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

Measurements have been made of the urinary content of inositol phosphoglycans IPG P-type and IPG A-type, putative insulin second messengers, in preeclampsia, in type I insulin-treated diabetic pregnant women and their matched control subjects, and nonpregnant women of child-bearing age. The content of IPG P-type and IPG A-type was also measured in the placenta from preeclamptic patients and from normal pregnancies. Pregnancy was associated with an increase, approximately twofold, in urinary output of IPG-P-type relative to nonpregnant controls (P<0.01). The 24-h output of IPG P-type in urine in preeclamptic women was significantly higher (2- to 3-fold) than in pregnant control subjects matched for age, parity, and stage of gestation (P<0.02). In contrast, insulin-dependent diabetic pregnant women did not show any significant change in urinary output of IPG P-type or IPG A-type relative to pregnant control subjects. Evidence for a possible relationship and correlation between the urinary excretion of IPG P-type and markers of preeclampsia, including proteinuria (r = 0.720, P<0.01), plasma aspartate transaminase (r = 0.658, P<0.05), and platelet counts (r = 0.613, P<0.05) is presented. A high yield of IPG P-type was extracted from human placenta, in preeclampsia some 3-fold higher (P = 0.03) than the normal value, whereas no IPG A-type (with lipogenic-stimulating activity) was found. Low concentrations of placental IPG A-type were detected relative to IPG P-type using assay systems dependent upon the effect of this mediator on cAMP-dependent protein kinase or on a proliferation assay using thymidine incorporation into DNA of EGFR T17 fibroblasts. It is postulated that the high urinary excretion IPG P-type in preeclampsia reflects high placental levels and relates to the accumulation of glycogen in the placenta. The paracrine effects of placental IPG P-type (stimulation off other endocrine glands and/or endothelial cells) could contribute to the pathogenesis of the maternal syndrome. A possible theoretical link between elevated placental IPG P-type and apoptosis is proposed.
 ...
PMID:Inositol phosphoglycans and signal transduction systems in pregnancy in preeclampsia and diabetes: evidence for a significant regulatory role in preeclampsia at placental and systemic levels. 1072 Apr 42

Pre-eclampsia--edema, proteinuria, hypertension (EPH-gestosis) is one of the more common complications observed during pregnancy. The umbilical cord vein walls were taken from newborns delivered by healthy mothers (control material) and by mothers with polysymptomatic pre-eclampsia (investigated material). Normal saphenous vein walls were collected from adult subjects undergoing varicose vein surgery. The collagen content was measured by the assay of hydroxyproline. Elastin was determined according to Fastin Elastin Assay and gravimetrically. Glycosaminoglycans content was determined by uronic acids assay. The collagen content decreased in the pre-eclampsia material. The amount of soluble elastin increased in the investigated material. The insoluble elastin content decreased in the umbilical cord veins of newborns delivered by mothers with pre-eclampsia. Reconstructing the umbilical cord vein wall may disturb fetal blood flow and affect the vascular system in adulthood.
 ...
PMID:Extracellular matrix components of the wall of umbilical cord vein and their alterations in pre-eclampsia. 1087

With the aim of developing an effective therapy for heavily pretreated refractory MM outpatients, we evaluated the OPPEBVCAD regimen, a Hodgkin's disease-derived protocol that includes many drugs effective in MM administered in a sequential schedule. Twenty-two pts aged 42-72 years, with symptomatic highly-pretreated refractory (18 cases), or primary resistant MM (four cases. including two pts with plasma cell leukemia-PCL) received this therapy every 28 days (2-4 cycles, followed by a maintenance program). Therapeutic response (Chronic Leukemia-Myeloma Task Force criteria) and performance status (PS) and pain (W.H.O.) were evaluated. All of the pts were evaluable for response. There were 9 (40%) objective responses (OR: stabilization of blood counts and bone lesions, serum calcium normalization, 50% or more reduction in the concentration of serum monoclonal component (MC), 90% reduction in Bence-Jones proteinuria), 8 (36%) partial responses (PR: 25-50% reduction in serum MC), 1 no response or stable disease (NR), and 4 (18%) cases of progressive disease (PD). OR plus PR were 77%. Of the 4 primary resistant tumors (2 PCL and 2 MM), 2 achieved PR, 1 OR (a PCL case) and 1 progressed. Median survival was 15 months for responding pts (OR plus PR) and 4.5 months for non-responders (NR plus PD). PS and pain improved in 15 pts and did not change in 9. The most frequent side effects were cytopenias, with one drug related infective death. The OPPEBVCAD regimen proved to be an effective therapy for refractory relapsing or primary resistant MM: in responders (two-thirds of the pts), survival was prolonged by about 10 months. Its efficacy in anthracycline-treated pts, as well as the feasibility of using it on an outpatient basis without any continuous drug infusions, make this regimen a promising third line salvage therapy.
 ...
PMID:OPP-EBV-CAD regimen as salvage treatment in advanced refractory or resistant multiple myeloma. 1142 32

Oedema/proteinuria/hypertension (EPH) gestosis is one of the more common complications observed during pregnancy. Our previous studies demonstrated some qualitative and quantitative changes in the extracellular matrix of Wharton's jelly in newborns delivered by mothers with EPH gestosis. For this reason it was decided to evaluate the effect of EPH gestosis on the activity of gelatinolytic and proteolytic enzymes which may be involved in collagen degradation in Wharton's jelly. Zymographic analysis of control and EPH gestosis samples of Wharton's jelly demonstrates different electrophoretic patterns of gelatinolytic enzymes. The control Wharton's jelly contains two latent forms of gelatinolytic enzymes: gelatinase A [metalloproteinase (MMP)-2, 72 kD] and gelatinase B (MMP-9, 92 kD). In contrast to control tissue, the main gelatinolytic enzyme of EPH gestosis Wharton's jelly is gelatinase A (MMP-2). It was found that the proteolytic activity in EPH gestosis Wharton's jelly differs from control. The decrease in gelatinase activity may be one of the factors which promote the accumulation of collagen in this tissue.
 ...
PMID:The activity of collagen-degrading enzymes of Wharton's jelly in EPH gestosis (pre-eclampsia). 1158 83

Edema, proteinuria, hypertension (EPH-gestosis), most commonly termed as pre-eclampsia, is the most common pregnancy-associated pathological syndrome. It is accompanied by a thorough remodelling of extracellular matrix in the umbilical cord tissues. It is commonly known that the presence of serum in culture medium strongly stimulates many functions of cells cultured in vitro. It was decided to check how the pre-eclamptic serum affects the fibroblast division in culture. Ki-67 is a protein present in proliferating cells and can be detected during all phases of the cell cycle (G1, S, G2/M) but not in resting (G0) cells. PCNA (proliferating cell nuclear antigen) is an intranuclear polypeptide whose synthesis rate is at its maximum during the S-phase of the cell cycle. The expression of Ki-67 and PCNA was measured by immunocytochemical methods and biosynthesis of DNA was evaluated by [14C]-thymidine incorporation. The activity of pre-eclamptic umbilical cord serum (UC-serum) was found to be distinctly lower in comparison to control one. The expression of Ki and PCNA in fibroblast cultures treated with pre-eclamptic serum was also distinctly lower. Also the incorporation of [14C]-thymidine to DNA was lower than in the cultures treated with control UC-serum. It may by concluded that pre-eclampsia reduces the mitogenic activity of the umbilical cord serum.
 ...
PMID:The effect of pre-eclamptic umbilical cord serum on fibroblast division in culture. 1250 91

Persistent proteinuria has been indicated to be a major risk factor for the development of tubulointerstitial damage through a process of proinflammatory molecule expression. Monocyte chemoattractant protein-1 (MCP-1) was shown to contribute to recruitment of immune cells into the renal interstitium in acute and chronic renal diseases. However, the molecular mechanisms by which proteinuria causes MCP-1 expression in proximal tubular cells have not been fully clarified. In this study, we examined whether albumin overload-induced MCP-1 expression was regulated by mitogen-activated protein kinase (MAPK) in mouse proximal tubular (mProx) cells. Exposure of mProx cells to delipidated bovine serum albumin (BSA) induced mRNA and protein expression of MCP-1 in a time- and dose-dependent manner. BSA activated extracellular signal-regulated kinase (ERK1/2) and p38 MAPK. The MEK inhibitor U-0126 partially suppressed BSA-induced MCP-1 expression and MCP-1 promoter/luciferase reporter activity. U-0126 also inhibited an increase in nuclear factor-kappaB and activator protein-1 DNA-binding activity of MCP-1 promoter by protein overload in mProx cells. In addition, we found that U-0126 inhibited BSA-induced nuclear factor-kappaB reporter activity and inhibitory protein degradation in mProx cells. In conclusion, these findings indicate that ERK signaling is involved in BSA-induced MCP-1 expression in mProx cells.
 ...
PMID:Involvement of ERK pathway in albumin-induced MCP-1 expression in mouse proximal tubular cells. 1251 35

Although dietary fish oil supplementation has been used to prevent the progression of kidney disease in patients with IgA nephropathy, relatively few studies provide a mechanistic rationale for its use. Using an antithymocyte (ATS) model of mesangial proliferative glomerulonephritis, we recently demonstrated that fish oil inhibits mesangial cell (MC) activation and proliferation, reduces proteinuria, and decreases histologic evidence of glomerular damage. We therefore sought to define potential mechanisms underlying the antiproliferative effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the predominant omega-3 polyunsaturated fatty acids found in fish oil, in cultured MC. DHA and EPA were administered to MC as bovine serum albumin fatty-acid complexes. Low-dose (10-50 micromol/L) DHA, but not EPA, inhibited basal and epidermal growth factor (EGF)-stimulated [(3)H]-thymidine incorporation in MCs. At higher doses (100 micromol/L), EPA and DHA were equally effective in suppressing basal and EGF-stimulated MC mitogenesis. Low-dose DHA, but not EPA, decreased ERK activation by 30% (P <.01), as assessed with Western-blot analysis using phosphospecific antibodies. JNK activity was increased by low-dose DHA but not by EPA. p38 activity was not significantly altered by DHA or EPA. Cyclin E activity, as assessed with a histone H1 kinase assay, was inhibited by low-dose DHA but not by EPA. DHA increased expression of the cell cycle inhibitor p21 but not p27; EPA had no effect on p21 or p27. We propose that the differential effect of low-dose DHA vs EPA in suppressing MC mitogenesis is related to down-regulation of ERK and cyclin E activity and to induction of p21.
 ...
PMID:Differential effects of low-dose docosahexaenoic acid and eicosapentaenoic acid on the regulation of mitogenic signaling pathways in mesangial cells. 1276 75

A dynamic cytoskeleton allows podocytes to withstand significant mechanical stress on elevation of intraglomerular capillary pressure (Pgc). However, vasoactive hormones, such as prostaglandin E2 (PGE2), may challenge the integrity of the actin cytoskeleton, alter podocyte morphology, and compromise glomerular permeability. PGE2 synthesis correlates with the onset of proteinuria and increased Pgc following reduced nephron mass. We investigated the interplay among mechanical stress, cyclooxygenase (COX), E-prostanoid (EP) receptor expression, and the actin cytoskeleton, using an in vitro model of cell stretch. Immortalized mouse podocytes grown on flexible silicone membranes were cyclically stretched (5% elongation, 0.5 Hz) for 2 h. EP4 and COX-2 mRNA increased three- and sevenfold above nonstretched controls, whereas EP1 and COX-1 levels were unchanged. Six hours of stretch resulted in a threefold increase in PGE2-stimulated cAMP accumulation, a measure of EP4 receptor function, and an increase in COX-2 protein. The stretch-induced effects on COX-2/EP4 expression and EP4-induced cAMP production were attributable to p38 MAP kinase, as blockade of this pathway, but not of ERK or JNK, abrogated the response. These stretch-induced changes in expression were transcriptionally dependent as they were actinomycin D sensitive. Finally, we investigated the influence of enhanced EP4 signaling on the actin cytoskeleton. Addition of PGE2 resulted in actin filament depolymerization observable only in stretched cells. Our results indicate that key components of the eicosanoid pathway are upregulated by mechanically stimulated p38 MAP kinase in podocytes. Enhanced EP4 receptor signaling may undermine podocyte cytoskeletal dynamics and thereby compromise filtration barrier function under conditions of increased Pgc.
 ...
PMID:p38 MAP kinase mediates mechanically induced COX-2 and PG EP4 receptor expression in podocytes: implications for the actin cytoskeleton. 1466 34

Glomerular endothelial cell (GEC) dysfunction due to oxidative stress and enhanced proinflammatory cytokines plays an important role in inducing proteinuria and procoagulant activity, namely blood hypercoagulability, hyperviscosity and local intravascular coagulation and altered hemorheology in NS. A dysfunctioning GEC releases fewer endothelium-dependent vasodilators but produces more vasoconstrictors. Severe intrarenal hemodynamic alteration associated with hemodynamic maladjustment with preferential constriction at the efferent arteriole has been uniquely implicated in severe GN and NS-FSGS. Such a constriction exerts three significant hemodynamic impacts. Proximal to the efferent arteriolar constriction, it induces (i) an overestimated GFR due to hyperfiltration and (ii) an elevated intraglomerular hydrostatic pressure. Distal to the efferent arteriolar constriction, it (iii) exaggeratedly reduces PTCF which correlates with the TIF.
 ...
PMID:A hemodynamically mediated mechanism of renal disease progression in severe glomerulonephritides or nephrosis. 1472 39

Apoptosis is implicated in the progressive cell loss and fibrosis both at glomerular and tubulointerstitial level. In this study, we examined the potential mechanisms by which persistent proteinuria (protein-overload model) could induce apoptosis. After uninephrectomy (UNX), Wistar rats received daily injections of 0.5 g of bovine serum albumin (BSA)/100 g body weight or saline. Both at day 8 and day 28, rats receiving BSA had proteinuria and renal lesions characterized by tubular atrophy and/or dilation and mononuclear cell infiltration. In relation to control-UNX rats, renal cortex of nephritic rats showed an increment in AT2 mRNA (reverse transcriptase-polymerase chain reaction) and protein (Western blot) expression. In both groups, AT2 receptor immunostaining was mainly localized in proximal tubular cells. Rats with persistent proteinuria showed a significantly increased number of terminal dUTP nick-end labeling positive apoptotic cells compared with UNX-controls, both in glomeruli and tubulointerstitium. Double staining for apoptosis and AT2 receptor showed that most terminal dUTP nick-end labeling positive cells were found in tubules expressing AT2 receptor. Using an antibody that recognizes the active form caspase-3, we observed an increment in caspase-3 activation in rats receiving BSA with respect to those receiving saline. Rats with persistent proteinuria showed a diminution in the phosphorylation of Bcl-2 with respect to UNX-controls both at day 8 and day 28. By contrast, no changes were observed either in the Bax or in the Bcl-2 protein levels. The administration of BSA to UNX rats induced a diminution in the phosphorylation of ERK with respect to UNX-control at all times studied. The changes observed in ERK activities took place without alterations of ERK1/2 protein levels. In summary, our data suggest that persistent proteinuria causes apoptosis in tubular cells through the activation of AT2 receptor, which can, in turn, inhibit MAP kinase (ERK1/2) activation and Bcl-2 phosphorylation.
 ...
PMID:Persistent proteinuria up-regulates angiotensin II type 2 receptor and induces apoptosis in proximal tubular cells. 1511 28


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>