Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The etiology of acute pancreatitis is based on several causes, among which idiopathic nature (< 30%) is second to biliary stone disease (60-70%). It is still under debate whether alcohol as the main cause of chronic pancreatitic disease can cause acute pancreatitis. Based on Opie's "obstruction theory" of 1901 and experimental data, it is now widely accepted that the gallstone passage into or through the terminal biliopancreatic ductal system triggers acute (necrotizing) pancreatitis by causing pancreatic ductal obstruction. However, the sequential intracellular mechanisms in the pathogenesis of acute pancreatitis remain unclear. A co-localization hypothesis has been proposed to explain the premature intracellular activation of trypsinogen to trypsin: due to a yet unknown defect in the intracellular protein transport and sorting system within the acinar cell, lysosomal hydrolases (i.e. cathepsin B) and secretory proteins (i.e. trypsinogen) co-localize in a fragile postgolgi vacuole where activation can occur. In addition, alterations of exo- and endocytosis at the apical pole exist (i.e. secretion block). The pathophysiological events are characterized by local and systemic hypovolemia and (micro)circulatory failure aggravating necrosis, followed by ARDS, renal failure and several other severe complications (i.e. sepsis and DIC). The systemic overflow of proteolytic enzymes (i.e. PLA-2) and kinins plays a major role as mediating factor in severe cases, resulting in multiorgan failure.
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PMID:[Etiology, pathogenesis and pathophysiology of acute pancreatitis]. 928 10

We describe here the broad spectrum of acute renal insufficiency occurring in the course of human immunoinsufficiency virus infection. In our renal unit in Tenon hospital, 90 human immunoinsufficiency virus-infected adult patients were admitted for acute renal insufficiency between June 1988 and December 1996. Sixty out of them had a pathological diagnosis. The remaining patients did not have renal biopsy because of obstructive renal failure (n = 2), bleeding risk (n = 11), or clinically evident hypovolemic and/or sepsis-related acute tubular necrosis (n = 17). Nine different causes of acute renal insufficiency were listed. Human immunoinsufficiency virus-associated nephropathy, the most specific human immunoinsufficiency virus-related renal disease, which was diagnosed in 14 patients, is characterized by focal and segmental glomerulosclerosis with an important hyperplasia and/or proliferation of podocytes and huge tubular distension. The rapid progression to end-stage renal failure was not a constant feature since 10/14 patients had a partial renal recovery. Hemolytic-uremic syndrome was the other major cause of acute renal failure in these patients (32 cases) and was found to be associated with active cytomegalovirus infection. Cytomegalovirus-infected cells were present in half of the renal biopsies performed in this group of patients. Furthermore, these patients had an increased plasma tissue-type plasminogen activator activity whereas its type 1 inhibitor was not significantly increased, as opposed to non human immunoinsufficiency virus-associated hemolytic-uremic syndrome. Half of the patients had a complete renal recovery. The other causes of acute renal insufficiency were 1) intratubular deposition of either drugs (Adiazine, Foscavir, Indinavir) in 13 patients, or monoclonal light chain in one patient with B cell-lymphoma; 2) lupus-like glomerulonephritis characterized in one case by a complete clinical remission after 6 month-treatment by antiproteases; 3) acute tubular necrosis. In this setting, rhabdomyolysis could reveal HIV infection. The heterogeneity of renal diseases could be explained by the variation of human immunoinsufficiency virus-associated infections along time and by the different drugs which permit a better survival. We can hypothesize that new HIV-associated diseases will occur with the long term use of antiproteases.
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PMID:[Human immunodeficiency virus and acute renal insufficiency]. 961 98

1493 patients were enrolled in 55 centers in Europe, Canada, Australia and the USA comparing the efficacy of mycophenolate mofetil (MMF) in daily doses of 2 and 3 g with placebo/azathioprine (PLA/AZA) for the prevention of acute rejection in renal transplant patients. Acute rejections and graft loss and death at 1 year were measured per trial and these data were combined and analyzed in a pooled fashion. The three pooled treatment groups were well balanced regarding demographic characteristics and cause of renal failure leading to transplantation. At one year the graft survival rate was 90.4% and 89.2% in the MMF 2 g and 3 g groups compared with 87.6% in the PLA/AZA-group. MMF 2 and 3 g were significantly better than PLA/AZA in reducing biopsy proven rejection at one year: 40.8% placebo/aza vs. 19.8% in the MMF 2 g group and 16.5% in the MMF 3 g group.
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PMID:[Mycophenolate mofetil (MMF) for prevention of kidney transplant rejection. A new immunosuppressive agent. International Mycophenolate Mofetil Study Group]. 964 26

We describe the clinical case of a patient with acute myocardial infarction treated with t-PA fibrinolysis, who developed renal failure and cutaneous lesions of the livedo reticularis type, probably caused by embolization of cholesterol crystals. The main characteristics of this rare clinical entity are reviewed.
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PMID:[Skin lesions and renal failure after myocardial infarction]. 1170 47

Crotoxin B (CB or Cdt PLA(2)) is a basic Asp49-PLA(2) found in the venom of Crotalus durissus terrificus and it is one of the subunits that constitute the crotoxin (Cro). This heterodimeric toxin, main component of the C. d. terrificus venom, is completed by an acidic, nontoxic, and nonenzymatic component (crotoxin A, CA or crotapotin), and it is related to important envenomation effects such as neurological disorders, myotoxicity, and renal failure. Although Cro has been crystallized since 1938, no crystal structure of this toxin or its subunits is currently available. In this work, the authors present the crystal structure of a novel tetrameric complex formed by two dimers of crotoxin B isoforms (CB1 and CB2). The results suggest that these assemblies are stable in solution and show that Ser1 and Glu92 of CB1 and CB2, respectively, play an important role in the oligomerization. The tetrameric and dimeric conformations resulting from the association of the isoforms may increase the neurotoxicity of the toxin CB by the creation of new binding sites, which could improve the affinity of the molecular complexes to the presynaptic membrane.
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PMID:Insights into the role of oligomeric state on the biological activities of crotoxin: crystal structure of a tetrameric phospholipase A2 formed by two isoforms of crotoxin B from Crotalus durissus terrificus venom. 1827 84

There are some doubts whether in a severe renal failure the dose of alteplase should not be modified, especially when its plasma clearance may be decreased by liver ischemia. The authors present a case of a 67-year old woman with massive pulmonary embolism (PE) and acute renal failure (creatinine 580 micromol/l) of a mixed etiology (renal calculosis with hydronephrosis and shock as PE presentation). Alteplase administration (10 mg bolus followed by reduced to 50 mg two hours infusion) resulted in hemodynamic stabilization but was complicated by gross subcutaneous hematomas, intensive epistaxis and hematuria, and hemoglobin decrease which required blood transfusions.
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PMID:[Massive pulmonary embolism treated with a reduced dose of alteplase in a patient with acute renal failure]. 1880 42

Aortic thrombosis is rarely observed in neonates and infants. Underlying conditions include the presence of umbilical artery catheters, thrombosed aneurysm of the ductus arteriosus, sepsis and different states of inherited thrombophilia. Treatment options include anticoagulation, thrombolytic therapy and thrombectomy. Due to the lack of large studies, neither diagnosis nor treatment of neonatal aortic thrombosis are standardized.From 2008-2010, 1 neonate and 1 infant were admitted to our hospital with symptomatic aortic thrombosis.In both patients, diagnosis was made by Doppler ultrasound. Both patients were effectively treated with recombinant tissue type plasminogen activator. Diagnosis and treatment of 2 infants with symptomatic aortic thrombosis are discussed and the literature is reviewed.Since aortic thrombosis is a life-threatening condition, early diagnosis by Doppler ultrasound is mandatory to initiate treatment without delay. Thrombolytic therapy is a safe measure to treat this condition if administered with caution and if the patient has not suffered from serious complications such as mesenteric infarction or renal failure prior to begin of therapy.
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PMID:Thrombosis of the aorta abdominalis in infants--diagnosis and thrombolytic therapy. 2237 39

The development of well-tolerated and effective therapies that target the pathogenesis of membranous nephropathy (MN) would be useful. Our objective was to evaluate the efficacy of rituximab in MN. We analyzed the outcome of 28 patients treated with rituximab for idiopathic MN. Anti-PLA(2)R antibodies in serum and PLA(2)R antigen in kidney biopsy were assessed in 10 and 9 patients, respectively. Proteinuria was significantly decreased by 56, 62 and 87% at 3, 6 and 12 months, respectively. At 6 months, 2 patients achieved complete remission (CR) and 12 partial remission (PR; overall renal response, 50%). At 12 months (n = 23), CR was achieved in 6 patients and PR in 13 patients (overall renal response, 82.6%). Three patients suffered a relapse of nephrotic proteinuria 27-50 months after treatment. Univariate analysis suggested that the degree of renal failure (MDRD estimated glomerular filtration rate <45/ml/min/1.73 m(2)) is an independent factor that predicts lack of response to rituximab. Anti-PLA(2)R antibodies were detected in the serum of 10 patients, and PLA(2)R antigen in immune deposits in 8 of 9 patients. Antibodies became negative in all 5 responsive patients with available follow-up sera. In this retrospective study, a high rate of remission was achieved 12 months after treatment.
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PMID:Rituximab treatment for membranous nephropathy: a French clinical and serological retrospective study of 28 patients. 2247 Mar 99

A 51-year-old male with untreated hepatitis C infection, cirrhosis, and dilated cardiomyopathy with a HeartMate II LVAD presented with right heart failure and cardiogenic shock, INR of 7, hemolysis, and renal failure. Acute LVAD thrombosis was suspected. Alteplase was injected into the inflow cannula of the LVAD with little effect. Intravenous alteplase was given but failed to restore an adequate pump output, resulting in the need for emergency pump exchange. The patient had an uncomplicated postoperative recovery and was discharged uneventfully. Inspection of the pump identified a thrombus wedged between the spines of the impeller. Our case highlights the challenges in managing pump thrombosis which is often resistant to thrombolysis and may instead rely upon prompt surgical intervention to be resolved.
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PMID:Failed repeated thrombolysis requiring left ventricular assist device pump exchange. 2271 66

Antibodies to myeloperoxidase (MPO) and proteinase 3 (PR3) have been demonstrated to mediate anti-neutrophil cytoplasmic antibody (ANCA)-associated disease. For membranous nephropathy, antibodies to the podocyte-expressed phospholipase A(2) receptor (anti-PLA(2)R) are highly associated with disease activity and have been reported in at least 70% of patients with idiopathic membranous nephropathy (IMN). We present a case of a 56-year-old male with a 1 year history of hypertension, leg edema, and proteinuria, who presented with advanced renal failure and was found to have both ANCA-associated glomerulonephritis (GN) and IMN on kidney biopsy. Consistent with the idea that this is due to the chance occurrence of two independent diseases, we found both anti-MPO and anti-PLA(2)R antibodies in the patient's sera. Treatment with methylprednisolone, plasmapheresis, and cyclophosphamide resulted in improvement in kidney function and proteinuria, together with the simultaneous decrease in both autoantibodies. This is the first demonstration of two pathogenic antibodies giving rise to ANCA-associated GN and IMN in the same patient. It confirms the importance of classifying disease based upon the underlying mechanism, in addition to renal histopathology, to both optimize therapy and predict prognosis.
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PMID:Coexistence of ANCA-associated glomerulonephritis and anti-phospholipase A(2) receptor antibody-positive membranous nephropathy. 2283 9


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