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)

Seventy-two long-surviving liver transplant recipients were evaluated prospectively, including a baseline allograft biopsy for weaning off of immunosuppression. Thirteen were removed from candidacy because of chronic rejection (n = 4), hepatitis (n = 2), patient anxiety (n = 5), or lack of cooperation by the local physician (n = 2). The other 59, aged 12-68 years, had stepwise drug weaning with weekly or biweekly monitoring of liver function tests. Their original diagnoses were PBC (n = 9), HCC (n = 1), Wilson's disease (n = 4), hepatitides (n = 15), Laennec's cirrhosis (n = 1), biliary atresia (n = 16), cystic fibrosis (n = 1), hemochromatosis (n = 1), hepatic trauma (n = 1), alpha-1-antitrypsin deficiency (n = 9), and secondary biliary cirrhosis (n = 1). Most of the patients had complications of long-term immunosuppression, of which the most significant were renal dysfunction (n = 8), squamous cell carcinoma (n = 2) or verruca vulgaris of skin (n = 9), osteoporosis and/or arthritis (n = 12), obesity (n = 3), hypertension (n = 11), and opportunistic infections (n = 2). When azathioprine was a third drug, it was stopped first. Otherwise, weaning began with prednisone, using the results of corticotropin stimulation testing as a guide. If adrenal insufficiency was diagnosed, patients reduced to < 5 mg/day prednisone were considered off of steroids. The baseline agents (azathioprine, cyclosporine, or FK506) were then gradually reduced in monthly decrements. Complete weaning was accomplished in 16 patients (27.1%) with 3-19 months drug-free follow-up, is progressing in 28 (47.4%), and failed in 15 (25.4%) without graft losses or demonstrable loss of graft function from the rejections. This and our previous experience with self-weaned and other patients off of immunosuppression indicate that a significant percentage of appropriately selected long-surviving liver recipients can unknowingly achieve drug-free graft acceptance. Such attempts should not be contemplated until 5-10 years posttransplantation and then only with careful case selection, close monitoring, and prompt reinstitution of immunosuppression when necessary.
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PMID:Weaning of immunosuppression in long-term liver transplant recipients. 783 42

We have previously reported that addition of 8-bromocyclic AMP enhances the stimulatory effect of dexamethasone on the expression of the angiotensinogen gene in mouse hepatoma cells in vitro. Isoproterenol is known to stimulate the synthesis of hepatic intracellular cyclic AMP via beta-adrenergic receptors. To study the possible effect of beta-adrenergic receptors on the expression of the angiotensinogen gene in mouse hepatoma cells, we transiently transfected them with a fusion gene with the 5'-flanking region of the angiotensinogen gene linked to a bacterial chloramphenicol acetyltransferase coding sequence as a reporter, pOCAT (ANG N-1498/+18). The addition of isoproterenol (10(-9) to 10(-5) mol/L) alone had no stimulatory effect on the expression of pOCAT (ANG N-1498/+18). In the presence of dexamethasone (10(-6) mol/L), however, isoproterenol enhanced the stimulatory effect on the dexamethasone on the expression of pOCAT (ANG N-1498/+18). The enhancing effect of isoproterenol was inhibited by the presence of propranolol (beta 1- and beta 2-adrenergic receptor antagonist) and ICI 118,551 (beta 2-adrenergic receptor antagonist) but not by the presence of atenolol (beta 1-adrenergic receptor antagonist). Furthermore, the addition of Rp-cAMP (an inhibitor of protein kinase A I and II) blocked the enhancing effect of isoproterenol. These studies demonstrated that isoproterenol enhances the stimulatory effect of dexamethasone on the expression of the angiotensinogen gene in mouse hepatoma cells via beta 2-adrenergic receptor and cyclic AMP-dependent protein kinase pathways. Our data may be important in understanding the molecular mechanism(s) of the stimulatory effect of catecholamines/glucocorticoid-induced expression of the angiotensinogen gene in the liver.
Hypertension 1995 Jan
PMID:Beta-adrenergic receptors and angiotensinogen gene expression in mouse hepatoma cells in vitro. 784 40

Angiotensinogen is shown to be produced by the liver and the hepatoma cell line HepG2. As a first step for understanding the molecular relationship between the transcriptional regulation of the angiotensinogen gene and the pathogenesis of hypertension, we have analyzed the basal promoter of the angiotensinogen gene. Chloramphenicol acetyltransferase (CAT) assays with 5'-deleted constructs showed that the proximal promoter region from -96 to +22 of the transcriptional start site was enough to express HepG2-specific CAT activity. Electrophoretic mobility shift assay and DNase I footprinting demonstrated that the liver- and HepG2-specific nuclear factor (angiotensinogen gene-activating factor [AGF2]) and ubiquitous nuclear factor (AGF3) bound to the proximal promoter element from -96 to -52 (angiotensinogen gene-activating element [AGE2]) and to the core promoter element from -6 to +22 (AGE3), respectively. The site-directed disruption of either AGE2 or AGE3 decreased CAT expression, and the sequential titration of AGF3 binding by in vivo competition remarkably suppressed HepG2-specific CAT activity. Finally, the heterologous thymidine kinase promoter assay showed that AGE2 and AGE3 synergistically conferred HepG2-specific CAT expression. These results suggest that the synergistic interplay between AGF2 and AGF3 is important for the angiotensinogen promoter activation.
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PMID:Molecular mechanism of transcriptional activation of angiotensinogen gene by proximal promoter. 816 41

A large number of ascitic fluid tests, e.g., fibronectin and cholesterol, have been proposed as helpful in detecting malignancy as the cause of ascites. Unfortunately, these "humoral tests of malignancy" are nonspecific. Although the ascitic fluid concentrations of these proteins or protein-bound substances tend to be quite high in patients with peritoneal carcinomatosis and low in the setting of cirrhotic ascites, the problem is that patients with tuberculous peritonitis, cardiac ascites, pancreatitis ascites, etc. usually have values in the malignancy range, i.e., false-positive results. This can lead to an extensive search for a nonexistent tumor, with confusion and anxiety for patient and physician. The cytology is the single best test to order when peritoneal carcinomatosis is suspected; its sensitivity approaches 100%. However, peritoneal carcinomatosis is only one of several mechanisms by which tumors can cause ascites. No one test can be expected to detect tumors as the cause of these diverse mechanisms of ascites formation. The serum-ascites albumin gradient is a helpful test in classifying ascitic fluid specimens into portal-hypertension-related and non-portal-hypertension-related categories. An elevated serum alpha-fetoprotein test can be useful in raising suspicion of hepatocellular carcinoma. Careful analysis of ascitic fluid, without measurement of "humoral tests of malignancy," combined with information obtained from the history and physical examination, usually lead to an accurate diagnosis of the cause of ascites.
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PMID:Malignancy-related ascites and ascitic fluid "humoral tests of malignancy". 818 30

To determine the effects of vasoactive agents on blood flow in lymph node metastases, the blood flow in the cervical lymph node metastases and normal tissue were meassured using a hydrogen clearance method, at normotensive state, angiotensin I (A I) induced hypertensive state and sodium nitroprusside (SNP) induced hypotensive state. The metastases occurred frequently in the cervical lymph nodes of 17 rats on day 11-14 after Yoshida ascites hepatoma. AH109A cells were subcutaneously inoculated into back of auricule of 20 rats. The blood flow in the liver, brain and bone marrow of normal rats was of no significant changes when the mean arterial blood pressure (MABP) was elevated to approximately 20 kPa by infusion of A I and decreased to approximately 9.06 kPa by infusion of SNP. But the blood flow in the metastatic lymph nodes was increased from 1.42 +/- 0.48 ml.kg-1/s to 3.45 +/- 1.33 ml.kg-1/s (n = 13, P < 0.05) when the MABP was elevated from 14.81 +/- 1.04 kPa to 18.93 +/- 0.92 kPa by A I. On the contrary, the blood flow in the metastatic lymph node was decreased to 0.55 +/- 0.25 ml.kg-1/s (n = 13, P < 0.05) when the MABP was decreased to 8.84 +/- 0.63 kPa by SNP. The results indicated that microcirculation characteristics in the cervical lymph node metastases were different from those in the normal tissues. A I induced hypertension was useful to selectively improve delivery of chemotherapeutic drugs to the site of metastases. On the other hand, SNP induced hypotension may be useful to suppress washout of the drugs.
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PMID:[Establishment of cervical lymph node metastasis in model rats and its microcirculation characteristics]. 938 2

A case control study on male primary hepatocellular carcinoma(HCC) and hepatitis B or C virus and some potential risk factors, e.g. blood transfusion, aldehyde dehydrogenase 2(ALDH2) genotype and drinking habits, was performed using two controls, i.e. a hospital control(HC) and a community control(CC) in Fukuoka and Saga Prefectures. Cases were obtained from the Second Department of Internal Medicine, Kurume University Hospital. The HCs were obtained from inpatients of two general hospitals in Kurume and the CCs were randomly sampled from the Kurume citizens being matched with age and sex to each case. Based on the HCs, odds ratios(ORs) of developing male HCC were statistically significant due to HBsAg or anti-HCV antibody positive status. Some discrepancies were observed between the two controls, i.e. higher proportions of past histories of diabetes or hypertension, of ALDH2 typical homozygote(ALDH2(1)/ALDH2(1)), and of heavy drinkers among the HCs, suggesting slight deviation of the HCs from the CCs in alcohol related aspects. Although ORs regarding accumulated amount of alcohol intake by age 40 based on the HCs were insignificant, two of the three corresponding ORs based on the CCs were statistically significant. Judging from alcohol related aspects between the two controls, the ORs for alcohol based on the HCs seems to be underestimated.
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PMID:A case-control study on male hepatocellular carcinoma based on hospital and community controls. 957 88

Although life expectancy in Spain is above seventy years, age over sixty is considered a relative contraindication for liver transplantation (LT) in most centers. The aim of this study was to assess the outcome of LT in patients over sixty years of age comparing them to patients under that age. From January 1992 to August 1995, 61 cirrhotic patients underwent LT at our institution; of them, 43 (group I) were younger than 60 years (mean +/- SEM: 51.9 +/- 0.9 years, range: 37-59) and 18 patients (group II) were 60 years or older (64.1 +/- 0.7, range: 60-71). Main pre-transplant variables (sex, etiology of liver disease, presence of hepatocarcinoma, Child-Pugh's score and renal function) were similar in both groups. The follow-up (median and range) for group I was 28 and 3-47 months, and for group II 16.5 and 3-48 months. Actuarial survival rates at one and four years post-LT were respectively 88.3% and 85.6% for group I, and 87.8% and 87.8% for the group II (p = n.s.). There were no differences between both groups regarding the incidence of rejection, major infections, neurologic complications, renal failure, pathological bone fractures, diabetes mellitus or hypertension. Nevertheless, cardiovascular complications were significantly more frequent in group II (p = 0.002) although they were not the cause of death. In conclusion, our results show that the outcome of LT in patients over sixty years old is comparable to that observed in patients under that age. LT should not be contraindicated on the only basis of an age greater than 60 years.
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PMID:Liver transplantation in cirrhotic patients over 60 years of age. 955 42

Lipoprotein(a) [Lp(a)] is well known to stimulate growth of vascular smooth muscle cells (VSMCs), resulting in atherosclerosis. Its mechanism is postulated to be decreased in active transforming growth factor (TGF)-beta. However, the exact mechanisms and cellular processing from apolipoprotein(a) [apo(a)] to Lp(a) have not yet been clarified because no cultured cells producing apo(a) are available. Therefore, it is necessary to establish apo(a)-producing cells to study the role of apo(a). We evaluated the effects of overexpression of human apo(a) gene on human aortic VSMC growth. First, we tested whether transfection of apo(a) gene into human hepatoma cells, HepG2 cells, producing human apoB resulted in the formation of Lp(a). Transfection of apo(a) gene into HepG2 cells resulted in detectable levels of Lp(a) in the medium, as assessed by ELISA and Western blot, whereas no Lp(a) was detected in the medium of HepG2 cells transfected with control vector and untransfected HepG2 cells. Expression of apo(a) mRNA was also confirmed by reverse transcription-polymerase chain reaction. In contrast, Western blotting showed a single band detected by specific anti-apo(a) antibody, but not anti-apoB antibody, in the medium of apo(a)-transfected VSMCs. These results demonstrate that Lp(a) can be formed from apo(a) on HepG2 cells, whereas transfection of apo(a) gene into VSMCs resulted in the production of apo(a) alone but not Lp(a). Next, we examined the biological effects of overexpression of apo(a) gene on growth of VSMCs and endothelial cells. Incubation of cultured medium of HepG2 cells transfected with apo(a) gene with human VSMCs or endothelial cells resulted in a significant increase in cell number compared with the conditioned medium of HepG2 cells transfected with control vector. In contrast, transfection of apo(a) gene directly into VSMCs caused no significant effect on VSMC growth. Therefore, we measured TGF-beta concentration in the conditioned medium of VSMCs. However, using ELISA, only latent but not active TGF-beta was detected in the medium of VSMCs. Moreover, addition of neutralizing anti-TGF-beta antibody did not alter VSMC growth. These results suggest that Lp(a) could stimulate growth of VSMCs via the independent mechanisms from the inhibition of TGF-beta activation. Overall, these data demonstrate that overexpression of apo(a) gene in cells producing apoB results in formation of Lp(a), resulting in a mitogenic action on human endothelial cells and VSMCs. These results provide new information to understand the mechanisms of the mitogenic action of Lp(a) and suggest the role of Lp(a) in the pathogenesis of atherosclerosis.
Hypertension 1998 Aug
PMID:Conditioned medium from HepG2 cells transfected with human apolipoprotein(a) gene stimulates growth of human vascular smooth muscle cells: effects of overexpression of human apolipoprotein(a) gene. 971 45

Gastrointestinal bleeding sometimes causes life-threatening state. It is important to understand the underlining risk factors for prevention and treatment of this condition. In 1997, 81 patients with massive gastrointestinal bleeding were admitted to the life-saving center in Kyoto First Red Cross Hospital. In these patients, 14 subjects (17%) had been receiving hemodialysis. Eight patients (10%) were taking anti-coagulant or antiplatelet drugs. Eight patients (10%) had hypertension and were given calcium antagonists. Seven subjects (9%) had liver cirrhosis and/or hepatocellular carcinoma. Because these patients often fall into life-threating state, we must pay special attention to the prevention and cure for gastrointestinal bleeding. For example, it may be necessary to change to heparin free hemodialysis for patients having active bleeding. In anticoagulated patients, it may be required that sufficient hemostatic therapy without risking thromboembolic sequelae. In addition to careful managements, we have better to consider the eradication therapy for all of these high risk groups with Helicobacter pylori infection.
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PMID:[Risk factors for gastrointestinal bleeding]. 978 Jul 11

-Angiotensinogen is the glycoprotein precursor of 1 of the most potent vasoactive hormones, angiotensin II. Human angiotensinogen gene contains a C/A polymorphism at -20 located between the TATA box and transcriptional initiation site. We show here that when nucleoside A is present at -20, this sequence binds to the estrogen receptor. We also show that transcriptional activity of reporter constructs containing human angiotensinogen gene promoter with nucleoside A at -20 is increased on cotransfection of an expression vector containing human estrogen receptor-alpha coding sequence in human hepatoma cells (HepG2) followed by estrogen treatment. On the other hand, adenoviral major late transcription factor binds preferentially to this region of the promoter when nucleoside C is present at -20. We also show that reporter constructs containing human angiotensinogen gene promoter with nucleoside C at -20 have increased basal promoter activity on transient transfection in HepG2 cells as compared with reporter constructs with nucleoside A at -20. Our data suggest that C/A polymorphism at -20 may modulate the expression of human angiotensinogen gene in a sex-specific manner.
Hypertension 1999 Jan
PMID:Role of C/A polymorphism at -20 on the expression of human angiotensinogen gene. 993 Oct 90


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