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)

Diaziquone (AZQ), a synthetic quinone with demonstrated activity against acute nonlymphocytic leukemia (ANLL), primary CNS tumors, and non-Hodgkin's lymphoma (NHL), is virtually devoid of nonhematopoietic toxicity at conventional doses. As a prelude to its inclusion into bone marrow transplant (BMT) preparative regimens, a phase I study of high-dose AZQ with autologous BMT (ABMT) was performed. Patients with refractory solid tumors and lymphomas were treated with a single 24-hour infusion of AZQ at 50 to 355 mg/m2 in dose escalations of 20%. Fifty-six patients received 69 courses. Those receiving greater than 60 mg/m2 had nadir granulocyte and platelet counts less than 500/microL and 20,000/microL, respectively. Nausea, vomiting, stomatitis, and diarrhea were mild, transient, and not dose-related. Transient minimal elevations of liver function tests were seen in five patients and were also not dose-related. The maximally tolerated dose (MTD) of high-dose AZQ was found to be 245 mg/m2, with nephrotoxicity being dose-limiting. Significant azotemia was seen in four of 12 patients treated at 295 and 355 mg/m2, including fatal anuric renal failure in three of these patients. Reversible proteinuria also occurred in 24 of 26 courses above 150 mg/m2, including nephrotic range proteinuria in eight courses, all at doses of 205 to 355 mg/m2. The proteinuria was also associated with multiple proximal tubular defects including generalized aminoaciduria and proximal renal tubular acidosis. There were six early deaths including two of early renal failure (295 and 355 mg/m2), two of sepsis (205 and 245 mg/m2), one of a pulmonary embolus (85 mg/m2), and one of progressive disease (60 mg/m2). Of 50 patients who were assessable for response, there were seven responses including two of 10 with primary CNS tumors, one of 12 with malignant melanoma, one of five with non-small-cell lung carcinoma, two of two with breast carcinoma, and one of one with ovarian carcinoma. Because of its activity in ANLL and NHL and its unique toxicity spectrum, high-dose AZQ may improve the efficacy of current BMT preparative regimens without significantly increasing their nonhematopoietic toxicity.
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PMID:A phase I trial of high-dose diaziquone and autologous bone marrow transplantation: an Illinois Cancer Council study. 207 48

The pathogenetic roles of complement, polymorphonuclear granulocytes, and monocytes were studied in a model of in situ immune complex glomerulonephritis employing a cationized antigen. Left kidneys of Wistar rats were perfused with 40 micrograms of cationized human IgG (isoelectric point greater than or equal to 9.5) followed by intravenous injection of rabbit anti-human IgG 1 hour later. This resulted in prominent subepithelial deposit formation in the perfused kidney accompanied by massive proteinuria. Groups examined were: (a) no additional treatment, (b) C3 depleted (cobra venom factor, (c) granulocyte depleted (specific antiserum), (d) monocyte depleted (specific antiserum), and (e) granulocyte depleted and monocyte depleted. The quantity of radiolabeled cationized antigen deposited in the left kidney was not affected by any of the treatment schedules. Proteinuria was abolished in all mediator depleted groups (b to e) for 5 to 7 days, thereafter rising to levels seen in the nondepleted group (a). This late onset of proteinuria is noteworthy since the deposits are then located subepithelially and may be less accessible to circulating mediators. C3 depletion, despite inhibition of proteinuria, did not prevent the intraglomerular accumulation of granulocytes and monocytes thereby suggesting that attraction and activation of these cells may occur independently. Apparently all three mediators are required for full expression of the lesion, a finding not paralleled in other experimental models of glomerulonephritis. The relevance of very low levels of inflammatory cell infiltration for provoking glomerular injury was clearly demonstrated.
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PMID:Mediator systems in a passive model of in situ immune complex glomerulonephritis. Role for complement, polymorphonuclear granulocytes and monocytes. 294 Apr 17

Applying c-BSA to duplicate immune complex in situ type glomerulonephritis in rabbits and treating it with Blood Circulation Promoting and Stasis-Removing Drugs Mai-Luo-Tong, the results showed that proteinuria in the treated group was decreased significantly, as compared to the control group (P < 0.01). Under light and electron microscope, although glomerular basement membrane was irregularly thickened and subepithelial dense electron deposits were found in both groups, but histopathologic damage in the treated group less than that of control one. In the treated group micro-thrombus, erythrocytes and platelets aggregation, leukocytes impaction were not seen within glomerular capillary. Also in the treated group mesangial cell proliferation and granulocyte infiltration were decreased significantly (P < 0.01) and there was no apparent glomerular fibrosis in former group.
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PMID:[Research on immune complex in situ type glomerulonephritis treated with mai-luo-tong in rabbits]. 849 32

We examined the circulating levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 alpha, IL-6, granulocyte macrophage-colony stimulating factor (GM-CSF), and the anti-inflammatory cytokine IL-10, and their expression in kidneys acutely infected with murine malaria parasite P. berghei ANKA in C57BL/6J mice. Groups of six mice sacrificed on days 5, 10, 15, and 20, and normal controls were used for cytokine analysis. High concentrations of TNF-alpha and IL-10 were detected in plasma as shown by ELISA, and elevated levels of mRNA specific for TNF-alpha and IL-10 in infected kidneys were demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Kidney sections stained with antibodies against TNF-alpha, IL-1 alpha, IL-6, GM-CSF and IL-10 for immunohistochemistry showed markedly enhanced staining for TNF-alpha, and progressively increased staining for IL-1 alpha and IL-6 both in the tubules and the walls of arteries during the course of infection. The endothelia of blood vessels and inflammatory cells located around small arteries showed positive staining for GM-CSF from day 10 onwards. Unlike the staining for proinflammatory cytokines, the anti-inflammatory cytokine IL-10 showed strongly positive staining in normal tubules and walls of arteries, especially in the brush border of proximal tubules, but the staining intensity decreased dramatically after day 15 post-infection. A strongly positive correlation was found between the antibody staining for TNF-alpha/IL-1 alpha in tubules, and the severity of proteinuria. In contrast, there was an inverse correlation between the staining for IL-10 with TNF-alpha/IL-1 alpha, and the degree of proteinuria. Plenty of pigmented macrophages showed positive staining both for proinflammatory and anti-inflammatory cytokines in the tubulointerstitium. Our findings imply that the up-regulation of proinflammatory cytokines and the dysregulation of anti-inflammatory cytokines are involved in the pathogenesis of tubulointerstitial nephritis associated with malaria.
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PMID:Dysregulation of cytokine expression in tubulointerstitial nephritis associated with murine malaria. 955 90

Malaria infections often cause glomerulonephritis (GN), and multiple factors have been implicated in the pathogenesis of glomerular injury. The role of cytokines in malaria associated glomerulonephritis has not been clearly defined. To study the importance of cytokines in malarial nephritis, we investigated the expression of tumour necrosis factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), IL-6, IL-10 and granulocyte macrophage-colony stimulating factor (GM-CSF) in kidneys acutely infected with murine malaria parasite Plasmodium berghei ANKA in C57BL/6 J mice. Groups of six mice sacrificed on days 5, 8-10, 15, and 20 postinfection, and normal controls were used for cytokine analysis. Elevated levels of messenger RNA (mRNA) specific for these cytokines in infected kidneys after day 5 postinfection were demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Kidney sections stained with specific antibodies against TNF-alpha, IL-1alpha, IL-6, IL-10 and GM-CSF by immunohistochemistry showed that the staining for these cytokines on the glomeruli was positive from day 10 postinfection, and increased progressively, mainly in the infiltrating macrophages and the glomerular mesangium. Strong correlation was found between the expression of TNF-alpha with IL-6, and IL-1alpha with IL-6. The expression of TNF-alpha, IL-1alpha, IL-6, and IL-10 also strongly correlated with the severity of proteinuria. Our findings show that there is up-regulation of cytokines in the pathogenesis of glomerulonephritis associated with murine malaria infection.
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PMID:Up-regulation of cytokines in glomerulonephritis associated with murine malaria infection. 1046 63

A computerized Urine Protein Expert System (UPES) measuring creatinine, total protein, albumin, IgG, alpha(1)-microglobulin, alpha(2)-macroglobulin, and N-acetyl-beta-D-glucosaminidase, together with urine dipstick testing for granulocyte esterase and hemoglobin pseudoperoxidase, and measurement of serum creatinine had been found to be useful in adults for differentiating between renal disorders. The objective of this study was to investigate UPES for identifying the different types of proteinuria and their underlying prerenal, glomerular, tubular, and postrenal causes in 146 children characterized by routine and invasive nephrological investigations. UPES proved to be a useful tool in pediatric renal patients after refinements were implemented in the program. Comparing UPES with the pediatric nephrologist's interpretation of all available clinical and laboratory data, UPES diagnosed glomerulopathies in 46 (75%) of 61 patients. In a further 23% it suggested glomerular involvement by indicating either a disturbed glomerular permeability or increased excretion of albumin. Tubular proteinuria was correctly described by UPES in 23 (100%) patients with different tubulopathies. UPES revealed normal kidney function in all healthy children and all children with remission of renal disorders. Therefore, UPES can be regarded as a useful tool in the automated differentiation of renal diseases in children.
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PMID:Evaluation of pediatric nephropathies by a computerized Urine Protein Expert System (UPES). 1060 45

A 67-year-old woman was admitted to our hospital with a fever. She had been experiencing arthralgia for about one month. On admission, she had a fever of 38.5 degrees C, was anemic and was experiencing tenderness in the joints of both hands, elbows and feet. Laboratory data revealed proteinuria, urinary cylinders, pancytopenia (WBC 900/mm3, Hb 9.5 g/dl, Plt 7.8 x 10(4)/mm3), liver dysfunction (GOT 414 IU/l, GPT 140 IU/l), and hyper-gamma globulinemia. Antibiotics and granulocyte-colony stimulating factor were administered intravenously. Bone marrow aspiration was unsuccessful, but a bone marrow biopsy revealed bone marrow fibrosis. Immunological examinations were positive for antinuclear antibodies, anti-deoxyribonucleic acid (DNA) antibodies, anti-double stranded anti- DNA antibodies, as well as a decreased level of serum complement and an increased level of serum immune complexes. Tests for viral antigens and antibodies known to cause hepatitis were negative. Based on these findings, a diagnosis of SLE accompanied by liver dysfunction and bone marrow fibrosis was made. Steroid pulse therapy was initiated, but her liver function deteriorated on the first day of steroid therapy, and she died three days later. SLE accompanied by myelofibrosis is extremely rare, and only 17 and cases have been reported to date. Among these reports, the present case is the second oldest subject and the first SLE patient to suffer from both myelofibrosis and severe liver dysfunction.
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PMID:[A case of elderly-onset systemic lupus erythematosus (SLE) complicated with severe liver dysfunction and pancytopenia due to myelofibrosis]. 1068

It has been suggested that reactive oxygen radicals (ROS) play a crucial role in the pathogenesis of proteinuria and podocyte injury. It was investigated whether changes in gene expression might account for ROS-induced podocyte dysfunction. Differentiated podocytes were incubated with control media or with exogenous ROS from the xanthine/xanthine-oxidase reaction for 4 h. A PCR-based suppressive subtractive hybridization assay was applied to isolate and clone mRNAs that were differentially expressed by exogenous ROS. One differentially expressed clone was identified as the proinflammatory cytokine granulocyte macrophage-colony-stimulating factor (GM-CSF). Regulation of GM-CSF in podocytes was further studied by Northern analysis and enzyme-linked immunosorbent assay. Exogenous ROS caused a concentration-dependent, >10-fold induction of GM-CSF mRNA after 4 h. A >50-fold increase in GM-CSF protein release in podocytes that had been stimulated with ROS could be detected. Induction of GM-CSF protein was inhibited by actinomycin D, which indicated that increased mRNA transcription was involved. The ROS scavengers dimethyl-thio-urea and pyrrolidone-dithio-carbamate strongly inhibited increased GM-CSF production induced by ROS. GM-CSF release was also induced when internal ROS production was triggered with NADH, whereas H2O2 had only a small effect. GM-CSF release by podocytes was also stimulated by lipopolysaccharide (LPS), interleukin-1 (IL-1), and phorbolester (PMA). Dimethyl-thio-urea significantly inhibited the LPS-, IL-1-, and PMA-induced GM-CSF production. Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) but not activator protein-1 was involved in the upregulation of ROS-induced GM-CSF production. The data indicate that GM-CSF is differentially expressed by ROS in podocytes. ROS also partially mediate the effects of PMA and IL-1 on podocyte GM-CSF production. Because GM-CSF can enhance glomerular inflammation and induces mesangial proliferation, these data might provide further insight into the mechanisms of ROS-induced glomerular injury.
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PMID:Reactive oxygen species alter gene expression in podocytes: induction of granulocyte macrophage-colony-stimulating factor. 1175 25

We report a girl with severe congenital neutropenia who has received long-term granulocyte-colony stimulating factor (G-CSF) therapy and has developed macroscopic hematuria, proteinuria, and decreased renal function associated with biopsy-proven membranoproliferative glomerulonephritis (MPGN) type I. Temporary discontinuation of G-CSF therapy as well as the use of glycosylated G-CSF has resulted in improvement in renal manifestations. We postulate that the MPGN was G-CSF-induced. Long-term G-CSF therapy should be used with great caution and close surveillance of kidney function.
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PMID:MPGN type I induced by granulocyte colony stimulating factor. 1204 97

We have shown the possibility to modulate various anemic syndromes during acquired immunodeficiency differed in pathogenesis and induced by graft versus host reaction (GVHR). There are different variants of combined erythro- and immunopoiesis disorders in the semiallogeneic system DBA/2 --> B6D2F1: immunodeficiency plus hemolytic anemia and immunodeficiency plus hemolytic anemia plus immunocomplex glomerulonephritis. In the allogeneic system C57BL/6 --> BALB/c there is immunodeficiency plus hypoplastic anemia with reduced bone marrow erythropoiesis. Differences in pathogenesis of anemic syndrome are connected with the functional properties of macrophages and cytokine production by macrophages. There is some positive effect of chronic hypoxia on GVHR-induced immunopathology in B6D2F1 mice: it increases humoral immune response, has favorable effect on anemia and corrects early and late committed precursor number. The absence of any influence of chronic hypoxia on the secreted activity of macrophages gives an evidence to the direct influence of erythron on the humoral immune response. VM-2-84 has favorable effect on anemia (suppresses IL-1 production, reduces the number of early erythroid precursors and stimulates the amount of the granulocyte and macrophage precursors) in B6D2F1 mice with glomerulonephritis. The compound from alkancarboxylic acids - VM-2-84, up to two months decreases proteinuria and reduces proliferation of mezangiocytes and chronic inflammation with the restoration of immune system. Trecrezan, while having beneficial effect on anemia, reduces a hyperplasia of erythron in mice with immunodeficiency; it influences the production of monokines. The obtained facts about effectiveness of preparation possessing combined erythro- and immunopoiesis-modulating properties, open new ways of a target regulation of disorders of immunity.
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PMID:The Correction of Combined Immuno- and Hemopoiesis Disorders Induced by Graft-Versus-Host Reaction. 1268 18


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