Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lung transplantation has become an accepted treatment modality for end stage lung disease including emphysema, fibrosing alveolitis, cystic fibrosis, pulmonary hypertension and bronchiectasis. Despite the use of potent immunosuppressive drugs, acute rejection occurs frequently, especially in the first few weeks and months after transplantation. Bacterial, viral and fungal infections frequently occur in lung transplant recipients. Rapid diagnosis and adequate treatment of infections is needed. The side effects with the use of long term immunosuppressive agents includes renal toxicity, hypertension, neurotoxicity, hyperlipidemia, leucopoenia, hyperglycaemia, weight gain, osteoporosis and malignancy. However, obliterative bronchiolitis (OB) which is regarded as a chronic rejection process remains the dominant cause of morbidity and mortality in the long-term survivors of lung transplantation. This article focuses on the postoperative and long term management of lung transplant recipients.
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PMID:Lung transplantation: management and complications. 1184 31

The epithelial Na+ channel (ENaC) forms the pathway for Na+ absorption in the kidney collecting duct and other epithelia. Dominant gain-of-function mutations cause Liddle's syndrome, an inherited form of hypertension resulting from excessive renal Na+ absorption. Conversely, loss-of-function mutations cause pseudohypoaldosteronism type I, a disorder of salt wasting and hypotension. Thus, ENaC has a critical role in the maintenance of Na+ homeostasis and blood pressure control. Altered Na+ absorption in the lung may also contribute to the pathogenesis of cystic fibrosis. Epithelial Na+ absorption is regulated in large part by mechanisms that control the expression of ENaC at the cell surface. Nedd4, a ubiquitin protein ligase, binds to ENaC and targets the channel for endocytosis and degradation. Liddle's syndrome mutations disrupt the interaction between ENaC and Nedd4, resulting in an increase in the number of ENaC channels at the cell surface. Aldosterone and vasopressin also regulate Na+ absorption to defend against hypotension and hypovolemia. Both hormones increase the expression of ENaC at the cell surface. The goal of this review is to summarize recent data on the regulation of ENaC expression at the cell surface.
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PMID:The epithelial Na+ channel: cell surface insertion and retrieval in Na+ homeostasis and hypertension. 1194 47

Mutations in WNK1 and WNK4, genes encoding members of a novel family of serine-threonine kinases, have recently been shown to cause pseudohypoaldosteronism type II (PHAII), an autosomal dominant disorder featuring hypertension, hyperkalemia, and renal tubular acidosis. The localization of these kinases in the distal nephron and the Cl(-) dependence of these phenotypes suggest that these mutations increase renal Cl(-) reabsorption. Although WNK4 expression is limited to the kidney, WNK1 is expressed in many tissues. We have examined the distribution of WNK1 in these extrarenal tissues. Immunostaining using WNK1-specific antibodies demonstrated that WNK1 is not present in all cell types; rather, it is predominantly localized in polarized epithelia, including those lining the lumen of the hepatic biliary ducts, pancreatic ducts, epididymis, sweat ducts, colonic crypts, and gallbladder. WNK1 is also found in the basal layers of epidermis and throughout the esophageal epithelium. The subcellular localization of WNK1 varies among these epithelia. WNK1 is cytoplasmic in kidney, colon, gallbladder, sweat duct, skin, and esophagus; in contrast, it localizes to the lateral membrane in bile ducts, pancreatic ducts, and epididymis. These epithelia are all notable for their prominent role in Cl(-) flux. Moreover, these sites largely coincide with those involved in the pathology of cystic fibrosis, a disease characterized by deranged epithelial Cl(-) flux. Together with the known pathophysiology of PHAII, these findings suggest that WNK1 plays a general role in the regulation of epithelial Cl(-) flux, a finding that suggests the potential of new approaches to the selective modulation of these processes.
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PMID:WNK1, a kinase mutated in inherited hypertension with hyperkalemia, localizes to diverse Cl- -transporting epithelia. 1252 52

The low affinity A(2B) adenosine receptor, like any other adenosine receptor subtype, belongs to the super-family of seven transmembrane domain protein-coupled receptors (7TMs GPCR) and is classified by the GPCR database in the family of rhodopsin like receptors (Class A of GPCR). It has been cloned from various species, including rat and human, and its sequences are highly similar across species, ranging from 85% identity between human and mouse and 95% identity between rat and mouse. The A(2B)receptors show a ubiquitous distribution, the highest levels are present in cecum, colon and bladder, followed by blood vessels, lung, eye and mast cells. Through A(2B) receptors adenosine seems to cause mast cells degranulation, vasodilation, cardiac fibroblast proliferation, inhibition of Tumor Necrosis Factor (TNF-alpha), increased synthesis of interleukin-6 (IL-6), stimulation of Cl(-) secretion in intestinal epithelia and hepatic glucose production. Hence, A(2B) adenosine receptor agonists could be useful in the treatment of cardiac diseases like hypertension or myocardial infarction and in the management of septic shock, while antagonists may serve as novel drugs for asthma, Alzheimer's disease, cystic fibrosis and type-II diabetes. No potent and selective A(2B) agonists have been reported so far; 5'-N-ethylcarboxamidoadenosine (NECA) is one of the most active. The monosubstitution on N(6)-position of adenosine is well tolerated and that position appears to be a useful site for increasing A(2B) potency. Among substituents in 2-position of adenosine only 1-alkynyl chains are effective for A(2B) potency. In particular, the (S)-2-hydroxypropynyl substituents brought about the highest activity demonstrating that the A(2B) receptors discriminate between (R) and (S) diastereomers. Hence, (S)-2-phenylhydroxypropynylNECA (PHPNECA), with an EC(50) = 0.22 micro M, proved to be the most potent A(2B) agonist reported so far. Classical antagonists for adenosine receptors are alkylxanthines which show considerable potency at A(2B) receptors. Para substituted 1,3-dialkyl-8-phenylxanthines possess high affinity in binding assays; the 3-unsubstituted 1-alkyl analogues resulted more A(2B) selective with the 8-[4-[(N-(2-hydroxyethyl)carboxamidomethyl)oxy]phenyl]-1-propylxanthine (60) showing the highest affinity (K(i) = 1.2 nM) and selectivity (A(1)/A(2B) = 60, A(2A)/A(2B) = 1,790, A(3)/A(2B) = 360). Among non-xanthine derivatives very promising are substituted purines, in which combination of appropriate substituents in 2-, 8-, and 9-position could lead to very potent and selective A(2B) antagonists.
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PMID:Medicinal chemistry and pharmacology of A2B adenosine receptors. 1257 Jul 60

The decisive limiting parameter in such patients is the lower oxygen partial pressure in inhaled air. It is, however, still possible for patients with coronary heart disease, high blood pressure or bronchial asthma to tolerate high altitudes without having to experience health problems. Prerequisites, however, are adequate acclimatization, optimal medication and pre-travel stable status. In addition, patients must be informed about emergency measures and how to recognize high-altitude sickness. To prevent pneumothorax leading to rapid decompression during flights, particular attention must be addressed to the problem of trapped air in patients with emphysema or cystic fibrosis.
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PMID:[Toleration of high altitudes by patients with heart and pulmonary diseases]. 1266 39

Following a pulmonary transplantation for cystic fibrosis, 2 patients exhibited a syndrome associating arterial hypertension, headache, visual trouble and generalized seizures. Cerebral magnetic resonance imaging revealed diffuse cortical and subcortical lesions predominantly in posterior regions. The exclusion of alternate diagnoses and the disappearance of the symptoms when the cyclosporine treatment was stopped confirmed the diagnosis of cyclosporine-related reversible posterior encephalopathy syndrome (PRES). Immediate appropriate management resulted in symptom disappearance and regression of radiological images.
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PMID:[Posterior reversible encephalopathy syndrome: about 2 cases related to the cyclosporine]. 1283 74

Alpha-fetoprotein (AFP) was 1 of the first serum protein markers to serve in the dual capacities of tumor marker and fetal defect marker, ie, an oncofetal protein, in the clinical laboratory. Although the serum-marker capacity of AFP has long been used, less is known of the fluid compartments of this oncofetal protein during fetal and perinatal development. In this review, the biologic activities of AFP are discussed in light of its presence in the various biologic fluid compartments: fetal serum, amniotic fluid, cord blood, urine, and maternal serum. AFP concentrations within the biologic fluids are considered in the context of gestational age, sex, body weight, and anatomic location. Discussion follows concerning the relationships and roles of AFP in various developmental disorders such as hypothyroidism, folate deficiencies, autoimmune disorders, acquired immunodeficiency disorder (AIDS), congenital heart defects, cystic fibrosis, preeclampsia/hypertension, and platelet aggregation disorders. Based on its presence in so many types of birth defects, malformations, and congenital anomalies, AFP can be seen to serve as a form of molecular "duct tape" during pregnancy and postnatal development.
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PMID:Levels of alpha-fetoprotein during pregnancy and early infancy in normal and disease states. 1466 62

Tissue microarrays (TMAs) are an ordered array of tissue cores on a glass slide. They permit immunohistochemical analysis of numerous tissue sections under identical experimental conditions. The arrays can contain samples of every organ in the human body, or a wide variety of common tumors and obscure clinical cases alongside normal controls. The arrays can also contain pellets of cultured tumor cell lines. These arrays may be used like any histological section for immunohistochemistry and in situ hybridization to detect protein and gene expression. This new technology will allow investigators to analyze numerous biomarkers over essentially identical samples, develop novel prognostic markers and validate potential drug targets. The ability to combine TMA technology with DNA microarrays and proteomics makes it a very attractive tool for analysis of gene expression in clinically stratified tumor specimens and relate expression of each particular protein with clinical outcome. Public domain software allows researchers to examine digital images of individual histological specimens from TMAs, evaluate and score them and store the quantitative data in a relational database. TMA technology may be specifically applied to the profiling of proteins of interest in other pathophysiological conditions such as congestive heart failure, renal disease, hypertension, diabetes, cystic fibrosis and neurodegenerative disorders. This review is intended to summarize the strengths and weaknesses of TMA technology which will have an increasingly important role in the laboratories of the post-genomic era.
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PMID:Post-genomic applications of tissue microarrays: basic research, prognostic oncology, clinical genomics and drug discovery. 1470 1

Lung transplantation is indicated for patients with cystic fibrosis, emphysema, pulmonary fibrosis or pulmonary hypertension whose life expectancy is less than two years. Criteria of severity are detailed. Three types of transplantation can be proposed: single lung transplant for fibrosis and dry emphysema; bilateral lung transplant for cystic fibrosis, and certain types of emphysema and pulmonary hypertension; heart-lung transplant for pulmonary hypertension and Eisenmenger syndrome. Due to insufficient supply of donor organs, one quarter of the candidates die on the waiting list and the limit for inscription is often 60 years. Postoperative mortality at two months is about 15% and is related to graft dysfunction, infection, bronchial complications,... Acute rejection usually occurs during the first year. Chronic rejection is expressed by obliterating bronchiolitis, the leading cause of death after one year. There is a risk of cancer (EBV-induced lymphoproliferative syndromes and skin cancer). Five-year survival is still only about 50%. Immunosuppressor treatments still cause numerous adverse effects (hypertension, renal toxicity...); function and quality-of-life have however greatly improved.
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PMID:[Lung transplantation]. 1513 44

G-protein-coupled receptor kinases (GRKs) interact with the agonist-activated form of G-protein-coupled receptors (GPCRs) to effect receptor phosphorylation and to initiate profound impairment of receptor signalling, or desensitization. GPCRs form the largest family of cell surface receptors known and defects in GRK function have the potential consequence to affect GPCR-stimulated biological responses in many pathological situations. This review focuses on the physiological role of GRKs revealed by genetically modified animals but also develops the involvement of GRKs in human diseases as, Oguchi disease, heart failure, hypertension or rhumatoid arthritis. Furthermore, the regulation of GRK levels in opiate addiction, cancers, psychiatric diseases, cystic fibrosis and cardiac diseases is discussed. Both transgenic mice and human pathologies have demonstrated the importance of GRKs in the signalling pathways of rhodopsin, beta-adrenergic and dopamine-1 receptors. The modulation of GRK activity in animal models of cardiac diseases can be effective to restore cardiac function in heart failure and opens a novel therapeutic strategy in diseases with GPCR dysregulation.
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PMID:Pathophysiological roles of G-protein-coupled receptor kinases. 1589 65


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