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Biomedical subjects

Richard A Dart

Publications and source records attributed to Richard A Dart.

9 recordsLinked to original sources
PubMed2006

Specific receptor for angiotensinogen on human renal cells.

BACKGROUND: We recently demonstrated the existence of an angiotensinogen (AGT) receptor on placental cells. It has been established that there is a tissue-specific renin-angiotensin system (RAS) in the human kidney. This study focused on whether human renal proximal tubule epithelial cells possessed an AGT receptor. METHODS: Human renal proximal tubule epithelial cells were cultured in plastic wells. Binding assays were carried out by adding iodinated angiotensinogen ((125)I-AGT) to each culture well, with or without unlabeled AGT. The cells were washed, lysed, and the radioactivity was measured. RESULTS: Human renal proximal tubule epithelial cells bound (125)I-AGT in a time-dependent manner. This binding was competitively and specifically inhibited by unlabeled AGT. Bound (125)I-AGT was competitively displaced by AGT. Acid washing removed 30% at 8 h, indicating that 70% bound AGT had been internalized. Scatchard plot binding analysis showed that the identified AGT receptor possessed a single class of high-affinity binding sites (K(d)=1.73 nmol, B(max)=23.39 pmol/10(6) cells). CONCLUSION: The results of this study provide evidence for the presence of an AGT receptor on human renal proximal tubule epithelial cells. Our finding suggests that the AGT receptor may be an integral component of the renal RAS.

Angiotensin I↗
PubMed2005

Variants in the Wilms' tumor gene are associated with focal segmental glomerulosclerosis in the African American population.

Wilms' tumor gene (WT1) is important for nephrogenesis and gonadal growth. WT1 mutations cause Denys-Drash and Frasier syndromes, which are characterized by glomerular scarring. To test whether genetic variations in WT1 and WIT1 (gene immediately 5' to WT1) associate with focal segmental glomerulosclerosis (FSGS), patients with biopsy-proven idiopathic and HIV-1-associated FSGS were enrolled in a multicenter study. We genotyped SNP rs6508 located in WIT1 exon 1, three SNPs (rs2301250, rs2301252, rs2301254) in the promoter shared by WT1 and WIT1, rs2234590 in exon 6, rs2234591 in intron 6, rs16754 in exon 7, and rs1799937 in intron 9 of WT1. Cases (n = 218) and controls (n = 281) were compared in the African American population. Stratification by HIV-1 infection status showed that SNPs rs6508, rs2301254, and rs1799937 were significantly associated with FSGS [rs6508 odds ratio (OR) 1.82, P = 0.006; rs2301254 OR 1.65, P = 0.049; rs1799937 OR 1.91, P = 0.005] in the non-HIV-1 group and rs2234591 (OR 0.234, P = 0.011) in the HIV-1 group. Haplotype analyses in the population revealed that seven SNPs were associated with FSGS; five SNPs had the highest contingency score [-log10(P value) = 13.57] in the HIV-1 group. This association could not be explained by population substructure. We conclude that SNPs in WT1 and WIT1 genes are significantly associated with FSGS, suggesting that variants in these genes may mediate pathogenesis by altering WT1 function. Furthermore, HIV-1 infection status interacts with genetic variations in both genes to influence this phenotype. We speculate that nephropathy liability alleles in WT1 pathway genes cause podocyte dysfunction and glomerular scarring.

Black or African American↗
PubMed2004

Palliative care.

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Advance Care Planning↗
PubMed2003

Treatment of systemic hypertension in patients with pulmonary disease: COPD and asthma.

We present a two-part review of the English-language literature pertaining to drug therapy for systemic high BP in patients with pulmonary diseases. Part I examines the literature pertaining to the use of antihypertensive drugs in patients with systemic hypertension and coexisting pulmonary conditions, especially COPD and asthma. Part II of the series reviews studies assessing the relationship between sleep-disordered breathing (including the role of the sympathetic nervous system) and systemic hypertension, and presents an approach to the management of these patients. It is the aim of both parts of this review to make qualified conclusions and recommendations applying a methodologic critique to assess the current literature. In the first part of this series, we review the demographics of hypertension in patients with COPD. This is followed by an extensive review of the use of specific classes of antihypertensive drug therapies in patients with pulmonary disease. The antihypertensive agents reviewed include diuretics, calcium antagonists, angiotensin-converting enzyme inhibitors, and angiotensin II receptor antagonists, beta-adrenergic blocking agents, and alpha-beta-blockers and other non-beta-blocker classes. Additionally, the renin angiotensin system is briefly reviewed, with a discussion of how angiotensin-converting enzyme inhibitors induce cough, especially in pulmonary and congestive heart failure patients.

Antihypertensive Agents↗
PubMed2003

The association of hypertension and secondary cardiovascular disease with sleep-disordered breathing.

We present a review of the English-language literature from 1972 through 2000 pertaining to systemic high BP in patients with sleep-disordered breathing (SDB). We reviewed studies assessing the relationship between obstructive sleep apnea, central sleep apnea or periodic breathing, and systemic high BP, and present an approach to the management of these patients. Complications of obesity and the role of the sympathetic nervous system are reviewed as well. It is the aim of these reviews to draw qualified conclusions, based on the current literature, with regard to SDB as a causative or contributory factor in systemic hypertension.

Cardiovascular Diseases↗