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)

A meeting in Singapore of principal investigators from 7 countries in a WHO collaborative study on hypertensive disease of pregnancy, also called pre-eclampsia or eclampsia, pointed out women at risk, suggested management guidelines, and summarized operations research projects involving administration of aspirin or calcium supplements. Hypertensive disease of pregnancy may ultimately end in fatal seizures. It is often marked by warning signs of severe headaches and facial and peripheral edema. A survey in Jamaica found that 0.72% of a group of 10,000 pregnant women had eclamptic seizures. These were the cause of almost one-third of all obstetric deaths in the period 1981-1983. 10.4% of the pregnant women had hypertension, and half of these had proteinuria. Associated risk factors were primigravida, age 30, abnormal weight gain, edema, 1+ proteinuria. A phased program of management guidelines for identifying and treating affected women is being instituted in half of Jamaica's parishes. An operations research project involves administration of low-dose aspirin vs. placebo. Another controlled trial, in Peru, is testing calcium supplements. A third trial in Argentina will compare 2 drug regimens.
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PMID:Hypertensive diseases of pregnancy. 1228 29

Pre-eclampsia is a pregnancy specific syndrome that is a principal cause of maternal morbidity and mortality, accounting for almost 15% of pregnancy associated deaths, and is one of the major causes of iatrogenic prematurity among new born babies. The mild form of pre-eclampsia most commonly presents with the features of maternal hypertension and proteinuria, but can swiftly and unpredictably become severe with numerous multisystem complications involving the maternal liver, kidneys, lungs, blood and platelet coagulation and nervous systems. The diverse symptoms of pre-eclampsia have made it a difficult disease not only to define, but also to identify a causative agent for the symptoms. This review examines the complex endocrinological mechanisms believed to be responsible for the extensive complications of pre-eclampsia from the role of placental and endothelial dysfunction, to the causes of the oxidative stress and the ensuing general inflammation. It also highlights current endocrine findings that exhibit the potential for clinical application, as either potential markers or novel therapeutic targets, with the aim of either preventing or altering the course of this life-threatening disease of pregnancy.
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PMID:The endocrinology of pre-eclampsia. 1235 23

1. Pre-eclampsia is a human disease of pregnancy characterized by high blood pressure, proteinuria and end-organ damage, if severe. Pre-eclampsia is thought to be related to changes in early placental development, with the formation of a shallower than normal placental bed. 2. Transforming growth factor (TGF)-beta1 is a multifunctional fibrogenic growth factor involved in immune regulation that is elevated in some populations with a high risk of hypertensive end-organ disease related to increases in endothelin release. Transforming growth factor-beta1 is also an important factor in placental implantation. Alterations in TGF-beta1 may be related to abnormal placental development in early pregnancy and, thus, are a candidate for the development of hypertension in pre-eclampsia. 3. The aim of the present study was to examine the placental distribution and serum concentration of TGF-beta1 in patients with pre-eclampsia compared with normal pregnancy. 4. Patients with pre-eclampsia (n = 12) were compared with patients with normal pregnancy (n = 14). Transforming growth factor-beta1 was determined by TGF-beta1 Max ELISA (Promega, Madsion, WI, USA) after serum dilution (1/150) and acid activation. Placental distribution was determined by immunostaining with TGF-beta1 (Santa Cruz, Santa Cruz, CA, USA; 20 ng/mL) and the villi and decidual trophoblast were scored for intensity and extent of staining. 5. Patients with pre-eclampsia had a mean gestational age of 36 weeks, whereas those with a normal pregnancy had a mean gestational age of 39.0 +/- 0.4 weeks. There was no difference in TGF-beta1 concentration between the two groups (mean (+/-SEM) 27.1 +/- 1.0 vs 26.4 +/- 0.7 pg/mL for normal pregnancy and pre-eclampsia, respectively; P = 0.73, Mann-Whitney U-test). There was no correlation between systolic or diastolic blood pressure and TGF-beta1 concentration (regression analysis P = 0.4 and 0.2). Immunostaining was absent in the villous trophoblast cells and endovascular and extravillous trophoblast of term placentas. 6. Although TGF-beta1 is present in trophoblast cells in early pregnancy during placental development, TGF-beta1 concentrations were not increased in the placenta at term in pre-eclampsia and there was no correlation between blood pressure and serum TGF-beta1, suggesting that TGF-beta1 does not play a role in the development of late gestation pre-eclampsia and hypertension.
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PMID:Transforming growth factor-beta 1 does not relate to hypertension in pre-eclampsia. 1236 87

Pre-eclampsia (PE) is a pregnancy-specific syndrome that is a principal cause of maternal morbidity and mortality, accounting for almost 15% of pregnancy-associated deaths. It is also one of the major causes of iatrogenic prematurity among new born babies, placing a heavy burden on both prospective parents and on the health service. The mild form of PE most commonly presents with the features of maternal hypertension and proteinuria but can swiftly and unpredictably become severe with many extensive complications, which can involve the maternal liver, kidneys, lungs, blood and platelet coagulation and nervous systems. These clinical problems normally only become apparent in the second half of pregnancy but are believed to start during the first trimester. The diverse symptoms of PE have made it a difficult disease not only to define but also to identify a causative agent for the symptoms. It has therefore proved difficult to develop specific drugs that can be used to manage the condition in the clinic. Therapeutic intervention so far has been primarily aimed at combating the two main complications of PE - the hypertension and seizures. Current therapies are widely recognised as inadequate. This review examines the complex pathological mechanisms believed to be responsible for the multi-system complications of PE. It highlights current findings that exhibit the potential to target these effects with the aim of either preventing or altering the course of this life-threatening disease of pregnancy.
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PMID:Emerging molecular targets for the treatment of pre-eclampsia. 1254 Feb 73

Preeclampsia (PE) is a complication of the second half of the pregnancy whose clinical course is hypertension and proteinuria with or without edema. Its pathogenesis is characterized with generalized vasoconstriction and endothelial dysfunction. The aim of this study is to evaluate the diagnostic value of the Doppler ultrasound examination of the renal interlobar vessels in pregnancy complicated with preeclampsia in the context of the theory of the increased vessel resistance in this pregnancy disorder.
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PMID:[Diagnostic value of the Doppler ultrasound of kidney vessels in pregnancy complicated with preeclampsia]. 1551 79

Pre-eclampsia, a disease of pregnancy, is a cause of maternal and fetal mortality worldwide and a major factor in preterm birth. Up to 10% of primipara suffer from this disorder, characterized by pregnancy-induced hypertension and proteinuria, usually in the third trimester when fetal demands on the placenta are greatly increased. The disease is thought to stem from an insufficiency in utero-placental blood flow triggering a cascade of events leading to the maternal syndrome, which may have been initiated by defective placentation early in pregnancy. Theories abound as to the primary cause of the placental pathologies associated with the disease, including those based on maternal immunity and the unique immune environment of the placental bed. Accumulating evidence from animal models, genetic studies, and isolated decidual leukocytes suggests that decidual natural killer (NK) cells supply factors necessary for development and arterial modification of the maternal-fetal interface. This beneficial role of NK cells to normal placentation may shed light on the cause of the placental pathologies observed in pre-eclampsia.
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PMID:NK cells and pre-eclampsia. 1828 77

Preeclampsia is a life-threatening hypertensive disease of pregnancy. The condition is characterized by the presence of autoantibodies that activate the major angiotensin receptor, AT(1). Research conducted during the past decade has shown that these autoantibodies activate AT(1) receptors on a variety of cell types and provoke biological responses that are relevant to the pathophysiology of preeclampsia. The introduction of these autoantibodies into pregnant mice results in hypertension, proteinuria and a variety of other features of preeclampsia including small fetuses and placentas. These findings demonstrate the pathophysiological role of these autoantibodies in preeclampsia. The biological properties of these autoantibodies can be blocked by a 7-amino acid peptide that corresponds to a specific sequence associated with the second extracellular loop of the AT(1) receptor. The fact that autoantibodies from different individuals are directed to a common epitope provides obvious diagnostic and therapeutic opportunities. Research reviewed here raises the intriguing possibility that preeclampsia may be a pregnancy-induced autoimmune condition characterized by the presence of disease-causing angiotensin receptor activating autoantibodies.
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PMID:Is preeclampsia an autoimmune disease? 1950 Oct 24

Renal injury is a common pathophysiological feature in women with preeclampsia as evidenced by increased protein leakage (proteinuria) and glomerular injury (glomerular endotheliosis). Recently, podocyturia was found in preeclampsia, suggesting podocyte shedding occurs in this pregnancy disorder. However, podocyte function in preeclampsia is poorly understood. In this study, the authors have examined podocyte-specific protein expressions for nephrin, glomerular epithelial protein 1 (GLEPP-1), and ezrin in kidney biopsy tissue sections from women with preeclampsia. Expressions for vascular endothelial growth factor (VEGF) and its receptor Flt-1 and oxidative stress marker nitrotyrosine and antioxidant CuZn-superoxide dismutase (CuZn-SOD) were also examined. Kidney tissue sections from nonhypertensive and chronic hypertensive participants were stained as controls. The findings were (1) nephrin and GLEPP-1 were mainly expressed in glomerular podocytes; (2) ezrin was expressed in both glomerular podocytes and tubular epithelial cells; (3) compared to tissue sections from nonhypertensive and chronic hypertensive participants, nephrin and GLEPP-1 expressions were much reduced in tissue sections from preeclampsia and ezrin expression was reduced in podocytes; (4) enhanced VEGF, Flt-1, and nitrotyrosine, but reduced CuZn-SOD, expressions were observed in both glomerular podocytes and endothelial cells in tissue sections from preeclampsia; and (5) the expression pattern for nephrin, GLEPP-1, ezrin, VEGF, Flt-1, and CuZn-SOD were similar between tissue sections from nonhypertensive and chronic hypertensive participants. Although the authors could not conclude from this biopsy study whether the podocyte injury is the cause or effect of the preeclampsia phenotype, the data provide compelling evidence that podocyte injury accompanied by altered angiogenesis process and increased oxidative stress occurs in kidney of patients with preeclampsia.
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PMID:Decreased nephrin and GLEPP-1, but increased VEGF, Flt-1, and nitrotyrosine, expressions in kidney tissue sections from women with preeclampsia. 1981 96

Preeclampsia is a common disease of pregnancy, characterized by high blood pressure and proteinuria appearing from the second trimester of gestation. Preeclampsia has been shown to have a strong genetic component. In 2005 a positional cloning project led to the discovery of the STOX1 transcription factor, and mutations of this gene were proposed as causal for preeclampsia in Dutch families. Despite the publication of three contradictory studies, we have shown by analyzing the functional effects of STOX1 that its overexpression in choriocarcinoma cells recapitulates several transcriptomic aspects of preeclampsia. In this review, the current literature is analyzed to evaluate the possible involvement of STOX1 in the pathogenesis of this disease. While preeclampsia obviously cannot be considered as a disease caused by mutation in a single gene, we argue that STOX1 may be at the center of common pathways leading to preeclampsia.
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PMID:Re-evaluation of the role of STOX1 transcription factor in placental development and preeclampsia. 1957 9

Preeclampsia is a heritable pregnancy disorder that presents new onset hypertension and proteinuria. We have previously reported genetic linkage to preeclampsia on chromosomes 2q, 5q and 13q in an Australian/New Zealand (Aust/NZ) familial cohort. This current study centered on identifying the susceptibility gene(s) at the 5q locus. We first prioritized candidate genes using a bioinformatic tool designed for this purpose. We then selected a panel of known SNPs within ten prioritized genes and genotyped them in an extended set of the Aust/NZ families and in a very large, independent Norwegian case/control cohort (1,139 cases, 2,269 controls). In the Aust/NZ cohort we identified evidence of a genetic association for the endoplasmic reticulum aminopeptidase 1 (ERAP1) gene (rs3734016, P (uncorr) = 0.009) and for the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene (rs2549782, P (uncorr) = 0.004). In the Norwegian cohort we identified evidence of a genetic association for ERAP1 (rs34750, P (uncorr) = 0.011) and for ERAP2 (rs17408150, P (uncorr) = 0.009). The ERAP2 SNPs in both cohorts remained statistically significant (rs2549782, P (corr) = 0.018; rs17408150, P (corr) = 0.039) after corrections at an experiment-wide level. The ERAP1 and ERAP2 genes encode enzymes that are reported to play a role in blood pressure regulation and essential hypertension in addition to innate immune and inflammatory responses. Perturbations within vascular, immunological and inflammatory pathways constitute important physiological mechanisms in preeclampsia pathogenesis. We herein report a novel preeclampsia risk locus, ERAP2, in a region of known genetic linkage to this pregnancy-specific disorder.
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PMID:The ERAP2 gene is associated with preeclampsia in Australian and Norwegian populations. 1957 76


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