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)

The klotho gene, originally identified by insertional mutagenesis in mice, suppresses multiple aging phenotypes (e.g., arteriosclerosis, pulmonary emphysema, osteoporosis, infertility, and short life span). We have previously shown that mice heterozygous for a defect in the klotho gene upon parabiosis with wild-type mice show improved endothelial function, suggesting that the klotho gene product protects against endothelial dysfunction. In the present study, using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat which demonstrates multiple atherogenic risk factors (e.g., hypertension, obesity, severe hyperglycemia, and hypertriglyceridemia) and is thus considered an experimental animal model of atherosclerotic disease, we show that adenovirus-mediated klotho gene delivery can (1) ameliorate vascular endothelial dysfunction, (2) increase nitric oxide production, (3) reduce elevated blood pressure, and (4) prevent medial hypertrophy and perivascular fibrosis. Based on these findings, klotho gene delivery improves endothelial dysfunction through a pathway involving nitric oxide, and is involved in modulating vascular function (e.g., hypertension and vascular remodeling). Our findings establish the basis for the therapeutic potential of klotho gene delivery in atherosclerotic disease.
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PMID:In vivo klotho gene delivery protects against endothelial dysfunction in multiple risk factor syndrome. 1102 45

Lung transplantation has become an accepted therapy for patients with end-stage lung disease. The survival rate after this operation is not, however, satisfactory, being 40-50% at 5 yrs after lung transplantation; infections and pulmonary rejection (acute and chronic) are the cause of this brief survival. Recently, it has been shown that lung transplantation is an advantageous solution only for selected pathologies. The introduction of alternatives to lung transplantation (lung volume reduction surgery in emphysema, prostacyclin therapy in primary pulmonary hypertension and pulmonary thromboendarterectomy in chronic thromboembolic hypertension) has modified the number of patients admitted to the lung transplantation waiting list. In this study, admission to the lung transplantation waiting list in the first 50 and in the following 50 months of activity of the Pulmonary Division Medical Centre of Montescano were retrospectively compared in order to verify whether experience gained has influenced admission to the lung transplantation waiting list. The mortality rate of patients with idiopathic pulmonary fibrosis (44%), chronic thromboembolic pulmonary hypertension (50%) and primary pulmonary hypertension (52%) before lung transplantation was high; the mortality after lung transplantation was low in idiopathic pulmonary fibrosis (16%), but rather high in primary pulmonary hypertension (55%) and chronic thromboembolic pulmonary hypertension (50%). In contrast, the mortality rate of patients with Eisenmenger's syndrome and emphysema was fairly low while on the lung transplantation waiting list, but rather high after lung transplantation. The trend in admission to the lung transplantation waiting list changed during the two observation periods, with a reduction in the number of patients with Eisenmenger's syndrome and emphysema, but not of those with idiopathic pulmonary fibrosis, chronic thromboembolic pulmonary hypertension and primary pulmonary hypertension. The experience gained modified the authors' approach to lung transplantation, but the "world" of lung transplantation still needs a lot more experience.
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PMID:Lung transplantation: the new point of view of an Italian centre. 1105 79

Pulmonary function, as measured by spirometry (FEV1 or FVC), is an important independent predictor of morbidity and mortality in elderly persons. In this study we examined the predictors of longitudinal decline in lung function for participants of the Cardiovascular Health Study (CHS). The CHS was started in 1990 as a population-based observational study of cardiovascular disease in elderly persons. Spirometry testing was conducted at baseline, 4 and 7 yr later. The data were analyzed using a random effects model (REM) including an AR(1) error structure. There were 5,242 subjects (57.6% female, mean age 73 yr, 87.5% white and 12.5% African-American) with eligible FEV1 measures representing 89% of the baseline cohort. The REM results showed that African-Americans had significantly lower spirometry levels than whites but that their rate of decline with age was significantly less. Subjects reporting congestive heart failure (CHF), high systolic blood pressure (> 160 mm Hg), or taking beta-blockers had significantly lower spirometry levels; however, the effects of high blood pressure and taking beta-blockers diminished with increasing age. Chronic bronchitis, pneumonia, emphysema, and asthma were associated with reduced spirometry levels. The most notable finding of these analyses was that current smoking (especially for men) was associated with more rapid rates of decline in FVC and FEV1. African-Americans (especially women) had slower rates of decline in FEV1 than did whites. Although participants with current asthma had a mean 0.5 L lower FEV1 at their baseline examination, they did not subsequently experience more rapid declines in FEV1.
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PMID:Predictors of loss of lung function in the elderly: the Cardiovascular Health Study. 1120 27

The article represents data characterizing course of chronic bronchitis in 78 machinery workers subjected to toxic irritative and sensibilizing aerosols. Findings are early bronchial obstruction and pulmonary emphysema, frequent disorders of microcirculation and lesser circle perfusion, propensity to interstitial pulmonary fibrosis and lung hypertension. The results could serve as a base for pathogenetic therapy and necessitate to include COLD into Occupational Diseases Register.
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PMID:[Some aspects of pathogenesis, clinical manifestations and diagnosis of occupational chronic occupational bronchitis]. 1171 17

Targeted disruption of the klotho gene induces multiple phenotypes characteristic of human aging, including arteriosclerosis, pulmonary emphysema and osteoporosis. Moreover, we previously observed that insufficient klotho expression in mice leads to endothelial dysfunction. In the present study, we used Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which exhibit hypertension, obesity, severe hyperglycemia and hypertriglyceridemia, and are thus considered an animal model of atherogenic disease, to test the effects of oral administration of troglitazone (200 mg/kg) on renal klotho mRNA expression and endothelial function. Systolic blood pressure, body weight, plasma glucose and triglyceride levels were all significantly higher in 30-week-old OLETF rats than in controls (LETO; Long-Evans Tokushima Otsuka) (p<0.05, n=7). In addition, endothelium-dependent relaxation of the aorta in response to 10(-5) M acetylcholine was significantly attenuated in OLETF rats (p<0.05, n=7), as was renal expression of klotho mRNA. Administration of troglitazone for 10 weeks significantly reduced systolic blood pressure, plasma glucose and triglyceride levels in OLETF rats, while augmenting endothelium-dependent aortic relaxation and renal klotho mRNA expression. These findings suggest that troglitazone protects the vascular endothelium against damage caused by the presence of multiple atherogenic factors.
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PMID:Troglitazone improves endothelial function and augments renal klotho mRNA expression in Otsuka Long-Evans Tokushima Fatty (OLETF) rats with multiple atherogenic risk factors. 1176 31

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

Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary hypertension characterized by capillary proliferation infiltrating the structures of the pulmonary parenchyma. Although veins are particularly involved, proliferation also affects bronchiolar, interstitial and other structures. We report a case of PCH in a 70-year-old man. Pulmonary artery hypertension was demonstrated by echocardiogram and angiography. Severe emphysema could be seen in a computed tomographic scan of the thorax, even though spirometric values indicated that airflow obstruction was mild. Dyspnea and respiratory insufficiency progressed with marked shunting until death. Tissue inspection at the autopsy revealed capillary proliferation in the alveolar walls with occasional oviform protrusions into air spaces or around small vessels and bronchioles. Endothelial cells in newly formed vessels were not atypical and mitosis was scarce; p53 expression was negative and Ki67 proliferation slight, indicating that PCH is not a neoplastic process as has sometimes been suggested.
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PMID:[Pulmonary capillary hemangiomatosis: a rare cause of pulmonary hypertension]. 1211 47

Here we report the utility of a molecular epidemiologic approach for common, polygenic diseases. Since 1992, the angiotensin I-converting enzyme (ACE) deletion/deletion (D/D) genotype has been linked to several cardiovascular diseases, including diabetic nephropathy. Earlier, the ACE D/D genotype had been associated with excess tissue ACE activity. We have observed an association of the ACE D/D genotype with a large number of common diseases, including chronic renal failure due to non-insulin-dependent diabetes mellitus or hypertension, hypertensive peripheral vascular disease, and emphysema [chronic obstructive pulmonary disease (COPD)]. ACE inhibitors have been in clinical use since 1977 and have a well-known safety record. Armed with the knowledge that ACE overactivity was associated with their disease, we gave what was intended to be a tissue ACE-inhibitory dose of a hydrophobic ACE inhibitor to 800 Caucasian and African-American male patients with hypertension and 200 Caucasian and African-American male patients with chronic renal failure, over a period of 3 years. We here report their outcomes, which include those of two patients with end-stage hypertensive peripheral vascular disease and one patient with end-stage emphysema (COPD). As a group, the outcomes are superior to what is available in the literature. This experience suggests the power of pharmacogenomics to improve clinical outcomes for common diseases safely, quickly, and inexpensively, if effective drugs already exist.
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PMID:From pharmacogenomics to improved patient outcomes: angiotensin I-converting enzyme as an example. 1239 47

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

The klotho gene, originally identified by insertional mutagenesis in mice, suppresses multiple aging phenotypes(e.g. arteriosclerosis, pulmonary emphysema, osteoporosis, infertility, short lifespan). We have shown that mice deficient for the klotho gene show endothelial dysfunction as manifested by an attenuated response of aortic relaxation in response to acetylcholine stimulation. Nitric oxide production was also significantly reduced in klotho deficient mice. A decrease in klotho gene expression in animals under sustained circulatory and metabolic stress(e.g. atherosclerosis). The klotho gene delivery improves endothelial dysfunction through a pathway involving nitric oxide, and is involved in modulating vascular function(e.g. hypertension, vascular remodeling). Our findings establish the basis for the therapeutic potential of klotho gene delivery in atherosclerotic disease.
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PMID:[klotho gene]. 1473 37


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