Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus is one of the major causes of chronic renal failure. Typical findings of diabetic nephropathy are early hyperfiltration followed by microalbuminuria and overt proteinuria, resulting in a progressive decrease in glomerular filtration rate. Rapidly progressive glomerulonephritis has rarely been reported in patients with diabetes mellitus. Here, we describe a patient with MPO-ANCA-associated vasculitis, presenting with pulmonary-renal syndrome. Immunosuppressive treatment, including pulse methyl-prednisolone and cyclophosphamide, was administered and the disease was resolved.
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PMID:MPO-ANCA-associated pulmonary-renal vasculitis in a patient with diabetes mellitus. 1249 92

Non-specific interstitial pneumonia developed as an initial manifestation in a patient with microscopic polyangiitis. A 62-year-old man was admitted to our hospital in March 2001, because of fever and intermittent myalgia of lower extremities. Chest X-ray had revealed reticular shadows in the bilateral middle and lower lung fields since 1996. Just before admission, the patient had been diagnosed as having nonspecific interstitial pneumonia (NSIP) from the specimen obtained by video-assisted thoracoscopic surgery (VATS) in another hospital. Physical examination on admission revealed bilateral episcleritis. Laboratory data showed elevated levels of CRP and KL-6, polyclonal gammaglobulinemia, positive rheumatoid factor and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). Sensory and motor nerve conducting velocities were delayed in left peroneal nerve, but not other nerves, suggesting mononeuropathy. Biopsied specimens of the left quadriceps revealed vasculitis of arteioles. In spite of positive proteinuria and hematuria, no pathological lesion was found in the kidney. From all of these findings, the patient was diagnosed as having microscopic polyangiitis (MPA) without renal involvement. Methylprednisolone pulse therapy followed by intravenous cyclophosphamide pulse therapy improved his clinical conditions such as pyrexia, cough, myalgia, episcleritis and respiratory symptoms with decreased titer of serum MPO-ANCA. Thereafter, the dose of prednisolone was successfully tapered to 10 mg/day without clinical relapse. In the present patient who developed demonstrated non-specific interstitial pneumonia as an initial manifestation of MPA, VATS provided useful diagnostic and prognostic information, leading to an appropriate therapeutic choice.
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PMID:[A case of non-specific interstitial pneumonia in patient with microscopic polyangiitis]. 1459 58

We report a 54-year-old woman with systemic sclerosis who presented alveolar hemorrhage. She noticed shortness of breath in May 1997. She was diagnosed having interstitial pneumonitis and systemic sclerosis with sclerodactylia of bilateral fingers in December. She developed bloody sputum and dyspnea suddenly on March 12, 1999. Bloody lavage fluid with hemosiderin-laden macropharge was observed by bronchial fiber scopic examination. The elevated level of MPO-ANCA was detected without anti-DNA antibody. Administration of intravenous methylprednisolone(1g per day, 3 days) followed by 40 mg per day of prednisolone achieved complete response, and MPO-ANCA level was decreased. Mild proteinuria and microhematuria was detected on admission, but renal biopsy revealed no findings of crescent formation or angiitis. With coadministration of oral cyclophosphamide she doesn't have any renal involvement or recurrence of alveolar hemorrhage during these four years. MPO-ANCA level remains negative. Alveolar hemorrhage, which is uncommon pulmonary event in systemic sclerosis, is often coexist with renal angiitis in the context of "pulmo-renal syndrome". MPO-ANCA is said to be related to pulmo-renal syndrome and is sometimes induced by D-penicillamine. This patient is really important in considering the pathogenesis of alveolar hemorrhage because she had no renal vasculitic lesions or D-penicillamine intake.
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PMID:[Case of systemic sclerosis presenting with alveolar hemorrhage and positive anti-neutrophil cytoplasmic myeloperoxidase antibody(MPO-ANCA) without pathological renal involvement]. 1459 64

We report a case with microscopic polyangiitis (MPA) complicated by varicella zoster encephalitis. A 60-year-old woman caught a common cold and had acute otitis media in April 1998. Proteinuria and hematuria with hyaline cast were noted at the routine medical check in May, and she was referred to our hospital because of high fever and chest pain. MPA was diagnosed with acute progressive renal failure, pleuritis and elevated anti-neutrophil cytoplasmic myeloperoxidase antibody (MPO-ANCA). Corticosteroid therapy was administered under hemodialysis but MPA was flared several times with various symptoms including interstitial pneumonitis, alveolar hemorrhage and erythema multiforme exudativum. During the course of the disease she developed disseminated varicella zoster and encephalitis. Positive polymerase chain reaction to varicella zoster in cerebrospinal fluid helped to differentiate her encephalitis from central nervous system symptoms due to microscopic angiitis and herpes simplex encephalitis. Combination of corticosteroid and acyclovir therapies for MPA and varicella zoster encephalitis under hemodialysis were successful. The diagnostic process and therapies to these complicated contexts were thought to be very important.
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PMID:[Successfully treated case with microscopic polyangiitis complicated severe varicella zoster virus infection including encephalitis and disseminated varicella zoster]. 1459 66

This study was carried out to elucidate whether the protective activity of (-)-epicatechin 3-O-gallate (ECg) against excessive peroxynitrite (ONOO(-)) production, is distinct from the activity of several well-known free radical inhibitors, the ONOO(-) inhibitors ebselen and uric acid, the superoxide anion (O(2)(-)) scavenger copper zinc superoxide dismutase (CuZnSOD) and the selective inducible nitric oxide synthase inhibitor L-N(6)-(1-iminoethyl)lysine hydrochloride (L-NIL). To generate ONOO(-), male Wistar rats (n = 6/group) were subjected to ischaemia-reperfusion process together with lipopolysaccharide (LPS) injection. Although ECg did not scavenge the ONOO(-) precursors nitric oxide (NO) and O(2)(-), it reduced the 3-nitrotyrosine level, a property similar to that of uric acid, but distinct from L-NIL. In addition, the elevation in myeloperoxidase activity was reversed by the administration of ECg, uric acid and SOD, but not by that of L-NIL. Furthermore, ECg was the more potent scavenger of the ONOO(-) decomposition product, the hydroxyl radical (*OH), than any other free radical inhibitor tested. The LPS plus ischaemia-reperfusion process resulted in renal dysfunction, estimated by measuring the parameters of renal function--serum urea nitrogen and creatinine levels. However, administration of ECg ameliorated renal dysfunction more than that of the other free radical inhibitors. Moreover, ECg reduced the excessive uric acid level, while the others did not, suggesting a property of ECg distinct from the others. Furthermore, proteinuria, which was demonstrated by the low- and high-molecular weight (LMW and HMW) protein bands of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis pattern, caused by LPS plus ischaemia-reperfusion, was attenuated by administration of ECg and L-NIL, after which the HMW band intensities decreased and LMW protein bands were absent. This study indicates that, in an in-vivo model of ONOO(-) generation, ECg, L-NIL and uric acid exert stronger protective activity against ONOO(-)-induced oxidative damage than SOD and ebselen, and that the mechanism whereby ECg protects against ONOO(-) is distinct from that of L-NIL or uric acid.
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PMID:(-)-Epicatechin 3-O-gallate ameliorates the damages related to peroxynitrite production by mechanisms distinct from those of other free radical inhibitors. 1500 82

Inflammatory infiltrates can modify (lipo)proteins via hypochlorous acid/hypochlorite (HOCl/OCl(-)) an oxidant formed by the myeloperoxidase-H(2)O(2)-halide system. These oxidatively modified proteins emerge in tubuli in some proteinuric and interstitial diseases. Human proximal tubular cells (HK-2) were used to confirm the hypothesis of detrimental and differential impact of HOCl-modified low density lipoprotein (HOCl-LDL), an in vivo occurring lipoprotein modification exerting proatherogenic and proinflammatory capacity. HOCl-LDL showed dose-dependent antiproliferative effects in HK-2 cells. Small dedicated cDNA macroarrays were used to identify differentially regulated genes. A rapid increase in the expression of genes involved in reactive oxygen species metabolism and cell stress, eg, heme oxygenase-1, thioredoxin reductase, cytochrome b5 reductase, Gadd 153, amino acid transporter E16, and HSP70 was found after HOCl-LDL treatment of HK-2 cells. In parallel, genes involved in tissue remodeling and inflammation eg, CTGF, VCAM-1, IL-1beta, MMP7, and VEGF were up-regulated. Quantitative RT-PCR verified differential expression of a subset of these genes in microdissected tubulointerstitia from patients with acute tubular damage, progressive proteinuric renal disease, and membranous glomerulonephritis (with declining renal function), but not in stable patients with proteinuria caused by minimal change disease. The demonstration of selective up-regulation of a subgroup of genes if proteinuria is accompanied by the presence of HOCl-modified (lipo)proteins support the potential pathophysiological role of the myeloperoxidase-H(2)O(2)-halide system and HOCl-LDL in renal disease.
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PMID:Influence of native and hypochlorite-modified low-density lipoprotein on gene expression in human proximal tubular epithelium. 1516 51

A 17-year-old woman was admitted because of proteinuria, microhematuria and liver dysfunction with increased antinuclear antibody and anti-myeloperoxidase antibody (MPO-ANCA). Fourteen months' previously, urinalysis and liver function showed normal range. At that time she suffered from tachycardia and weight reduction, diagnosed as Graves' disease, she was given propylthiouracil for treatment of her Graves' disease. The histological finding of renal biopsy was compatible with minor glomerular abnormalities. Liver biopsy finding was compatible with autoimmune hepatitis. After we had administered prednisolone, liver function returned to normal range and urine protein became negative. Then we performed subtotal thyroidectomy, and she was not given propylthiouracil. MPO-ANCA decreased gradually.
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PMID:Graves' disease accompanied by anti-myeloperoxidase antibody-related nephropathy and autoimmune hepatitis. 1528 91

Granulopoiesis-related genes are distinctively upregulated in peripheral leukocytes of patients with antineutrophil cytoplasmic autoantibodies (ANCA)-associated glomerulonephritis. Affymetrix microarrays identified the upregulation of nine neutrophilic primary granule genes, including myeloperoxidase (MPO) and proteinase 3 (PR3), plus five secondary granule genes. Coordinate expression of granulocyte maturation marker CD35, measured by TaqMan PCR, and positive in situ staining for PR3 transcripts in polymorphic neutrophils and monocytes indicate that these genes are expressed in "mature" cells. Increased transcripts correlated with disease activity and absolute neutrophil values but not with "left shift," drug regimen, cytokine levels, hematuria, proteinuria, ANCA titer, serum creatinine, gender, or age. Upregulation of PR3 and MPO transcripts was specifically associated with ANCA disease (n = 56) as these changes were not detected in patients with ESRD (n = 25) or systemic lupus erythematosus (n = 17), as determined by TaqMan PCR. This is the first report of this phenomenon in nonneoplastic cells. The data raise the hypothesis that, in addition to the presence of anti-MPO or anti-PR3 autoantibodies, a second critical component in the cause of this disease is the reactivation of once-silenced genes leading to increased antigen availability.
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PMID:Circumvention of normal constraints on granule protein gene expression in peripheral blood neutrophils and monocytes of patients with antineutrophil cytoplasmic autoantibody-associated glomerulonephritis. 1528 96

Infiltrated neutrophils is believed to contribute to the progression of vasculitis. In particular, myeloperoxidase (MPO)-specific antibodies against neutrophils, anti-neutrophil cytoplasmic antibodies (MPO-ANCA) is involved in the development of vasculitis microscopic polyangiitis etc. In Japan a higher percentage of MPO-ANCA than that in Europe has been reported In addition, we showed a correlation of MPO-ANCA epitopes of Kawasaki disease patients by 47% with that of mothers'. On the other hand, mice having CADS/CAWS-induced vasculitis is a good model for the analysis of the production of MPO-ANCA. We have clarified that MPO is a major antigen for MPO-ANCA production using MPO KO mice. We also investigated the role of activated neutrophils in nephritis renal lesions using SCG/Kj mice. In the phase of nephritis with low grade of proteinuria, the spontaneous release of MPO from peripheral neutrophils increased, indicating that neutrophils are activated and contribute to the development of active crescentic lesion in SCG/Kj mice.
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PMID:Contribution of myeloperoxidase in vasculitis development. 1550 59

We report on successful induction of remission in a patient with necrotizing crescentic glomerulonephritis associated with myeloperoxidase-antineutrophil-cytoplasm antibodies by primary use of the anti-tumor necrosis factor (TNF)-alpha chimeric monoclonal antibody infliximab in combination with corticosteroids only. The standard treatment containing cyclophosphamide has reduced the former high mortality from systemic vasculitides. However, the toxicity of this alkylating agent limits its long-term use. As TNF-alpha has been shown to play a central pathogenic role in vasculitis as well as in crescentic glomerulonephritis, anti-TNF-alpha treatment in combination with cyclophosphamide has been found to be effective in therapy-resistant vasculitis. Previous reports on TNF-alpha-blocking therapies without additional cyclophosphamide did not include patients with active and severe crescentic glomerulonephritis. As our patient refused cyclophosphamide, he was given four infusions of infliximab (4 mg/kg on weeks 0, 2, 6 and 10) and methylprednisolone pulses (1 g on days 1-3), followed by daily oral prednisolone (starting with 2 mg/kg and tapering down to 5 mg daily within 3 months). After 12 weeks, control biopsy demonstrated lack of active glomerular inflammation while initially reduced renal function (creatinine 271 versus 172 mol/l, clearance 26 versus 62 ml/min) and proteinuria (2.4 versus 1.0 g/d) improved. Under remission maintenance therapy with azathioprine and prednisolone, the patient showed no relapses during a 1-year follow-up. Finally we demonstrate that there might be patients with crescentic glomerulonephritis who do not require therapy with alkylating substances and that less toxic agents such as the TNF-alpha-blocking monoclonal antibody infliximab could play a role in future primary treatment of crescentic glomerulonephritis.
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PMID:Crescentic glomerulonephritis associated with myeloperoxidase-antineutrophil-cytoplasmic antibodies: first report on the efficacy of primary anti-TNF-alpha treatment. 1564 40


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