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PubMed1979

Myocardial uptake of technetium-99m stannous pyrophosphate in experimental viral myopericarditis.

Distribution of technetium-99m stannous pyrophosphate was studied in mice with experimentally induced viral myopericarditis. Myocardial and bone uptakes of Tc-PPi were compared in 55 mice inoculated with coxsackievirus B3 (Nancy strain). The myocardium-to-bone uptake ratio in 33 mice with myopericarditis was increased to a greater extent than that seen in 22 mice without myopericarditis (p less than 0.001). In the severely involved heart, the uptake per gram exceeded that in the bone. Myocardial uptake in myopericarditis can be visualized on a whole-body image using a pinhole collimator and a left lateral view. Our experimental studies suggest the potential clinical usefulness of myocardial scintigraphy in viral myopericarditis.

Animals↗
PubMed1979

Comparison of Tc-99m pyrophosphate and Tc-99m methylene diphosphonate in acute myocardial infarction: concise communication.

This study compared Tc-99m pyrophosphate (PPi) and Tc-99m methylene diphosphonate (MDP) for myocardial infarct imaging in 24 patients with diagnosed acute myocardial infarction. The radiopharmaceuticals were administered randomly and interpreted without knowledge of the sequence used. Twenty-three patients (96%) had positive Tc-99m PPi scintigrams, but only 17 (71%) had a positive Tc-99m MDP study (P less than 0.05). In addition, a comparison of the relative intensity with each agent revealed greater intensity with Tc-99m in 21 cases, equal intensity in two cases, and less intensity in only one case (p less than 0.001). These findings support the superiority of Tc-99m PPi as the agent of choice for myocardial scintigraphy in acute infarction.

Acute Disease↗
PubMed1979

[The use of bone scintigraphy with technetium 99 m pyrophosphates in the diagnosis of algodystrophies. A report on 74 observations (author's transl)].

Bone scintigraphy with technetium 99m pyrophosphates was used to study a series of 74 cases of algodystrophies. Though non-specific, this investigation was the determining factor for confirming the diagnosis in more than 48% of cases, by demonstrating early bone hyperfixation, its topographical characteristics, and the return to normal conditions after 3 to 12 months. Bone hyperfixation has to be exaluated together with clinical, biological, and radiological signs when considering the diagnosis, and though in half the cases it is not indispensable for diagnosis, it is always of value for determining the amount of extension of the algodystrophic process.

Adult↗
PubMedDate not supplied

[Analogs of pyrophosphate in a pyrophosphorolysis reaction catalyzed by DNA polymerases].

The reaction of pyrophosphorolysis catalyzed by Escherichia coli DNA polymerase I Klenov fragment, calf thymus DNA polymerase alpha, rat liver DNA polymerase beta and AMV reverse transcriptase was studied. Some pyrophosphate (PPi) analogs were taken as low molecular weight substrates. It was shown that only imidodiphosphonic acid acted as the PPi substrate analog for the reactions catalyzed by DNA polymerases I and alpha, both imidodiphosphonic acid and methylenediphosphonic acid were active in the case of DNA polymerase beta and reverse transcriptase. Other analogs tested were neither nucleotide residue acceptors, nor inhibitors of the pyrophosphorolysis reaction with PPi. The abilities of some PPi analogs to inhibit the DNA elongation catalyzed by reverse transcriptase were investigated. The principles of specificity of low molecular substrates recognition by DNA polymerases and some problems concerning the mechanisms of DNA synthesis inhibition by PPi analogues are discussed.

Animals↗
PubMed1988

The effects of pyrophosphate on myosin heads and on fiber stiffness.

We have investigated the effect of magnesium pyrophosphate (MgPPi) on the orientation and stiffness of myosin heads in glycerinated muscle fibers. MgPPi is known to bind to the nucleotide site of myosin and to weaken the bond between myosin and actin. The spectra of paramagnetic probes attached to the reactive sulfhydryl on the myosin head were used to monitor the orientation of the head. Addition of 3 mM MgPPi to rigor fibers resulted in a shift of approximately 50% of the myosin heads from a state in which the probes are highly oriented to a state in which the probes are disordered. Experiments in which MgPPi dissociated labeled subfragment-1 from unlabeled fibers support the conclusion that the disordered probes are on myosin heads that are not attached to actin. Addition of MgPPi causes only a small decrease in fiber stiffness, measured by step changes in fiber length. We conclude that up to 50% of the myosin heads can be dissociated from actin with little change in muscle stiffness. Thus stiffness is not a linear measure of the fraction of myosin heads attached to actin. We present a model in which one head of the pair of a myosin molecule binds more weakly to actin and can be dissociated preferentially by the binding of MgPPi.

Animals↗
PubMed1988

Hypophosphatasia: biochemical screening of a Dutch kindred and evidence that urinary excretion of inorganic pyrophosphate is a marker for the disease.

Hypophosphatasia is an inherited disease in which a deficiency of the bone/liver/kidney or tissue nonspecific isoenzyme of alkaline phosphatase (AP; EC 3.1.3.1) occurs. All forms of the disease are characterized clinically by defective mineralization. Several biochemical abnormalities are associated with the deficiency of AP activity, e.g., increased urinary excretion of inorganic pyrophosphate (PPi) and phosphoethanolamine (PEA). Measurement of these analytes in kindreds of patients with hypophosphatasia may be useful in identifying carriers, and in understanding the inheritance of the disease. We studied biochemically 22 members of the kindred of a 24-year-old woman with hypophosphatasia. We measured activity of AP in serum and leukocytes, and the urinary excretion of PPi and PEA. Within this kindred, urinary excretion of PPi appeared to indicate carrier status, and among the clinically normal adults, values for this analyte were inversely correlated with the activity of AP in serum. These results suggest that urinary excretion of PPi is sensitive to subtle changes in the activity of AP.

Adolescent↗
PubMed1989

Identification and regulation of a rat liver cDNA encoding farnesyl pyrophosphate synthetase.

CR39 is a cholesterol-repressible rat liver cDNA previously isolated by differential hybridization (Clarke, C.F., Tanaka, R.D., Svenson, K., Wamsley, M., Fogelman, A.M., and Edwards, P.A. (1987) Mol. Cell. Biol. 7, 3138-3146). To precisely identify the function of CR39 a fusion protein was constructed that contained the amino-terminal region of the bacterial protein anthranilate synthetase fused to the full length CR39 polypeptide. Affinity purified antisera directed against the fusion protein inactivated rat liver cytosolic prenyltransferase activity in vitro. In addition, affinity purified antisera made to purified chicken prenyltransferase cross-reacted with the fusion protein containing CR39. Rat hepatic prenyltransferase activity and enzyme mass were quantitated in animals fed diets or drugs known to alter endogenous cholesterol biosynthesis. Rats fed a diet supplemented with cholestyramine and mevinolin showed a 3.5-fold increase in activity and a 5.0-fold increase in mass of cytosolic prenyltransferase. A diet supplemented with cholesterol resulted in approximately a 4.0-fold decrease in hepatic enzyme activity and a 10-fold decrease in enzyme mass. Under these same dietary regimens the mass of prenyltransferase in the testes remained unchanged. We conclude that CR39 encodes the prenyltransferase of cholesterol biosynthesis, farnesyl pyrophosphate synthetase. Furthermore, in the liver this enzyme shows coordinate regulation with two other enzymes, 3-hydroxy-3-methylglutaryl-CoA reductase and 3-hydroxy-3-methylglutaryl-CoA synthase, in response to cholesterol feeding and hypocholesterolemic drugs.

Amino Acid Sequence↗
PubMedDate not supplied

[The influence of diphosphonic analogues of inorganic pyrophosphate on activity of RNA-polymerases from the calf thymus].

Diphosphonic analogues of inorganic pyrophosphate (PPi): methylene-, oxyethylidene-, aminomethylenediphosphonic acids as well as phosphonacetic, imidodiphosphoric bis- (phosphonomethyl)-phosphonic acids and methylenediphosphonic and phosphonic acid monoanhydrides were studied for their effect on the RNA-synthesizing activity of thymocytes. DNA-dependent RNA-polymerases I and II from the calf thymus nuclei were used for these studies. The analogues and PPi under study are shown to be inhibitors of both RNA-polymerases in nuclei from calf thymus and of purified RNA-polymerase II, which is more sensitive to the effect of diphosphonates. Methylenediphosphonic acid is the strongest inhibitor among the studied analogues, and imidodiphosphoric and phosphonacetic acids are the weakest inhibitors. Inhibition of purified RNA-polymerase II by diphosphonates has a complex character and includes both interaction of the PPi analogues with enzymes and chelating by them of Mn ions which are cofactors for RNA polymerase.

Animals↗
PubMed1985

[Inorganic pyrophosphates and parathormone in hypophosphatasia. Study of a family].

The serum concentration of parathormone is usually normal in hypophosphatasia, a rare disease with a defect of bone mineralisation and low serum alkaline phosphatase activity. Nevertheless there are three cases in the literature presenting a hyperparathyroidism with or without hypercalcemia. No anomaly of parathyroid was found at autopsy. The authors describe the first cases of hypophosphatasia with low serum concentration of parathormone and raise the possibility of a trouble in the calcium-parathormone feed-back. They also emphasize the interest of the urinary pyrophosphate excretion. Its increase seem to be the most constant and the most specific biological disorder.

Adult↗
PubMed1977

Acute myocardial infarction: clinical application of technetium 99m stannous pyrophosphate infarct scintigraphy.

Acute myocardial infarction is being recognized as a spectrum of clinical subsets. This appreciation has been brought about to a large degree by the development of several new tools that can be applied clinically to aid in evaluation of patients with acute infarction, and in some cases to provide short and long-term prognostic information. In the realm of noninvasive methods, several tests utilizing radiopharmaceuticals and scintillation cameras have emerged and are rapidly becoming reliable diagnostic parameters in patients with coronary disease and infarction. Technetium 99m (stannous) pyrophosphate (TcPYP) scintigraphy, one of the first of these techniques to find clinical use, has been shown to be an accurate indicator of acute transmural myocardial infarction and provides added sensitivity and specificity to the diagnosis. Increased diagnostic accuracy, the dimension of visible localization and the potential for infarct sizing promise physicians better understanding of a patient's clinical presentation and a more rational approach to management.

Acute Disease↗
PubMed1987

3-Hydroxy-3-methylglutaryl-CoA reductase, mevalonate-5-pyrophosphate decarboxylase and acyl-CoA: cholesterol acyl-transferase from mucosa scrapings and isolated enterocytes from chick duodenum, jejunum and ileum.

3-Hydroxy-3-methylglutaryl-CoA reductase, mevalonate-5-pyrophosphate decarboxylase and acyl-CoA: cholesterol acyltransferase activities were assayed in mucosal scrapings and isolated enterocytes from chick duodenum, jejunum and ileum. Maximal reductase and decarboxylase specific activities were found in ileum and jejunum, while ileum exhibited the minimal acyltransferase specific activity. The isolated epithelial cells showed levels of reductase and acyltransferase specific activities higher than those found in mucosa scrapings, probably due to the contact of these microsomal proteins with proteolytic enzymes during homogenization of the mucosa. However, no protecting effect of the trypsin inhibitor (2mg/ml) could be observed on reductase activity in mucosa scrapings. The cytosolic location of decarboxylase may account for the similar levels of specific activities found in mucosa scrapings and isolated enterocytes.

Animals↗
PubMedDate not supplied

Evaluation of myocardial revascularization utilizing Tc-99m pyrophosphate.

Early clinical application of technetium 99m labeled pyrophosphate for cardiac imaging has revealed a safe noninvasive method of determining areas of impaired myocardial perfusion in patients with atherosclerotic occlusive coronary artery disease. Using this method, we were able to demonstrate improvement in myocardial blood supply following coronary artery bypass surgery.

Coronary Circulation↗
PubMed1979

Rat liver glutamine 5-phosphoribosyl-1-pyrophosphate amidotransferase [EC 2.4.2.14]. Purification and properties.

Glutamine 5-phosphoribosyl-1-pyrophosphate (PRPP) amidotransferase (amidophosphoribosyltransferase), [EC 2.4.2.14] was purified 1,600-fold from rat liver. The preparation gave two protein bands on acrylamide gel electrophoresis, of which only the main band showed enzyme activity. The molecular weight of the enzyme was estimated to be 215,000, 200,000, and 195,000 by Sephadex G-150 gel filtration, polyacrylamide gel electrophoresis, and sucrose density grandient ultracentrifugation, respectively. The apparent Km values for glutamine and PRPP were 1.24 mM and 0.57 mM, respectively. The concentration-activity curve for PRPP changed from a hyperbolic to a sigmoidal form on addition of AMP or GMP, and this inhibition by AMP was prevented by increasing the PRPP concentration. In the presence of high concentrations of inorganic phosphate, the catalytic activity was decreased and the sensitivity to AMP inhibition was slightly increased. The molecular size of liver amidotransferase was not changed by the addition of PRPP, AMP, or 2-mercaptoethanol. The purified rat liver enzyme has a broad pH-range of activity between 6.5 and 8.5.

Amidophosphoribosyltransferase↗
PubMed1979

[Long-time follow-up scintigraphy with 99m Tc pyrophosphate after myocardial infarction (author's transl)].

Follow-up scintigraphies with 99m Tc pyrophosphate 3--4 weeks and 6--12 months after a myocardial infarction revealed the possibility of persisting a myocardial tracer activity in cases in which reinfarction can be excluded. There was a relation between the persistence of the tracer activity and the pressure in the pulmonary artery under stress conditions. The diastolic pulmonary pressure was regular in those patients whose scintiphotos showed no tracer activity in the myocardial area in the follow-up scintigraphy. Patients who showed a persisting tracer activity in the infarcted areal had elevated pressures in the pulmonary artery under stress conditions or even at rest. The elevation of the diastolic pulmonary pressure is a sign of an elevated enddiastolic pressure in the left ventricle caused by a limited left ventricular function. This could be proved by left ventriculography. The results in follow-up scintigraphy 3--4 weeks and 6--12 months after the infarction were quite similar. Therefore we believe that the results of a follow-up scintigraphy 3--4 weeks after an infarction allows to draw prognostic inferences about the further course of the disease.

Blood Pressure↗
PubMed1975

Technetium-99m labeling by means of stannous pyrophosphate: application to bleomycin and red blood cells.

A new technique of technetium labeling using stannous pyrophosphate instead of stannous chloride as reducing agent for pertechnetate has been applied to red blood cells and bleomycin. Results are so encouraging that this technique could be extended to other compounds capable of forming stable complexes with reduced technetium. No saline washes of red cells are necessary before or after the addition of pertechnetate. No purification step is performed after labeling of bleomycin.

Bleomycin↗
PubMed1979

Survival of red blood cells in rabbits after acute administration of unlabeled stannous pyrophosphate: Concise communication.

We investigated the possibility that acute administration of unlabeled stannous pyrophosphate may adversely affect red blood cells in the rabbit. Our method was similar to the in vivo labeling of RBCs with technetium-99m for blood-pool scanning. The investigation showed that dosages recommended in the literature produce no demonstrable difference between pre- and postdose RBC survival, which strongly suggests that the stannous content of the pharmaceutical is not harmful to red blood cells.

Animals↗
PubMed1980

A study of irradiated bone. Part II. changes in Tc-99m pyrophosphate bone imaging.

Quantitative Tc-99m pyrophosphate bone imaging was carried out in locally irradiated and control areas of New Zealand albino rabbits to determine the potential role of bone imaging in assessing the time course of radiation effects in bone and surrounding tissues. In vitro Tc-99m tissue assays, and serial radiographs. from the irradiated and contralateral limbs were obtained at regular intervals over the first 12 mo following irradiation for comparison with quantitative results from the camera studies. The autoradiographic localization of TcPPi was also studied in the x-irradiated and contralateral bones of the rabbits. The results show that TcPPi bone imaging is a sensitive in vivo indicator of early radiation effects upon vasculature and bone remodeling. The findings suggest that the quantitative bone-imaging technique may be useful in the evaluation of the effects of treatment modalities on the skeleton.

Animals↗