Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PYROPHOSPHATES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 991 records · Page 55Linked to original sources
PubMed1982

Muscle uptake of 99mtechnetium pyrophosphate in patients with neuromuscular disorder. A quantitative study.

99mTechnetium pyrophosphate (99mTc PYP) muscular scanning was carried out in 28 patients affected by neuromuscular diseases. To express the muscle tracer retention quantitatively, the soft tissue to bone uptake ratio was calculated in the thigh and in the lower leg. Significantly increased ratio values were found in all the patients with polymyositis and in most patients with different types of muscular dystrophy, while high values were seen in a few subjects with myasthenia gravis and with neurogenic disorders. These findings are compared with those of previous studies, and the factors playing a role in determining some discrepant observations are discussed. The use of 99mTc muscular scanning in the investigation of patients with suspected inflammatory myopathy is suggested.

Adolescent↗
PubMed1995

Role of cellular ribose-5-phosphate content in the regulation of 5-phosphoribosyl-1-pyrophosphate and de novo purine synthesis in a human hepatoma cell line.

5-Phosphoribosyl-1-pyrophosphate (PRPP) is an important regulator of de novo purine synthesis. However, the role of ribose-5-phosphate (R5P), the precursor for PRPP, in the regulation of PRPP and de novo purine synthesis has not yet been clarified conclusively. This study was designed to clarify interrelationships between R5P content, PRPP availability, and the rate of de novo purine synthesis in the cultured human hepatoma cell line (HepG2), a plausible model for normal human hepatocytes. Increasing glucose concentration in the culture media from 0 to 10 mmol/L resulted in a 2.9-fold elevation of cellular R5P content (from 107 +/- 31 to 311 +/- 57 nmol/g protein), associated with a correlated increase of 7.14-fold in cellular PRPP availability (from 4.76 +/- 3.4 to 34 +/- 8.4 pmol/mg protein/min) and of 149-fold in the rate of de novo purine synthesis (from 55 to 8,204 dpm/mg protein/h). Plotting the rate of de novo purine synthesis versus R5P content indicates that at a wide range of R5P content, including that prevailing in hepatocytes under physiological conditions, the rate of purine synthesis depends on R5P content. A similar dependence was also demonstrated for PRPP availability. The rate of de novo purine synthesis exhibited a sigmoidal dependence on PRPP availability. The demonstration in human hepatocytes of dependence of the rate of purine synthesis on R5P content has implications concerning the pathogenesis of purine overproduction associated with several inborn and acquired conditions in man.

Carcinoma, Hepatocellular↗
PubMed1992

Diseases associated with calcium pyrophosphate deposition disease.

Although many metabolic and endocrine diseases have been reported to predispose to calcium pyrophosphate dihydrate crystal deposition, the validity of many of these associations remains unclear. A critical review of the literature relating to these associations, with illustrative cases and data derived from the authors' own experience, is presented. It is concluded that there is good evidence to associate hypophosphatasia, hypomagnesemia, and hyperparathyroidism with chondrocalcinosis and acute attacks of "pseudogout." Meta-analysis also suggests a small but significant association between hypothyroidism and chondrocalcinosis. Hemochromatosis stands alone in clearly associating not only with chondrocalcinosis but also with structural change and chronic arthropathy. The biochemical mechanisms that may produce these various associations are discussed. Recommendations are made concerning appropriate screening for metabolic and endocrine disease in patients with chondrocalcinosis.

Acromegaly↗
PubMed1989

Early mitogenic stimulation of metabolic flux through phosphoribosyl pyrophosphate into nucleotides in Swiss 3T3 cells and requirement of external magnesium for the response.

5-Phosphoribosyl 1-pyrophosphate (PRPP) is a common precursor for the synthesis of all nucleotides and also serves as a critical regulator for the synthesis. In spite of a number of studies in vitro on mammalian PRPP synthetase, our understanding of the regulation of PRPP synthesis in situ is very limited. Various mitogens are known to activate purine and pyrimidine de novo biosynthesis and purine base phosphoribosylation as an early response in quiescent mouse fibroblasts. We aimed at elucidation of the underlying mechanism for the possible increase in PRPP synthesis in mitogen-stimulated mouse fibroblasts in culture. In order to quantitatively follow metabolic flux through PRPP into nucleotides, [ribosyl-14C]inosine was enzymatically prepared and used as a tracer to preferentially label intracellular ribose phosphate. The radioactivity incorporation into cellular nucleotides was measured. Evidence supported the validity of the method. Prior exposure of quiescent Swiss 3T3 cells in culture to epidermal growth factor (EGF) plus insulin for 45-60 min enhanced approximately 2-fold the radioactivity incorporation from [ribosyl-14C]inosine into nucleotides, without increasing the specific radioactivity of intracellular free ribose 5-phosphate. [14C]Uracil incorporation into nucleotides, a measure for PRPP-independent ribose phosphate utilization for nucleotide synthesis, was not increased. These and other results indicate that EGF plus insulin stimulates the metabolic flux through PRPP. A similar stimulation was induced by bombesin and melittin in combination with insulin and by fibroblast growth factor alone. Quiescent Swiss 3T6 cells and human fetal fibroblasts showed a similar stimulation of nucleotide synthesis in response to exposure to serum. For characterization of intracellular signaling pathways, we examined effects of several inhibitors and agents on the stimulation. The divalent cation ionophore A23187 mimicked the response to EGF and insulin in Swiss 3T3 cells, thereby suggesting involvement of divalent cation mobilization in this increase. The effect of the ionophore was not additive to that of the growth factors. Omission of Ca2+ from the incubation medium did not affect the response to EGF and insulin, whereas the omission of Mg2+ did abolish the response. Furosemide, an inhibitor of Mg2+ influx, partially inhibited the stimulated synthesis of nucleotides. Thus, the entry of external Mg2+ into the cells may play a critical role in this signal transduction. These results provided an important access to elucidation of the intracellular mechanisms for the mitogen-induced increase in PRPP and nucleotide syntheses.

Animals↗
PubMed1987

Technetium-99m pyrophosphate single-photon emission computed tomography of the heart in familial amyloid polyneuropathy.

A patient with familial amyloid polyneuropathy and congestive heart failure underwent myocardial imaging using technetium-99m pyrophosphate. Planar scintigraphy showed an intense, diffuse biventricular uptake of the radiotracer. Single-photon emission computed tomography demonstrated an unevenly distributed uptake of the isotope. The greatest activity corresponded to regions with marked echocardiographic changes. Emission tomography may aid in assessing the degree and distribution of the infiltrative lesions in cardiac amyloidosis.

Aged↗
PubMed1991

Tumourous deposition of calcium pyrophosphate dihydrate crystals in the wrist. A case report.

A 63-year-old man had a tumourous deposition of calcium pyrophosphate dihydrate crystals in the palmar aspect of the wrist. Traumatic micro-fracture or osteoarthritis was thought to have triggered the deposition of these crystals. It should be possible to differentiate the lesion clinically and radiologically from tumoural calcinosis, in which the deposits consist of calcium carbonate and/or calcium phosphate.

Calcium Pyrophosphate↗
PubMed1986

Superactivity of human phosphoribosyl pyrophosphate synthetase due to altered regulation by nucleotide inhibitors and inorganic phosphate.

Phosphoribosyl pyrophosphate (PPRibP) synthetase activity was studied in cultured fibroblasts and lymphoblasts from a male child (patient 2-A) in whom inherited purine nucleotide and uric acid overproduction are accompanied by neurological deficits. Chromatographed or partially purified preparations of the child's enzyme showed 5-6-fold increased inhibitory constants (I0.5) for the noncompetitive inhibitors GDP and 6-methylthioinosine monophosphate but normal responsiveness to the competitive inhibitors ADP and 2,3-diphosphoglycerate. Activation of the PPRibP synthetase of patient 2-A by Pi was also abnormal with 3-4-fold reduced apparent KD values for Pi. Superactivity of the PPRibP synthetase of this child thus appeared to result from a combination of regulatory defects; selective resistance to noncompetitive inhibitors and increased responsiveness to Pi activation. Selective growth of the patient's fibroblasts in medium containing 6-methylthioinosine confirmed the functional significance of the in vitro inhibitor resistance of the aberrant enzyme. Fibroblasts and lymphoblasts derived from patient 2-A showed increased concentrations and rates of generation of PPRibP as well as increased rates of the pathways of purine base salvage and purine nucleotide synthesis de novo. The magnitudes of these increases in the child's cells exceeded those in cells with catalytically superactive PPRibP synthetases. These alterations as well as the in vitro kinetic abnormalities in the patient 2-A enzyme were expressed to a reduced degree in fibroblasts from the child's affected mother, supporting the proposal that this woman is a heterozygous carrier for X-linked enzyme superactivity.

Cells, Cultured↗
PubMed1988

Deposition of calcium pyrophosphate dihydrate crystals in the hand.

A rare case with deposition of calcium pyrophosphate dihydrate crystals around the proximal portion of the first and second metacarpal bones is reported. The second metacarpal had a cystic lesion, and the cortex of the first metacarpal had irregular osteolytic change. There were degenerative changes in the first carpometacarpal joint, trapeziotrapezoid articulation, and second carpometacarpal joint. The patient had recurrent acute inflammatory attacks at the affected site. Initially the patient was thought to have tumoral calcinosis, or a calcifying soft-tissue tumor, with the possibility of a malignant tumor because of angiographic evidence of tumor stain and hypervascularity. Surgical biopsy with partial curettage of the calcified mass resulted in early recurrence of deposition of the crystals. Total excision would seem to be necessary to avoid recurrence.

Calcium Pyrophosphate↗
PubMed1993

Scapholunate advanced collapse pattern of arthritis in calcium pyrophosphate deposition disease of the wrist.

Chondrocalcinosis is a well-described radiographic finding in patients with calcium pyrophosphate dihydrate deposition disease of the wrist and other joints. The medical records and x-ray films of 12 patients evaluated over an 18-month period for chondrocalcinosis of the wrist were examined for symptoms and physical and x-ray film findings. Thirteen wrists were affected. All wrists were noted to have calcification of the triangular fibrocartilage complex. Twelve of 13 wrists had the characteristic features of the scapholunate advanced collapse pattern of arthritis. In addition, there was a correlation in our series between chondrocalcinosis and carpal tunnel syndrome. Destruction of the interosseous soft tissues caused by crystalline deposition could alter the biomechanics of the wrist in a similar fashion to that of the post-traumatic scapholunate advanced collapse wrist leading to arthritic symptoms.

Aged↗
PubMed1990

Inflammatory reactions induced by various calcium pyrophosphate crystals.

Various inflammatory reactions can be induced by different crystals responsible for various arthropathies. The aim of this work was to study modifications induced in the rat, locally and at distance, by intrapleural injection of 3 forms of pyrophosphate crystals (CaPP dihydrated monoclinic (M), CaPP dihydrated triclinic (T) and CaPP anhydrous (beta]. The data presented here show that the structure of irritants plays a decisive role in the kinetics of inflammatory reactions from a local and systemic point of view.

Acute-Phase Reaction↗
PubMed1988

The effect of a somatostatin analogue (SMS 201-995, Sandostatin) on the concentration of phosphoribosyl pyrophosphate and the activity of the pentose phosphate pathway in the early renal hypertrophy of experimental diabetes in the rat.

The effect of a long-acting somatostatin analogue on the acute renal hypertrophy following induction of experimental diabetes in the rat has been studied. The kidney weight increase occurring at 2 and 7 days after alloxan injection was significantly lower in the diabetic group receiving somatostatin. Similarly, the previously reported increase in glucose-6-phosphate dehydrogenase (EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (EC 1.1.1.44) found in the kidney at 2 and 7 days of diabetes was less marked in the group receiving SMS 201-995. The fall in renal phosphoribosyl pyrophosphate associated with early diabetic renal hypertrophy (7) was also lessened by administration of SMS 201-995. No effects of the drug were found in the normal rat on the same regimen of treatment. These observations indicate involvement of glucagon and/or growth hormone in the initiation of kidney growth in diabetes.

Animals↗
PubMed1991

Stimulation of ribose-5-phosphate and 5-phosphoribosyl-1-pyrophosphate generation by pyrroline-5-carboxylate in mouse liver in vivo: evidence for a regulatory role of ribose-5-phosphate availability in nucleotide synthesis.

Pyrroline-5-carboxylase (P5C), a physiological stimulator of hexose-monophosphate-pentose pathway activity, was found before to increase 5-phosphoribosyl-1-pyrophosphate (PRPP) generation and nucleotide synthesis in human erythrocytes and cultured fibroblasts. We now report the stimulation of PRPP generation by P5C also in mouse liver in vivo. In addition we demonstrated a simultaneous elevation in ribose-5-phosphate (R5P) concentration, which was relatively smaller and transient. The demonstrated effect of P5C on liver R5P and PRPP content in vivo provides strong evidence for the physiological role of R5P availability in the regulation of PRPP and purine production.

Animals↗
PubMed1991

Localization of the 5-phospho-alpha-D-ribosyl-1-pyrophosphate binding site of human hypoxanthine-guanine phosphoribosyltransferase.

Human erythrocyte hypoxanthine-guanine phosphoribosyltransferase (HPRT) is inactivated by iodoacetate in the absence, but not in the presence, of the substrate, 5-phospho-alpha-D-ribosyl-1-pyrophosphate (PRib-PP). Treatment of HPRT with [14C]iodoacetate followed by tryptic digestion, peptide separation and sequencing has shown that Cys-22 reacts with iodoacetate only in the absence of PRib-PP; this strongly suggests that Cys-22 is in or near the PRib-PP binding site. In contrast, Cys-105 reacts with [14C]iodoacetate both in the presence and absence of PRib-PP. Carboxymethylation of Cys-22 resulted in an increase in the Km for PRib-PP, but no change in Vmax. Storage of HPRT also resulted in an increase in the Km for PRib-PP and a decrease in its susceptibility to inactivation by iodoacetate. Dialysis of stored enzyme against 1 mM dithiothreitol resulted in a marked decrease in Km for PRib-PP. The stoichiometry of the reaction of [14C]iodoacetate with Cys-22 in HPRT leading to inactivation (approx. 1 residue modified per tetramer) showed that, in this preparation of HPRT purified from erythrocytes, only about 25% of the Cys-22 side chains were present as free and accessible thiols. Titration of thiol groups [with 5,5'-dithiobis(2-nitrobenzoic acid)] and the effect of dithiothreitol on Km for PRib-PP indicate that oxidation of thiol groups occurs on storage of HPRT, even in the presence of 1 mM beta-mercaptoethanol.

Binding Sites↗
PubMed2004

Accumulation of 5-phosphoribosyl-1-pyrophosphate in human CCRF-CEM leukaemia cells treated with antifolates.

Amido phosphoribosyltransferase (APRT) catalyzes the first step of the de novo biosynthesis of purine nucleotides, the conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) into 5-phosphoribosylamine (PRA). APRT is a valid target for development of inhibitors as anticancer drugs. We have developed a thin layer chromatographic assay for PRPP extracted from cells. Using coupling enzymes, PRPP with excess [2-14C]orotate (OA) is quantitatively converted to [2-14C]OMP and then [2-14C]UMP with hydrolysis of the PPi. The reaction products are isolated on poly(ethyleneimine)-cellulose (PEI-C) chromatograms. Human CCRF-CEM leukaemia cells growing in culture have been exposed to a number of antifolates and their effects upon cellular levels of PRPP determined. The steady-state level of PRPP measured in CCRF-CEM cells was 102+/-11 microM. Following addition of an antifolate to a culture, accumulation of PRPP in cells indicates the degree of inhibition of APRT. In human CCRF-CEM leukaemia cells, lometrexol (LTX), 2,4-diamino-6-(3,4,5-trimethoxybenzyl)-5,6,7,8-tetrahydro-quinazoline (PY899), methotrexate (MTX), N(alpha)(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-L-ornithine (PT523), piritrexim (PTX), metoprine, 2,4-diamino-6-(3,4,5-trimethoxyanilino)-methylpyrido[3,2-d]pyrimidine (PY873) and multitargeted antifolate, N-[4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid (MTA) directly or indirectly induce inhibition of APRT indicated by time-courses for accumulation of PRPP to maximum values of 3-12-fold. These data indicate that LTX induces the most potent inhibition of APRT.

Amidophosphoribosyltransferase↗
PubMed2006

Tc-99m pyrophosphate imaging of poloxamer-treated electroporated skeletal muscle in an in vivo rat model.

OBJECTIVE: This study investigates whether (99m)Tc pyrophosphate (PYP) imaging provides a quantitative non-invasive assessment of the extent of electroporation injury, and of the effect of poloxamer in vivo on electroporated skeletal muscle. METHODS: High-voltage electrical shock was used to produce electroporation injury in an anesthetized rat's hind limb. In each experiment, the injured limb was treated intravenously by either poloxamer-188, dextran, or saline, and subsequently imaged with (99m)Tc PYP. The radiotracer's temporal behavior among the experimental groups was compared using curve fitting of time-activity curves from the dynamic image data. RESULTS: The washout kinetics of (99m)Tc PYP changed in proportion to the electric current magnitude that produced electroporation. Also, (99m)Tc PYP washout from electroporated muscle differed between poloxamer-188 treatment and saline treatment. Finally, 10-kDa dextran treatment of electroporated muscle altered (99m)Tc PYP washout less than poloxamer-188 treatment. CONCLUSIONS: Behavior of (99m)Tc PYP in electroporated muscle appears to be an indicator of the amount of electroporation injury. Compared to saline, intravenous polaxamer-188 treatment reduced the amount of (99m)Tc PYP uptake. Coupled to results showing poloxamer-188 seals ruptured cellular membranes, lessens the extent of electroporation injury and improves cell viability, (99m)Tc PYP imaging appears to be a useful in vivo monitoring tool for the extent of electroporation injury.

Animals↗
PubMed2004

Calcium pyrophosphate dihydrate crystal associated induction of neutrophil activation and repression of TNF-alpha-induced apoptosis is mediated by the p38 MAP kinase.

The role of p38 mitogen-activated protein (MAP) kinase in the activation of human neutrophils and repression of TNF-alpha-induced apoptosis in response to plasma opsonized crystals of calcium pyrophosphate dihydrate (CPPD) was investigated. We monitored the endogenous phosphotransferase activity of p38 kinase in neutrophils stimulated with CPPD crystals (25 mg/ml) alone or in the presence of TNF-alpha (10 ng/ml), and with TNF-alpha alone. CPPD crystals induced a 2-fold activation of p38 kinase activity over the basal activity that was observed in untreated neutrophils. Furthermore, CPPD crystals repressed the TNF-alpha associated 6-fold induction of p38 kinase phosphotransferase activity to levels associated with CPPD crystal incubation alone in a PD98059 (20 ng/ml) and Wortmannin (100 nM) sensitive manner. Inhibition of CPPD crystal-induced activation of the neutrophil inflammatory response as measured by chemiluminescence, superoxide anion generation and degranulation as determined by myeloperoxidase and lysozyme release was observed in the presence of the specific p38 MAP kinase inhibitor SB203580 (5 microM). CPPD crystal associated repression of TNF-alpha-induced activation of neutrophil apoptosis as determined by DNA fragmentation correlated with the CPPD crystal mediated inhibition of p38 kinase activity, probably through crystal inhibition of caspase 3. Together, our results indicate that the CPPD crystal associated inflammatory response is regulated through the activation of p38 kinase to sub-apoptotic levels, and that the repression of the TNF-alpha-induced apoptosis program in neutrophils is mediated via the repression of caspase 3 mediated apoptosis-associated p38 kinase activity.

Androstadienes↗
PubMed2005

Monosodium urate and calcium pyrophosphate dihydrate (CPPD) crystals, inflammation, and cellular signaling.

Monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD) crystals are responsible for acute synovial inflammation but also contribute to cartilage degradation and bone lesions within the joint. They activate multiple signal transduction pathways leading to cell activation and recruitment. Some signalling pathways are activated by both types of crystals, and other pathways may only be activated by one type depending on cell type, namely neutrophils, monocytes, macrophages, synovial fibroblasts, endothelial cells and chondrocytes. Cascades of activated proteins involve cytoplasmic membrane related proteins (FAK complex, Src family tyrosine kinases), but also MAPK and NF-kB pathways, leading to NO, prostanoid and cytokine production, and protease activation. This review will also focus on potential therapeutic targets related to cellular signalling in MSU and CPPD crystal-induced inflammation.

Animals↗
PubMed2006

Comparison of characteristics of patients with and without calcium pyrophosphate dihydrate crystal deposition disease who underwent total knee replacement surgery for osteoarthritis.

OBJECTIVE: To compare characteristics of patients with severe osteoarthritis with and without calcium pyrophosphate dihydrate (CPPD) crystal deposition disease. STUDY METHODS: Patients undergoing total knee replacement surgery participated in this study and completed questionnaires. Radiographs of the index knee (extended anteroposterior, lateral and skyline) were reviewed for the presence of chondrocalcinosis. Synovial fluids were obtained during surgery and analyzed under compensated polarized light microscopy. RESULTS: The presence of CPPD crystals was identified in 52.9% of 102 patients. The use of both radiographs and synovial fluid analysis increased the identification of crystals. There was no difference in the following characteristics of the patients with and without CPPD crystals: age of pain onset, gender, difficulty in performing daily functions (including cooking, standing up from chairs, using restroom, going upstairs, and going shopping), history of previous joint inflammation, use of walking aids, and number and types of medications ever used. CPPD patients underwent knee arthroplasty at older age compared to non-CPPD patients (70.3+/-6.37 and 67.5+/-7.15 years old, respectively) (P = 0.037). All but one CPPD patients were unaware of the presence of crystals. CONCLUSION: High prevalence of CPPD crystals was found in patients undergoing total knee replacement surgery. All but one CPPD patients were unaware of calcium deposition in the index joints. Patients with these crystals experienced similar difficulties in performing daily activities and received similar treatment to patients without CPPD crystals. CPPD patients did not undergo knee arthroplasty at earlier age than non-CPPD patients.

Aged↗