9% to 18.1%). The mean total lung capacity was 83.8% +/- 15.4% for patients with abnormal distal reflux and 77.9% +/- 22.7% for patients with normal distal reflux (difference, 5.9%; CI, -7.6% to 19.4%). Among potential confounders of pulmonary measures, only smoking was related to decreased pulmonary function (smoking related to decreased DLco P < 0.01). Smoking was more common in patients with abnormal distal reflux than in those with normal distal reflux (65% compared with 25%, P = 0.03). After adjusting for smoking, the difference in mean DLco between patients with abnormal compared with normal distal reflux was 7.19% (Cl, -8.5% to 22.9%). CONCLUSION: Important measures of lung volume indicative of interstitial lung disease (total lung capacity, forced vital capacity) do not appear to be related to abnormal gastroesophageal acid reflux in patients with systemic sclerosis.

Esophagus↗
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

Immunoglobulin E-mediated increase in vascular permeability correlates with eosinophilic inflammation.

An increase in bronchovascular permeability is thought to play an important role in the pathogenesis of allergic asthma. We sought to determine whether the increase in permeability observed 24 h after segmental antigen challenge in ragweed-allergic human volunteers was associated with the infiltration and degranulation of a specific cell type. A 20,000-fold range of antigen concentrations was used to alter the number and type of inflammatory cells recruited to the lung by challenge. Although large numbers of inflammatory cells were recruited to lung air spaces over a large range of antigen concentrations, significant numbers of eosinophils (731.3 +/- 232.9 x 10(3)/ml) were recruited only when the concentration of antigen used for segmental challenge was > or = 100-fold higher than the concentration needed to produce an 8 to 10 mm wheal 20 min after intradermal skin testing. In addition, large increases in bronchoalveolar lavage (BAL) albumin concentration (636.3 +/- 170.5 micrograms/ml) were observed only in this same group of subjects. The correlation coefficient between the logarithms of the BAL eosinophil concentration and albumin concentration was +0.82 (p < 0.001), and between eosinophil-derived neurotoxin and albumin it was +0.88 (p < 0.001). In a stepwise, multiple regression analysis, eosinophils accounted for 67% of the variance in BAL albumin concentration, whereas no other cell type was a significant predictor of albumin flux into BAL fluid. We conclude that eosinophil recruitment and degranulation are associated with large increases in bronchovascular permeability after segmental antigen challenge in humans.

Adult↗
PubMed1993

Neutrophils recruited to the lungs of humans by segmental antigen challenge display a reduced chemotactic response to leukotriene B4.

Allergic asthma is characterized by an infiltration of the lung with inflammatory cells including eosinophils and neutrophils. The mechanism by which inflammatory cells are recruited to the lung in IgE-mediated disorders is unknown. In order to explore the mechanism responsible for cell recruitment, ragweed-allergic volunteers underwent segmental (bronchoscopic) antigen challenge, followed 24 h later by bronchoalveolar lavage (BAL). Experimental conditions were chosen to favor neutrophil, rather than eosinophil, recruitment. Chemotactic responses of purified BAL neutrophils (under agarose) were then compared with blood neutrophils obtained from the same subjects. We hypothesized that neutrophils recruited to the lung would be desensitized to the chemotaxin(s) responsible for their recruitment. BAL neutrophils showed a profound inhibition of their chemotactic response to an optimal concentration of leukotriene B4 (LTB4) ex vivo (approximately 40% of the response of blood neutrophils) with a slightly reduced response to the anaphylatoxin C5a and to FMLP. In addition, they displayed a normal production of superoxide anion in response to phorbol myristate acetate. These results demonstrate that neutrophils recruited to the lung of humans by local antigen challenge display a marked inhibition of their chemotactic response to LTB4, and are consistent with the hypothesis that LTB4 is instrumental in recruiting neutrophils to the lung in IgE-mediated reactions.

Adult↗
PubMed1992

Effect of antigen dose on the recruitment of inflammatory cells to the lung by segmental antigen challenge.

Bronchoscopic antigen challenge of atopic volunteers results in an immediate release of inflammatory mediators and, after a number of hours, the recruitment of inflammatory cells to the lung. The purpose of this work was to investigate the effect of antigen dose on the subsequent recruitment of inflammatory cells to the lung. Twenty-two volunteers without asthma, eight nonatopic control subjects, and 14 ragweed-allergic subjects underwent 25 local antigen-challenge procedures that consisted of a baseline lavage of a control segment, antigen challenge of another segment in the contralateral lung, and lavage of the challenged segment 24 hours later. A 25,000-fold range of antigen doses was used from 0.004 to 100 PNU/ml (0.02 to 500 ng/ml of ragweed antigen E [Amb a I]). Challenge of nonatopic control subjects resulted in the recruitment of only a small number of inflammatory cells, less than a twofold increase in comparison with the cells of control lavage; this increase was primarily due to an increase in neutrophils. Challenge of atopic subjects, in contrast, resulted in approximately a threefold to ninefold increase in inflammatory cells with more cells recruited at larger doses of antigen. Only subjects challenged with a "high" dose of antigen (greater than or equal to 1 PNU/ml) recruited significant quantities of eosinophils to the lung. In these subjects, a twofold increase in macrophages, a fourfold increase in lymphocytes, a 90-fold increase in neutrophils, and an 800-fold increase in eosinophils were observed; the number of neutrophils and eosinophils recruited averaged between 30 and 60 million.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Ciliated respiratory epithelial surface changes after formaldehyde exposure.

The investigation sought to identify alterations of specific ciliated epithelial surface components after exposure to formaldehyde (HCHO) levels that decrease respiratory ciliary function. Bovine tracheae were reacted with an analog of N-hydroxysuccinimidobiotin to label epithelial surface-accessible components before exposure to HCHO. The tracheae were then exposed to 0, 16, 33, and 66 micrograms HCHO/cm2 epithelial surface for 30 min. Cilia were isolated from the epithelium, separated into membrane and internal axonemal portions, analyzed on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and either stained to detect proteins or transblotted to detect biotin-labeled components. Densitometric analysis of axoneme proteins showed a decrease in the total amount extracted with increased HCHO concentration, including axoneme-specific proteins, dynein, and tubulin. However, biotinylated proteins in the axoneme fractions proportionately increased. Membrane fractions showed little change in protein with increasing HCHO concentration. The majority of these is not biotin-labeled and thus not surface-accessible components. Biotinylated material in the membrane fractions showed a significant decrease with increased HCHO concentration, particularly of bands at 92, 98, and 105 kD. These data suggest that increasing HCHO exposure reduces both extractable ciliary axonemes and detergent-soluble surface components, possibly by stabilizing respiratory epithelial membranes. This process apparently strengthens association of certain surface components with the internal axoneme, thereby reducing subsequent solubilization in detergent.

Adenosine Triphosphatases↗
PubMed1992

A multicenter registry of patients with acute respiratory distress syndrome. Physiology and outcome.

In a multicenter registry conducted over 2 yr of patients with acute respiratory distress syndrome (ARDS), we enrolled 153 patients and collected data daily for 7 consecutive days and weekly thereafter until death or hospital discharge. The purposes of the registry were (1) to determine whether a more liberal definition of ARDS (PaO2/FIO2 < or = 250; bilateral pulmonary infiltrates within 7 days) than those commonly used would result in enrollment of patients earlier in their clinical course, and (2) to study the clinical course of the syndrome in survivors and nonsurvivors. The mortality rate was 54% and it was significantly greater in older versus younger patients (75% versus 37%) and in septic versus nonseptic patients (60% versus 43%). We found that the definition of ARDS used for the registry resulted in enrollment of patients 1 to 7 days earlier than was the case when other published definitions of ARDS were applied to the patient population. Fewer than 2% of the patients failed to meet one of the nonregistry definitions of ARDS within 7 days. The mortality rate was independent of the definition used to identify ARDS patients. Our results suggest that a more liberal definition of ARDS than those commonly used can result in identification of the same population of patients earlier in their clinical course.

Academic Medical Centers↗
PubMed1992

Risk factors for increased airway responsiveness to methacholine challenge among laboratory animal workers.

As a first step in a prospective study of the incidence of asthma to laboratory animals, a group of 364 adults 18 to 48 yr of age who were beginning employment with laboratory animals were evaluated in terms of their past history, health status, allergy, and airway responsiveness to methacholine. At entry to the study, 269 had previous occupational contact with animals, 109 had chest symptoms in the previous year, 168 had a history of allergic symptoms to laboratory animals (any with asthmatic responses were systematically excluded), and 118 had positive immediate skin tests (29 had positive skin tests to laboratory animals). When defined as a PD20FEV1 of 80 breath units or less, 18.4% of these young adults had methacholine hyperresponsiveness (HRA). Significant risk factors for HRA were found to be younger age, female sex, lower educational level, a history of allergic symptoms to laboratory animals, and a history of chest symptoms. Positive skin tests to laboratory animals were present in 8% of workers; this was not a significant risk factor for HRA although positive skin tests to pollen and household allergens were. Previous work experience was a risk factor, especially among those with allergic symptoms, and a trend toward self-selection was suggested in that the rate of HRA was lowest in workers with more than 2 yr of experience or with two or more previous jobs with laboratory animals.

Adolescent↗
PubMed1991

Recurrent noncardiac pulmonary edema accompanying pregnancy-induced hypertension.

Severe pulmonary edema occurred in a patient during the third trimester of two consecutive pregnancies, 17 months apart. Noncardiac origin of the pulmonary edema was demonstrated by normal pulmonary capillary wedge pressures, normal roentgenographic cardiac dimensions with absence of effusions, normal echocardiographic ejection fraction, and elevated thermodilution cardiac outputs; moderate reduction in serum albumin levels may have contributed. In the setting of pregnancy-induced hypertension, the development of ARDS on each occasion suggests a pathophysiologic link.

Adult↗
PubMed1990

Inhibition and recovery of mammalian respiratory ciliary function after formaldehyde exposure.

Formaldehyde (HCHO) has been reported to impair mucociliary clearance. The present investigation using rabbit and porcine tracheal explants in vitro examined (1) the impairment of ciliary activity, an essential component of mucociliary clearance; (2) the reversibility of ciliary dysfunction after HCHO exposure; and (3) the mechanism by which ciliary activity is reduced by HCHO. HCHO treatment of rabbit tracheal rings significantly decreased zones of active ciliated epithelium in direct proportion to concentration and exposure duration. There was also a significant concentration-dependent reduction of ciliary beat frequency. Removal of HCHO permitted recovery of zones of ciliary activity to normal beat frequencies; greater inhibitory concentrations of HCHO required greater time for return of function. Treatment of porcine tracheae with increasing concentrations of HCHO for time periods inhibitory to rabbit ciliary activity correspondingly reduced the yield of cilia extractable from treated epithelium. Furthermore, the specific activity of ATPase of extracted ciliary axonemes was diminished with increasing HCHO concentration, indicating loss of function. A recovery period following identical exposures of the porcine tracheae to the lower HCHO concentrations resulted in normal yields of functionally intact ciliary axonemes. Similarly, a recovery period after the highest HCHO concentration produced more functional axonemes than obtained from exposed tracheae without a recovery period, although less than normal yields. Therefore, ciliary dysfunction elicited by a defined range of HCHO concentrations is reversible. The yield and functional integrity of ciliary axonemes from epithelium exposed to HCHO with a recovery period are significantly greater than those without such a recovery period, suggesting an alteration and subsequent repair of epithelial surface components following HCHO exposure.

Adenosine Triphosphatases↗
PubMed1990

Physiology of aging related to outcome in the adult respiratory distress syndrome.

Thirty-nine patients with adult respiratory distress syndrome (ARDS) were enrolled in a study to identify potential age-related changes in organ system function that may help explain the apparent association between age and poor outcome in these patients. Criteria for enrollment included an arterial PO2-to-inspired O2 concentration ratio less than or equal to 200 in a clinical setting consistent with ARDS. Patients were excluded if they were less than 18 yr old, had clinical manifestations of congestive heart failure, were seropositive for the human immunodeficiency virus, or had stage II metastatic lung cancer. Patients were divided into two groups: those less than 60 yr old (mean 42 +/- 3 yr, n = 17) and those greater than or equal to 60 yr old (73 +/- 2 yr, n = 16). A group of six patients was analyzed as a separate subset based on a body temperature less than or equal to 97.5 degrees F at enrollment (hypothermic patients, 73 +/- 4 yr old). Sepsis was present in 67% of the nonhypothermic patients and in all the hypothermic patients. Mortality rates were 12% in the patients less than 60 yr and 69% in the nonhypothermic patients greater than or equal to 60 yr. All the hypothermic patients died. Sequential data obtained over 6 days were compared within and between groups. The following results were obtained. 1) The ratio of arterial PO2 to inspired O2 fraction was greater and the positive end-expiratory pressure used was significantly less in the patients greater than or equal to 60 yr old compared with the younger group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Arachidonic acid metabolism in normal human alveolar macrophages: stimulus specificity for mediator release and phospholipid metabolism, and pharmacologic modulation in vitro and in vivo.

Arachidonic acid (AA) metabolism in normal human alveolar macrophages including phospholipid turnover, stimulus specificity for mediator release including trigger synergy, and the pharmacologic control of the release of AA metabolites was explored. Macrophages labeled overnight with [3H]AA, then activated, released three major AA metabolites, thromboxane B2 (TxB2), leukotriene B4 (LTB4), and 5-hydroxyeicosatetraenoic acid (5-HETE), as characterized by thin layer chromatography, high performance liquid chromatography, and radioimmunoassay. Although all triggers (phorbol myristate acetate [PMA], serum-activated zymosan, and ionophore A23187) resulted in the release of TxB2 and free AA, efficient synthesis of lipoxygenase products, particularly LTB4, required A23187. A23187 was the most effective single agent in producing LTB4 synthesis, was synergistic with PMA in causing LTB4 release, and was associated with significant turnover of phosphatidylcholine and phosphatidylinositol. Incubation of macrophages in vitro with cyclooxygenase inhibitors resulted in an inhibition of the formation of cyclooxygenase products; however, no shunting of metabolites into products of the lipoxygenase pathway was observed. Although overnight incubation of macrophages in vitro with dexamethasone (1 microM) resulted in an inhibition of both the spontaneous and A23187/PMA-triggered release of all AA metabolites, treatment of 5 volunteers with dexamethasone (4 mg po bid x 7 doses, in a single-blind, placebo-controlled, crossover protocol) resulted in no significant inhibition of the release of AA metabolites from macrophages triggered ex vivo. We conclude that activation of normal human alveolar macrophages results in phospholipid turnover (phosphatidylcholine and phosphatidylinositol) and the release of three major AA metabolites (TxB2, LTB4, and 5-HETE); that optimal synthesis of lipoxygenase product requires the presence of a calcium signal (A23187), although PMA can synergize with A23187 in the production of lipoxygenase products; and that glucocorticoids may have a different effect on the release of AA metabolites from alveolar macrophages when administered in vitro versus in vivo.

Arachidonic Acids↗
PubMed1989

Infection with Mycobacterium avium complex in patients without predisposing conditions.

Pulmonary disease caused by Mycobacterium avium complex usually occurs in patients with chronic lung disease or deficient cellular immunity, and its prevalence is increasing. We describe 21 patients (mean age, 66 years) with such infection without the usual predisposing factors, representing 18 percent of the 119 patients surveyed. Seventeen women and 4 men were given a diagnosis of M. avium complex from 1978 to 1987, with a stable incidence over the decade, on the basis of pulmonary symptoms, abnormalities on chest films, positive cultures, and in 14, biopsy evidence of invasive disease. Most of the patients (86 percent) presented with persistent cough and purulent sputum, usually without fever or weight loss. The cough was present for a mean of 25 weeks before the correct diagnosis was made. Radiographic patterns of slowly progressive nodular opacities predominated (71 percent); only five patients had cavitary disease at presentation. All patients responded initially to antimycobacterial therapy, but eight eventually relapsed when it was stopped. Four patients died of progressive pulmonary infection caused by M. avium complex. The extent of the initial pulmonary involvement was greater in patients with progressive disease than in those whose condition improved. We conclude that pulmonary disease caused by the M. avium complex can affect persons without predisposing conditions, particularly elderly women, and that recognition of this disease is often delayed because of its indolent nature.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Absence of changes in airway responsiveness during the menstrual cycle.

The effect of sex hormones on airway function has not been well studied in spite of much evidence to suggest that they are important. We asked if the normal physiologic variation in hormone levels during the menstrual cycle resulted in changes in airway responsiveness and pulmonary function that were not clinically apparent. Nine women with asthma and with normal menstrual cycles but not taking systemic asthma medication were asked to chart temperatures, asthma attacks, and use of asthma medication for four menstrual cycles. We measured baseline spirograms, skin and airway responsiveness to histamine, and serum levels for estradiol, progesterone, and testosterone on approximately day 7 and day 24 of two consecutive cycles. None of the women reported cyclic asthma symptoms, and review of subjects' charts demonstrated no menstrual variation in asthma attacks or use of asthma medications. We found no differences in forced vital capacity or FEV1 early compared to late in the menstrual cycle. Neither did we find a change in airway responsiveness, as indicated by the histamine dose causing a 15% fall in FEV1 or a 35% fall in specific airway conductance. Skin responsiveness as indicated by the wheal response to intradermal histamine was also unchanged. We conclude that physiologic changes in hormone levels during the menstrual cycle are not in themselves associated with changes in airway or skin responsiveness to histamine.

Adrenal Cortex Hormones↗