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W Pruzanski

Publications and source records attributed to W Pruzanski.

At least 55 records · Page 3Linked to original sources
PubMed1992

Serum phospholipase A2 enzyme activity and immunoreactivity in a prospective analysis of patients with septic shock.

Massive elevations of serum phospholipase A2 activity have been documented in patients with septic shock. Serum PLA2 activity correlated to the degree and duration of circulatory collapse, while purified native PLA2 reproduced hypotension in experimental animals. In a prospective study of patients with septic shock, we have determined the relationship of PLA2 enzyme activity to PLA2 immunoreactivity using radiolabelled E. coli phospholipid substrate and an ELISA specific for group II human nonpancreatic PLA2. In all patients, there was a clear concordance of the two assays. Maximal PLA2 concentration was increased a mean of 554-fold over normal levels. We found no evidence to support the presence of activating or inhibitory proteins. These data confirm that the observed increase in serum PLA2 activity in septic shock is due to intravascular release of group II nonpancreatic PLA2.

Antibodies, Monoclonal↗
PubMed1992

Induction of circulating phospholipase A2 activity by intravenous infusion of endotoxin in patients with neoplasia.

The purpose of this study was to evaluate the impact of repeated intravenous infusions of endotoxin (EN) in patients with cancer on the systemic release of extracellular proinflammatory phospholipase A2 (PLA2) and its relationship to the release of tumor necrosis factor (TNF) and interleukin-6 (IL-6). Six patients received 15 infusion of EN isolated from Salmonella abortus equi at a dose of 4 ng/kg. Marked increase in the activity of circulating PLA2 was noted within 3 h after the first EN infusion and reached a maximal level of 20.4-fold greater than baseline 24 h after infusion. In five patients challenged with EN 2 weeks later, PLA2 reached peak levels 15.5-fold greater than baseline. In two patients who received three sequential daily infusions, the incremental increase in PLA2 activity after the second and third challenge reached maximum levels 6 h after EN infusion. PLA2 response followed those of TNF and IL-6 but was quantitatively different. Whereas maximal levels of TNF and IL-6 declined substantially after repeat EN challenges, no such decline occurred in PLA2 activity. Since, in the clinical setting of gram-negative sepsis, there is recurrent increase in circulating EN, our study approximates this clinical situation and shows that extracellular release of PLA2 follows temporally that of proximal cytokines such as TNF and IL-6. These cytokines may be related to PLA2 release and sustained high activity in the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Induction of circulating group II phospholipase A2 expression in adults with malaria.

High levels of interleukin 1 and tumor necrosis factor are found in both cases of malaria and cases of septic shock. Since both interleukin 1 and tumor necrosis factor induce expression of the proinflammatory enzyme phospholipase A2 (PLA2), we examined serum PLA2 levels in 14 adults with malaria. Mean serum PLA2 activity was elevated 40-fold above normal (P less than 0.001). Serum PLA2 activity correlated with PLA2 immunoreactivity (r = 0.987; P less than 0.001) by an enzyme-linked immunosorbent assay specific for human group II PLA2, showing that serum PLA2 in cases of malaria is host derived. This article describes the novel finding of elevated PLA2 levels in cases of malaria, further strengthening the notion that mediators of the host response in cases of malaria are similar to those in cases of septic shock.

Adult↗
PubMed1991

Variable region gene analysis of pathologic human autoantibodies to the related i and I red blood cell antigens.

To investigate the molecular basis of the autoimmune response to the related i and I carbohydrate antigens, we studied cold agglutinins (CA) from B-cell clones and from the peripheral circulation of patients with lymphoproliferative syndromes. Sequence analyses of expressed variable region genes indicate that both anti-i and anti-I specificities from B-cell clones from two patients are encoded by the VH4.21 or a very closely related VH4 heavy chain gene, whereas the expressed light chain genes differed. The anti-i-secreting B-cells express unmutated germline-encoded VH4.21 and VKI gene sequences. The VH region gene encoding anti-I has the closest homology (97%) to the VH4.21 germline gene and differs at the protein level by only three amino acids. In contrast, while the VL region gene encoding anti-I is most homologous (96%) to the VKIII, kv328 germline gene, there are seven amino acid differences due to nonrandom replacement mutations, which suggests a role for antigen-mediated selection in the anti-I response of this individual. These studies were extended by a structural survey of 20 additional serum CA using antipeptide antibodies specific for determinants in VH and VL regions. All anti-I and anti-i CA were shown to express VH4 heavy chains, and 14 of 17 CA expressed a previously described VH4 second hypervariable region determinant, termed VH4-HV2a. We also found that 13 of 14 anti-I CA used VKIII light chains, while the anti-i CA used light chains from at least three VL families. Taken together, the data show that anti-i and anti-I CA probably both derive from the VH4.21 gene (or a closely related gene). Furthermore, the restricted VH and different VL gene use in anti-i and anti-I CA may reflect the close structural relationship of the i and I antigens.

Autoantibodies↗
PubMed1991

Interleukin-1 alpha stimulates the release of prostaglandin E2 and phospholipase A2 from fetal rat calvarial cells in vitro: relationship to bone nodule formation.

We have shown previously that interleukin-1 (IL-1) has biphasic effects on the formation of bone nodules in long-term cultures of fetal rat calvarial (RC) cells (Ellies and Aubin, Cytokine 2:430-437, 1990). To determine the role of arachidonic acid metabolism in this process, we have examined the release of prostaglandin E2 (PGE2) and phospholipase A2 (PLA2) from RC cells under conditions that allowed concomitant analysis of the formation of bone nodules. Recombinant human IL-1 alpha (rhIL-1 alpha) stimulated PGE2 and PLA2 release in a time- and dose-dependent manner. PGE2 release was highest in preconfluent cultures (days 1-6) and was stimulated up to 8.5-fold in response to 50 U/ml of rhIL-1 alpha. In contrast, extracellular PLA2 activity was maximal in postconfluent cultures, with 50 U/ml of rhIL-1 alpha causing a 20-fold increase by day 15. PLA2 release by RC cells was not significantly affected by PGE2, the glucocorticoid dexamethasone, or the cyclooxygenase inhibitor indomethacin. Indomethacin partially blocked the inhibition of bone nodule formation caused by rhIL-1 alpha, and exogenous PGE2 reversed this effect. Addition of group I PLA2 from Naja naja venom to RC cells had no effect on bone nodule development; however, group II PLA2 from Crotalus adamanteus venom inhibited the formation of bone nodules in a dose range similar to that induced by rhIL-1 alpha. These results indicate that PGE2 release does not have a direct temporal correlation with increases in PLA2 activity. In addition, the data show that only part of the inhibition of bone formation seen with rhIL-1 alpha is mediated by PGE2 and suggest that extracellular PLA2 also accounts for part of the inhibition.

Animals↗
PubMed1991

Comparison of group I and II soluble phospholipases A2 activities on phagocytic functions of human polymorphonuclear and mononuclear phagocytes.

Soluble phospholipase A2 (PLA2) purified from rheumatoid synovial fluid (group II) and repurified Naja naja venom PLA2 (group I) were compared for their influence on phagocytic activity of human polymorphonuclear (PMN) and mononuclear (MO) phagocytes. Group II PLA2 reduced chemotaxis, adhesiveness, and intracellular bactericidal activity (ICBA) and induced release of muramidase from PMNs. Group I PLA2 suppressed chemotaxis, and enhanced ICBA but had no influence on other phagocytic functions. Group II PLA2 purified from synovial fluid or from placenta caused marked spontaneous superoxide generation followed by inhibition of phagocytosis-induced burst of energy. Group I Naja naja and porcine pancreatic PLA2 had no effect on superoxide generation. Group II but not group I PLA2 reduced markedly ICBA of monocytes. It may be concluded that human group II soluble PLA2, in concentrations comparable to those present in inflamed joints or in sera of patients with active arthritis or septic shock, causes spontaneous formation of the oxygen radical superoxide and release of lysosomal enzymes, and suppresses conventional phagocytic activities of PMNs and monocytes. Marked differences between group I and group II PLA2s may mean that these enzymes exert different influences on cell membrane.

Arthritis, Rheumatoid↗
PubMed1991

Enzymatic activity and distribution of phospholipase A2 in human cartilage.

Extracellular phospholipase A2 (PLA2) with proinflammatory activity has recently been discovered in synovial fluids in inflammatory arthritides. In the search for the sources of synovial fluid PLA2, human synovium and articular cartilage were found to contain large quantities of the enzyme. In rheumatoid arthritis (RA), PLA2 activity in synovium, superficial and deep layers of articular cartilage was 20 +/- 14 (SEM), 168 +/- 62 and 533 +/- 176 nmol/min/mg protein respectively. Corresponding values in osteoarthritis (OA) were 49 +/- 11, 569 +/- 109 and 1709 +/- 243 nmol/min/mg protein, all significantly higher (p less than .01) than in RA. Nasal septal cartilage contained much less PLA2, 19 +/- 5.6. PLA2 in human articular and nasal cartilage has sn-2 specificity, a neutral pH optimum and absolute calcium dependence. High PLA2 concentration in articular cartilage may imply that, at least in part, cartilage is the source of PLA2 in the joint space. Since RA cartilage and synovium have less PLA2 activity than the corresponding OA tissues, additional sources of PLA2 in RA synovial fluids are implicated.

Arthritis, Rheumatoid↗
PubMed1991

Extracellular phospholipase A2 secretion is a common effector pathway of interleukin-1 and tumour necrosis factor action.

Inflammatory processes are characterized by increased levels of extracellular phospholipase A2 (PLA2) and cytokines such as interleukin 1 (IL-1) and tumour necrosis factor (TNF). IL-1, TNF and PLA2 share a number of proinflammatory, arthritogenic effects. The sequential induction, first of the cytokines followed by PLA2, suggests that these cytokines may regulate synthesis and secretion of PLA2. To test this postulate, foetal rat calvarial bone-forming cells (FRCC) were treated with recombinant human IL-1 and TNF and extracellular PLA2 release was quantitated. Both IL-1 and TNF induced the de novo synthesis of PLA2 in a concentration-dependent manner. Continuous exposure of FRCC in primary culture to IL-1 (50 units/ml) over 15 days resulted in as much as 100-fold increase in PLA2 secretion. IL-1 (50 units/ml) added to post-confluent cultures for a 48-h pulse increased PLA2 activity 9.4-fold. The combination of IL-1 (50 units/ml) and TNF (500 units/ml) was synergistic with an observed increase in extracellular PLA2 secretion of 146-fold following a 48-h pulse. Interleukin-6, alone or in combination with IL-1 or TNF, did not further enhance PLA2 synthesis of secretion. Cytokine-induced synthesis of PLA2 was inhibited 80% by 10 microM cycloheximide but not by dexamethasone over the range of 10(-6) to 10(-8) M. FRCC-derived PLA2 was neutral-active with a pH optimum of 6-7.5 and was calcium-dependent with optimal activity in the presence of 2-7 mM calcium. It had absolute 2-acyl specificity using micellar phosphatidylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Simultaneous occurrence of subacute cutaneous lupus erythematosus and Sweet syndrome. A marker of Sjögren syndrome?

A 78-year-old man presented simultaneously with subacute cutaneous lupus erythematosus (SCLE) and Sweet syndrome (neutrophilic dermatosis). He was subsequently investigated for and found to have Sjögren syndrome. We believe that the simultaneous occurrence of the above cutaneous manifestations are very suggestive of and should prompt investigation for Sjögren syndrome.

Aged↗
PubMed1991

Acute lung injury induced by phospholipase A2. Structural and functional changes.

On the basis of the observation that serum levels of phospholipase A2 (PLA2) are elevated in pancreatitis and systemic sepsis, and the association of these conditions with the subsequent development of acute lung injury, the present investigation examined the structural and physiologic consequences of intratracheal administration of PLA2 to adult male rats. Rats received direct intratracheal instillation of either control vehicle or 40,000 units/kg of PLA2 repurified from Naja naja venom. Animals treated with PLA2 showed higher cumulative mortality (33% versus 0%, n = 79; p less than 0.01) than did their control littermates. The PLA2-treated animals showed histologic evidence of acute lung injury characterized by interstitial and alveolar edema, accumulation of inflammatory cells, and alveolar wall thickening, which reached maximal severity 48 h after enzyme instillation. Forty-eight hours after PLA2 administration experimental animals had lower arterial oxygen tensions (73.9 +/- 7.66 mm Hg versus 96.7 +/- 2.52 mm Hg, mean +/- SEM; p less than 0.01), higher alveolar-arterial oxygen gradients (35.3 +/- 6.3 mm Hg versus 18.8 +/- 1.42 mm Hg, p less than 0.01), and higher wet-dry lung weight ratios (5.08 +/- 0.26, mean +/- SEM, n = 7 versus 3.29 +/- 0.08, n = 3; p less than 0.002) than did control animals. Lung lavage from experimental animals 48 h after PLA2 instillation showed increased total cell counts [(26.6 +/- 5.04) x 10(6) cells versus (4.69 +/- 1.48) x 10(6) cells; p less than 0.01], an increased percentage of neutrophils (34.2 +/- 4.6% versus 1.25 +/- 0.25%, mean +/- SEM; p less than 0.01), and increased protein concentrations in lavage fluid (0.38 +/- 0.06 mg/ml, mean +/- SEM, n = 4 versus 0.27 +/- 0.02 mg/ml, n = 5; p less than 0.05). The histologic and physiologic abnormalities had largely resolved by 240 h. These results suggest that PLA2 may be a potent mediator of lung inflammation and that intratracheal administration of PLA2 to adult rats may provide a useful experimental model of acute lung injury.

Acute-Phase Reaction↗
PubMed1991

A predictive model for the clearance of soluble phospholipase A2 during septic shock.

Circulating phospholipase A2 (PLA2) has been recognized as a mediator of cardiovascular collapse in septic shock. Proximal mediators of endotoxemia, including tumor necrosis factor and interleukin 1, induce PLA2 synthesis and release, but the factors regulating PLA2 elimination are unknown. Similarly, the kinetics of PLA2 clearance during recovery from septic shock have not been examined. An autoregressive mathematical model was developed to describe the rate of PLA2 clearance during the recovery phase of septic shock. This model (which estimates that the current day's PLA2 level is 77% of the previous day's level), accounted for 89% of the variability seen in the data. The estimated circulating half-life of soluble PLA2 in septic shock in man was 32 hours. Since elevation in serum PLA2 activity is closely associated with bacteremia or endotoxemia, a significant deviation from predicted PLA2 values may denote impending relapse.

Adult↗
PubMed1991

Pneumocystis carinii pneumonia associated with methotrexate therapy in rheumatoid arthritis.

Opportunistic infections occur in patients with rheumatic diseases treated with low dose methotrexate (MTX) with or without other immunosuppressants. Our case report illustrates a fatal case of Pneumocystis carinii pneumonia in a patient with rheumatoid arthritis treated with low dose MTX and glucocorticoid. A review of the literature reveals other opportunistic infections such as Cryptococcus, Nocardia, and herpes zoster presenting in such patients. These occurrences suggest that MTX should be used cautiously in patients with rheumatic disease receiving concomitant medical therapy.

Adolescent↗
PubMed1991

The role of phospholipase A2 in the physiopathology of osteoarthritis.

High activity of phospholipase A2 (PLA2) was found in 58 synovial fluids of patients with osteoarthritis (OA), with a range of 2.2-75.1 nmol/min/ml and mean +/- SEM of 22.0 +/- 1.4 nmol/min/ml. This PLA2 was a calcium dependent enzyme composed of 2 isoforms called A and B. Twelve of 25 patients with OA (48%) were found to have high circulating PLA2, but no correlation to the numbers or size of affected joints was found. High concentrations of PLA2 were detected in human articular cartilage ranging from 33 to 4257 nmol/min/mg protein. The deep layers of the cartilage contained on average 3-fold more PLA2 than the superficial layers. Also synovial cells cultures and chondrocyte cultures that derived from OA joints synthesized and released PLA2 extracellularly. Since PLA2 is proinflammatory, its role in the inflammation that complicates OA process is highly probable. Further studies of PLA2 impact on OA joints and clinical trials with PLA2 inhibitors in OA are warranted.

Cartilage, Articular↗