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)

Angiotensin I-converting enzyme (ACE) inhibitors have been proven to be highly effective and are for the most part the drugs of choice in the treatment and control of hypertension, congestive heart failure, and left ventricular dysfunction. Despite this, questions regarding side effects and compliance with this traditional pharmacological strategy remain. In view of these observations, coupled with recent advances in gene-transfer technology, our objective in this study was to determine whether the expression of ACE could be controlled on a permanent basis at a genetic level. We argued that the introduction of ACE antisense to inhibit the enzyme would be a prerequisite in considering the antisense gene therapy for the control of hypertension and other related pathological states. Retroviral vectors (LNSV) containing ACE sense (LNSV-ACE-S) and ACE antisense (LNSV-ACE-AS) sequences were constructed and were used in rat pulmonary artery endothelial cells (RPAECs) to determine the feasibility of this approach. Infection of rat RPAECs with LNSV-ACE-S and LNSV-ACE-AS resulted in a robust expression of transcripts corresponding to ACE-S and ACE-AS, respectively, for the duration of these experiments, ie, 8 consecutive passages. The expression of ACE-AS but not of ACE-S was associated with a permanent decrease of approximately 70% to 75% in ACE expression and a 50% increase in the B(max) for the AT(1)s. Although angiotensin II caused a concentration-dependent stimulation of intracellular Ca(2+) levels in both ACE-S- and ACE-AS-expressing cells, the stimulation was significantly higher in ACE-AS-expressing RPAECs. In vivo experiments demonstrated a prolonged expression of ACE-AS transcripts in cardiovascularly relevant tissues of rats. This was associated with a long-term reduction in blood pressure by approximately 15 mm Hg, exclusively in the spontaneously hypertensive rat. These observations demonstrate that delivery of ACE-AS by retroviral vector results in a permanent inhibition of ACE and a long-term reduction in high blood pressure in the spontaneously hypertensive rat.
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PMID:Sustained inhibition of angiotensin I-converting enzyme (ACE) expression and long-term antihypertensive action by virally mediated delivery of ACE antisense cDNA. 1050 86

In a cross-sectional, non-randomized, prospective study in an outpatient clinic a possible relationship between the cerebrospinal fluid (CSF) concentrations of the potent vasoconstrictor peptide endothelin-1 (ET-1) and prevalence and degree of HIV-encephalopathy was studied. Forty-eight CSF samples from HIV-infected patients undergoing lumbar punction for diagnostic reasons were investigated for ET-1 concentrations. In 37 patients ET-1 was also measured in plasma. Patients were investigated clinically and staged with respect to HIV encephalopathy. Patients with arterial hypertension, diabetes or acute opportunistic infections were excluded from the study. In the remaining, 18 of the CSF samples were from patients with normal neurological findings (grade 0-0.5), whereas 30 were from patients with HIV encephalopathy (grade 1-3). The mean CSF ET-1 concentration was significantly elevated (P = 0.001) in patients with HIV encephalopathy (1.97 +/- 2.33 pmol/l) as compared to those patients without encephalopathy (0.57 +/- 0.67 pmol/l). Moreover, there was a significant correlation between ET-1 CSF concentrations and the degree of HIV encephalopathy (r = 0.49, P < 0.001). In addition, there was a significant correlation between ET-1 levels in the CSF and the IgG serum to CSF ratio. However, we found no correlation between HIV encephalopathy and neither CSF total protein, IgG, albumin or the serum to CSF ratio of IgG or albumin. In conclusion, we could demonstrate a close relationship between CSF ET-1 concentrations and the degree of HIV encephalopathy. Thus, by virtue of its long-lasting and potent vasoconstrictor activity ET-1 might contribute to the pathogenesis of HIV encephalopathy.
Infection 1999
PMID:Endothelin-1 is elevated in the cerebrospinal fluid of HIV-infected patients with encephalopathy. 1088 34

Previous infection has been shown to be a risk factor for acute cerebral ischemia. We tested the hypothesis that recent infection is also a risk factor for intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). We performed a case-control study with 56 consecutive patients with ICH, 44 consecutive patients with SAH, and 56 and 44 neurological control patients, respectively. Infection within 4 weeks was associated with SAH independently of hypertension and smoking (p = 0.049). There was no significant association between infection and ICH. Recent infection, primarily upper respiratory tract infection, may be a risk factor for SAH by contributing to the formation and rupture of aneurysms.
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PMID:Recent infection as a risk factor for intracerebral and subarachnoid hemorrhages. 1097 Oct 20

The amiloride-sensitive epithelial sodium channel (ENaC) mediates Na(+) reabsorption in many epithelial tissues including the distal nephron, colon, lung, and secretory glands and plays an important role in pathophysiology of hypertension and cystic fibrosis. The ENaC is a multimeric integral membrane protein formed by the association of highly homologous,alpha-, beta-, and gamma-ENaC subunits. Here we explored the Sf9 insect cell-baculovirus expression system as a source to obtain high yields of recombinant ENaC for functional and structural studies. Although this expression system is widely used, coexpression of ENaC subunits could not be accomplished by the conventional procedures. We thus developed a protocol in which the alpha- and gamma-ENaC cDNA's were first fused individually with polyhedrin promoters at their 5'-ends and then inserted in the multiple cloning sites of pVL1393 transfer vector carrying the beta-ENaC cDNA. Utilizing this transfer vector, a recombinant baculovirus carrying all of the three ENaC cDNA's was prepared. Infection of Sf9 insect cells with this recombinant baculovirus resulted in the expression all of the three ENaC subunits in high yield. Planar lipid bilayer reconstitution procedure revealed the presence of approximately 6 pS sodium channels that are amiloride-sensitive. The results presented point out certain underlying rules for the expression of multiple genes in Sf9 cells, which may be useful in the expression other multimeric proteins and in the studies of protein-protein interactions as well.
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PMID:Expression of amiloride-sensitive sodium channel: a strategy for the coexpression of multimeric membrane protein in Sf9 insect cells. 1106 42

Although the mortality and incidence of cervical cancer have been decreasing, those of uterine-body, or endometrial, cancer have been increasing. The proportion of endometrial cancer was reported to have become 33.6% of primary uterine cancers in 1995. Infection with certain types of human papilloma virus (HPV) is considered to be etiologically important for the occurrence of cervical cancer. Because HPV is sexually transmitted, some risk factors for cervical cancer are associated with certain kinds of sexual behavior such as a young age at first intercourse, multiple partners, and infrequent use of barrier-type contraceptives such as condoms. Frequent conceptions and deliveries and histories of sexually transmitted diseases like infection with herpes simplex virus type 2 or chlamydia also have been suggested to be associated with the risk of cervical cancer. Smoking habits and infrequent intake of vegetables and fruits may be related to the increased risk of cervical cancer by supporting persistent infection of HPV through impaired immunological function. Although host factors such as a variant of a tumor suppressor gene like p53 have been assessed in terms of the risk of cervical cancer, these are not yet clearly elucidated. Estrogen stimulation of the endometrium unopposed by progesterone stimulation, namely, unopposed estrogen stimulation, is thought to be involved in the etiology of endometrial cancer. Frequent intake of animal fat, obesity or being overweight, infertility, and histories of diabetes mellitus, hypertension, and polycystic ovary syndrome have been reported to be risk factors for endometrial cancer, and they are thought to increase unopposed estrogen stimulation. Estrogen replacement therapy for postmenopausal symptoms, tamoxifen therapy for breast cancer, and taking sequential-type oral contraceptives have been shown to be exogenous risk factors for endometrial cancer in that they increase unopposed estrogen stimulation to endometrium.
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PMID:[Recent progress in epidemiologic research of uterine cancer]. 1124 42

Although the true incidence of urinary tract infections (UTIs) in children is difficult to estimate, they are one of the most common bacterial infections seen by clinicians who care for young children. Except for the first 8 to 12 weeks of life, when infection of the urinary tact may be secondary to a haematogenous source, UTI is believed to arise by the ascending route after entry of bacteria via the urethra. Enterobacteriaceae are the most common organisms isolated from uncomplicated UTI. Infection with Staphylococcus aureus is rare in children without in-dwelling catheters or other sources of infection, and coagulase-negative staphylococci and Candida spp. are associated with infections after instrumentation of the urinary tract. The diagnosis of UTI in young children is important as it is a marker for urinary tract abnormalities and, in the newborn, may be associated with bacteraemia. Early diagnosis is critical to preserve renal function of the growing kidney. A urine specimen for culture is necessary to document a UTI in a young child. Prior to culture, urinalysis may be useful to detect findings supporting a presumptive diagnosis of UTI. The goals of the management of UTI in a young child are: (i) prompt diagnosis of concomitant bacteraemia or meningitis, particularly in the infant; (ii) prevention of progressive renal disease by prompt eradication of the bacterial pathogen, identification of abnormalities of the urinary tract and prevention of recurrent infections; and (iii) resolution of the acute symptoms of the infection. Delay in initiation of the antibacterial therapy is associated with an increased risk of renal scarring. The initial choice of antibacterial therapy is based on the knowledge of the predominant pathogens in the patient's age group, antibacterial sensitivity patterns in the practice area, the clinical status of the patient and the opportunity for close follow-up. Imaging studies to detect congenital or acquired abnormalities are recommended following the first UTI in all children aged <6 years. Patients with significant urinary tract abnormalities and/or frequent symptomatic UTI may benefit from prophylactic antibacterials. The main long term consequence of UTI is renal scarring which may lead to hypertension and end-stage renal disease. Prevention of recurrent UTI focuses on detection, and correction if possible, of urinary tract abnormalities. Interventions that have been associated with a decrease in symptomatic UTI in children with a history of recurrent UTI include relief of constipation and voiding dysfunction.
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PMID:Urinary tract infections in children younger than 5 years of age: epidemiology, diagnosis, treatment, outcomes and prevention. 1131 Jul 18

Infection with microorganisms such as Helicobacter pylori and Chlamydia pneumoniae has been associated with coronary heart disease (CAD) and hypertension (HT). Infection increases the release of pro-inflammatory cytokines, thus facilitating interactions that lead to vascular damage and other effects. We hypothesized that genetically determined differences in activity or responsiveness of cytokine(s) might contribute to HT. The interleukin-1 gene (IL1) cluster on chromosome 2q14 contains three related genes (IL1A, IL1B, and IL1RN) located within a 430-kb region. These encode IL-1alpha and IL-1beta, as well as their endogenous receptor antagonist, IL-1ra. The IL1RN gene has a penta-allelic 86-bp tandem repeat in intron 2. Allele IL1RN* 2 is associated with a wide range of chronic inflammatory and autoimmune conditions, and its combination with the -31T variant of an IL1B C(-31)T polymorphism constitutes a pro-inflammatory haplotype that leads to vigorous IL-1beta production. We therefore tested each of these polymorphisms for association with HT. Subjects were white Anglo-Celtic residents of Sydney, Australia. Frequencies of IL1B C(-31)T genotypes CC, CT, and TT were 0.50, 0.40, and 0.10 in normotensive (NT) and 0.46, 0.46, and 0.08 in HT, respectively (chi(2) = 1.2, P = 0.55). T allele frequency in NT (0.30) was similar to that in HT (0.31). For the IL1RN variant, frequencies of alleles IL1RN* 1 and * 2 and combined minor alleles * 3, * 4, and * 5 were 0.61, 0.36, and 0.03 in NT and 0.54, 0.36, and 0.10 in HT, respectively (chi(2) = 11, P = 0.004). In conclusion, no association of the IL1B C(- 31)T with HT was found, whereas combined frequency of the minor alleles of the IL1RN polymorphism was increased in the HT cohort studied.
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PMID:Association analysis of polymorphisms at the interleukin-1 locus in essential hypertension. 1184 Apr 88

We retrospectively analyzed the results of 75 living-related pediatric renal transplants performed at our center between January 1986 and December 1999. The major causes of end-stage renal disease (ESRD) were glomerulonephritis (26%) and nephrolithiasis (16%), while the etiology was unknown in 50%. The mean age of the recipients was 12 yr (range 6-17 yr) and that of the donors was 39 yr (range 20-65 yr). The majority (73%) of donors were parents. Eighty five per cent of donors were one-haplotype matched and the rest identical. Immunosuppression was based on a triple drug regimen. Thirty per cent of recipients were rapid metabolizers of cyclosporin A (CsA) (area under the curve [AUC]: < 6,000 ng/mL/h), while 16% were slow metabolizers (AUC: > 8,000 ng/mL/h). Forty three (57%) children encountered 59 rejection episodes, the majority of which (59%) were recorded in the first month post-transplant. Seventy-four per cent of the rejection episodes were steroid sensitive and the rest, except two, were resolved by therapy with antithymocyte globulin (ATG) or orthoclone thymocyte 3 (OKT3). After a mean follow-up of 37 months, 17 (22%) grafts had chronic rejection and 76% of these recipients had previously experienced acute rejection episodes. The overall infection rate was high, necessitating two hospital admissions/patient/year. The majority (53%) of the infections were bacterial. Urinary tract infections (UTIs) were seen in 17 (23%) recipients. Twelve of these had ESRD as a result of stone disease and eight grafts were lost because of UTIs. Eight per cent of recipients developed tuberculosis (TB), and extra-pulmonary lesions were seen in 50%. Surgical complications were encountered in eight patients. Free medication to all recipients and parental support ensured a compliance rate of 93%. Baseline growth deficit was seen in children of the two groups studied (the 6-12 yr and 13-17 yr age-groups), with Z-scores of - 2.39 and - 2.12, respectively. No growth catch-up was observed at 12 and 24 months in either group. Post-donation complications were seen most commonly in donors > 50 yr of age and included: proteinuria (> 300 mg/24 h, four patients), hypertension (three patients), and diabetes (one patient). Twenty-four grafts were lost, 54% as a result of immunological and the rest as a result of non-immunological causes, and 17 recipients died during the follow-up period. Infections were the main cause of patient and graft loss. Overall 1- and 5-yr graft and patient survival rates were 88% and 65%, and 90% and 75%, respectively.
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PMID:Living-related pediatric renal transplants: a single-center experience from a developing country. 1200 Apr 64

An enormous proportion of the worlds elderly live in rural areas and show wide variations in health status. Many, particularly those in the developing countries, are vulnerable to greater socioeconomic and health marginalization mainly due to inadequate provision of services and economic deprivation. As with the urban elderly, locomotor, visual and hearing disabilities, as well as life-threatening conditions of coronary heart disease, diabetes and hypertension are common among rural elders also. Infections continue to take a heavy toll in many parts of the world. Higher prevalence of health and functioning impairments and of risk factors like sedentarism and current smoking have been reported for the rural elderly in developed countries like the United States, where less frequent use of certain preventive services also has been observed among the rural elderly. The positive association of well-being and health with variables such as living with family, having children, and community involvement, which has been reported from developing countries like Ghana and India, supports the usefulness of the time-honored value of joint family systems and lifelong social and physical activity--all known to foster healthy aging. Such traditional virtues therefore need to be preserved and strengthened. Effective geriatric health care services need to stress a community approach to primary health care, with provision of support and training for both family caregivers and professionals. In addition, emphasis on health promotion, cost-effective indigenous systems of medicine and gender-sensitive programs is needed.
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PMID:Health status of the rural elderly. 1207 55

Emergency treatment of such major complications of pregnancy as obstructed labor, hemorrhage, infection, hypertension disorders, and the effects of unsafe abortion, helps ameliorate morbidity and prevent mortality. Access to life-saving treatment (e.g., antibiotics, Cesarean sections, and blood transfusions) in developing countries is limited. Maternal mortality in one area of The Gambia, for example, is 2200 per 100,000 births. Improving access to care depends upon the availability of these services in communities, trained health personnel, service improvements, transportation provision, and community education. Detection of complications and early referral to an appropriate facility with a supportive and professional environment is key to saving lives. Political will and public pressure are needed before improvement in services can be successfully accomplished; politicians may ignore women with low status. Barriers to care are physical, cultural, technical, and economic. Cost or distance from home may prevent women from seeking care. Infection, hemorrhage, and uterine injury are frequently related to unsafe abortions, particularly among teenage women. Hospitals must be equipped with a reliable management system, surgical facilities, and clinical services. The WHO recommends upgrading community health centers with trained personnel, adequate supervision, and equipment. In Uganda, midwives are specially trained in advanced skills for use in remote areas: administration of oxytocin to evacuate the uterus and reduce bleeding, use of antibiotics for infections, and surgical repair of vaginal tears. Nurses in Zaire are trained to do Cesarean sections. In Sierra Leone and Nigeria, doctors are encouraged to receive training in obstetrics and to be posted in rural areas. In Sierra Leone, young men are trained to bring pregnant women in to care on stretchers. Maternity waiting homes near hospitals are another means to save lives. Lack of permission from a male relative may prevent use of medical care. Time, money, and women's place in society determine whether a woman receives care. Superstitions, such as difficult labor being blamed on the woman's unfaithfulness, interfere. Women with knowledge of complications may not have available services. Cost of care may discourage or delay decisions. Governments must support maternal health policies.
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PMID:Access to care save lives. 1228 2


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