PubMed Health⌕ Search

Biomedical subjects

S Idell

Publications and source records attributed to S Idell.

69 records · Page 4Linked to original sources
PubMed1988

A peptide from alveolar macrophages that releases neutrophil enzymes into the lungs in patients with the adult respiratory distress syndrome.

A monoclonal antibody has been made to a peptide that is released by human alveolar macrophages. This enzyme-releasing peptide (ERP) causes neutrophils to secrete azurophilic granule enzymes. Normal subjects, patients with pulmonary fibrosis, and patients with sarcoidosis had similar concentrations of this peptide in their bronchoalveolar lavage fluids. However, patients with the adult respiratory distress syndrome (ARDS) had about 2.7 times higher concentrations in their lavage fluids. The enzyme-releasing activity in the lavage fluids was significantly correlated with 2 indices of the severity of the clinical illness in patients with ARDS, the APACHE score, and the chest radiograph score. The correlation was diminished or ablated by removing the peptide with the monoclonal antibody bound to staphylococcal Sepharose 4B. This peptide accounted for 62.08% (SD = 15.88%) of the enzyme-releasing activity in fluids from lungs of patients with ARDS and 86.39% (SD = 24.46%) of the activity in fluids from lungs of normal control subjects. Therefore, ERP is the major neutrophil enzyme-releasing agent in the bronchoalveolar lavage fluid from patients with ARDS and from normal persons. There was a significant correlation between the neutrophil enzyme-releasing activity and the ERP concentrations in BAL of patients with ARDS. These observations suggest that modulation of neutrophil function by ERP significantly controls the protease and peroxidase loads in the lungs of patients with ARDS.

Adolescent↗
PubMed1988

Local abnormalities of coagulation and fibrinolysis and alveolar fibrin deposition in sheep with oleic acid-induced lung injury.

Extravascular, primarily intra-alveolar, fibrin deposition is a histologic hallmark of acute lung injury in humans and experimental animals, but the mechanisms leading to this finding are poorly understood. To determine whether local abnormalities in the fibrinolytic-procoagulant balance contribute to alveolar fibrin deposition in acute lung injury, we studied bronchoalveolar lavage (BAL) fluids of anesthetized sheep that received intravenous oleic acid. Prominent alveolar fibrin deposition was observed within 2 h after oleic acid-induced lung injury. Procoagulant and fibrinolytic activities were determined in BAL samples of anesthetized, mechanically ventilated sheep before and 2 h after intravenous oleic acid or saline. BAL procoagulant activity was found to be due mainly to tissue factor associated with Factor VII. In baseline BAL samples, we found relatively low levels of procoagulant activity and relatively high levels of fibrinolytic activity. After induction of oleic acid-induced lung injury, the procoagulant activity of BAL was markedly increased, whereas fibrinolytic activity was either depressed or undetectable. Antiplasmin activity was detectable in BAL of sheep after oleic acid-induced lung injury, which contributed at least in part to the depressed fibrinolytic activity observed. These perturbations occurred with the appearance of extensive alveolar fibrin deposition. In control sheep, BAL fibrinolytic activity was decreased, and antiplasmin activity increased modestly after 2 h of mechanical ventilation, but procoagulant activity was unchanged and alveolar fibrin was not observed. Procoagulant activity in lung lymph and plasma after lung injury did not differ from baseline values, and fibrinolytic activity was undetectable in lymph or plasma samples. These data indicate that increased procoagulant activity and concurrent disruption of the balance of coagulation and fibrinolysis establish local conditions that promote acute fibrin deposition in the alveoli of mechanically ventilated, oleic acid-injured sheep.

Animals↗
PubMed1988

Recombinant alpha 1-antitrypsin Pittsburgh attenuates experimental gram-negative septicemia.

Alpha 1-antitrypsin-Pittsburgh (AT-P), a naturally occurring lethal mutation (358Met----Arg), has been genetically engineered (rAT-P). The protein has been shown to be a potent active site-directed inhibitor of thrombin and the contact enzymes Factor XIIf, Factor XIa, and kallikrein. Because activation of the contact system is known to occur in gram-negative septicemia, the authors have hypothesized that the administration of rAT-P might modulate the course of this syndrome. Yorkshire piglets anesthetized with pentobarbital and infused with viable Pseudomonas aeruginosa (2 X 10(8) CFU) were untreated (Group I) or treated with rAT-P (Group II) and studied in a 6-hour protocol. Coagulation studies revealed that rAT-P significantly inhibited the rapid decrease in the functional concentrations of Antithrombin III, Factor XI, and fibrinogen. In addition, rAT-P markedly reduced the serum levels of fibrinogen degradation products. Survival in Group II was significantly increased during 2-5 hours but not at 6 hours when the functional levels of rAT-P in plasma were the lowest. These results indicate that this recombinant inhibitor, even at low concentrations, affords protection in experimental gram-negative septicemia.

Animals↗
PubMed1987

Bronchoalveolar lavage procoagulant activity in bleomycin-induced lung injury in marmosets. Characterization and relationship to fibrin deposition and fibrosis.

Although pulmonary fibrin deposition and coagulation abnormalities have been observed in acute lung injury in humans, their role in the pathogenesis of pulmonary disorders is unclear. In order to gain further insights into the role of the coagulation in lung injury, we examined the relationship between procoagulant activity in bronchoalveolar lavage (BAL) fluids and the evolution of bleomycin-induced lung injury in marmosets. The BAL procoagulant activity was increased at 1, 2, and 4 wk after bleomycin challenge compared with that in control subjects, and it was capable of shortening the recalcification times of plasmas deficient in factor VII and factor VIII but not in factor X. This profile suggested the presence in BAL of an activator of factor X. Activation of purified human factor X by BAL was demonstrated by measuring the amidolytic activity of the generated factor Xa on its N-benzoyl-L-isoleucyl L-glutamyl-glycyl-L-argenine-p-nitroanilide substrate. Factor X activating activity was increased in BAL at 2 wk after bleomycin challenge. Cleavage of 125I-labeled human factor X by BAL from bleomycin-challenged marmosets yielded a 55,500 Mr product that comigrated with factor Xa, the appearance of which correlated strongly with amidolytic evidence of factor Xa activity. Electron microscopy of the lungs of animals from all groups revealed pulmonary fibrin deposition at 2 wk after bleomycin challenge, at the time of increased BAL procoagulant and factor X activating activity. The BAL procoagulant activity was completely sedimentable by ultracentrifugation and was inhibited by concanavalin A and phospholipase C. Activation of purified factor X by BAL was inhibited by monospecific polyclonal goat and rabbit antibodies to human factor VII as well as antibody to bovine tissue factor, demonstrating that factor X activating activity in BAL was attributable to tissue factor associated with material similar to factors VII or VIIa. We conclude that procoagulant activity in BAL increases after bleomycin challenge in marmosets and is attributable to activation of factor X by tissue factor associated with factors VII or VIIa-like material. Increased BAL procoagulant activity is temporally associated with pulmonary fibrin deposition and pulmonary fibrosis during bleomycin-induced pulmonary injury in the marmoset.

Animals↗
PubMed1987

Procoagulant activity in bronchoalveolar lavage in the adult respiratory distress syndrome. Contribution of tissue factor associated with factor VII.

Alveolar fibrin deposition commonly occurs in the lungs of patients with the adult respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) from patients with ARDS, control patients with interstitial lung disease (ILD), congestive heart failure, or exposure to hyperoxia, and normal healthy subjects was studied to determine whether local alterations in procoagulant activity favor alveolar fibrin deposition in the lungs in ARDS. Procoagulant activity capable of shortening the recalcification time of plasma deficient in either factor VII or factor VIII was observed in unconcentrated BAL of all patients, but was significantly greater in BAL from patients with ARDS when compared with that of control subjects (p less than 0.001). Unconcentrated BAL from patients with ARDS shortened the recalcification time of plasma deficient in factor X, but no functional thrombin was detectable. BAL procoagulant from patients with ARDS was inhibited by concanavalin A, an inhibitor of tissue factor. The hydrolysis of purified human factor X by BAL from the ARDS and other patient groups was determined by measuring the amidolytic activity of generated factor Xa on its N-benzoyl-L-isoleucyl-L-glutamyl-glycyl-L-arginine-p-nitroanilide substrate. The procoagulant activity of BAL was associated with the development of amidolytic activity, indicating activation of factor X. BAL from patients with ARDS contained more factor X activating activity than did BAL from control groups (p less than 0.001). This activity was calcium dependent and was maximal at 1 mM ionized calcium. The BAL factor X activating activity was most active at neutral pH and was sedimented by ultracentrifugation at 100,000 x g.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Angiotensin converting enzyme in bronchoalveolar lavage in ARDS.

Angiotensin converting enzyme (ACE) is present in the endothelial cells of the normal lung where it converts angiotensin I to angiotensin II and inactivates bradykinin. It has been suggested that during endothelial injury ACE is sloughed into the blood, and that if the alveolar capillary membrane is injured, also into the alveolar lining fluid. Seven patients with adult respiratory distress syndrome (ARDS), were compared to 11 normal control subjects, nine patients with sarcoidosis, and six with idiopathic pulmonary fibrosis. Total, differential cell counts and ACE determinations were performed on bronchoalveolar lavage fluid in the ARDS group. ACE was detectable in the BAL of all but one ARDS patient. It was concluded that BAL ACE is elevated in some ARDS patients, especially those with infectious causes of lung injury. Increased ACE may reflect endothelial damage or local increase in ACE production in response to sepsis.

Adult↗
PubMed1985

Neutrophil elastase-releasing factors in bronchoalveolar lavage from patients with adult respiratory distress syndrome.

Bronchoalveolar lavage fluid (BAL) was obtained from patients with adult respiratory distress syndrome (ARDS). Controls included BAL from normal subjects and from patients with sarcoidosis or pulmonary fibrosis. Neutrophil elastase measured immunologically was found in all BAL samples, but it was strikingly greater in BAL from patients with ARDS than in the BAL from normal subjects or patients with sarcoidosis. There was no significant difference in the neutrophil elastase antigen concentrations in BAL samples from patients with ARDS and those with pulmonary fibrosis. No elastolytic activity was found in either group. The alpha-1-antitrypsin and the bronchial mucus inhibitor were greater in BAL from patients with ARDS. There was a highly significant correlation between the alveolar-arterial oxygen tension difference and the neutrophil elastase concentration in BAL from the patients with ARDS. Kallikrein, prekallikrein, factor XIa-like activity, and high molecular weight kininogen antigen were found in BAL of patients with ARDS, suggesting that the kallikrein-kinin cascade may be activated in the lungs of patients with ARDS. Kallikrein-like activity in the BAL from the patients with ARDS was significantly correlated with the number of neutrophils in the BAL, the neutrophil elastase concentration, and the ability of the BAL to release elastase from cytochalasin-B-treated neutrophils. There was no correlation between these variables and C5a concentration. These studies demonstrated an association between BAL neutrophil elastase and the clinical state of patients with ARDS.

Adult↗
PubMed1985

Bronchoalveolar lavage in patients with the adult respiratory distress syndrome.

BAL in patients with ARDS provides material containing the soluble and cellular constituents of the alveolar compartment, and hence is a useful tool for the study of the pathogenesis of ARDS. The technique is imperfect as it is prone to problems of data acquisition and interpretation. However, it is lung-specific and may be used in serial studies of patients over the course of their disease. A large amount of evidence is rapidly being accumulated which documents the presence of effectors of inflammation in the BAL fluids of patients with ARDS. Confirmation of the importance of such mediators, pathways, or cellular constituents of BAL fluid in establishing the pathogenesis of ARDS ultimately depends upon proof of the efficacy of specific clinical interventions which both arrest the activity of the effector and predictably alter the course of the disease.

Capillary Permeability↗
PubMed1984

Plasma prekallikrein assay: reversible inhibition of C-1 inhibitor by chloroform and its use in measuring prekallikrein in different mammalian species.

The assay of plasma prekallikrein requires activation of prekallikrein to kallikrein and sufficient inactivation of the plasma protease inhibitors of kallikrein to accurately measure the generated kallikrein activity. One method of elimination of the plasma protease inhibitors to kallikrein is to chemically pretreat the plasma. Methylamine has previously been employed to selectively inactivate alpha 2-macroglobulin. Our study examines the effect of sequential preincubation of plasma with chloroform and methylamine on the plasma prekallikrein assay. Chloroform was demonstrated to be a chemical inhibitor of purified C-1 inhibitor, but alpha 2-macroglobulin was not. Chloroform inhibition of C-1 inhibitor was not caused by precipitation of the protein into the interface between the water and organic solvent phase. Greater than 95% of C-1 inhibitor antigen was recovered in the supernatant of chloroform-treated purified C-1 inhibitor, and chloroform-saturated buffer inhibited purified C-1 inhibitor. Chloroform did not dissociate a preformed complex of kallikrein and C-1 inhibitor, but its inhibition of C-1 inhibitor was reversible. The addition of methylamine to plasma pretreated with chloroform in the plasma prekallikrein assay allowed for only a slight increase in the amount of kallikrein measured at 1 minute kaolin activation times, but provided for sustained measurement of activated prekallikrein when kaolin activation times were 5 to 7 minutes. Without chemical pretreatment, prekallikrein was not measurable in rabbit plasma. Both rabbit and pig plasma prekallikrein was measurable after exposure of the plasma to chloroform and methylamine, although the peak activation times and the contribution of each animals' protease inhibitors varied with the species. Our results show that chloroform is a reversible inhibitor of C-1 inhibitor, and that the plasma prekallikrein assay in which it is used is useful for the measurement of prekallikrein in nonhuman mammalian plasma samples.

Animals↗
PubMed1981

Redistribution on the thallium scan in myocardial sarcoidosis: concise communication.

Resting and redistribution thallium studies were performed in four young patients with sarcoidosis to evaluate the possibility of myocardial involvement. In each case the resting scan showed marked defects that resolved on the redistribution studies. In a different patient population, these results would have implied significant coronary artery disease.

Adult↗
PubMedDate not supplied

Interleukin-8: an important neutrophil chemotaxin in some cases of exudative pleural effusions.

It was hypothesized that IL-8, a neutrophil chemotaxin, contributes to the influx of neutrophils into the pleural cavity of patients with pleural effusions. Pleural fluids were collected from 57 patients including 13 with effusions due to congestive heart failure, 28 with pleural involvement by carcinoma, 5 with empyema, 4 with parapneumonic effusions complicating bacterial pneumonia, 3 with hemothorax, 3 with tuberculosis, and 1 with rheumatoid arthritis. All exudate groups had significantly higher IL-8 concentrations than the CHF group (p < .001). In 18 of the exudate fluids, the concentrations of IL-8 was equal to or in excess of the optimal concentration of IL-8 which causes neutrophil chemotaxis in vitro. Between 20 and 90% of the chemotactic activity in the fluids was removed by absorbing the IL-8 with an IL-8 affinity column. These data showed that IL-8 is a major chemotaxin in the fluid. The percentage of neutrophils in the fluids was not correlated with the IL-8 concentration. Although TNF alpha, a potent stimulator of IL-8 production, is present in some pleural effusions, no correlation was found between the concentrations of IL-8 and TNF alpha in the fluids. The data suggest that IL-8 contributes to the neutrophil influx into the pleural space of patients with pleural exudates in conjunction with other chemoattractants. It is unlikely that TNF alpha is the sole stimulus for the IL-8 production in pleural disease states.

Chemotaxis, Leukocyte↗
PubMedDate not supplied

Primary systemic amyloidosis with a retroperitoneal mass.

A 73-year-old black woman presented with congestive heart failure, abdominal distension and ascites. A large retroperitoneal mass was demonstrated by gray-scale abdominal ultrasonography and confirmed by laparatomy and postmortem examination. This retroperitoneal mass consisted mainly of amyloid, as demonstrated by green birifringence with alkaline Congo red staining. Resistance of this staining pattern to permanganate treatment and the absence of inflammatory disease or malignancy at autopsy suggest the diagnosis of primary systemic amyloidosis. This is the first reported case of this disease manifesting as a retroperitoneal mass.

Aged↗