Biomedical subjects

B F King

Publications and source records attributed to B F King.

At least 73 records · Page 4Linked to original sources

PubMed1996

Peptidyl conjugates of adenosine 5'-carboxylic acid synthesized and evaluated as ligands for P2 purinoceptors.

The role of extracellular ATP in vivo and the various cellular responses mediated by P2 purinoceptors have not yet been fully elucidated, in part depending on the lack of subtype-specific high affinity antagonists. Here we describe the synthesis of a new class of compounds, peptidyl derivatives of adenosine 5'-carboxylic acid, among which some have inhibitory effects in certain P2 purinoceptor-carrying biological systems, e.g., glioma and smooth muscle cell lines and isolated smooth muscle tissue preparations from guinea pig vas deferens and urinary bladder.

Adenosine↗

PubMed1996

P2 purinoceptor-activated inward currents in follicular oocytes of Xenopus laevis.

1. ATP, UTP and 2MeSATP (10 microM) evoked fast, transient (2-20 s duration) and slow, sustained (60-120 s duration) inward currents in 118 of 285 follicular Xenopus oocytes but failed to activate inward currents in defolliculated Xenopus oocytes (n = 136). 2. The potency order for nucleotides was (at 10 microM): UTP = 2MeSATP > 2ClATP = ATP > ADP > alpha, beta-methylene-ATP > adenosine > ITP, with beta, gamma-methylene-ATP, CTP and GTP inactive. This potency order is atypical for any single P2 purinoceptor subtype. 3. EC50 values (for fast and slow inward currents) were (microM): ATP, 5.6 +/- 2.1 and 6.7 +/- 3.0; UTP, 1.0 +/- 0.3 and 0.9 +/- 0.3; 2MeSATP, 0.6 +/- 0.2 and 9.2 +/- 7.4 (n = 3). Suramin inhibited fast (IC50: 65 +/- 20 microM; n = 7) and slow (IC50: 57 +/- 10 microM; n = 7) inward currents evoked by ATP. Suramin also inhibited slow inward currents produced by UTP but potentiated those caused by 2MeSATP. 4. Fast and slow inward currents evoked in response to ATP and UTP reversed at -12 +/- 3 mV (n = 3), a value close to Erev for Na(+)-permeable ion channels present in oocytes. These same currents were reduced significantly when extracellular Na+ was substituted with choline and Erev changed to -30 +/- 5 mV (n = 3). Inward currents evoked by ATP and UTP were inhibited in a dose-dependent manner by amiloride (10-100 microM). 5. Fast and slow inward currents caused by 2MeSATP reversed at -29 +/- 3 mV (n = 3), a value close to Erev for Cl- channels in oocytes. Fast and slow responses to 2MeSATP were inhibited in a dose-dependent manner by the Cl- channel blocker NPPB (10-100 microM) and were only reduced slightly by amiloride (100 microM). 6. We conclude that two P2 purinoceptor subtypes are present on follicular Xenopus oocytes. 2MeSATP activates fast and slow Cl- currents (Erev = -30 mV) via a suramin-insensitive P2Y purinoceptor, while UTP and ATP activate fast and slow Na(+)-dependent currents (Erev = -10 mV) via a suramin-sensitive P2U purinoceptor.

Adenosine Triphosphate↗

PubMed1996

Effects of P2-purinoceptor antagonists on degradation of adenine nucleotides by ecto-nucleotidases in folliculated oocytes of Xenopus laevis.

The aim of the present study was to examine the effects of a number of P2-purinoceptor antagonists on degradation of adenine nucleotides by Xenopus laevis oocyte ecto-nucleotidase. Folliculated oocytes readily metabolize all three naturally-occurring nucleotides, the order of preferential substrates being ATP >ADP > AMP. The degradation of ATP and ADP was decreased significantly in the presence of several P2X- and P2Y-purinoceptor antagonists, including suramin, PPADS, Cibacron blue, Coomassie Brilliant blue, Evans blue, Trypan blue, Congo red, and PIT (each compound was used at 100 microM). All these compounds inhibited the degradation of ATP by up to 60%, whereas the hydrolysis of ADP was inhibited by Congo red and PIT by 75-80%. In addition, DIDS (100 microM) and TNP-ATP (100 microM) selectively inhibited the breakdown of ATP, and sodium azide (10 mM) selectively inhibited the breakdown of ADP. The enzymatic breakdown of either ATP or ADP was unaffected by 8-pSPT (100 microM), an antagonist of P1-purinoceptors, or by oxidized ATP (100 microM), an antagonist of P2Z-purinoceptors. The degradation of AMP was prevented completely by PIT (100 microM) and ingibited significantly by Congo red (100 microM). In conclusion, the present study shows that most of currently available antagonists of P2-purinoceptors inhibit the enzymatic breakdown of extracellular ATP and ADP. The inhibitory effect on ecto-nucleotidase activity should be taken into account when these antagonists are used in pharmacological experiments.

Adenine Nucleotides↗

PubMed1996

Macaque intra-arterial trophoblast and extravillous trophoblast of the cell columns and cytotrophoblastic shell express neural cell adhesion molecule (NCAM).

BACKGROUND: During placental development in higher primates trophoblast cells originating in the cell columns migrate along endometrial surfaces to form the cytotrophoblastic shell. A subpopulation of these cells invades uterine arteries, where they migrate on the surface of endothelium, against the flow of blood. These intra-arterial cells become sequestered in the walls of the arteries where they are referred to as intramural trophoblast. Because migration depends upon binding the cell surface to other cells or to extracellular matrix, we investigated the potential role of neural cell adhesion molecule (NCAM, CD56) in arterial invasion by trophoblast cells. METHODS: Tissues from macaque placentas and endometrium were fixed and embedded in paraffin. Standard immunoperoxidase methods were used to identify NCAM. RESULTS: NCAM labeled cells were present within spiral arteries of the decidua basalis. Trophoblast cells within or adjacent to the arterial lumen were distinctly NCAM positive, whereas most intramural trophoblast cells revealed reduced or no reactivity for NCAM. Maternal endothelial cells and villous trophoblast cells were negative. Uterine veins were tapped by trophoblast but did not contain migratory cells. The cell columns of early pregnancy contained cells outlined by rims of reactivity for NCAM. Labeled cells were also seen in the cytotrophoblastic shell, arranged as discontinuous groups. These groups variably occupied the entire thickness of the shell, or only the proximal (adjacent to the intervillous space) or distal layers of the shell. Later in gestation, the cytotrophoblastic shell developed a different pattern of staining, such that only cells located nearer to the intervillous space or near the tips of the anchoring villi were positive. CONCLUSIONS: We conclude that NCAM is one of a group of cell adhesion molecules that participates in trophoblast cell adhesion during migration within maternal arteries. NCAM appears to be active in trophoblast-trophoblast cell interactions. It may also contribute to binding trophoblast cells to the surfaces of arterial endothelium as well as extracellular matrix molecules of the arterial wall. After secondary invasion into the arterial walls NCAM is down-regulated, possibly in response to the appearance of extracellular matrix capsules, where other cell adhesion molecules may appear.

Age Factors↗

PubMed1996

Multiple breathhold 3D time-of-flight MR angiography of the renal arteries.

A technique is described for angiographic imaging of the renal arteries with acquisition performed over several periods of suspended respiration. The 3D Fourier transform (FT) gradient-echo angiographic sequence uses magnetization preparation and appropriately chosen delay times for background nulling and time-of-flight enhancement of the vasculature. The sequence was applied to 10 volunteers, each of whom was imaged in three ways: (i) over a series of breathholds in which feedback was provided to enable reproducible breathholding; (ii) over a series of breathholds with no feedback; and (iii) over continuous respiration. Results were evaluated by measuring the transverse extent of the well-delineated renal vasculature and by noting the distal extent of the vasculature branching (main, segmental, and interlobar branches). The transverse extent of renal vasculature visible with breathhold feedback, breathholding, and free breathing was 6.1 +/- 0.9 cm, 5.0 +/- 1.8 cm, and 4.0 +/- 1.4 cm, respectively (mean +/- SD). Breathhold feedback enabled visualization of segmental renal arteries bilaterally in all 10 volunteers.

Fourier Analysis↗

PubMed1996

Dynamic MR digital subtraction angiography using contrast enhancement, fast data acquisition, and complex subtraction.

A dynamic MR angiography technique, MR digital subtraction angiography (MR DSA), is proposed using fast acquisition, contrast enhancement, and complex subtraction. When a bolus of contrast is injected into a patient, data acquisition begins, dynamically acquiring a thick slab using a fast gradient echo sequence for 10-100 s. Similar to x-ray DSA, a mask is selected from the images without contrast enhancement, and later images are subtracted from the mask to generate angiograms. Complex subtraction is used to overcome the partial volume effects related to the phase difference between the flowing and stationary magnetization in a voxel. Vessel signal is the enhancement of flow magnetization resulting from the contrast bolus. MR DSA was performed in 28 patients, including vessels in the lungs, brains, legs, abdomen, and pelvis. All targeted vessels were well depicted with MR DSA. Corresponding dynamic information (contrast arrival time ta and duration of the arterial phase tav) was measured: ta/tav = 3.4/4.7 s for the lung, 10.3/4.9 s for the brain, 12.8/19.3 for the aorta, 15.2/12.6 s for the leg. MR DSA can provide dynamic angiographic images using a very short acquisition time.

Abdomen↗

PubMed1996

Diadenosine polyphosphate-activated inward and outward currents in follicular oocytes of Xenopus laevis.

Ionic currents evoked by alpha, omega-adenine dinucleotides (ApXA; X = 2-6) in follicular oocytes of Xenopus laevis were studied under voltage-clamp conditions. Dinucleotides evoked inward and outward currents in Xenopus oocytes by activating native P1 and P2 purinoceptors known to be present on the follicle cell monolayer enveloping oocytes. Inward currents were mediated by a suramin-sensitive P2 purinoceptor which showed an agonist potency order (at 10 microM): Ap4A > ATP > Ap3A > > Ap5A, while Ap2A and Ap6A were inactive. Outward currents were mediated by a novel theophylline-sensitive P1 purinoceptor which showed an agonist potency order (at 10 microM): Ap2A > ATP > > Ap4A = Ap5A = Ap6A > Ap3A. Chromatographic analysis confirmed ectonucleotidase activity at the follicle cell layer of oocytes but at a very low rate of dinucleotide cleavage, indicating that currents evoked by dinucleotides resulted from a direct activation of oocyte P1 and P2 purinoceptors and not through their breakdown to ATP, ADP and AMP. There was no evidence for specific receptors (i.e., P4 purinoceptors) for diadenosine polyphosphates in Xenopus oocytes.

Animals↗

PubMed1996

Differential degradation of extracellular adenine nucleotides by folliculated oocytes of Xenopus laevis.

The degradation of extracellular ATP and ADP by Xenopus oocytes was studied to investigate whether one or two ecto-enzymes are responsible for breakdown of both nucleotides. At a concentration of 100 microM, the half-life of ATP and ADP was 33 and 40 min, respectively. Degradation of ATP caused an initial fast and then a sustained accumulation of ADP in the buffer, while the concentration of AMP in the buffer increased slowly, but progressively, in a relatively linear manner. The rates of degradation of ATP and ADP were similar at pH levels between 7 and 10, but the velocity of breakdown of ATP was significantly higher than that of ADP at pH of 5-6. In divalent cation-free buffer, the addition of 0.1 mM of Ca2+, but not equimolar Mg2+, significantly potentiated the degradation of ATP by oocytes while, in the case of ADP, each of these divalent cations were able to potentiate its degradation. The rate of hydrolysis of ATP and its kinetic constants were not significantly different in the presence or absence of ADP (50 microM). In conclusion, differences in pH- and cation-dependency, and absence of inhibitory effect of ADP on degradation of ATP suggest that degradation of ATP and ADP by oocytes is provided by separate enzymes, namely Ca2+/Mg(2+)-dependent ecto-ATPase and ecto-ADPase, rather than by one ecto-enzyme.

Adenine Nucleotides↗

PubMed1996

P2 purinoceptors in rat cortical astrocytes: expression, calcium-imaging and signalling studies.

Extracellular ATP is known to activate intracellular enzymes in astrocytes via P2 purinoceptors that appear to play important physiological and pathological roles in these supporting brain cells. In this study, major P2 purinoceptor subtypes on astrocytes of neonatal rat cerebral cortices were identified in receptor expression experiments, when astrocytic messenger RNA was injected into Xenopus oocytes and recombinant P2 purinoceptors were characterized pharmacologically. In messenger RNA-injected oocytes, ATP evoked inward chloride currents (ICl,Ca) typical of stimulating metabotropic receptors that release intracellular Ca2+. Half-maximal activation with ATP occurred at 40 nM: the Hill coefficient was 0.5, which indicated that ATP stimulated two subtypes of P2 purinoceptor. UTP and 2-methylthioATP were the most active (and equipotent) of a series of nucleotides activating recombinant P2 purinoceptors. These results indicated that the two P2 purinoceptors expressed by astrocytic messenger RNA were of P2U and P2Y subtypes. Responses to ATP were antagonized by the P2 purinoceptor antagonist (suramin) but not by the P1 purinoceptor blocker (sulphophenyltheophylline). Findings in expression studies were confirmed in assays of intracellular signalling systems using primary cultures of rat astrocytes. UTP and 2-methylthioATP stimulated mitogen-activated protein kinase to the same extent as ATP, although UTP was less potent than either ATP or 2-methylthioATP. Both UTP and ATP increased intracellular Ca2+ (as measured by fura-2/AM luminescence) which, in cross-desensitization experiments, indicated the involvement of two subtypes of P2 purinoceptors. In conclusion, rat cortical astrocytes express two major subtypes (P2U and P2Y) of metabotropic ATP receptor which, when activated, raise intracellular Ca2+ and also stimulate mitogen-activated protein kinase.

Adenosine Triphosphate↗

PubMed1996

Renal oncocytoma: magnetic resonance imaging characteristics.

PURPOSE: We investigated the magnetic resonance imaging (MRI) appearance of renal oncocytomas. MATERIALS AND METHODS: Between 1985 and 1993, 11 patients at our institution underwent MRI of the kidneys and were subsequently diagnosed with renal oncocytoma. Patient charts and MRI were reviewed. RESULTS: Of 11 T1-weighted images 8 showed a mass with decreased signal intensity compared to renal cortex and 3 of 6 T2-weighted images revealed masses with increased intensity. In addition, 5 tumors were surrounded by a well defined capsule, 3 demonstrated a central stellate architecture and 1 contained an area of central decreased signal, all of which corresponded pathologically to scar. These MRI findings differ somewhat from those of renal cell carcinoma, which typically show intermediate to high signal intensity compared to renal cortex on T1 and T2-weighted pulse sequences and usually contain evidence of either hemorrhage or necrosis. CONCLUSIONS: A low intensity homogeneous mass on T1-weighted images, which appears as increased intensity on T2-weighted images, the presence of a capsule, central scar or stellate pattern and the absence of either hemorrhage or necrosis suggest oncocytoma. It is in the evaluation of patients with a solitary kidney, poor renal function, advanced age or a small easily resectable renal mass when MRI may help diagnose an oncocytoma and, thus, allow renal sparing surgery. The optimal MRI to evaluate renal masses should include T1-weighted spin echo images and without gadolinium, T2-weighted images and gradient recalled echo images.

Adenoma, Oxyphilic↗

PubMed1996

Neurofibromatosis with involvement of the prostate gland.

Urologic manifestations of neurofibromatosis type 1 are rare. The most common urologic area of involvement has been the urinary bladder. Prostate involvement in generalized neurofibromatosis has been noted previously in only 10 patients, 3 of whom were adults. Of these 3, 1 had a neurofibroma, 1 had a malignant schwannoma, and 1 patient died before tissue diagnosis could be obtained. The patient discussed in this report is the second known adult patient with biopsy-proven neurofibroma of the prostate gland. In addition, this is the first reported use of endorectal magnetic resonance imaging of the prostate to localize and specify the extent of neurofibromas in these patients.

Adult↗

PubMed1996

MR angiography of the renal arteries.

MR angiography (MRA) has shown considerable promise as a noninvasive tool in the evaluation of renal vascular morphology. There are two fundamental approaches to MRA of the renal arteries: time of flight and phase contrast imaging. Recently, three-dimensional, gradient-echo, gadolinium-enhanced MRA using breath-hold techniques also has been introduced. These techniques have made MRA of the renal arteries a very promising, noninvasive tool in the detection of main renal artery stenosis, with sensitivities between 90% and 100%. MRA is used most often in the evaluation of renal arteries of patients with abdominal aortic aneurysms or allergies to iodinated contrast media, or when other noninvasive screening examinations have been inconclusive. One of the most helpful and unique applications of MRA is in patients who have accelerating hypertension and accelerating renal insufficiency. These patients often have preexisting unilateral renal artery stenosis with a new contralateral renal artery stenosis. Conventional angiography is risky in these patients because of possible contrast nephropathy. MRA, in such cases, is very helpful for differentiating between bilateral renal artery stenosis and end-stage nephrosclerosis.

Humans↗

PubMed1996

Full sensitivity of P2X2 purinoceptor to ATP revealed by changing extracellular pH.

A full pharmacological characterization was carried out on a recombinant ATP-gated ion channel (P2X2 purinoceptor) expressed in Xenopus oocytes. This slowly-desensitizing neuronal P2X2 purinoceptor, activated by ATP (EC50 = 4.6 +/- 1 microM at pH 7.4; n = 4), showed the agonist potency order: ATP > or = 2-MeSATP = ATP gamma S > or = ATP alpha S > > Bz-ATP. The receptor affinity for ATP was enhanced 5-10 fold by acidifying the bathing solution (to pH 6.5) but was diminished 4-5 fold in an alkaline solution (pH 8.0). The maximum activity of P2X2 purinoceptors and the activity order of a series of nucleotides were unaltered by changing extracellular pH. Interestingly, ATP sensitivity at a recombinant P2Y1 purinoceptor remained unaltered with changing extracellular pH. These results indicate that acidotic conditions in the synaptic cleft could strengthen purinergic transmission at neuronal P2X2 purinoceptors.

Adenosine Triphosphate↗

PubMed1996

Selectivity and activity of adenine dinucleotides at recombinant P2X2 and P2Y1 purinoceptors.

1. Adenine dinucleotides (Ap3A, x = 2-6) are naturally-occurring polyphosphated nucleotidic substances which are found in the CNS and are known to be released in a calcium-dependent manner from storage vesicles in brain synaptosomes. The selectivity and activity of adenine dinucleotides for neuronally-derived recombinant P2 purinoceptors were studied using P2X2 and P2Y1 subtypes expressed in Xenopus oocytes. 2. For the P2Y1 subtype derived from chick brain, Ap3A was equipotent and as active as ATP (EC50 values: 375 +/- 86 nM and 334 +/- 25 nM, respectively). Ap4A was a weak partial agonist and other dinucleotides were inactive as agonists. None of the inactive dinucleotides were antagonists nor modulated the activity of Ap3A and ATP. 3. For the P2X2 subtype derived from rat PC12 cells, Ap4A was as active as ATP but less potent (EC50 values: 15.2 +/- 1 microM and 3.7 +/- 0.7 microM, respectively). Other adenosine dinucleotides were inactive as either agonists or antagonists. 4. Ap5A (1-100 nM) potentiated ATP-responses at the P2X2 subtype, showing an EC50 of 2.95 +/- 0.7 nM for this modulatory effect. Ap5A (10 nM) shifted the concentration-response curves for ATP to the left by one-half log10 unit but did not alter the Hill co-efficient for ATP (nH = 2.1 +/- 0.1). Ap5A (10 nM) failed to potentiate Ap4A-responses but did enhance the efficacy of the P2 purinoceptor antagonist, suramin, by 12 fold at the P2X2 subtype. 5. In conclusion, the results show that ionotropic (P2X2) and metabotropic (P2Y1) ATP receptors which occur in the CNS are activated selectively by naturally-occurring adenine dinucleotides which are known to be released with nucleotides from storage vesicles. The observed potentiation of P2X2-responses by Ap5A, where co-released with ATP by brain synaptosomes, may have a functional bearing in purinergic signalling in the CNS.

Animals↗

PubMed1996

Potentiation by 2,2'-pyridylisatogen tosylate of ATP-responses at a recombinant P2Y1 purinoceptor.

1. 2,2'-Pyridylisatogen tosylate (PIT) has been reported to be an irreversible antagonist of responses to adenosine 5'-triphosphate (ATP) at metabotropic purinoceptors (of the P2Y family) in some smooth muscles. When a recombinant P2Y1 purinoceptor (derived from chick brain) is expressed in Xenopus oocytes, ATP and 2-methylthioATP (2-MeSATP) evoke calcium-activated chloride currents (ICl,Ca) in a concentration-dependent manner. The effects of PIT on these agonist responses were examined at this cloned P2Y purinoceptor. 2. PIT (0.1-100 microM) failed to stimulate P2Y1 purinoceptors directly but, over a narrow concentration range (0.1-3 microM), caused a time-dependent potentiation (2-5 fold) of responses to ATP. The potentiation of ATP-responses by PIT was not caused by inhibition of oocyte ecto-ATPase. At high concentrations (3-100 microM), PIT irreversibly inhibited responses to ATP with a IC50 value of 13 +/- 9 microM (pKB = 4.88 +/- 0.22; n = 3). PIT failed to potentiate inward currents evoked by 2-MeSATP and only inhibited the responses to this agonist in an irreversible manner. 3. Known P2 purinoceptor antagonists were tested for their ability to potentiate ATP-responses at the chick P2Y1 purinoceptor. Suramin (IC50 = 230 +/- 80 nM; n = 5) and Reactive blue-2 (IC50 = 580 +/- 130 nM; n = 6) reversibly inhibited but did not potentiate ATP-responses. Coomassie brilliant blue-G (0.1-3 microM) potentiated ATP-responses in three experiments, while higher concentrations (3-100 microM) irreversibly inhibited ATP-responses. The results indicated that potentiation and receptor antagonism were dissociable and not a feature common to all known P2 purinoceptor antagonists. 4. In radioligand binding assays, PIT showed a low affinity (pKi < 5) for a range of membrane receptors, including: alpha 1, alpha 2-adrenoceptors, 5-HT1A, 5-HT1B, 5-HT2, 5-HT3, D1, D2, muscarinic, central benzodiazepine, H1, mu-opioid, dihydropyridine and batrachotoxin receptors. PIT showed some affinity (pKi = 5.3) for an adenosine (A1) receptor. 5. In guinea-pig isolated taenia caeci, PIT (12.5-50 microM) irreversibly antagonized relaxations to ATP (3-1000 microM); PIT also directly relaxed the smooth muscle and histamine was used to restore tone. Relaxations to nicotine (10-100 microM), evoked by stimulating intrinsic NANC nerves of taenia caeci preparations in the presence of hyoscine (0.3 microM) and guanethidine (17 microM), were not affected by PIT (50 microM, for 25-60 min). 6. These experiments indicate that PIT causes an irreversible antagonism of ATP receptors but, for recombinant chick P2Y1 purinoceptors, this effect is preceded by potentiation of ATP agonism. The initial potentiation by PIT (and by Coomassie brilliant blue-G) of ATP-responses raises the possibility of designing a new class of modulatory drugs to enhance purinergic transmission at metabotropic purinoceptors.

Adenosine Triphosphatases↗

PubMed1996

Systemic gadolinium toxicity in patients with renal insufficiency and renal failure: retrospective analysis of an initial experience.

OBJECTIVE: To study the possible deleterious systemic effects of gadolinium in patients with impaired renal function. DESIGN: We retrospectively analyzed the routine laboratory data and clinical course of patients who had undergone a gadolinium-enhanced magnetic resonance imaging (MRI) examination of the brain and spine and had evidence of impaired glomerular filtration. MATERIAL AND METHODS: Between October 1988 and October 1992, 15,830 patients underwent gadolinium-enhanced MRI at our institution, 151 of whom had a serum creatinine value of more than 2 mg/dL. The clinical records of these 151 patients were thoroughly examined for the period from 3 days before to 30 days after the gadolinium-enhanced MRI examination. All data were analyzed in an attempt to detect any adverse events that could be related to free gadolinium as a result of dissociation from the chelating agent due to prolonged elimination times (that is, increased serum creatinine concentrations). In addition, we calculated the 90-day mortality rate for both the study group and a matched control population of 80 patients who had undergone MRI of the brain and spine before gadolinium was available. RESULTS: The overall incidence of adverse events in the study group was 3.6%. No event was severe or life threatening--nausea and rash occurred in two patients each, and seizure and headache occurred in one patient each. These findings were not significantly different from those in previous studies performed in populations with normal elimination times. Moreover, no significant difference was noted in the 90-day mortality rate (14.6% of the study group) in comparison with that in the control group (13.8%). CONCLUSION: On the basis of this initial retrospective analysis, we were unable to detect any clinical deleterious effects of administration of gadolinium for MRI examination in patients with impaired renal function. Further investigation with prospective studies is needed to confirm these initial retrospective findings.

Adult↗

PubMed1996

A novel P1 purinoceptor activates an outward K+ current in follicular oocytes of Xenopus laevis.

Follicular oocytes of Xenopus laevis possess P1 purinoceptors where, seemingly, both adenosine (Ado) and ATP are agonists. The basis of ATP agonism at this P1 purinoceptor was investigated using electrophysiological and biochemical procedures. Ado and ATP activated an outward K+ current that reversed at -90 mV, was reduced by TEA and was inhibited by theophylline and 8-(p-sulphophenyl)-theophylline but not by suramin. Outward K+ current to ATP and Ado also was inhibited by alpha, beta-methylene ATP. The affinity constants for Ado and ATP were identical, although ATP was a partial agonist. The potency order of nucleosides/nucleotides was 5'-N-ethylcarboxamide- adenosine > Ado > AMP > CGS-21680 > beta, gamma-methylene ATP = ATP > ADP > R-N6 phenylisopropyl-adenosine, whereas 2-methylthioadenosine, ATP-O-(3-thiotriphosphate), uridine 5'-triphosphate and alpha, beta-methylene ATP were inactive. Outward K+ current to ATP and nondegradable Ado analogs was unaffected by adenosine deaminase (although this enzyme prevented Ado agonism), which suggests that ATP is not broken down to Ado before activating K+ channels. The activity of oocyte ecto-ATPase was determined by HPLC analysis of ATP breakdown and by the production of inorganic phosphate. Oocyte ecto-ATPase showed a low rate of ATP hydrolysis and was incapable of generating sufficient Ado/AMP to activate P1 purinoceptors. The results show that a P1 purinoceptor that is not typical of other known Ado receptors (and ATP receptors) is present in the follicle cell layer of Xenopus oocytes and represents a novel purinoceptor subtype where both Ado and ATP are agonists in their own right.

Adenosine↗

PubMed1996

Laparoscopic marsupialization of symptomatic polycystic kidney disease.

PURPOSE: Although laparoscopic unroofing of simple renal cysts has proved to be an effective form of therapy, its use for treatment of multiple renal cysts or symptomatic autosomal dominant polycystic kidney disease only recently has been investigated. MATERIALS AND METHODS: The results of laparoscopic marsupialization of symptomatic renal cysts in 13 patients was determined 12 to 28 months postoperatively by assessing subjective pain relief, and comparing preoperative and postoperative computerized tomography (CT). Eight patients had autosomal dominant polycystic kidney disease. Multiple dominant (more than 3 cm.) cysts were marsupialized in 11 patients and 1 dominant cyst was treated in 2. RESULTS: Of 13 patients with symptomatic renal cysts and 8 with autosomal dominant polycystic kidney disease 8 (62%) and 4, respectively, were pain-free 12 to 28 months postoperatively. Two patients had persistent pain, while 3 had recurrent pain 7 to 16 months postoperatively. All 5 patients had persistent or recurrent dominant cysts on followup CT. Followup CT demonstrated resolution or a significant decrease of the largest and all or all but 1 of the other dominant cysts in 6 of 7 pain-free patients. Intraoperative ultrasound detected unidentified cysts during an open and laparoscopic procedure. No deleterious effects on serum creatinine were observed. CONCLUSIONS: Laparoscopic marsupialization is a safe, relatively successful technique for providing persistent pain relief in patients with autosomal dominant polycystic kidney disease. Although the 2-year pain-free rate approaches the 62% rate reported for open surgical cyst resection, continued efforts to improve current laparoscopic techniques are clearly indicated. Persistence or recurrence of dominant cysts on CT correlated with persistent or recurrent symptoms. Intraoperative ultrasound is effective in identifying dominant cysts.

Adult↗