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)

Osteosarcomas were produced by the intratibial inoculation of New Zealand black rats with Moloney sarcoma virus (MSV) at 1 day and 4 days of age. Radiographic evidence of osteosarcoma development was first demonstrated at 10 to 15 days postinoculation in both groups. Subsequent radiographic and light and electron microscopic evaluation of tumor-bearing rats demonstrated that osteosarcomas in rats inoculated at Day 4 of age were more osteoproliferative osteosarcomas than those in rats inoculated on Day 1. Rats inoculated at 4 days of age lived longer, had more slowly growing osteosarcomas, and developed a consistent tumor-associated cachexia compared to tumor-bearing rats inoculated at Day 1. Both groups of rats had a 93% metastasis rate involving either sublumbar lymph nodes, lungs, or both. Tumor-bearing rats inoculated at 4 days of age had consistent elevations in both urinary hydroxyproline excretion (HOP/CR) and serum alkaline phosphatase levels, and in serum calcium levels at some time points. The high tumor incidence after a short latent period and the morphologic and biochemical similarities between the MSV-induced murine osteosarcoma and the osteosarcoma in human beings makes this discrete tumor and a valuable animal model for the evaluation of new therapeutic regimens.
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PMID:Virus-induced animal model of osteosarcoma in the rat: Morphologic and biochemical studies. 18 16

Concentrations of serum alkaline phosphatase and total urinary hydroxyproline were measured in 36 children to study the effect of phenobarbital administration with respect to the development of rickets in patients receiving anticonvulsive medications over prolonged periods of time. Administration of phenobarbital led to the appearance of increased AP and HOP values very early in the course of treatment and without any obvious bone changes suggestive of rickets; a single large oral dose of vitamin D had no appreciable effects in restoring the biochemical derangement. On the other hand, the administration of vitamin D in a daily dose of 4,000 IU for a period of two months hampered the appearance, or restored already existing changes of latent rickets, in children receiving anticonvulsive medication. The results in the present study favor the concept that phenobarbital administration is implicated in the development of rickets. The need for simultaneous daily administration of supplements of vitamin D in subjects receiving anticonvulsive drugs is stressed.
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PMID:Serum alkaline phosphatase and urinary hydroxyproline values in children receiving phenobarbital with and without vitamin D. 80 98

Fifty eight patients with thyrotoxicosis were examined as well as 9 patients with hypothyroidism and 40 healthy subjects. A tendence towards hypercalcemia and hyperphosphatemia, hypercalciuria, hyperhydroxiprolinuria, elevated alkaline phosphatase were found in hyperthyroidism. In hypothyroidism--hypocalcemia, hypocalciuria, hypohydroxiprolinuria. The changes are associated with the direct effect of thyroid hormones upon bone system (intensified bone metabolism with predominance of destruction). Calciuria and HOP-uria in thyrotoxicosis depend on the severity of the disease. The elevated calcium excretion in thyrotoxicosis speaks for the presence of ostemalacic component. TRP, PEI, mean diametrically opposite in hyper- and hypothyroidism, support the hypothesis of the secondary hypoparathyroidism in thyrotoxicosis and hyperparathyroidism--in the hypothyroidism.
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PMID:[Studies of calcium-phosphorus metabolism in thyrotoxicosis]. 91 16

Ipriflavone (IP), an isoflavone derivative, seems to prevent the loss of bone mass through the inhibition of bone resorption, mainly inhibiting the recruitment of osteoclasts. We investigated whether a brief course of treatment with IP can reduce biochemical parameters of accelerated bone turnover and bone pain in patients with active Paget's disease of bone. Sixteen patients (9 males and 7 females) with active Paget's disease were randomly allocated to two different crossed-over dose regimens of treatment with IP (600 mg/day vs. 1200 mg/day). Each treatment course lasted 30 days and the wash-out period between the two sequences was 15 days. Serum alkaline phosphatase (Al.Ph.) and urinary hydroxyproline/creatinine excretion (HOP/Cr) were reduced after each sequence. At the end of the 600/1200 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 32% and 25.6% respectively. At the end of the 1200/600 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 33% (P < 0.01) and 24.1% (P < 0.05) respectively. Furthermore, a significant decrease in bone pain was observed during the 1200/600 mg/day sequence (P < 0.01). Both treatment schedules were well tolerated and the patients' compliance resulted excellent. Our results indicate that short-term treatment with IP can reduce biochemical parameters of disease activity and bone pain in patients with active Paget's disease of bone.
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PMID:Short-term treatment of Paget's disease of bone with ipriflavone. 142 19

A human dental pulp tissue was explanted in culture and the outgrowing cells were transfected with the plasmid, pMT1-neo, which included the early region of SV 40 DNA and the neomycin-resistant gene. The transfected cells were cloned and cultured beyond the period of senescence for the non-transfected HOP cells, over 170 passages (360 population doubling levels and 730 days). The characteristics of the transfected LSC cells and the non-transfected HOP cells were investigated during in vitro aging. The results were as follows: 1. The alkaline phosphatase (ALPase) activity of the HOP cells decreased as the culture passages increased. In contrast, the ALPase activity of the LSC cells did not change during the entire serial culture period. 2. The ALPase inhibitory test indicated that the ALPase in the LSC cells was the bone/liver/kidney type. 3. The addition of 250 micrograms/ml of L-ascorbic acid resulted in an increased collagen synthesis compared with that of 50 micrograms/ml. 4. The growth rate and the ALPase activity of the LSC cells were affected by 1 alpha, 25-dihydroxyvitamin D3, L-ascorbic acid, beta-sodium glycerophosphate, epidermal growth factor or transforming growth factor-beta even after the serial culture. These results suggest that the LSC cells preserve some properties of the dental pulp and may be useful in the future research for exploring the mechanisms of the dental hard tissue formation and for testing the biocompatibility of the dental restorative materials.
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PMID:[Immortalization of human dental pulp cells with transfecting of the plasmid, pMT1-neo]. 255 37

It is possible to assess bone resorption from a determination of urinary excretion of hydroxyproline, which is the specific amino-acid of collagen. As dietary collagen affects 24-hour urinary excretion of hydroxyproline, it has been stated that the urine should be collected under a gelatin-free diet. A new sampling method was described in the present paper for the determination of hydroxyproline in urine, which could eliminate the affection of dietary collagen by simple fasting. The method was useful for the evaluation of bone metabolism in patients with parathyroid disorders. 10 patients with primary hyperparathyroidism (3 skeletal types and 7 non-skeletal types), 3 patients with idiopathic hypoparathyroidism and 5 normal subjects were studied. It was found that the urinary excretion of hydroxyproline increased at night and diminished during the day in patients with primary hyperparathyroidism as well as in normal subjects, but this diurnal rhythm was not clear in a patient with idiopathic hypoparathyroidism. A pilot study revealed that 10 g gelatin administered orally did not affect the urinary excretion of hydroxyproline after a 12-hour fast. Therefore, 2-hour urine samples (700 h-900 h) were collected, and blood samples were drawn at 800 h after a 13-hour fasting from 1800 h on the previous day to 700 h in the morning studied. The urinary excretion of hydroxyproline was expressed as follows: HOP (microgram/ml)/Cr(mg/dl). The 2-hour urinary excretion of hydroxyproline thus determined was highly correlated with that determined in 24-hour urine collected under a gelatin-free diet (r = 0.995, p less than 0.001) and with the total serum alkaline phosphatase activity (r = 0.987, p less than 0.001). The levels of 2-hour urinary excretion of hydroxyproline in normal subjects were 0.18-0.28 in range, and those in patients with the skeletal type of primary hyperparathyroidism were high. However, the levels were not always higher than those in the patients with the non-skeletal type, in which cases the 2-hour excretion of hydroxyproline was higher than 0.50 except in one patient. The 9 patients with primary hyperparathyroidism who had elevated levels of the 2-hour urinary excretion of hydroxyproline showed tetany after parathyroidectomy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Urinary excretion of hydroxyproline in parathyroid disorders, with special reference to its changes before and after parathyroidectomy in primary hyperparathyroidism]. 668 63

A major problem in developmental bone biology is the inability to clearly identify early progenitor cells of the osteogenic and related lineages. Identification of these cells is important for the study of their normal development and for determination of potential changes in skeletal diseases. The objective of the present study was to obtain specific markers for early progenitor cells. Monoclonal antibodies were raised against human marrow stromal fibroblastic cell cultures, known to be rich in progenitors for the stromal lineages. Antibodies were selected initially by their reactivity with these marrow cultures and their immunohistochemical localization in human fetal tissues, in progenitor cell regions adjacent to osteoblastic cells. Antibody HOP-26 was strongly reactive with cells in marrow stromal colonies at early stages of differentiation, before the induction of alkaline phosphatase activity, and decreased dramatically after the cells reached confluence. In sections of human fetal limb, binding of HOP-26 was restricted to cells in close proximity to the developing bone, in periosteum, and between the developing bone trabeculae. In adult trabecular bone tissue, HOP-26 was reactive with occasional cells present within the marrow spaces with osteoblasts, adipocytes, and fibrous tissue unreactive. No antibody binding was detected in sections of skin, muscle, appendix, brain, tonsil, or liposarcoma, or cultured SaOS II, MG63, or skin cells. In primary cell suspensions, HOP-26 was unreactive with blood cells but strongly reactive with 0.59 +/- 0.27% of nucleated marrow cells. The antigen associated with these cells was detectable both intracellularly and on the cell surface, and by using immunopanning, HOP-26 selected the marrow stromal fibroblastic colony-forming units (CFU-F). HOP-26 provides the means to identify osteogenic progenitor cells directly and with high specificity. The present studies demonstrate the value of this antibody in providing enriched populations of progenitor cells for experimental studies of osteogenic differentiation and in histopathology.
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PMID:Identification and enrichment of human osteoprogenitor cells by using differentiation stage-specific monoclonal antibodies. 921 1

The specific effects of interferon alpha (IFNalpha), on the differentiation pathways of human osteogenic cells are not known. The aim of this study was to investigate possible effects of IFNalpha on osteogenic development by investigating cell differentiation, colony formation (colony forming unit-fibroblastic, CFU-F), cell proliferation, and gene expression, in particular bone morphogenetic protein (BMP) expression, of human bone marrow osteoprogenitor cells. Human bone marrow fibroblasts were cultured with or without the addition of IFNalpha (5-1,000 IU/ml) in the presence and absence of dexamethasone (10 nM) and ascorbate (100 microM), which are agents known to affect osteogenic differentiation. IFNalpha produced a significant dose-dependent inhibition of cell proliferation and alkaline phosphatase specific activity at concentrations as low as 50 IU/ml. IFNalpha (50-1,000 IU/ml) inhibited the stimulation of alkaline phosphatase specific activity induced by ascorbate and dexamethasone. Examination of CFU-F showed dose- and time-dependent inhibitions of colony formation and reductions in both colony size and alkaline phosphatase-positive CFU-F colonies particularly at earlier times. Reactivity with an antibody specific for osteoprogenitors (HOP-26), was reduced in IFNalpha-treated cultures. Northern blot analysis showed a significant dose-dependent up-regulation of BMP-2 mRNA, estrogen receptor alpha mRNA and osteocalcin mRNA expression in ascorbate/dexamethasone cultures. In contrast, IFNalpha significantly inhibited BMP-2 mRNA expression in the absence of ascorbate and dexamethasone. In conclusion, IFNalpha inhibits human osteoprogenitor cell proliferation, CFU- F formation, HOP-26 expression, and alkaline phosphatase specific activity and modulates BMP-2 gene expression. These results suggest a role for IFNalpha in local bone turnover through the specific and direct modulation of osteoprogenitor proliferation and differentiation.
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PMID:Effects of interferon alpha on human osteoprogenitor cell growth and differentiation in vitro. 1041 39

We studied 21 patients (11 men and 10 women) with osteogenesis imperfecta (OI) and 21 age- and sex-matched controls. In all patients we measured serum levels of total alkaline phosphatase (ALP), type I procollagen carboxy-terminal propeptide (PICP), osteocalcin (BGP), urinary excretion of hydroxyproline (HOP/Cr), and pyridinoline crosslinks (Pyr/Cr). Bone mineral density was measured at the distal radius (BMD-R) and at the lumbar spine (BMD-LS) by dual X-ray absorptiometry (DXA). Ultrasound parameters were also performed at the calcaneous with the Achilles device and at the phalanxes with DBM Sonic 1200. A significant reduction (P < 0.001) in BMD and in ultrasound parameters was found in OI patients compared with normals. PICP was significantly reduced in the OI patients compared with controls (P < 0.001); other markers of bone turnover were higher in OI than in controls, but the difference did not reach the statistical significance. A significant correlation (P < 0.05) was found between PICP and BMD at the lumbar spine and between PICP and ultrasound parameters at the calcaneous. On the basis of our data, we conclude that patients with OI show low values of BMD and ultrasound parameters; therefore in these patients, not only is bone mass disturbed but also bone quality. The reduced levels of PICP in OI patients confirm that most OI patients have defects in collagen I biosynthesis. These defects may contribute to the fragility of OI bone by interfering with complete mineralization and/or normal tissue structure. PICP may be considered a useful marker in the clinical management of OI.
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PMID:Osteogenesis imperfecta: bone turnover, bone density, and ultrasound parameters. 1043 Jun 45

There is widespread interest in the use of bone marrow stromal cells (BMSC) for tissue reconstruction and repair and for gene therapy. BMSC represent the differentiated progeny of CFU-F, which however comprise a developmentally heterogeneous population as is reflected in the cellular heterogeneity of the cell populations to which they give rise. We have compared the efficacy of monoclonal antibodies recognising a series of stromal antigens, viz. STRO-1, HOP-26, CD49a and SB-10/CD166, as tools for the enrichment of CFU-F prior to culture and as developmental markers for culture-expanded BMSC. In freshly isolated bone marrow mononuclear cells (BMMNC), the proportion of antigen-positive cells was 27%, 46%, 5% and 19% for STRO-1, HOP-26, CD49a and CD166, respectively. All CD49a(+) cells co-expressed STRO-1. The degree of CFU-F enrichment obtained with anti-CD49a (approximately 18-fold) by a one-pass immunoselection strategy was significantly greater than that of all other antibodies tested. BMSC expressed higher levels of all antigens investigated (except for HOP-26) compared with BMMNC. Expression of STRO-1 and CD49a remained restricted to a subset of BMSC, whereas all BMSC were SB-10/CD166 positive. Treatment with dexamethasone (10 nM), which promotes the differentiation and further maturation of cells of the osteogenic lineage in this cell culture system, increased the expression of CD49a and HOP-26. The CD49a(+) and HOP-26(+) fractions of BMSC were further subdivided by dual-labelling with anti-STRO-1 and B4-78 (an antibody recognising the B/L/K isoform of the enzyme alkaline phosphatase), respectively. By using a variety of criteria, the HOP-26 antigen was identified as CD63, a member of the tetraspanin family of proteins thought to modulate integrin compartmentalisation and signalling.
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PMID:STRO-1, HOP-26 (CD63), CD49a and SB-10 (CD166) as markers of primitive human marrow stromal cells and their more differentiated progeny: a comparative investigation in vitro. 1288 98


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