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PubMedDate not supplied

[The bony scan at 99m Tc pyrophosphate in the chronic kidney deficiency treated by hemodialysis (author's transl)].

The bony scan at 99m Tc pyrophosphate of thirty chronic hemodialyzed patients have been classified in four groups of increasing fixation according to Olgaard's criterions. The clinical, radiological symptoms of renal osteodystrophy the alkalin phosphatases and the PTHi rate have been compared. Twenty-six scans show a noticeable fixation (stage II) or an important one (stage III--eleven patients). The third stage patients have more important radiographical symptoms, a more important rate of alkalin phosphatases and PTHi rate than those of the second stage. According to our observations and those of literature, the scan at 99m Tc PP allow an early and faithful diagnosis of renal osteodystrophy. It seems to represent the increase of the osteoid immature tissue, which is the usual characteristic of the renal osteodystrophy.

Adult↗
PubMed1980

Fluoride, pyrophosphate, and base release from 2'-deoxy-2'-fluoronucleoside 5'-diphosphates by ribonucleoside-diphosphate reductase.

Ribonucleoside-diphsophate reductase from Escherichia coli catalyzes release of fluoride, inorganic pyrophosphate, and base from 2'-deoxy-2'-fluoronucleoside diphosphates. This reaction is accompanied by inactivation of the enzyme and an increase in absorbance at 314 nm of the inactivated protein. 2'-Deoxy-2'-fluoroadenosine 5'-diphosphate requires two turnovers per inactivation, whereas 2'-deoxy-2'-fluorocytidine 5'-diphosphate requires 100 turnovers per inactivation.

Adenosine Diphosphate↗
PubMedDate not supplied

Variation in plasma and urinary inorganic phosphate and pyrophosphate in normal subjects and in patients with acromegaly or osteoarthritis.

Plasma inorganic pyrophosphate (PPi) and inorganic orthophosphate (Pi) levels, urinary PPi and Pi excretion were measured every 2 h for a day in 4 normal subjects on a normal diet and again while fasting; 5 patients with osteoarthritis and 4 patients with acromegaly were also studied. Plasma Pi values were elevated at night in all subjects and were highest in the acromegalic patients. Mean plasma PPi was lower during fasting and correlated with Pi levels in all non-fasting subjects. Urinary Pi and PPi were strongly correlated; both were lower in fasting subjects. Food intake and the time of blood sampling are important biological variables that must be considered when interpreting plasma PPi levels.

Acromegaly↗
PubMed1980

Differential accumulation of Tc-99m DTPA and Tc-99m pyrophosphate within cerebral and cranial lesions: concise communication.

We sought to determine the clinical utility of using a bone-scanning agent in addition to a brain-scanning agent for the imaging of cerebral and cranial lesions. Images were obtained in 51 patients with Tc-99m diethylene-triamine-pentacetic-acid (DTPA) followed by Tc-99m pyrophosphate (PPi) within 2--5 days. The scans were qualitatively analyzed and the lesion-to-background count density ratios were determined from the corresponding brain and skull images. Only four of 20 cerebral infarctions were better demonstrated with PPi, whereas they were better with DTPA in 14 patients. They were equally good in two patients. The average lesion-to-background count-density ratio for infarction was 1.555 +/- 0.335 with DTPA and 1.428 +/- 0.573 with PPi (p < 0.05). Primary brain tumors were better visualized with DTPA in four out of five cases (p < 0.05). Metastases to brain showed up better with DTPA in 15 of 16 patients (p < 0.05), whereas all ten metastases to skull were seen better with PPi (p < 0.01). These results support previous reports regarding the radiopharmaceutical of choice for tumor imaging but not for infarction. This may be due to the differences in blood clearance for the various imaging agents.

Brain Neoplasms↗
PubMed1981

Tc-99m pyrophosphate myocardial scanning in Chagas' disease.

Chagas' disease is a serious protozoan infection affecting up to 20% of populations in some endemic areas. Myocarditis and cardiomyopathy occur in 50% of patients who go on to develop chronic Chagas' disease. We have studied a patient with no overt cardiac symptoms who revealed intense myocardial uptake of Tc-99m pyrophosphate. The significance of this finding in relation to early detection and progress of therapy is explored.

Chagas Cardiomyopathy↗
PubMedDate not supplied

[Comparison of ATP-pyrophosphate exchange reactions, catalyzed by two different "one-site" forms of tryptophanyl-tRNA-synthetase and by native enzyme].

Kinetic parameters of the reaction of ATP-PPi exchange, catalysed by "one-site" form of beef pancreas tryptophanyl-tRNA-synthetase are determined. The one-site form was obtained by affinity labelling of one active centre of the enzyme with alkylated analog of tryptophan. The comparison of kinetic parameters of this one-site form with the other one produced earlier by affinity labelling with analog of tryptophanyl-tRNA and the native enzyme was carried out. It was shown that the presence of tRNA improves the discrimination properties of the enzyme and diminishes the concentrations of "dead-end" complexes. Negative cooperativity in binding of two molecules of tryptophan is observed, which disappears in the presence of ATP, leading to an apparent synergistic effect. The molecule of tryptophan, which is present in the active centre, diminishes affinity of pyrophosphate.

Adenosine Triphosphate↗
PubMed1983

Alterations of the [59Fe]ferric citrate biodistribution in hyperferremic mice after the administration of pyrophosphate and desferrioxamine.

One of the most efficient anions in enhancing the ability of desferrioxamine (DFO) to remove iron from transferrin in vitro has been shown to be pyrophosphate (PYP). To evaluate the in vivo effect of PYP in hyperferremic mice, the biodistribution of [59Fe]ferric citrate was studied after the i.p. administration of: 1) only saline in the control animals; 2) an aqueous solution of tetrasodium diphosphate (PYP; 40 gm/2 g of b.wt.); 3) desferral (DFO; 12 mg/20 g of b.wt.); and 4) PYP + DFO at the respective dosages shown above. The radioactivity in each organ, blood, urine and feces was measured and referred to as percentage of the injected dose. PYP administered alone acted as a weaker chelator of iron than DFO. The combined administration of DFO and PYP contributed more than DFO or PYP separately, to the increase of urinary excretion of 59Fe and to the significant decrease of the radioiron concentration in liver (.01 less than P less than .05). The above induced changes are not, however, the additive result of the separate effect of DFO and PYP. That observation would suggest that DFO + PYP combined in a unique treatment, interact with iron through a common reaction pathway and that PYP plays in vivo a synergistic role in that interaction. The kind of iron with which DFO + PYP interacts is then suggested to be the transferrin-bound iron located in extracellular spaces of tissues.

Animals↗
PubMedDate not supplied

[X-ray study of the effect of pyrophosphate on thick filament structure in skinned fiber bundles of the rabbit psoas muscle].

Structure of thick filaments in the chemically skinned fibre bundles of rabbit psoas muscle in a state of pseudorelaxation induced by adding 2 mM pyrophosphate (PP) and of PP-mixture with 40% ethyleneglycol to the bathing rigor solution was studied with the help of X-ray diffraction technique. Reduction in the isometric rigor tension by about 50-70% in a state of pseudorelaxation is accompanied by significant changes in the relative intensities of a number of meridional reflections, indicating that in situ the structure and location of S-2 segment may be regulated by the structural changes in the acto S-1-complex during its cyclic interaction with ATP.

Animals↗
PubMed1982

Specific recognition of pyrophosphate in nucleotides.

The lipophilic diammonium cation 1 was demonstrated to be a reagent to discriminate the number of the phosphate in nucleotides. Thus the highly hydrophilic nucleotides were selectively extracted into an organic phase by the formation of ion-pairs and selectively transported through a membrane by a carrier mechanism. The compound was also shown to be an efficient phase transfer reagent which activated the phosphate anion of AMP to give a facile synthesis of pyrophosphate linkages, ADP and ATP, without any protection of the sugar moiety.

Adenine Nucleotides↗
PubMed1983

Effects of ATP and pyrophosphate on properties of glucocorticoid-receptor complexes from rat thymus cells.

Cytosols from rat thymus cells incubated with glucocorticoid contain nonactivated and activated receptors and mero-receptor complexes, in relative amounts that depend on the incubation conditions. These forms can be separated by a rapid minicolumn chromatographic technique based on their differential affinities for DNA, DEAE, and hydroxylapatite. We have used this method to examine the effects of ATP, pyrophosphate (PPi), and related compounds on cytosolic complexes. In addition to ATP, already known to promote activation at 0 degrees C, PPi, ADP, and other triphosphates at millimolar concentrations promoted activation of nonactivated complexes. AMP and Pi had little effect. ATP and PPi at millimolar concentrations also reduced binding of activated complexes to DNA. Characterization of the ATP- and PPi-activated complexes by gel filtration and ion exchange chromatography revealed two DNA-binding forms. One was essentially identical (Stokes radius of approximately 5.4 nm, elution from DEAE at approximately 50 mM KCl) to the normal activated complex obtained directly from cells incubated at 37 degrees C. The other had a Stokes radius of approximately 3.1 nm and had no affinity for DEAE. Analysis by minicolumns and gel filtration showed that ATP and PPi prevented formation of mero-receptor complexes, a process which occurs relatively rapidly in untreated thymus cytosols. These compounds did not alter properties of preformed mero-receptor. The accumulation of 3.1-nm complexes in thymus cytosols in which formation of mero-receptor is prevented suggests that this form is an intermediate, normally short-lived, in the conversion of 5.4 nm complexes to mero-receptor.

Adenosine Triphosphate↗
PubMed1984

Multiple forms of pyrophosphate:D-fructose-6-phosphate 1-phosphotransferase from wheat seedlings. Regulation by fructose 2,6-bisphosphate.

Two forms of pyrophosphate:D-fructose-6-phosphate 1-phosphotransferase have been isolated from wheat seedlings. One of these enzymes, termed PFP-1, has been purified to homogeneity. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicates that the enzyme is composed of two different polypeptide chains of Mr = 67,000 (alpha) and 60,000 (beta). PFP-1 has been assigned a molecular structure consisting of alpha 2 beta 2 based on an estimated Mr of 234,000 for the native enzyme. PFP-2, the other form of phosphotransferase, has also been purified extensively. Preliminary data suggest that the active form of PFP-2 is probably a dimer of a polypeptide chain of Mr = 60,000. Immunological studies indicate that the two enzyme preparations share common antigenic determinants. The two forms of enzyme have very similar kinetic properties. The phosphotransferases are activated by fructose 2,6-bisphosphate (Fru-2,6-P2) which lowers the Km of the enzymes for fructose 6-phosphate but not that for PPi. Interestingly, PFP-1 is significantly more active than PFP-2 in the absence of Fru-2,6-P2. Also, PFP-1 exhibits a greater affinity (Ka = 7 nM) than PFP-2 (Ka = 26 nM) for the activator. Based on kinetic, immunological, and physicochemical parameters, it is suggested that the two enzymic forms are related in that they share the same catalytic moiety, i.e. the 60,000-dalton or beta subunit. The beta subunit when in complex formation with the alpha subunit, as in PFP-1, becomes more active in the absence of Fru-2,6-P2 as well as exhibits a greater sensitivity toward the effector.

Enzyme Activation↗
PubMed1984

Altered 5-phosphoribosyl 1-pyrophosphate amidotransferase activity in 6-thioguanine-resistant HL-60 human acute promyelocytic leukemia cells.

A novel mechanism of resistance to the antileukemic agent 6-thioguanine (TGua) was demonstrated in a clone (TGuo-30-2) derived from HL-60 human acute promyelocytic leukemia cells. The clone was isolated by prescreening mutagenized HL-60 cells in hypoxanthine-amethopterin-thymidine medium, followed by selection with 6-thioguanosine. TGuo-30-2 cells were cross-resistant to TGua and beta-2'-deoxythioguanosine. TGuo-30-2 cells exhibited a marked decrease in the capacity to accumulate intracellular TGua nucleotides after treatment with TGua. The decrease in accumulation was not caused by a defect in transport, a lack or alteration of hypoxanthine-guanine phosphoribosyltransferase activity, or enhanced degradation of TGua nucleotides but appeared to be due to the maintenance of a lowered level of 5-phosphoribosyl 1-pyrophosphate (PRPP) in the resistant variant, which corresponded to 20% of the parental concentration. Despite the decrease in PRPP levels, incorporation of glycine into purine nucleotides was greater in TGuo-30-2 than in parental cells. Measurement of PRPP amidotransferase activity using cell homogenates revealed altered kinetics for the enzyme from TGuo-30-2 cells, which included significant loss of sensitivity to feedback inhibition by 6-thioguanosine 5'-phosphate and greater catalytic activity at low concentrations of PRPP.

Amidophosphoribosyltransferase↗
PubMed1978

Sequential myocardial scintigraphy with technetium-99m stannous pyrophosphate following myocardial infarction.

Studies have shown that technetium-99m stannous pyrophosphate (Tc-PPi) is effective for the detection and imaging of acute myocardial infarction. Positive Tc-PPi myocardial scintigrams, however, have been reported in patients with other forms of heart disease and no evidence of recent myocardial infarction. To help define the usefulness of this test, we undertook a prospective study to ascertain when Tc-PPi myocardial scintigrams return to normal after myocardial infarction. Twenty patients with acute myocardial infarction were followed with Tc-PPi scintigrams at 1 and 2 wk, and 1, after infarction. The serial scintigrams revealed that a) 15 of 18 scintigrams were positive within the first week after infarction, b) the number of markedly positive scintigrams decreased promptly after the first week, and c) some scintigrams (11 of 18 at 1 mo, and 3 of 18 at 9 mo) remained positive throughout the study. The possible explanations for persistently positive scintigrams are discussed. Persistently positive scintigrams may hinder the usefulness of Tc-PPi myocardial scintigraphy for the diagnosis of acute myocardial infarction in patients who have had a myocardial infarction within the previous 9 mo.

Acute Disease↗
PubMed1994

Effects of pyrophosphate and nucleotide analogs suggest a role for ATP hydrolysis in cystic fibrosis transmembrane regulator channel gating.

Single channel analysis of artificial lipid planar bilayers reconstituted with wild-type human cystic fibrosis transmembrane regulator (CFTR) revealed a 10.3 pS Cl- selective channel that was activated upon phosphorylation with protein kinase A. Gating of this channel was described by a simple kinetic model consisting of a single open burst state and two closed states. The open probability of CFTR channels in bilayers increased as a function of increasing Mg-ATP concentration and exhibited negative cooperativity, suggesting the interaction of two or more ATP binding sites in channel gating. Mg-ATP increased channel open probability by decreasing the duration of the long-lived closed state but had no effect on either the mean open time or the fast closed state. ADP inhibited channel opening by precisely antagonizing the effect of ATP, suggesting that ADP inhibits the CFTR channel by competing with ATP for binding. Poorly hydrolyzable ATP analogs such as AMP-PNP and ATP gamma S, polyphosphates such as pyrophosphate (PPi) and tripolyphosphate (PPPi), and orthovanadate failed to support channel activity alone. When applied in the presence of ATP, these compounds all caused the CFTR channel to "lock" into a prolonged open burst state. These data support a model in which hydrolysis of ATP leads to closure of channels that have been opened by ATP.

Adenosine Monophosphate↗
PubMed1995

Inhibition of human 5-phosphoribosyl-1-pyrophosphate synthetase by 4-amino-8-(beta-D-ribofuranosylamino)-pyrimido[5,4-d]pyrimidine-5'- monophosphate: evidence for interaction at the ADP allosteric site.

The kinetics of inhibition by the aminopyrimidopyrimidine nucleotide 4-amino-8-(beta-D-ribofuranosylamino)pyrimido[5,4-d]pyrimidine[-5' -monophosphate (APP-MP) were assessed with two human isozymes of 5-phosphoribosyl-1-pyrophosphate synthetase (PRS) (PRS1 and PRS2) and a mutant enzyme, S.M. PRS1, derived from an individual with PRS hyperactivity. In the presence of 1 mM potassium phosphate, APP-MP inhibited PRS1 and PRS2 with half-maximal inhibition (IC50) at 5.2 microM and 23.8 microM, respectively. The degree of inhibition for both enzymes was highly dependent on the phosphate concentration; IC50 values were 70 times higher in the presence of 50 mM potassium phosphate. APP-MP exhibited mixed noncompetitive-uncompetitive inhibition against PRS1, with a Kii value of 6.1 microM and a Kis value of 14.6 microM, and produced parabolic secondary plots of slope or intercept versus APP-MP concentration. In comparison, inhibition of PRS1 by ADP was of a mixed noncompetitive-competitive type, with a Kii value of 9.6 microM and a Kis value of 2.8 microM. A similar kinetic analysis was completed using S.M. PRS1, a mutant enzyme with a single amino acid substitution resulting in diminished sensitivity to feedback inhibition by nucleotides. The noncompetitive component of ADP inhibition of PRS1 was absent with S.M. PRS1 and ADP inhibition was purely competitive, with a Ki of 6.4 microM, APP-MP was a very poor inhibitor of S.M. PRS1, displaying uncompetitive characteristics and a Ki of 1.6 mM. These data indicate that APP-MP inhibits PRS1 with a strong element of noncompetitive inhibition and appears to interact specifically at the allosteric site used by ADP. These results contrast with those obtained with ADP, which has a strong component of ATP competitive inhibition and binds at the ATP site as well as at a second, allosteric, site.

Adenosine Diphosphate↗
PubMed1995

Calcium pyrophosphate dihydrate crystal deposition disease in the elderly.

Calcium pyrophosphate dihydrate deposition disease can mimic a large number of joint diseases. We report on three patients with predominantly systemic symptoms. Diagnostic pitfalls and treatment delays in these patients are discussed. Once the diagnosis is considered, confirmation is readily obtained by examination of the joint fluid and treatment promptly relieves symptoms.

Aged↗
PubMed1994

Cervical radiculomyelopathy due to deposition of calcium pyrophosphate dihydrate crystals in the ligamentum flavum: historical and histological evaluation of attendant inflammation.

Deposition of calcium pyrophosphate dihydrate (CPPD) crystals in the yellow ligament occasionally leads to neurological deficits through compression of the spinal cord. Although it is widely accepted that CPPD crystal induces severe inflammation in arthropathy, little attention has been paid to the acute inflammation that may accompany the CPPD crystals in the ligamentum flavum. The present study reviews eight patients with radiculomyelopathy due to calcification of the cervical yellow ligament. Acute inflammation of the yellow ligament accompanying the crystalline deposits, both with and without attendant granulation tissue-proliferation, was evaluated as contributing to cervical radiculomyelopathy. Three cases with attendant granulation tissue suffered from recurrent attacks of neck pain and fever with coincidental radicular pain in the upper arm. The local inflammation of the ligamentum flavum might have participated in the exacerbation of the cervical radiculopathy.

Aged↗