Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies about chondrocalcinosis in the Chiloe Islands (Chile) showed the high frequency of the disease there and how most of it is aggregated in a few highly involved families. Pedigrees and the high degree of consanguinity among parents of index cases pointed to a recessive inheritance. The presence of common Caucasian anthropological features of genetic value in the patients and the lack of Indian mixture in three of the involved families, documented back to 1600, suggest a Caucasian origin of the mutation. Biochemical studies of the patients' synovial fluid showed a significant rise in pyrophosphate concentration. Calcium, phosphorus, and alkaline phosphatase concentrations were not different from a control group.
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PMID:Familial chondrocalcinosis in the Chiloe Islands, Chile. 16 17

The distribution of calcium pyrophosphate mineral phase, almost exclusively confined to articular cartilage in chondrocalcinosis, and the high level of pyrophosphate (PPi) ion relative to serum in synovial fluid in patients with either chondrocalcinosis or advanced osteoarthritis led to an investigation of whether cartilage cells elaborate PPi ions. Incubates of articular cartilage from young rabbits but not from mature rabbits, as well as growth plates cartilage, released PPi into incubation media during a 4h period. Control rabbit ear cartilage and synovial membrane elaborated negligible amounts of PPi. The PPi was shown to be undialyzable but could be dissociated from the alkaline phosphatase by ultracentrifugation. In 16 patients with osteoarthritis, a substantial output of PPi by samples of articular cartilage from the knee was demonstrated. It is postulated that either rapid cell division and matrix synthesis found in the base of ulcerating osteoarthritic cartilage or remodeling calcified sites are the source of the PPi in such osteoarthritic cartilage. It is further hypothesized that this PPi output accounts at least in part for the elevated PPi levels found in synovial fluid of patients with osteoarthritis.
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PMID:Extrusion of pyrophosphate into extracellular media by osteoarthritic cartilage incubates. 17 32

Chondrocalcinosis is known to be common in hyperparathyroidism. In order to discover the effect of parathyroidectomy on chondrocalcinosis and to investigate this association further, we studied two groups of patients. In one group were 41 postparathyroidectomy patients, and in the other 100 admissions to the acute geriatric unit. The total incidence of chondrocalcinosis in the parathyroidectomy group was 32%, and in the elderly control group 11%. There was little or no osteoarthrosis in these patients. It was found that chondrocalcinosis occurred in the normal population from the age of 75 and in the hyperparathyroid group from the age of 45. In both groups the incidence rose steadily with age. In the hyperparathyroid group alone, preoperative serum calcium levels were no different in those without chondrocalcinosis, suggesting that hypercalcaemia alone is not a sufficient stimulus for chondrocalcinosis. Those with chondrocalcinosis had higher mean preoperative alkaline phosphatase levels, nearly twice as much radiological bone disease, and were older. Parathyroidectomy had no effect on attacks of pseudogout or on preexisting cartilage calcification. A connection with high levels of circulating parathyroid hormone is suggested, and a link with physical age-related changes in cartilage postulated.
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PMID:Chondrocalcinosis in primary hyperparathyroidism. Influence of age, metabolic bone disease, and parathyroidectomy. 85 41

We report on a 43-year-old patient with short stature (hyposomia), allegedly the result of vitamin-D-resistant rickets, previously treated for ankylosing spondylitis. In addition, a uricostatic drug therapy was also necessary because of hyperuricemia with gout attacks. Further examinations revealed the accurate diagnosis: Rathbun's disease. Hypophosphatasia is a hereditary disorder characterized by a deficiency of liver/bone/kidney alkaline phosphatase activity in serum and tissues with defective bone mineralization, bone deformities, short stature, early loss of teeth, and craniosynostosis. In our patient radiographic features were spinal hyperostosis, but with syndesmophytes, chondrocalcinosis of peripheral joints and intervertebral discs, calcific periarthritis and premature closure of skull sutures. Curved ribs and short stature were suggestive of rickets. The aim of this case report is to demonstrate the close relations between hypophosphatasia and spondylitis ankylosans in respect to radiology and clinical symptoms.
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PMID:[Rathbun syndrome (hypophosphatasia). Clinical aspects: dwarfism and Bechterew symptoms]. 179 58

Two very dissimilar cases of hypophosphatemia in the adult patient are described by the authors. The first case was symptomatic since childhood, with typical clinical and radiologic findings (fissures, diaphyseal bone spurs, bony deformities), whereas the second case was minimally symptomatic (loss of teeth and back pain). Articular chondrocalcinosis was observed in both cases, as was a decrease in alkaline phosphatase and the increased urinary excretion of phosphoethanolamine. Histological examination demonstrated an increase in osteoid. Review of the literature revealed 40 cases of this inborn error of metabolism seen in adulthood, enabling a detailed description of the characteristics of this polymorphic condition.
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PMID:[Hypophosphatasia in adults. Apropos of 2 cases]. 399 53

Osteoarthritis or 'Joint Failure' is a multi-factorial disease with a final common pathway of cartilage degeneration and bone eburnation. The association of arthritic disease and joint degeneration with the deposition of sodium urate crystals in gout and calcium pyrophosphate crystals in pseudogout (chondrocalcinosis) is clinically well established. Electron microscopy coupled with electron probe analysis has revealed the presence of various other calcium phosphate crystals in joint tissues and fluids. We have found three new morphological types of apatite crystals in human articular cartilage which are too small to be detected by X-rays of human joints or even by light microscopy of joint tissues. Two morphologically distinct types of apatite crystals in articular cartilage are associated with extracellular matrix vesicles formed from the cell processes of chondrocytes. 'Cuboid' crystals, which are found in the pericellular regions near the surface zone of articular cartilage, appear to be a variant of apatite and may even be 'Whitlockite' because there are traces of magnesium present. There are increased numbers of these microscopic 'cuboid' crystals (Type II) and Mineral Nodules (Type I) in arthritic cartilage and this is coupled with increased numbers of matrix vesicles and alkaline phosphatase activity. Clusters of fine needle-shaped apatite crystals (Type III) found on the surface of articular cartilage are not associated with matrix vesicles. Thus some forms of osteoarthritis are closely associated with apatite type crystal deposition and may imply abnormal mineral formation in articular cartilage as a pathogenic mechanism.
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PMID:Apatite-type crystal deposition in arthritic cartilage. 409 1

One abnormality in calcium pyrophosphate deposition disease (CPDD) which fosters consistently high synovial fluid pyrophosphate ion (PPi) and large accumulations of calcium pyrophosphate dihydrate crystals (Ca pyrophosphate) might be an aberration in chondrocytes involving elaboration of PPi and failure of its hydrolysis within cartilage matrix. Exploration of this hypothesis required further information on the phosphohydrolases in relevant human articular cartilages. Triton X-100 extracts of whole homogenized cartilage from 18 patients with primary osteoarthritis (OA), 10 patients with CPDD and secondary OA, as well as 6 "normal" subjects were partially purified by DE-52 chromatography and eluates studied for phosphohydrolase activity in a variety of substrates, inhibitors, and environmental conditions. Almost all the protein as well as crude alkaline phosphatase and pyrophosphatase activities were clustered in peaks designated I and II. Findings in CPDD cartilage not observed in OA controls were: 1) consistent alkaline phosphatase activity in the void volume of DE-52 columns, 2) high levels of 5'nucleotidase activity, 3) abundant generation of PPi by CPDD cartilage during in vitro incubation of cartilage extract fractions with ATP. This enzymatic behavior is likely to bear a regulatory relationship to PPi production by chondrocytes in CPDD.
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PMID:Comparison of phosphohydrolase activities from articular cartilage in calcium pyrophosphate deposition disease and primary osteoarthritis. 611 22

Three sisters, each with chondrocalcinosis/arthropathy, are described who have the clinical, laboratory and pathologic findings characteristic of the adult form of hypophosphatasia. Premature loss of adult teeth, arthralgias and pain from bilateral femoral pseudo-fractures were associated with subnormal circulating alkaline phosphatase levels, phosphoethanolaminuria and osteomalacia diagnosed by iliac crest biopsy. Assay of alkaline phosphatase activity in the blood of kindred members revealed hypophosphatasemia in one of two younger brothers. Several subjects in subsequent generations also had suspiciously low alkaline phosphatase activity, but did not have histories of significant dental, bone or joint disease. Review of the medical records of the sisters' parents, aunts and uncles revealed normal alkaline phosphatase levels in their father and five of his siblings, but consistently low levels in their mother and two of her siblings. Despite hypophosphatasemia, the sisters' mother and her siblings lived to old age without clinical or radiographic evidence of bone disease. Our findings suggest that although adult hypophosphatasia can be transmitted as a dominant trait in some kindreds, there is considerable variation in the clinical expression of the biochemical defect. One person, generation or family may manifest clinical bone disease and arthropathy whereas the biochemical defect may be present but remain asymptomatic in others. Furthermore, in some cases, the adult form of hypophosphatasia may represent a developmental disorder with hypophosphatasemia appearing during adulthood.
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PMID:Adult hypophosphatasia with chondrocalcinosis and arthropathy. Variable penetrance of hypophosphatasemia in a large Oklahoma kindred. 707 44

A bone and cartilage enzyme with both 5'-nucleotide phosphodiesterase I and nucleotide pyrophosphohydrolase (NTPPPH) activity modulates physiologic mineralization and pathologic chondrocalcinosis by generating inorganic pyrophosphate. We hypothesized that, as for alkaline phosphatase, expression of an NTPPPH gene can be shared by cells from bone, cartilage, and liver and by certain leukocytes. Recently, we demonstrated the hepatocyte and murine plasma cell membrane glycoprotein PC-1 to have both 5'-nucleotide phosphodiesterase I and NTPPPH activity. We detected polypeptides cross-reactive with PC-1 in human U20S osteosarcoma cells, articular chondrocytes, homogenized human knee cartilages, human knee synovial fluids, hepatoma cells, and murine plasmacytoma cells. Constitutive low abundance PC-1 mRNA expression was detected in U20S cells and chondrocytes by a nested RNA-PCR assay and by Northern blotting. TGF beta is known to substantially increase NTPPPH activity in primary osteoblast cultures. We demonstrated that TGF beta 1 increased NTPPPH activity and the level of PC-1 mRNA and immunoprecipitable [35S]-methionine-labeled PC-1 polypeptides in U20S cells. The identification of PC-1 as an NTPPPH expressed in cells derived from bone and cartilage may prove useful in furthering the understanding of the role of NTPPPH i n physiologic and pathologic mineralization.
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PMID:Expression of the murine plasma cell nucleotide pyrophosphohydrolase PC-1 is shared by human liver, bone, and cartilage cells. Regulation of PC-1 expression in osteosarcoma cells by transforming growth factor-beta. 804 Mar 11

Fifteen patients on regular dialytic treatment for more than 15 years were given X-rays of the skull, spine, shoulders, wrists, pelvis and knees with the purpose of studying the principal skeletal and articular alterations due or not due to the uraemic status. Serum calcium, phosphorus, parathyroid hormone, alkaline phosphatase and basal aluminium were recorded. Osteopenia was evident in all the patients. Ten of whom (67%) showed alterations due to hyperparathyroidism. Nine patients presented the marks of dialysis spondyloarthropathy; in 14/15 cases geodes were present in the wrists, humeral heads or hip-joints; in ten patients there were multiple amyloid lesions. Two patients with serum basal aluminum above 100 micrograms/L showed the typical radiographic marks of osteomalacia. The majority of the long-term survivors showed multifactorial osteo-articular alterations resulting mainly from the combination of hyperparathyroidism and dialysis-related amyloidosis. The less frequent joint alterations were represented by arthrosis, enthesopathy and chondrocalcinosis. Disability and decreased articular mobility resulted in being mainly due to amyloid osteo-arthropathy.
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PMID:Clinical and radiological features of bone disease in long-term (15 or more years) hemodialysis patients. 812 16


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