Search PubMed⌕ Search

Biomedical subjects

R R Townsend

Publications and source records attributed to R R Townsend.

At least 19 recordsLinked to original sources
PubMed2001

Von Hippel-Lindau disease masquerading as autosomal dominant polycystic kidney disease.

The diagnostic confusion in differentiating the various causes of renal cystic diseases in adults is well documented. This confusion can include misclassifications between autosomal dominant polycystic kidney disease (ADPKD) and von Hippel-Lindau disease (VHL). We describe such a case of VHL. A review of the literature and of the patients in our database regarding typical features of each disease, mean age of onset, and frequency of these features was undertaken to provide helpful differentiating features. Pancreatic cysts are one differentiating feature. In VHL, pancreatic cysts can occur in 70% of patients, often are multiple, and rarely may cause exocrine or endocrine insufficiency. Pancreatic islet cell tumors occur. In ADPKD, pancreatic cysts are found in only 9% of patients, usually are single and asymptomatic, generally occur in conjunction with cystic liver disease, and are not found in children or unaffected family members. Pancreatic malignancies do not occur with increased frequency in ADPKD. A different pattern, especially in patients without a strong family history of ADPKD, may be a clue to VHL masquerading as ADPKD. Genetic mutation screening of the VHL gene should be used in these patients.

Adult↗
PubMed2001

Dramatic recovery of renal function after 6 months of dialysis dependence following surgical correction of total renal artery occlusion in a solitary functioning kidney.

Revascularization of renal artery stenosis for the treatment of hypertension is an established procedure. In selected clinical scenarios, successful revascularization procedures may preserve or restore renal function. We present a 31-year-old man who underwent successful renal revascularization of a solitary functioning kidney after being dialysis dependent for approximately 190 days. He had dramatic improvement of renal function and has remained off dialysis since his surgery 18 months ago. He continues to have severe but controllable hypertension.

Acute Kidney Injury↗
PubMed2001

The effects of angiotensin-II on lipolysis in humans.

Adipocytes express many of the proteins of the renin-angiotensin system including angiotensinogen and AT(1)-receptors. A principal function of adipocyte tissue is the provision of energy substrate through lipolysis. This study was undertaken to determine if angiotensin-II (Ang-II) infusion or blockade of the renin-angiotensin system by angiotensin-converting enzyme (ACE) inhibitor therapy with enalapril altered lipolytic activity and substrate oxidation. Eleven healthy male subjects were enrolled in the first study and postabsorptive whole-body lipolysis activity was measured using a stable isotope of glycerol ((2)H(5)-glycerol). Substrate oxidation was determined using indirect calorimetry in the Clinical Research Center. Subjects were then sequentially treated with low-dose Ang-II infusion (0.3 and then 1.0 ng/kg/min) on separate days, and the lipolysis and oxidation studies were repeated. Lastly, each subject was treated with 2 weeks of ACE inhibitor with enalapril (20 mg daily) and underwent lipolysis and oxidation studies for a fourth time. In a second study, 14 healthy male subjects were enrolled and underwent an identical baseline lipolysis and substrate oxidation assessment. These subjects then received an Ang-II infusion at pressor doses (10 ng/kg/min), and changes in lipolytic activity and substrate oxidation were measured again. In the first study, there was no effect on lipolysis activity from low-dose Ang-II infusion (baseline lipolysis activity (mean +/- SD) 2.06 +/- 0.55 micromol/kg/min, 2.10 +/- 0.69 micromol/kg/min after 0.3 ng/kg/min, and 2.32 +/- 0.56 micromol/kg/min after 1.0 ng/kg/min) or enalapril therapy (2.35 +/- 1.00 micromol/kg/min). In the second study, the larger dose of Ang-II increased blood pressure by 14/17 mm Hg, but there was no effect on lipolysis activity (1.36 +/- 0.49 micromol/kg/min v 1.63 +/- 0.82 micromol/kg/min). Substrate oxidation rates were largely unaffected by Ang-II infusions or enalapril therapy. There was no evidence that treatment with subpressor or pressor dosages of Ang-II produced a significant alteration in lipolytic activity. Moreover, blockade of the renin-angiotensin system with enalapril was equally unremarkable in its effects on whole-body lipolysis. These data support the general concept that the renin-angiotensin system in adipocytes serves more to regulate the regional blood flow to adipose tissue and the size and number of fat cells rather than participating directly in the regulation of energy substrate.

Adult↗
PubMed2000

Safety of intravenous gadolinium (Gd-BOPTA) infusion in patients with renal insufficiency.

The safety of gadolinium (Gd-benzyloxypropionictetra-acetate [BOPTA] dimeglumine) infusion was evaluated in 32 patients with severe or moderate chronic renal failure in a prospective, randomized, double-blind, placebo-controlled study. Renal failure was defined as severe if creatinine clearance was between 10 and 29 mL/min, and as moderate if creatinine clearance was between 30 and 60 mL/min. Serum creatinine level and 24-hour urine samples for creatinine clearance were followed up serially for 7 days after the administration of either gadolinium (Gd-BOPTA dimeglumine), 0.2 mmol/kg, or a saline infusion. No patient experienced a significant change in renal function, defined as an increase in serum creatinine level greater than 0.5 mg/dL more than baseline, and no patient required hospitalization or dialysis during the study period. Gadolinium (Gd-BOPTA dimeglumine) appears to be well tolerated in patients with moderate to severe renal failure.

Contrast Media↗
PubMed1999

Proteomic definition of normal human luminal and myoepithelial breast cells purified from reduction mammoplasties.

Normal human luminal and myoepithelial breast cells separately purified from a set of 10 reduction mammoplasties by using a double antibody magnetic affinity cell sorting and Dynabead immunomagnetic technique were used in two-dimensional gel proteome studies. A total of 43,302 proteins were detected across the 20 samples, and a master image for each cell type comprising a total of 1,738 unique proteins was derived. Differential analysis identified 170 proteins that were elevated 2-fold or more between the two breast cell types, and 51 of these were annotated by tandem mass spectrometry. Muscle-specific enzyme isoforms and contractile intermediate filaments including tropomyosin and smooth muscle (SM22) alpha protein were detected in the myoepithelial cells, and a large number of cytokeratin subclasses and isoforms characteristic of luminal cells were detected in this cell type. A further 134 nondifferentially regulated proteins were also annotated from the two breast cell types, making this the most extensive study to date of the protein expression map of the normal human breast and the basis for future studies of purified breast cancer cells.

Adult↗
PubMed1999

Frequency of ovarian cysts in patients with autosomal dominant polycystic kidney disease.

Extrarenal cysts occur in patients with autosomal dominant polycystic kidney disease (ADPKD) most frequently in the liver. Ovarian cysts have been reported in women with ADPKD, but their frequency has not been determined. Therefore, we analyzed the historical data in our database of 337 women with ADPKD and 199 of their unaffected female family members (NADPKD). In addition, we prospectively studied 25 nonpregnant, premenopausal women with ADPKD and 25 nonpregnant, premenopausal, age-matched control women recruited from the general population to assess the occurrence of ovarian cysts. No women in either the control or ADPKD groups were receiving exogenous estrogen or progesterone. All women underwent sonographic examination using a 5- or 7.5-MHz vaginal probe. A normal ovarian follicle was defined as a fluid-filled structure less than 2 cm in average diameter, and an ovarian cyst as one of 2 cm or greater. From the historical data, 28% of the women with ADPKD gave a history of ovarian cysts compared with 18% of the NADPKD women (P < 0.05). In the prospective study, the mean age of the women with ADPKD was not different from that of the control women (40.9 +/- 1.2 v 39.3 +/- 1.2 years; P = not significant [NS]). There was no difference in frequency of normal follicles found in women with ADPKD or controls (80% v 96%; P = NS), nor was there a difference in the frequency of ovarian cysts found in women with ADPKD or controls (12% v 12%; P = NS). There was no difference in the calculated ovarian volumes between the women with ADPKD and controls (9.9 +/- 2. 5 v 7.2 +/- 1.2 cm3). Among the women with ADPKD, there was no correlation between mean ovarian volume and mean renal volume, nor was there a significant relationship between the occurrence of hepatic cystic disease and ovarian cysts. Therefore, a prospective imaging study suggests that ovarian cysts have no increased frequency in women with ADPKD compared with women in the general population.

Adult↗
PubMed1999

Effect of aspirin on blood pressure in hypertensive patients taking enalapril or losartan.

The ability of angiotensin converting enzyme (ACE) inhibitors to lower blood pressure may in part be due to the formation of vasodilatory prostaglandins. Inhibition of prostaglandin synthesis with aspirin may therefore theoretically attenuate the antihypertensive effect of ACE inhibitors. This trial studied the interaction between aspirin (ASA) and enalapril, an ACE inhibitor, and ASA and losartan, an angiotensin subtype 1 receptor antagonist. Seventeen essential hypertensive patients were studied, maintained on a stable dose of either enalapril (n = 7) or losartan (n = 10) monotherapy for > or =12 weeks before and throughout the study. Each patient received a 2-week course of placebo, 81 mg/day ASA, and 325 mg/day ASA, each treatment separated by a 2-week washout period. Blood pressure (BP) and serum thromboxane B2 (TXB2) samples were obtained at the end of each treatment period. Placebo was compared with each dose of ASA for each group. In both the enalapril and losartan groups, mean, systolic, and diastolic BP were unchanged with the addition of ASA. Concentrations of TXB2 were suppressed to <10% in both groups with ASA. This study demonstrates that 81 to 325 mg/day ASA exerts no significant effect on BP in essential hypertensives taking enalapril or losartan.

Adult↗
PubMed1999

Glycan composition of serum alpha-fetoprotein in patients with hepatocellular carcinoma and non-seminomatous germ cell tumour.

Although estimation of serum alpha-fetoprotein (AFP) is widely used in the diagnosis of hepatocellular carcinoma (HCC) and non-seminomatous germ cell tumours (NSGCT), the clinical usefulness of this test is limited by a low specificity. However, there exist glycoforms of AFP which may be more specific for particular tumours. Previously, detailed analysis has been prevented by the low levels of AFP in human serum. We report here the application of fluorescence labelling, sequential exoglycosidase digestion, high-performance liquid chromatography and matrix-assisted laser desorption ionization in time-of-flight mass spectrometry, to determine the glycan structures of purified serum AFP from patients with HCC and NSGCT. Eleven major glycans were found, of which seven were N-linked, and four were O-linked, to the protein backbone. The structure of the N-linked glycans (all of bi-antennary complex-type with varying degrees of sialylation, fucosylation and galactosylation) were consistent with those previously reported. The O-linked glycans (three mucin O-GalNAc type glycans with variable degrees of sialylation, one O-HexNAc monosaccharide glycan) have not previously been reported. The finding of mucin O-GalNAc type glycans was supported by the prediction of potential O-GalNAc glycosylation sites on the protein backbone by analysis of the AFP structure by molecular modelling. With knowledge of these structures it may be possible to develop more specific assays for the detection of HCC and NSGCT.

Amino Acid Sequence↗
PubMed1999

Muscarinic blockade inhibits gastric emptying of mixed-nutrient meal: effects of weight and gender.

We compared the vagal contribution to gastric emptying in lean and obese subjects by monitoring gastric emptying of a meal during muscarinic blockade. Lean (n = 6) and obese subjects (n = 6) underwent two treatments: 1) saline infusion and 2) atropine infusion [0.4 mg/m2 bolus, 0.4 mg. (m2)-1. h-1] for 2 h, initiated 30 min before ingestion of a 600-kcal breakfast (64% carbohydrate, 23% fat, 13% protein) composed of orange juice (labeled with Indium-111), egg sandwich (labeled with Technetium-99m), cereal, milk, and banana. Anterior and posterior images were taken every 90 s for 90 min using a dual-headed camera. Atropine significantly delayed emptying of both solid (P < 0.007) and liquid (P < 0.002). Obese subjects exhibited a greater delay in liquid emptying during muscarinic blockade compared with lean subjects (P < 0.02). Female subjects exhibited a slower rate of gastric emptying and were less sensitive to atropine. These data suggest that obese subjects exhibit altered gastric cholinergic activity compared with lean subjects and that gender differences in gastric emptying rate may be due to differences in autonomic tone.

Adult↗
PubMed1999

Early phase insulin infusion and muscarinic blockade in obese and lean subjects.

The effect of early phase insulin on postprandial levels of insulin, C-peptide, glucose, and glucagon was investigated in lean (n = 10) and obese (n = 12) subjects. Subjects underwent four conditions during ingestion of a meal (600 kcal): 1) saline infusion; 2) 10-min insulin infusion simultaneously with meal ingestion (0.24 U bolus, 15 mU. m(-2). min(-1)); 3) atropine infusion (0.4 mg/m(2) bolus, 0.4 mg. m(-2). h for 4 h); 4) insulin and atropine infusion. Blood samples were taken for 3.5 h. Insulin infusion had no effect on postprandial insulin levels in either population but significantly reduced postprandial glucose in the obese subjects (P < 0.05). Obese subjects with elevated postprandial glucose levels in the presence of muscarinic blockade exhibited a decline in glucose with insulin supplementation. Atropine reduced postprandial insulin levels in both groups, with a greater attenuation in the obese (P < 0.01), but postprandial glucose levels were also significantly reduced, suggesting that atropine inhibited gastric emptying. Thus the effects of muscarinic blockade on postprandial insulin levels cannot be evaluated. These data suggest that insulin supplementation during the preabsorptive time period may contribute to glucoregulation in the obese population.

Adult↗
PubMed1998

Expression and characterization of the NBD1-R domain region of CFTR: evidence for subunit-subunit interactions.

To study interactions between the contiguous NBD1 and R domains of CFTR, wild-type and DeltaF508 NBD1-R (amino acids 404-830, in fusion with His6 tag) were expressed as single proteins in Escherichia coli. NBD1-R (10-25 mg/L culture) was purified from inclusion bodies in 8 M urea by Ni-affinity chromatography, and renatured by rapid dilution at pH 5. In vitro phosphorylation by protein kinase A increased the apparent size of NBD1-R from approximately 52 to approximately 56 kDa by SDS-PAGE. The fluorescent ATP analogue TNP-ATP bound to renatured NBD1-R with of 0.81 +/- 0.1 microM (wild-type), 0.93 +/- 0.1 microM (wild-type, phosphorylated), 0.75 +/- 0.1 microM (DeltaF508 NBD1-R), and 0.72 +/- 0.1 microM (DeltaF508 NBD1-R, phosphorylated) with a stoichiometry of approximately 1 TNP-ATP site per NBD1-R molecule; TNP-ATP binding was reversed by ATP, AMP-PCP, and AMP-PNP with KIs of approximately 3.2, 4.2, and 4.6 mM, respectively. Secondary structure analysis by circular dichroism gave 19% alpha-helix, 43% beta-sheet and turn, and 38% "other" structure. To determine if nucleotide binding to NBD1 influenced R domain phosphorylation, NBD1-R was in vitro phosphorylated with protein kinase A and [gamma-32P]ATP in the presence of AMP-PCP, AMP-PNP, or TNP-ATP. Whereas the nucleotide analogues did not affect 32P-incorporation in control proteins (Kemptide, GST-R domain), phosphorylation of NBD1-R was reduced >75% by AMP-PNP or AMP-PCP (0.25 mM) and >50% by TNP-ATP (0.25 microM). Analysis of phosphorylation sites indicated that inhibition involved multiple sites in NBD1-R, including serines 660, 712, 737, 795, and 813. These results establish the conditions for NBD1-R expression, purification, and renaturation. The inhibition of R domain phosphorylation by nucleotide binding to the NBD1 domain indicates significant domain-domain interactions and suggests a novel mechanism for regulation of CFTR phosphorylation.

Adenine Nucleotides↗
PubMed1998

Hypertension in renal failure.

Hypertension is a common component of the morbidity associated with renal failure. The mechanisms that contribute to high blood pressure are reviewed in this section. Also covered are therapies to reduce hypertension, the treatment goals of those therapies, and the outcomes of antihypertensive therapy on kidney function in patients with renal failure. Various antihypertensive agents are specifically addressed, and a treatment paradigm is presented for combination antihypertensive drug therapy, which is usually necessary in the antihypertensive therapy of patients with renal failure.

Antihypertensive Agents↗
PubMed1998

The clinical utility of ambulatory blood pressure and heart rate monitoring in psychiatric inpatients.

Alterations in heart rate and blood pressure (BP) may occur in patients receiving psychiatric medication. Twenty-four-hour ambulatory blood pressure (ABP) monitoring was compared with nurses' conventional vital signs (CVS) for systolic (SBP) and diastolic (DBP) and heart rate (HR) measurements in psychiatric inpatients receiving multidrug treatments. Twelve consecutive subjects were enrolled. ABP monitoring and CVS measurements were concurrent but independent in each subject. Ambulatory BP monitoring recorded SBP, DBP, and HR thrice hourly from 6:00 AM to 10:00 PM and once hourly between 10:00 PM and 6:00 AM; CVS were obtained an average of 3.6 times/24 h. The frequency with which each BP and HR measurement method detected Level-1 (SBP 90 to 100 or 180 to 209 mm Hg; DBP 40 to 60 or 110 to 119 mm Hg; HR 50 to 60 or 110 to 119 beats/min) or Level-2 (SBP < 90 or > or = 210 mm Hg; DBP < 40 or > or = 120 mm Hg; HR < 50 or > or = 120 beats/min) events was determined, and disagreements between the two measurement systems were analyzed using the McNemar test for paired sample data. Ambulatory BP monitoring detected significantly more Level-1 and Level-2 events than CVS. A significant number of mostly low BP were documented by ABP monitoring and were undetected by the CVS obtained by the nursing staff. This finding may be of clinical relevance in view of the potential hemodynamic consequences of hypotension, especially in older patients receiving psychotropic multidrug treatment.

Adult↗
PubMed1998

Health and disease management: what is it and where is it going? What is the role of health and disease management in hypertension?

Health and disease management, a clinical improvement process that integrates best practice principles in a comprehensive manner throughout the entire continuum of care, is likely to be the dominant style of health care delivery in the future. The goal of these programs is to eliminate or reduce unacceptable variations in cost and quality between various providers by developing guidelines that will achieve measurable outcomes for specific diseases. These protocols also emphasize wellness and disease prevention, coordinate resources across the entire continuum of care, and define interventions for the entire duration of the disease. Conditions most suited to this management strategy include diseases that are of high volume and cost, complex to manage, and present chronically over a long period of the patient's life. Such programs are developed by a multidisciplinary team that is also charged with obtaining buy-in and championing the program to their peers. Among the many components of a comprehensive health and disease management program, intensive education for patients and families and altering physician behavior to obtain compliance are key areas on which to focus. Hypertension is an ideal condition to manage in this way. It is frequently the most common reason for patients to be seen by a primary care provider, is an expensive disease to treat, and is an important cause of major organ damage from inadequate treatment. Successfully adopting a disease management model for hypertension treatment that will integrate all health care providers and offer intensive education of patients and providers to encourage adherence to the highly effective therapies currently available should afford a major opportunity for a dramatic reduction in complications and costs, with enhanced clinical outcomes and quality of life for these patients.

Delivery of Health Care↗
PubMed1997

The N-linked oligosaccharides of the beta-subunit of rabbit gastric H,K-ATPase: site localization and identification of novel structures.

The gastric H,K-ATPase is responsible for acid secretion by parietal cells. Its beta-subunit is a glycoprotein which is exposed to the harsh, acidic environment of the stomach. The location and structural features of the N-linked oligosaccharides were determined using matrix-assisted laser desorption ionization mass spectrometry (MALDI/MS) (in conjunction with mass composition analysis and exoglycosidase digestions), Edman degradation, and monosaccharide composition analysis. All seven N-linked sequons at positions 99, 103, 130, 146, 161, 193, and 222 were fully glycosylated. An unusual restricted array of oligosaccharides was observed at individual Asn residues. Asn99 was modified exclusively with oligomannosidic-type structures (Man6GlcNAc2-Man8GlcNAc2). Asn193 contained both oligomannosidic (Man5GlcNAc2-Man8GlcNAc2) and lactosamine-type structures, indicating significant "leakiness" in the pathway which converts oligomannose to lactosamine-type at a single glycosylation site. MALDI/MS with collision-induced dissociation was required to demonstrate that sequons separated by a single residue (99Asn-Ile-Ser-Asp-Asn-Arg-Thr105) were modified with only oligomannose and lactosamine structures, respectively. Analysis of the total oligosaccharide pool using MALDI/MS and exoglycosidase analysis revealed 24 lactosamine species (bi-, tri-, and tetraantennary structures), with all branches terminated in alpha-linked Gal residues, most possessing a single Fuc residue. Nine novel oligosaccharides contained multiple alpha-linked Gal residues per branch. Bi- and triantennary structures, with and without lactosamine repeats, were observed at Asn146 and Asn161. Tetraantennary structures with lactosamine repeats were found only at Asn130, and this site also contained most of the structures with multiple alpha-linked Gal residues per branch.

Amino Acid Sequence↗
PubMed1997

Evidence for phosphorylation of serine 753 in CFTR using a novel metal-ion affinity resin and matrix-assisted laser desorption mass spectrometry.

The cystic fibrosis transmembrane conductance regulator (CFTR) gene encodes an apical membrane Cl- channel regulated by protein phosphorylation. To identify cAMP-dependent protein kinase (PKA)-phosphorylated residues in full-length CFTR, immobilized metal-ion affinity chromatography (IMAC) was used to selectively purify phosphopeptides. The greater specificity of iron-loaded (Fe3+) nitrilotriacetic (NTA). Sepharose compared to iminodiacetic acid (IDA) metal-chelating matrices was demonstrated using a PKA-phosphorylated recombinant NBD1-R protein from CFTR. Fe(3+)-loaded NTA Sepharose preferentially bound phosphopeptides, whereas acidic and poly-His-containing peptides were co-purified using the conventional IDA matrices. IMAC using NTA Sepharose enabled the selective recovery of phosphopeptides and identification of phosphorylated residues from a complex proteolytic digest. Phosphopeptides from PKA-phosphorylated full-length CFTR, generated in Hi5 insect cells using a baculovirus expression system, were purified using NTA Sepharose. Phosphopeptides were identified using matrix-assisted laser desorption mass spectrometry (MALDI/MS) with post-source decay (PSD) analysis and collision-induced dissociation (CID) experiments. Phosphorylated peptides were identified by mass and by the metastable loss of HPO3 and H3PO4 from the parent ions. Peptide sequence and phosphorylation at CFTR residues 660Ser, 737Ser, and 795Ser were confirmed using MALDI/PSD analysis. Peptide sequences and phosphorylation at CFTR residues 700Ser, 712Ser, 768Ser, and 813Ser were deduced from peptide mass, metastable fragment ion formation, and PKA consensus sequences. Peptide sequence and phosphorylation at residue 753Ser was confirmed using MALDI/CID analysis. This is the first report of phosphorylation of 753Ser in full-length CFTR.

Amino Acid Sequence↗
PubMed1997

Lipolytic sensitivity and response to fasting in normotensive and hypertensive obese humans.

Obese persons with hypertension are at greater risk for diabetes and hyperlipidemia than normotensive obese persons. It has been postulated that increased lipolytic rates contribute to these metabolic diseases. Therefore, we evaluated the glycerol rate of appearance (Ra) in plasma, an index of whole-body lipolytic activity, during basal conditions and during 60 minutes of epinephrine infusion after 12 and 84 hours of fasting in six normotensive (body mass index [BMI], 39.9 +/- 1.8 kg/m2) and six hypertensive (BMI, 38.7 +/- 1.6 kg/m2) obese persons. Basal glycerol Ra was lower in hypertensive than in normotensive subjects at both 12 hours (1.58 +/- 0.21 v 2.27 +/- 0.28 mumol/kg/min, respectively; P < .01) and 84 hours (2.04 +/- 0.06 v 2.50 +/- 0.13 mumol/kg/min, respectively; P < .01) of fasting. Peak glycerol Ra during epinephrine infusion after 84 hours of fasting (5.69 +/- 0.72 and 11.40 +/- 0.78 mumol/kg/min for hypertensive and normotensive subjects, respectively) was significantly greater than at 12 hours (3.09 +/- 0.29 and 5.06 +/- 0.69 mumol/kg/min) in both hypertensive and normotensive subjects. However, peak glycerol Ra was lower in hypertensive than in normotensive subjects after 12 and 84 hours of fasting (P < .01 for 84 hours). We conclude that hypertension in obese persons is associated with a decrease in both basal lipolytic rates and lipolytic sensitivity to epinephrine infusion.

Adult↗