Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A 43 year old man was admitted because of fatigue and swelling of the knees. Swelling of both knees, acropachy and turtle-back nails were registered during clinical investigation and laboratory tests showed leucocytosis, increased blood-sedimentation rate and alkaline phosphatase. Leucine aminopeptidase was normal. X-ray showed symmetric metaphyseal periosteal reactions on femora and tibiae of both sides compatible with hypertrophic osteoarthropathy. A parahilar round tumor measuring 5 x 7 cm infiltrating the right upper lobe was detected on chest x-ray suggestive of lung cancer. Pierre-Marie-Bamberger syndrome was diagnosed (hypertrophic osteoarthropathy associated with cancer of the lung). Under radiotherapy to the tumor the osteoarthropathy subsided and alkaline phosphatase returned to normal.
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PMID:[Swelling of the knee, fatigue]. 192 95

Osteoarticular complications, which are characterized by osseous pain, pathologic fractures, and decreased articular mobility, represent one of the major problems affecting long-term (over 15 years) hemodialysis patients. These changes seem to have a multifactorial etiology; they include osteomalacia, secondary hyperparathyroidism, and dialysis-related amyloidosis. Ten patients (5 males and 5 females, mean age 55 +/- 7 years) on long-term (over 15 years) hemodialysis were submitted to X-ray examinations of the skull, spine, shoulders, wrists, pelvis, and knees. Serum calcium, phosphorous, parathyroid hormone, alkaline phosphatase, and basal aluminium levels were also calculated. Osteopenia was demonstrated in all patients. Seven of them had alterations due to hyperparathyroidism. Six patients exhibited signs related to dialysis spondyloarthropathy; in 9 cases amyloid lesions, geodes, and erosions were present in wrists, humeral heads, or hips. One patient exhibited osteomalacic changes. Most long-term dialysis patients presented multifactorial osteoarticular changes due to hyperparathyroidism, osteomalacia, and dialysis-related amyloidosis. Clinical symptoms and decreased articular mobility appeared to be due mainly to amyloid osteoarthropathy.
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PMID:[Radiology of osteoarticular changes in patients undergoing periodic hemodialysis for more than 15 years]. 205 86

To investigate our impression that hypercalciuria is relatively common in children with osteogenesis imperfecta, we performed a retrospective study of data accumulated from our pediatric population with this skeletal disorder. Children with osteogenesis imperfecta (17 girls, 30 boys; mean (+/- SD) age 7.8 +/- 4.6 years; range 0.7 to 16.8 years) had undergone detailed inpatient evaluation of mineral homeostasis during periods of clinical stability and controlled dietary calcium intake. Hypercalciuria was found in 36% of the patients and averaged (+/- SEM) 6.1 +/- 0.3 mg/kg per 24 hours (0.15 +/- 0.01 mmol/kg per 24 hours) or 392 +/- 28 mg/gm of creatinine (1.10 +/- 0.07 mmol calcium/mmol creatinine) in the group with hypercalciuria. There were no statistically significant differences in age, gender, or dietary calcium intake (per kilogram of body weight) between the normocalciuric and hypercalciuric children. However, the group with hypercalciuria was shorter than the normocalciuric group and had a greater lifelong fracture rate. When patient height z scores were regressed against urinary calcium levels, a significant negative correlation was found in the group with hypercalciuria (r = -0.76; p less than 0.001). Although serum alkaline phosphatase activity was lower in the group with hypercalciuria, no difference was found between groups with regard to serum levels of calcium, phosphate, magnesium, creatinine, immunoreactive parathyroid hormone, or osteocalcin. The groups were also similar with respect to both their total body mineral density, as determined by dual-photon absorptiometry (n = 17), and their static indexes of bone formation and resorption, as assessed histomorphometrically with iliac crest specimens (n = 19). We conclude that hypercalciuria occurs frequently in children with osteogenesis imperfecta, and that its magnitude appears to reflect the severity of the skeletal disease.
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PMID:Hypercalciuria in children severely affected with osteogenesis imperfecta. 206 61

This is a report of two brothers, born within a year of each other, with a similar skeletal disorder of severe congenital metaphyseal involvement, mild rhizomelic shortness of upper limbs, and mild platyspondyly. Both died at three days of cardio-respiratory insufficiency, but only one had ante-mortem lab tests which showed low calcium, high phosphorus, and high alkaline phosphatase levels attributed to a renal defect. On autopsy this same infant was found to have pulmonary, renal and adrenal hemorrhage, and subendocardial myocarditis and myocardial necrosis. The pathogenetic relationship between these manifestations is presently unclear; however, since parents are normal and recently had an affected baby girl, it is presumed that this disorder is an autosomal recessive trait.
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PMID:Congenital lethal metaphyseal chondrodysplasia: a newly recognized complex autosomal recessive disorder. 721 44

99Tcm-methylene diphosphonate (MDP) global skeletal uptake (4 h GSU) was determined by quantitative measurement of activity on bone scan images 4 h after injection in whole skeleton regions of interest (ROI) in 16 normal subjects, in five patients with hypertrophic pulmonary osteoarthropathy (HPO) and in 12 with Paget's disease. Values were correlated with those of whole body retention (24 h WBR), and serum bone gla protein (BGP), i.e. osteocalcin, alkaline phosphatase (AP) and type 1 procollagen (P1CP). They were 40% higher in HPO than in the normal controls, while in Paget's disease they increased more in polyostotic than in monostotic patients. A statistically significant difference was noted between 4 h GSU and 24 h WBR values in the two groups of patients compared with the controls. Of the bone metabolism markers, serum AP and P1CP were higher in the patients and positively correlated with their enhanced 4 h GSU values, whereas BGP was always within the normal range. This method may thus be regarded as a useful way of simultaneously determining bone 99Tcm-MDP uptake and altered bone turnover sites, especially in patients with systemic bone disease.
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PMID:99Tcm-MDP global skeletal uptake and markers of bone metabolism in patients with bone diseases. 835 16

Increased concentration of serum alkaline phosphatase (ALP) is a common feature in rheumatoid arthritis (RA), although its origin remains unclear. The aim of this study is to analyze the origin and clinical significance of the elevated ALP value in RA. In 123 RA and 63 age- and sex-matched OA (osteoarthropathy) patients, concentrations of total ALP and its isozymes in serum and synovial fluid were studied. Serum CRP, Fe, ferritin, and Cu values were examined, respectively. The expression of ALP as protein was also investigated by using an enzymehistochemical and an immunohistochemical staining methods. Serum ALP values were elevated in 37.4% of RA (245.2 +/- 91.2 IU/L), and significantly higher than those of OA (192.3 +/- 45.2 IU/L: P < 0.01, RA v.s. OA). The serum CRP, and ferritin values each had a relation with the serum ALP activity. Fluid ALP concentration of RA was 110.3 +/- 40.1 IU/L, and that of OA, 83.6 +/- 15.0 IU/L (P < 0.05), respectively. In RA, a predominant isozyme was liver-type one both in the sera (91%) and the synovial fluid (59%). However, this result means that bone-type one was more abundant in the synovial fluids (41%) than those in the sera (9%). An enzymehistochemical and an immunohistochemical studies revealed that ALP was positive in a perivascular area, sublining cells, and a part of vascular endothelium in RA. In contrast, the synovial tissue from OA and a healthy patient exhibited only a weak staining. In RA, a positive correlation between the elevation of serum ALP and the disease activity was confirmed. Furthermore, we elucidated that ALP is produced in RA synovium.
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PMID:[Alkaline phosphatase (ALP) activity in rheumatoid arthritis (RA): its clinical significance and synthesis of ALP in RA synovium]. 978 85

Osteoectasia with hyperphosphatasia is a rare skeletal disorder, characterised by demineralisation and expansion of tubular bones and elevated serum alkaline phosphatase. We present a girl diagnosed as having osteoectasia with hyperphosphatasia who had swelling of phalanges of both hands and motor retardation. She was treated with synthetic human calcitonin. Clinical and radiological findings showed remarkable improvement after 2 years' treatment.
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PMID:Calcitonin treatment in osteoectasia with hyperphosphatasia (juvenile Paget's disease): radiographic changes after treatment. 1055 64

Sclerosteosis, a skeletal disorder characterized by high bone mass due to increased osteoblast activity, is caused by loss of the SOST gene product, sclerostin. The localization in bone and the mechanism of action of sclerostin are not yet known, but it has been hypothesized that it may act as a bone morphogenetic protein (BMP) antagonist. We show here that SOST/sclerostin is expressed exclusively by osteocytes in mouse and human bone and inhibits the differentiation and mineralization of murine preosteoblastic cells (KS483). Although sclerostin shares some of the actions of the BMP antagonist noggin, we show here that it also has actions distinctly different from it. In contrast to noggin, sclerostin did not inhibit basal alkaline phosphatase (ALP) activity in KS483 cells, nor did it antagonize BMP-stimulated ALP activity in mouse C2C12 cells. In addition, sclerostin had no effect on BMP-stimulated Smad phosphorylation and direct transcriptional activation of MSX-2 and BMP response element reporter constructs in KS483 cells. Its unique localization and action on osteoblasts suggest that sclerostin may be the previously proposed osteocyte-derived factor that is transported to osteoblasts at the bone surface and inhibits bone formation.
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PMID:Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. 1502 46

Hypophosphatasia is a rare inherited disorder characterized by defective bone and teeth mineralization, and deficiency of serum and bone alkaline phosphatase activity. The prevalence of severe forms of the disease has been estimated at 1/100 000. The symptoms are highly variable in their clinical expression, which ranges from stillbirth without mineralized bone to early loss of teeth without bone symptoms. Depending on the age at diagnosis, six clinical forms are currently recognized: perinatal (lethal), perinatal benign, infantile, childhood, adult and odontohypophosphatasia. In the lethal perinatal form, the patients show markedly impaired mineralization in utero. In the prenatal benign form these symptoms are spontaneously improved. Clinical symptoms of the infantile form are respiratory complications, premature craniosynostosis, widespread demineralization and rachitic changes in the metaphyses. The childhood form is characterized by skeletal deformities, short stature, and waddling gait, and the adult form by stress fractures, thigh pain, chondrocalcinosis and marked osteoarthropathy. Odontohypophosphatasia is characterized by premature exfoliation of fully rooted primary teeth and/or severe dental caries, often not associated with abnormalities of the skeletal system. The disease is due to mutations in the liver/bone/kidney alkaline phosphatase gene (ALPL; OMIM# 171760) encoding the tissue-nonspecific alkaline phosphatase (TNAP). The diagnosis is based on laboratory assays and DNA sequencing of the ALPL gene. Serum alkaline phosphatase (AP) activity is markedly reduced in hypophosphatasia, while urinary phosphoethanolamine (PEA) is increased. By using sequencing, approximately 95% of mutations are detected in severe (perinatal and infantile) hypophosphatasia. Genetic counseling of the disease is complicated by the variable inheritance pattern (autosomal dominant or autosomal recessive), the existence of the uncommon prenatal benign form, and by incomplete penetrance of the trait. Prenatal assessment of severe hypophosphatasia by mutation analysis of chorionic villus DNA is possible. There is no curative treatment for hypophosphatasia, but symptomatic treatments such as non-steroidal anti-inflammatory drugs or teriparatide have been shown to be of benefit. Enzyme replacement therapy will be certainly the most promising challenge of the next few years.
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PMID:Hypophosphatasia. 1791 36

Based on studies of hypophosphatasia, which is a systemic skeletal disorder resulting from tissuenonspecific alkaline phosphatase (TNSALP) deficiency, TNSALP was suggested to be indispensable for bone mineralization. Recently, we demonstrated that there was a significant difference in bone mineral density (BMD) among haplotypes, which was lowest among TNSALP (787T [Tyr-246Tyr]) homozygotes, highest among TNSALP (787T > C [Tyr246His]) homozygotes, and intermediate among heterozygotes. To analyze protein translated from the TNSALP gene 787T > C, we performed the biosynthesis of TNSALPs using TNSALP cDNA expression vectors. TNSALP (787T) and TNSALP (787T > C) were synthesized similarly as a high-mannose-type 66-kDa form, becoming an 80-kDa form. Expression of the human 787T > C TNSALP gene using the cultured mouse marrow stromal cell line ST2 demonstrated that the protein translated from 787T > C exhibited an ALP-specific activity similarly to that of 787T. Interestingly, the Km value for TNSALP in ST2 cells transfected with the 787T > C TNSALP gene was decreased significantly compared to that of cells carrying the 787T gene (P < 0.01). These results suggest that the significant difference in Km values between the proteins translated from 787T > C and 787T may contribute to regulatory effects on bone metabolism.
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PMID:Molecular effects of the tissue-nonspecific alkaline phosphatase gene polymorphism (787T > C) associated with bone mineral density. 1872 9


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