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)

Steroid 17 alpha-hydroxylase (cytochrome P-450(17)alpha) mediates both 17 alpha-hydroxylase and 17,20-lyase activities. A relatively rare disease, 17 alpha-hydroxylase deficiency is characterized by defects in either or both of these activities. The molecular basis for variability of the defect is not well understood. We have determined the exonic sequence of the mutant P-450(17)alpha gene from one Japanese patient with combined 17 alpha-hydroxylase/17,20-lyase deficiencies. A stop codon (TGA) due to a single point mutation was found at the position of amino acid 17 in exon 1 of the P-450(17)alpha gene. The presence of a stop codon in the N-terminal region of this gene leads to the absence of a functional P-450(17)alpha protein in adrenal cortex and ovary, and consequently hypertension, primary amenorrhea and osteoporosis in this patient.
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PMID:Combined 17 alpha-hydroxylase/17,20-lyase deficiency due to a stop codon in the N-terminal region of 17 alpha-hydroxylase cytochrome P-450. 326 89

CONVERSION OF CORTISOL TO CORTISONE: 11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) is a microsomal enzyme complex which, in humans, catalyses the interconversion between biologically active cortisol and inactive cortisone. This prereceptor signalling mechanism is essential for maintaining the aldosterone selectivity of the intrinsically non-specific mineralocorticoid receptor and for modulating glucocorticoid access to the glucocorticoid receptor. Apparent mineralocorticoid excess (AME) is a syndrome of severe low-renin mineralocorticoid hypertension associated with marked hypokalaemia which arises from a congenital deficiency of 11 beta-HSD. In AME patients, therefore, it is cortisol and not aldosterone which behaves as a potent mineralocorticoid. ISOFORMS OF 11 BETA-HSD: Two isoforms of human 11 beta-HSD have now been characterized and cloned. The type 1 isoform (11 beta-HSD1) is a low-affinity reduced nicotinamide adenine dinucleotide phosphate (NADP) dependent dehydrogenase-oxoreductase which is expressed in predominantly glucocorticoid target tissues and the encoding sequence of which is normal in patients with AME. In contrast, the type 2 isoform (11 beta-HSD2) is a high-affinity NADP-dependent unidirectional dehydrogenase which is expressed in placenta and mineralocorticoid target tissues such as renal collecting ducts and distal colonic epithelia. Exon- and intron-specific polymerase chain reaction amplification of the 11 beta-HSD2 gene from genomic DNA from members of a consanguinous kindred with AME consistently revealed a single missense mutation (C1228T) in two affected sibs and twin stillbirths. This mutation in codon 374 of exon 5 of the 11 beta-HSD2 gene creates an inframe premature stop (TGA) and, as such, results in a truncated 11 beta-HSD2 protein lacking the carboxyl-terminal proline-rich 32 amino acids. In keeping with an autosomal recessive mode of inheritance, both parents were phenotypically and biochemically normal but were heterozygous for this mutation. Unique to this kindred were expression analyses of the native mutant 11 beta-HSD2 enzyme in the stillbirth-affected placenta, which was almost completely devoid of NADP-dependent 11 beta-dehydrogenase activity. Immunohistochemical and Western blot analyses revealed the absence of 11 beta-HSD2 protein using antisera raised against synthetic peptide sequences corresponding either to the carboxyl terminus or other domains of the enzyme. MISSENSE MUTATION: In this kindred with AME, congenital deficiency of 11 beta-HSD activity is due to a single missense mutation in exon 5 of the 11 beta-HSD2 gene. Simultaneous studies by two other groups have similarly revealed no gross deletions or rearrangements of the 11 beta-HSD2 gene, but have described a number of single point mutations and oligonucleotide deletions in exons 3, 4 and 5, and adjacent to a splice site in intron 3. Recombinant expression analysis of site-directed mutant 11 beta-HSD2 complementary DNA constructs suggests a correlation between the predicted severity of these mutations and the biochemical and clinical phenotype. AME AS A CAUSE OF HYPERTENSION: The mutations in the 11 beta-HSD2 gene, together with those currently being sought by us for other kindreds with AME, establishes AME as a monogenic cause of human hypertension and will provide insight into the structure-function relationships of this important enzyme.
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PMID:Human hypertension caused by mutations in the 11 beta-hydroxysteroid dehydrogenase gene: a molecular analysis of apparent mineralocorticoid excess. 912 Jun 78

A 7-year-old boy was admitted for RVOT restenosis. The patient was born following an unremarkable pregnancy and delivery. He was carried out Jatene's procedure for TGA at 23rd day after birth. At 19 month of age, he was removed pulmonary stenosis using patch angioplasty with mono cusp. When he was 6 year of age, the onset of edem, ascites and hepatomegaly were pointed out. At 7 year of age, he was admitted for edema, hypoproteinemia and protein loosing enteropatchy. After he was treated medical therapy, cardiac catheterization showed markedly right atrial and right ventricular hypertension and ventricular septal defect (VSD). Cine angiography suggested the right ventricular outflow tract stenosis, pulmonary valve and tricuspid valve insufficiency. On August 1, 1996, the patient underwent surgical repair: direct closure of VSD, aortic homograft (20mm) replacement for RVOT stenosis and tricuspid valve annuloplasty by DeVega's procedure. Postoperative course was uneventful. At 23rd postoperative day, cardiac catheterization and cine angiography showed no problems. He was not treated with anticoagulation.
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PMID:[A case report: right ventricular outflow tract (RVOT) reconstruction using homograft for RVOT restenosis after Jatene's procedure of transposition of the great arteries (TGA)]. 952 29

A 61 year old male patient with left mandibular cyst, received marsupialization of the left mandible under general anesthesia. Four hours after the end of anesthesia, his memory for the past 4 months and short term memory plastisity were impaired. No neurological abnormalies were found at that time. On the 2nd postoperative day, he recovered his lost memory for the past 4 months. The memory of events between 6 hours before operation and next morning, however, remained lost. It is suggested that the memory disorder is the TGA due to various causes including transient hypertension, operative stress, postoperative pain and diazepam.
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PMID:[Transient global amnesia after general anesthesia]. 959 23

Prostacyclin inhibits platelet aggregation, smooth muscle cell proliferation, and vasoconstriction. The prostacyclin synthase (PGIS) gene is a candidate gene for cardiovascular disease. The purpose of this study was to locate possible mutations in the PGIS gene related to hypertension and cerebral infarction. Using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method, we discovered a T to C transition at the +2 position of the splicing donor site of intron 9 in patients with essential hypertension (EH). In vitro expression analysis of an allelic minigene consisting of exons 8-10 revealed that the nucleotide transition causes skipping of exon 9. This in turn alters the translational reading frame of exon 10 and introduces a premature stop codon (TGA). A three-dimensional model shows that the splice site mutation produces a truncated protein with a deletion in the heme-binding region. This splice site mutation was found in only one subject in 200 EH patients and 200 healthy controls. Analysis of the patient's family members revealed the mutation in two of the three siblings. The urinary excretion of prostacyclin metabolites in subjects with the mutation was significantly decreased. All subjects displaying the splice site mutation in the PGIS gene were hypertensive. In this study, we report a novel splicing mutation in the PGIS gene, which is associated with hypertension in a family. It is thought that this mechanism may involve in the pathophysiology of their hypertension.
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PMID:Splicing mutation of the prostacyclin synthase gene in a family associated with hypertension. 1237 4

The objective of this work was to investigate the insulin sensitivity (SI) and the beta cell function (BCF) in different glucose tolerance statuses in a comparative cross-sectional study. Eighty-four patients with different glucose tolerance statues were classified as normoglicemic-control group (NC) patients without family history of type 2 diabetes (DM2) or hypertension (HTN); normoglicemic-patients with familiar history of DM2 or HTN (FPDM2); patients with glucose intolerance (IGT group) and patients with diagnostic of DM2 <10 years (DM2 group). In each patient was obtained a clinical history and an oral glucose tolerance test (75 g) was performed. Glucose (GOD-PAP) and insulin (RIA) were quantified. Insulin Sensitivity (IS) (Whole Body Insulin Sensitivity Index), Insulin resistance (IR) (HOMA) and BCF (insulinogenic index) were evaluated. The statistical analysis was realized in SPSS v. 10.0. It was found that glucose was similar among NC, FPDM2 and IGT groups. Insulin was higher in the FPDM2 (26.71 +/- 22.25 microU/mL), and IGT (34.10 +/- 34.98 microU/mL) in comparison with NC (22.83 +/- 21.26 microU/mL) (p < 0.01). IS was different among NC and IGT group (0.74 +/- 0.43 to 0.29 +/- 0.18, p < 0.05) and among IGT and DM2 (0.29 +/- 0.18 to 0.86 +/- 0.55, p < 0.001). BCF was different among the DM2 and NC (0.051 +/- 0.05 to 1.28 +/- 1.99 microU.mL/mg.dL, p < 0.05), DM2 and FPDM2 group (0.051 +/- 0.05 to 1.23 +/- 1.51 microU.mL/mg.dL, p < 0.01), DM2 and IGT (0.051 +/- 0.05 to 2.64 +/- 2.22 microU.mL/mg.dL, p < 0.001). SI was inversely related to corporal weight and IMC (r = -0.38, p = 0.001 and r = -0.33, p = 0.004, respectively). BCF was related to age (r = -0.27, p = 0.016), the area under curve of glucose (r = -0.30, p = 0.010) and body weight (r = 0.34, p = 0.002). In conclusion, the decrease of glucose tolerance was associated with the lowering of Insulin Sensitivity (IS). The beta cell function (FCB) was lower in the diabetic patients group in comparison with the TGA and FPDM2 groups. These measurements need to be included in patients with high risk for early identification and changes in life style to protect the normal functioning of beta cell and to prevent the onset of IGT or DM2.
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PMID:[Insulin sensitivity and beta cell function in different glucose tolerance status]. 1688 77

Indapamide is used in the treatment of hypertension. In the European Pharmacopoeia it is specified that indapamide may contain up to 3 wt.% of water. On the basis of the results of thermal (TGA, DSC), DVS and X-ray powder diffraction analyses it has been supposed that this feature arises from the fact that indapamide exists in the form of a non-stoichiometric hydrate. The water molecules are only weakly and reversibly bound into the crystal structure. The major framework of the crystal structure, built of indapamide molecules, remains practically unchanged upon dehydration and/or hydration processes. In order to prove this hypothesis and understand the hydration-dehydration behavior, the as yet unknown crystal structure of indapamide needed to be determined. Since it was not possible to grow any adequate single crystals, we decided to solve the structure from laboratory X-ray powder diffraction data. The solved structure confirmed the hypothesis of weakly bound water in the voids between the indapamide molecules and also served as a basis to evaluate and explain the relative humidity dependence of the unit cell parameters of indapamide.
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PMID:Crystal structure of indapamide determined from powered diffraction data. 1728 56

Persistent pulmonary hypertension of the newborn (PPHN) occurs in 1-4% of neonates with transposition of the great arteries with intact ventricular septum (TGA/IVS). This association is often lethal. To our knowledge, only eight survivors have been described in the literature, two of whom benefited from extracorporeal membrane oxygenation (ECMO). We report two cases of PPHN complicating a TGA/IVS that were refractory to multiple therapies and resolved 48 hours after initiation of bosentan therapy. Bosentan, an oral dual endothelin-1 receptor antagonist, is a new treatment for pulmonary arterial hypertension that was both effective and safe in these two cases of TGA/IVS with PPHN. To our knowledge, it is the first use of bosentan in newborns.
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PMID:Persistent pulmonary hypertension of the newborn with transposition of the great arteries: successful treatment with bosentan. 1770 Dec 14

Atherosclerosis is the most common pathophysiologic substrate of coronary artery disease (CAD). Whereas plaque progression and arterial remodeling are critical components in chronic CAD, intracoronary thrombosis over plaque disruption is causally related to acute CAD. It was the objective of this study to investigate the differences between prior acute CAD and chronic CAD by a simple global coagulation assay measuring thrombin generation. A cross-sectional study involving 15 healthy controls, 35 patients with chronic stable CAD, and 60 patients after an episode of acute myocardial infarction (AMI) was performed. Thrombin generation was measured between three and 11 months after the initial diagnosis (mean 6 months) by a commercially available fluorogenic assay (Technothrombin TGA). In each patient the lag phase, velocity index and peak thrombin were obtained from the thrombogram profile. Traditional cardiovascular risk factors were recorded, and the inflammatory markers, fibrinogen and hs-C-reactive protein were determined. Compared with stable CAD patients, showing normal thrombograms, those with previous AMI showed earlier lag phase (p < 0.05) and significant increase of both the velocity index (p < 0.001) and peak thrombin (p < 0.05), indicating faster and higher thrombin generation in the AMI group. Differences in thrombin generation between stable and acute CAD patients remained significant (p < 0.001) after adjusting for conventional CAD risk factors (age, gender, diabetes, hypertension, smoking, and hypercholesterolemia). In conclusion, patients with a previous history of acute CAD showed earlier, faster and higher thrombin generation than stable chronic CAD patients. The thrombin generation test may be of clinical value to monitor hypercoagulable/vulnerable blood and/or guide therapy in CAD.
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PMID:Increased thrombin generation after acute versus chronic coronary disease as assessed by the thrombin generation test. 1827 89

Nuclear genes succinate dehydrogenase B subunit and succinate dehydrogenase D subunit, which encode two mitochondrial complex II subunits, are associated with the development of familial paraganglioma (PGL). Succinate dehydrogenase B subunit gene mutation is highly associated with extraadrenal PGL and subsequent distant metastasis. We describe the case of a 29-year-old Japanese man with a 3-year history of hypertension, headache, and palpitation. Endocrinological examinations showed that the patient had elevated levels of catecholamines, and imaging studies revealed a right paraaortic PGL without distant metastases. The PGL was surgically removed. Genetic analysis of the patient showed a heterozygous thymine deletion at position 470 (c.470delT) in exon 5 of the succinate dehydrogenase B subunit gene complementary DNA. This thymine deletion changed TTG (leucine) to TGA (stop codon) at codon 157 (L157X). It remains unclear whether this mutation was associated with PGL malignancy because the patient has had no metastases for the past 3 years. It has been recently reported that L157X is associated with malignant paraaortic PGL. Thus, strict follow-up is required because this succinate dehydrogenase B subunit gene's nonsense mutation (L157X) may be related to the malignancy.
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PMID:L157X nonsense mutation of the succinate dehydrogenase subunit B gene in a Japanese patient with right paraaortic paraganglioma. 2096 97


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