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B F King

Publications and source records attributed to B F King.

At least 55 records · Page 3Linked to original sources
PubMed1998

Metabotropic receptors for ATP and UTP: exploring the correspondence between native and recombinant nucleotide receptors.

In the past five years, an extended series (P2Y1-n) of metabotropic nucleotide (P2) receptors has been cloned from vertebrate tissues; these receptors are activated by either ATP or UTP, or both nucleotides. While certain cloned P2Y receptors appear to correspond functionally to particular native P2 receptor phenotypes, such pharmacological phenotypes could be explained by either a combination of several members of the P2Y1-n series being coexpressed in the same tissue or the existence of novel, uncloned P2Y subtypes. Here, Brian King, Andrea Townsend-Nicholson and Geoffrey Burnstock review recent findings on the matter of pharmacological relationships between native P2 and cloned P2Y receptors.

Adenosine Triphosphate↗
PubMed1998

Cystic fibrosis and the phenotypic expression of autosomal dominant polycystic kidney disease.

Recent experiments in cultured cyst epithelial cells from kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) have shown that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is present in the apical surface of these cells and mediates chloride (Cl-) and fluid secretion in vitro. To determine whether the presence of CF with the expression of mutated CFTR proteins modifies cyst formation in ADPKD, we studied a large family with both inherited diseases. ADPKD in this family is linked to PKD1. The family is composed of 26 members; 11 members with ADPKD, 4 members with CF, and 2 members with both diseases. Renal volumes measured by computerized tomography (CT), calculated creatinine clearances, and other clinical parameters in the family members with ADPKD and CF were compared with those in the family members with ADPKD alone, as well as to a large population of patients with ADPKD. The patients with CF and ADPKD, but not the CF heterozygote carriers with ADPKD, had less severe polycystic kidney and liver disease, as indicated by normal renal function; smaller renal volume, even when corrected for height and body surface area; and the absence of hypertension and liver cysts. These observations suggest that the coexistence of CF may reduce the severity of ADPKD.

Adult↗
PubMed1998

Zn2+ modulation of ATP-responses at recombinant P2X2 receptors and its dependence on extracellular pH.

1. Using recombinant P2X2 receptors expressed in Xenopus oocytes, the modulatory effects of zinc (Zn2+) on ATP-responses were studied under voltage-clamp conditions and at different levels of extracellular pH. 2. Zn2+ (0.3-300 microM) added to the bathing medium potentiated ATP-activated membrane currents, increasing ATP-responses by up to 20 fold. This potentiating effect was reversed on washout. Zn2+-potentiation was reduced in an exponential manner (decaying 1/e in 42 s) as the interval was lengthened between adding Zn2+ then ATP to the superfusate. 3. The potentiating effect of Zn2+ was progressively diminished by acidic shifts in extracellular pH (pHe) which, of itself, also potentiated ATP-responses at P2X2 receptors. The maximal potentiating effects of Zn2+ and H+ were not additive. 4. Neither Zn2+ nor H+ potentiation of ATP-responses was abolished by diethylpyrocarbonate (DEPC, 0.3-3 mM), which irreversibly denatures histidyl residues. Nine histidyl residues are present in the extracellular loop of P2X2 receptors. 5. Zn2+ also enhanced the blocking activity of the P2 receptor antagonist suramin at P2X2 receptors. Therefore, Zn2+ also mimics H+ in increasing suramin-activity at P2X2 receptors. 6. In summary, Zn2+ and H+ potentiate agonist and antagonist activity at P2X2 receptors but their effects are not wholly alike for receptor agonism. There, the potentiating effects of Zn2+ are time-dependent and gradually convert to inhibition while those of H+ are time-independent, persistent and more potent, suggesting that either these modulators interact in a different way with a single allosteric site or with different allosteric sites.

Adenosine Triphosphate↗
PubMed1998

Molecular cloning and characterization of rat P2Y4 nucleotide receptor.

An intronless open reading frame encoding a protein (361aa in length) was isolated from a rat genomic library probed with a DNA fragment from rat heart. This protein showed 83% sequence identity with the human P2Y4 (hP2Y4) receptor and represents a homologue of the human pyrimidinoceptor. However, the rP2Y4 receptor is not selective for uridine nucleotides and, instead, shows an agonist potency order of ITP = ATP = ADP(pure) = UTP = ATPgammaS = 2-MeSATP = Ap4A > UDP(pure). ADP, ATPgammaS, 2-MeSATP and UDP are partial agonists. Thus, in terms of agonist profile, rP2Y4 is more like the P2U receptor subtype. The rP2Y4 receptor was reversibly antagonized by Reactive blue 2 but not by suramin which, otherwise, inhibits the hP2Y2 receptor (a known P2U receptor). Thus, rP2Y4 and the P2Y2 subtype appear to be structurally distinct forms of the P2U receptor (where ATP and UTP are equi-active) but can be distinguished as suramin-insensitive and suramin-sensitive P2U receptors, respectively.

Adenosine Triphosphate↗
PubMed1998

Hepatic lymphangiomatosis mimicking polycystic liver disease.

Hepatic lymphangiomatosis is a rare disorder characterized by cystic dilatation of the lymphatic vessels in the hepatic parenchyma. It can occur in the liver alone, in the liver and spleen, or in multiple organs. Clinically, diagnosis can be difficult because of the rarity and protean manifestations of this disorder. We describe a 53-year-old woman with hepatic lymphangiomatosis in whom polycystic liver disease had been previously diagnosed. In addition, we review 12 cases of hepatic, splenic, and hepatosplenic lymphangiomatosis with or without systemic lymphangiomatosis and discuss the differential diagnosis.

Cysts↗
PubMed1998

Current status of transurethral thermotherapy at the Mayo Clinic.

With the ever-expanding elderly population in the United States, benign prostatic hyperplasia (BPH) has become a widespread condition. Although surgical intervention (open prostatectomy and transurethral resection of the prostate) was the typical management approach for BPH in the past, other options currently include drug therapy and transurethral thermotherapy, a minimally invasive procedure that involves the targeting of heat deep within the prostate transition zone while cooling the surrounding anatomic structures with circulating water. Two thermo-therapy-devices--the Prostatron and the T3 transurethral thermoablation therapy catheter--have been studied in randomized controlled clinical trials at the Mayo Clinic. Both devices were shown to be effective in a substantial subset of patients with BPH: symptom scores decreased, peak urinary flow rates increased, and total serum prostate-specific antigen levels increased, an indication of destruction of adenomatous tissue. All patients were able to complete the treatment without the need for general or regional anesthesia, and thermotherapy was associated with few postprocedural events. Although this therapeutic strategy is currently used selectively in patients with lateral lobe prostatic adenoma, improvements in technology and understanding of the thermoregulatory properties of the prostate should broaden the application of thermotherapy devices in the management of BPH.

Adult↗
PubMed1998

Antagonism of an adenosine/ATP receptor in follicular Xenopus oocytes.

Follicular Xenopus oocytes possess a novel receptor where both adenosine and ATP activate a cAMP-dependent, nonrectifying K+-current. Five compounds, alpha,beta-methylene ATP (alpha, beta-meATP), 8-(p-sulfophenyl)theophylline (8-SPT), theophylline, 2, 2'-pyridylisatogen tosylate (PIT) and suramin, were tested as antagonists of adenosine- and ATP-activated K+-currents. The descending order of activity (pIC50 values) against adenosine responses was: alpha,beta-meATP (6.72) = 8-SPT (6.68) > theophylline (5.32) > PIT (4.58), whereas suramin was relatively inactive. The blocking actions of alpha,beta-meATP and alkylxanthine compounds were reversible with washout, whereas blockade by PIT was irreversible. These antagonists showed similar blocking activity against ATP responses, except for PIT which was more effective at ATP responses than at adenosine responses. The selectivity of antagonists was tested against cAMP-dependent K+-currents evoked by forskolin and follicle-stimulating hormone (FSH). 8-SPT and theophylline did not inhibit but instead augmented forskolin and FSH responses; this augmentation may be caused by inhibition of phosphodiesterase activity inside follicle cells. On the other hand, alpha,beta-MeATP and PIT inhibited forskolin and FSH responses; both compounds apparently are nonselective antagonists. Thus, only alkylxanthine derivatives (8-SPT and theophylline) were selective antagonists of the novel adenosine/ATP receptor in Xenopus oocytes, whereas alpha,beta-meATP and PIT were nonselective in their blocking actions and suramin was relatively inactive.

Adenosine↗
PubMed1997

Early expression of a novel nucleotide receptor in the neural plate of Xenopus embryos.

Extracellular ATP functions as a neurotransmitter and neuromodulator in the adult nervous system, and a signaling molecule in non-neural tissue, acting either via ligand-gated ion channels (P2X) or G-protein-coupled receptors (P2Y). ATP can cause an increase in intracellular Ca2+ (Ca2+i) in embryonic cells and so regulate cell proliferation, migration, and differentiation. We have isolated a Xenopus cDNA encoding a novel P2Y receptor, XlP2Y, which is expressed abundantly in developing embryos. Recombinant XlP2Y responds equally to all five naturally occurring nucleoside triphosphates (ATP, UTP, CTP, GTP, and ITP), which elicit a biphasic Ca2+-dependent Cl- current (ICl,Ca) where the second phase persists for up to 60 min. XlP2Y also causes a continuous release of Ca2+i and a low level persistent activation of ICl,Ca in Xenopus oocytes through the spontaneous efflux of ATP. mRNAs for XlP2Y are expressed transiently in the neural plate and tailbud during Xenopus development, coincident with neurogenesis. This restricted pattern of expression and novel pharmacological features confer unique properties to XlP2Y, which may play a key role in the early development of neural tissue.

Amino Acid Sequence↗
PubMed1997

Picture archive and communication systems implementation in a community medicine practice.

In order to gain experience with vendor-supplied picture archive and communication system (PACS) products, a Vantage PACS from Lockheed-Martin was installed in a Mayo community medicine practice in Rochester. This practice produces about 45,000 radiology examinations annually. The PACS includes central long- and short-term storage devices, 10 image display workstations, and a dedicated high-speed image distribution network. Digital images are produced using two Fuji computed radiography readers. Custom worklists were created to facilitate efficient system usage. Currently, all radiographic examinations for this practice are acquired digitally, and interpreted and distributed using the PACS. Remote softcopy interpretation via PACS has decreased the turnaround time for both routine and urgent examinations, and has allowed subspecialty interpretation or consultation for pediatric examinations. These results have significantly improved the radiology component of this community medicine practice.

Community Health Centers↗
PubMed1997

Initial experience with soft-copy display of computed radiography images on three picture archive and communication systems.

We recently installed picture archive and communication systems (PACS) from three different vendors on our campus for evaluation. A major part of this evaluation involved assessing the capabilities of these systems for displaying computed radiography (CR) images for primary interpretation. The three PACS provided different functionality for CR image display in terms of availability of the proprietary Fuji CR image processing algorithms, availability of user-specified contrast look-up tables, and application of the processing at the time of CR image capture or image display. We found that the Fuji processing algorithms were important for printing film, but were not necessary for acceptable soft-copy display. Non-linear contrast processing produced superior results compared to simple linear processing (via standard window width and level controls). Display processing was best applied immediately prior to the display operation, as opposed to at the image capture time. This allows the display to be adjusted to demonstrate the full 10-bit range of the CR image, and also allows raw CR data (i.e. not optimized for any particular display device) to be stored in the long-term archive.

Algorithms↗
PubMed1997

Potentiation of ATP-responses at a recombinant P2x2 receptor by neurotransmitters and related substances.

1. The modulator effects of a series of neurotransmitters and related substances were tested on responses to adenosine 5'-triphosphate (ATP) at a recombinant P2x2 receptor expressed in defolliculated Xenopus oocytes. 2. Nicotine, 5'-hydroxytryptamine (5-HT), noradrenaline, adenosine, bradykinin and histamine (all 100 microM) potentiated the responses to ATP (3 microM). an effect found due to acidification of the bathing solution by these drugs. 3. Arachidonic acid, met-enkephalin, substance P, calcitonin gene-related peptide (CGRP) (all 100 microM) and nerve growth factor (NGF; 50 ng ml-1) potentiated the responses to ATP (3 microM) through a largely or wholly pH-independent effect. 4. Small acidic and alkaline shifts, as little as 0.03 pH-units, enhanced or diminished the responses to ATP, respectively. A linear relationship existed between the degree of potentiation of the ATP-induced responses caused by nicotine, 5-HT, noradrenaline, adenosine, bradykinin and histamine and the potentiation of these responses induced by the addition of acid to the superfusate. 5. Since P2x receptors on sensory neurones include P2x2 subunits, the attendant acidosis and ATP-release associated with tissue injury may play a role in sensitizing sensory nerve fibres.

Adenosine Triphosphate↗
PubMed1997

Effects of extracellular pH on agonism and antagonism at a recombinant P2X2 receptor.

1. Under voltage-clamp conditions, the activity of agonists and antagonists at a recombinant P2X2 receptor expressed in Xenopus oocytes was examined at different levels of extracellular pH (pHe). 2. In normal Ringer (Mg2+ ions absent), the amplitude of submaximal inward currents to ATP was increased by progressively lowering pHe (8.0-5.5). ATP-responses reached a maximum at pH 6.5 with a 5 fold increase in ATP-affinity; the apparent pKa was 7.05 +/- 0.05. 3. Receptor affinity for ATP was lowered when extracellular Ca2+ ions were replaced with equimolar Mg2+ ions. However, the amplitude of the ATP-responses was still enhanced under acidic conditions, reaching maximal activity at pH 6.5 with a 5 fold increase in ATP-affinity; the apparent pKa was 7.35 +/- 0.05. 4. ATP species present in the superfusate (for the above ionic conditions and pH levels) were calculated to determine the forms of ATP which activate P2X2 receptors: possible candidates include HATP, CaHATP and MgHATP. However, levels of these protonated species increase below pH 6.5, suggesting that receptor protonation rather than agonist protonation is more important. 5. The potency order for agonists of P2X2 receptors was: ATP> 2-MeS-ATP ATPgammaS> ATPalphaS> >CTP >BzATP, while other nucleotides were inactive. EC50 and nH values for full agonists were determined at pH 7.4 and re-examined at pH 6.5. Extracellular acidification increased the affinity by approximately 5 fold for full agonists (ATP, 2-MeSATP, ATPyS and ATP alpha S), without altering the potency order. 6. The potency order for antagonists at P2X2 receptors was: Reactive blue-2 >trinitrophenol-ATP > or = Palatine fast black > or = Coomassie brilliant blue > or = PPADS>suramin (at pH 7.4). IC50 values and slopes of the inhibition curves were re-examined at different pH levels. Only blockade by suramin was affected significantly by extracellular acidification (IC50 values: 10.4 +/- 2 microM, at pH 7.4; 78 +/- 5 nM, at pH 6.5; 30 +/-6 nM, at pH 5.5). 7 In summary, a lowered pHe enhanced the activity of all agonists at P2X2 receptors but, with the exception of suramin, not antagonists. Since a lowered pHe is also known to enhance agonist activity at P2x receptors on sensory neurones containing P2X2 transcripts, the sensitization by metabolic acidosis of native P2x receptors containing P2X2 subunits may have a significant effect on purinergic cell-to-cell signalling.

Adenosine Triphosphate↗
PubMed1997

Effect of iron on transferrin receptor expression by human placental syncytiotrophoblast cells.

Transferrin receptor expression has been examined in primary cultures of morphologically differentiated placental syncytiotrophoblast cells. More than 90% of the cells were multinucleated. Incubation of syncytiotrophoblast for 4 days in the presence of iron salts had no effect on receptor expression assessed by measuring the binding of 125I-labelled transferrin. However, incubation of cells in the presence of human diferric transferrin (10-100 microM) led to a 50% decrease in surface and intracellular receptor expression. This down-regulation was not accompanied by a significant decrease in receptor synthesis. In contrast to syncytiotrophoblast, expression of intracellular transferrin receptors in non-differentiated cytotrophoblast cells decreased when cells were cultured with iron salts; this was accompanied by decreased receptor synthesis. Addition of diferric transferrin to cytotrophoblast cells led to a 50% reduction in surface and intracellular receptor expression, similar to that seen in the syncytiotrophoblast. This reduction was accompanied by a decrease in receptor synthesis. In contrast to that of most cell types, the expression and distribution of trophoblast transferrin receptors were not altered by insulin, epidermal growth factor or hydrocortisone. These characteristics of syncytiotrophoblast transferrin receptor expression may assist in ensuring a supply of iron to the fetus regardless of the maternal iron status.

Cells, Cultured↗
PubMed1997

Fluoroscopically triggered contrast-enhanced three-dimensional MR angiography with elliptical centric view order: application to the renal arteries.

PURPOSE: To determine the reliability of obtaining arterial-phase, contrast-material-enhanced three-dimensional (3D) magnetic resonance (MR) angiograms of the renal arteries by using a technique that combines two-dimensional real-time MR fluoroscopy and a 3D MR angiographic acquisition with elliptical centric view order. MATERIALS AND METHODS: Twenty-five consecutive patients suspected of having renal artery disease were evaluated with the fluoroscopically triggered technique by using a mean dose of 0.18 mmol/kg gadoteridol. Left renal vein suppression, inferior vena cava suppression, motion artifact, and image quality for depiction of the renal arteries were each evaluated on a five-point scale (1 = best). The findings were compared with those of another 25 consecutive patients who underwent conventional gadolinium-enhanced 3D MR angiography. RESULTS: The fluoroscopically triggered technique produced 4.6 times less left renal vein enhancement than did the conventional method (P < .01). With the fluoroscopically triggered technique, visualization of the renal arteries was adequate for diagnosis in 24 patients (96%) and the overall result (score of 1-3 for all criteria) was of good quality in 22 patients (88%). CONCLUSION: With this fluoroscopically triggered MR angiographic technique, high-quality, arterial phase, relatively motion immune angiograms can be routinely obtained.

Adolescent↗