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)

In order to determine whether bone turnover varies during the normal menstrual cycle, we measured biochemical markers of bone resorption (serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (sICTP), fasting urinary hydroxyproline/creatinine, fasting urinary pyridinoline/creatinine and fasting urinary deoxypyridinoline/creatinine) and bone formation (plasma osteocalcin, serum carboxy-terminal propeptide of type I procollagen and serum alkaline phosphatase) in ten healthy premenopausal women every two or three days for a complete menstrual cycle. A cyclic pattern was detected in sICTP, with its nadir during the follicular phase and its peak during the luteal phase, and an overall variation of 17% during the menstrual cycle (p = 0.004). No cyclic changes were observed in the urinary parameters of bone resorption or in the biochemical markers of bone formation. We conclude that sICTP, a new biochemical marker of bone resorption, undergoes small variations during a normal menstrual cycle in premenopausal women, whereas the biochemical markers of bone formation remain constant.
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PMID:Possible variation in bone resorption during the normal menstrual cycle. 827 19

We compared the procollagen synthetic properties of MG-63 osteosarcoma cells with those of cultured human skin fibroblasts. In both cells, the expressions of type I and III procollagens are largely dependent on the constant presence of ascorbate and coordinately decreased by the neutral polymer dextran T-40. The amino-terminal propeptides of pro-alpha 1 and pro-alpha 2 chains of type I procollagen are phosphorylated and those of the pro-alpha 1 and pN-alpha 1 chains of type III procollagen both phosphorylated and sulfated, there being no difference in net charge in the propeptides between these cell types. The major differences between MG-63 and normal fibroblasts are the exceptionally high relative synthesis of type III procollagen by MG-63 cells, up to about 40% of the total of types I and III (6% in cultured skin fibroblasts), and the inability of ascorbate-supplemented MG-63 cells to deposit collagens into an insoluble pericellular matrix. A longer dextran treatment shifts up to one-fourth of the proline-labeled extracellular macromolecules into the matrix fraction within 4 days (in control 4%). Despite processing of the procollagens to the respective collagens in the matrix, neither control matrices nor those induced by dextran induced increased production of alkaline phosphatase. In cultures up to 4 days postconfluence the proportion of type III collagen produced tended to increase over that in early confluent cultures. With respect to collagen production, the MG-63 cell line is not a representative of the osteoblast lineage but rather resembles a proliferative wound fibroblast.
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PMID:Procollagen synthesis and extracellular matrix deposition in MG-63 osteosarcoma cells. 832 6

In this study we tested the hypothesis that exercise induces an adaptive response in the developing skeleton which may be monitored in vivo by measuring biochemical markers of bone metabolism. The effects of exercise on two biochemical markers of bone formation were determined; the carboxy-terminal propeptide of type I procollagen (PICP), and the bone-specific isoenzyme of alkaline phosphatase (BAP), and one putative marker of resorption, the pyridinoline crosslinked telopeptide domain of type I collagen (ICTP). All three markers were measured for a year in 2-year-old thoroughbred horses exercised three times a week on a treadmill, and values compared to a control group of age-matched animals. Levels of all three markers fell in both exercised and control groups over the 12-month period reflecting normal age changes. However, there were differences between groups in the pattern of this decrease. When expressed as a percentage of baseline values, BAP was higher (p < 0.05) at 2 months and both BAP and the PICP were higher at 4 months (p < 0.01 and p < 0.05, respectively) in the exercised group, reflecting an increase in bone turnover in this group in the early stages of training. PICP levels were also elevated in the exercised group at 10 months and this result indicates an increase in bone turnover at this time. The changes in ICTP were different; at 2 months, levels were higher in exercised animals than in controls, but there was no significant difference between the two groups at 4 and 6 months. After 8 months, ICTP levels in the exercised group increased returning to near baseline values at 10 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The response of the skeleton to physical training: a biochemical study in horses. 854 Nov 34

The serum concentrations of the carboxy-terminal propeptide of type I procollagen (PICP) were monitored in 52 serum samples from 13 patients receiving renal transplants and the values compared with bone alkaline phosphatase (BAP) concentrations and intact parathyrin levels. There was a significant correlation between BAP and PICP values in all 52 serum samples examined (r = +0.770; P < 0.0001). Before transplantation BAP (P < 0.0001), but not PICP (P > 0.1), was correlated with intact parathyrin levels. BAP concentrations increased from 7.3 +/- 1.2 micrograms/l (median +/- S.E.M.) before transplantation to 13.3 +/- 1.2 micrograms/l 3 months after transplantation (P < 0.01). There was a concomitant rise in PICP levels from 95 +/- 19 micrograms/l to 166 +/- 27 micrograms/l (P < 0.05). No correlation was found between BAP or PICP levels on the one hand and intact parathyrin concentrations on the other at any time following renal transplantation (P > 0.5). In conclusion, PICP may be a useful parameter for monitoring bone formation following renal transplantation.
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PMID:Comparison between serum levels of bone alkaline phosphatase and the carboxy-terminal propeptide of type I procollagen as markers of bone formation in patients following renal transplantation. 854 52

We report on the diagnostic validity of the serum concentrations of the C-terminal propeptide of type I procollagen (a marker of bone formation) and of the urinary excretion of deoxypyridinoline (a marker of bone resorption) in a consecutive series of 89 tumour patients who were routinely examined by 99mTc-methylene bisphosphonate bone scintigraphy for detection of bone metastases. Z score analysis reveals that the discriminating power of deoxypyridinoline is superior to that of calcium excretion whereas the discriminating power of the C-terminal propeptide concentrations is inferior to that of bone alkaline phosphatase values. Accuracy (as assessed by the area under the receiver-operating characteristic curve) was 0.75 for deoxypyridinoline and 0.82 for the C-terminal propeptide. Combination of both markers did not yield an increase of accuracy (0.82) compared with the determination of the C-terminal propeptide concentrations alone. There was a correlation (r = +0.398; p < 0.0001) between C-terminal propeptide concentrations and deoxypyridinoline excretion values in the group of 89 patients examined. Further studies should be done to elucidate whether the determination of bone collagen turnover is suitable as a screening procedure for detecting bone metastases.
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PMID:Simultaneous assessment of bone collagen synthesis and degradation in patients with different malignant tumours. Comparison with the results of 99mTc-methylene bisphosphonate bone scintigraphy. 854 30

Three new collagen markers deriving from the collagenous matrix, e.g. carboxyterminal propeptide of type I procollagen (PICP), carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), and aminoterminal propeptide of type III procollagen (PIIINP) were used for the diagnose of prostatic bone metastases. Blood samples were obtained prior to biopsy or TURP. Serum PICP, PIIINP and ICTP were measured with commercial available RIAs and PSA by IRMA. Serum PSA was increased in patients with local prostatic cancer compared with patients with hyperplasia (p < 0.05). The level of PIIINP, ICTP, and PICP did not differ between these two groups. In patients with metastatic prostatic cancer all five markers were increased compared to the level measured in patients with localized cancer (p < 0.0001). All variables showed a significant positive relationship with alkaline phosphatase. The sensitivity ranged from 0.53 to 0.62 and specificity from 0.91 to 0.95. The sensitivity for alkaline phosphatase and PSA was 0.69 and 0.66 and specificity 0.91 and 0.68, respectively.
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PMID:Collagen derived serum markers in carcinoma of the prostate. 857 75

We evaluated the effects of recombinant insulin-like growth factor-I (IGF-I) and growth hormone (GH) on calciotropic hormones and bone turnover markers in 16 healthy elderly women 71.9 +/- 1.3 years of age (mean +/- SEM). Subjects consumed a fixed diet providing 1000 mg of calcium and 0.9 g/kg of protein for 10 days before starting baseline 24-h urine and blood collections. Specimens were collected for 6 consecutive days before initiating subcutaneous injections of GH (25 micrograms/kg/day, n = 5) and IGF-I at 60 micrograms/kg b.i.d. (high-dose, n = 5) or at 15 micrograms/kg b.i.d. (low-dose, n = 6) for 28 days. Resorption markers included urine hydroxyproline (OHP), total pyridinolines (PYD), and N-telopeptide; formation markers include osteocalcin, skeletal alkaline phosphatase (sALP), and type I procollagen carboxy-terminal extension peptide (CICP). For each subject, baseline daily turnover markers varied substantially (DV = 16-22%). With GH and high-dose IGF-I, resorption and formation markers increased progressively to maximum levels at day 21. For GH, the increase in day 21 PYD, N-telopeptide, osteocalcin, and CICP was 143, 111, 53, and 81%, respectively (p < 0.96-0.02). For high-dose IGF-I, these increases were 108, 81, 77, and 111% (p < 0.02-0.002). However, with low-dose IGF-I no change was observed in resorption markers while osteocalcin and CICP increased progressively (day 21, % increases = 88 +/- 51, 36 +/- 14). Twenty-four hour urine collections during the last days of baseline and of study drug were taken as six 4 h aliquots. When deoxyPYD was measured on these samples in the low-dose IGF-I group, a significant increase was observed only on the 0800-1200 h aliquot. Serum phosphorus concentrations increased with GH (21.2 +/- 3.3%) and high-dose IGF-I (8.8 +/- 3.6%) by day 21 but actually decreased by day 28 (-9.7 +/- 2.7, p < 0.02) with low-dose IGF-I. Urinary phosphorus excretion decreased with high-dose IGF-I only. Twenty-four hour calcium excretion increased with all treatments. These results indicate that both GH and high-dose IGF-I activate remodeling osteons. By contrast, low-dose IGF-I may directly increase osteoblastic function with only a minimal increase in bone resorption and may therefore provide a useful means to increase bone mass. The results also suggest some of the GH action on renal phosphorus handling represents a direct action of GH on the nephron which does not involve the intermediacy of IGF-I. Finally, even under controlled conditions bone turnover markers exhibit substantial daily variation so that a very large treatment effect will be required for these markers to have clinical utility.
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PMID:Effects of recombinant insulin-like growth factor-I and growth hormone on bone turnover in elderly women. 861 64

Thirty-six patients with bone metastases included in a trial of supportive calcitonin on the treatment response to systemic therapy were monitored by conventional radiography, conventional indicators of bone metabolism [alkaline phosphatase (AP), osteocalcin (gla), urinary hydroxyproline excretion (OHP), urinary calcium (uCa), serum calcium (sCa)] and collagen metabolites (ICTP, the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen; PICP, the carboxy-terminal propeptide of type I procollagen; and PIIINP the amino-terminal propeptide of type III procollagen). All patients had been on the same systemic treatment for at least 3 months at the start of the trial. There was a positive correlation between the concentrations of ICTP and PICP at baseline (Spearman's rank-order correlation coefficient rs = 0.62). Both ICTP and PICP showed statistically significant correlations to the other markers of bone metabolism (except sCa and uCa) as well as to the number of bone metastases on bone scans. Reduction in ICTP correlated significantly with the treatment response at three months (rs = - 0.57). while PICP showed a borderline negative correlation to therapy response (rs = - 0.37). Of all the biochemical parameters studied the changes in ICTP showed the best correlation with the treatment response. PICP and ICTP changes in patients with progressive disease differed significantly from those in patients with responding and stable metastases, whereas no difference was found between responders and stable patients.
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PMID:Markers of type I collagen degradation and synthesis in the monitoring of treatment response in bone metastases from breast carcinoma. 862 66

A study was undertaken to evaluate the clinical usefulness of measurements of serum concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) as parameters of bone metastasis in patients with prostate cancer. Serum PICP, ICTP, prostate-specific antigen (PSA), and alkaline phosphatase (ALP) were evaluated in 82 patients with prostate cancer and 26 patients with benign prostatic hyperplasia (BPH). These markers were measured serially in 16 prostate cancer patients during treatment. The serum levels of PICP, ICTP, ALP, and PSA were significantly higher in prostate cancer patients with bone metastasis than in patients with either BPH or prostate cancer without bone metastasis. Although the rate of detection of bone metastasis with PICP and ICTP was slightly lower than that with PSA determined by the receiver operating characteristic curve, the correlation between both PICP and ICTP and the extent of disease was much higher than that of PSA. PICP and ICTP levels varied with ALP and PSA levels, the patient's clinical course after the start of endocrine therapy and the progression of bone metastasis. The levels of PICP and ICTP did not change substantially in patients who developed local regrowth or lymph node metastasis, and decreased as bone metastases responded to radiotherapy. PICP and ICTP thus reflect the metastatic burden in bone and are useful for monitoring the response of bone metastasis to therapy.
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PMID:Clinical usefulness of serum carboxyterminal propeptide of type I procollagen and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen in patients with prostate cancer. 865 56

Although biochemical markers of skeletal turnover cannot replace bone density scanning for the diagnosis of osteoporosis, it is thought that they may help add to prediction of fracture risk and help determine adequacy of osteoporosis therapy. Nevertheless, whether biochemical markers in the serum or urine can predict individual rates of bone loss in the spine or hip region is unknown. We studied a heterogeneous group of women (n = 81) who were premenopausal, untreated postmenopausal, and estrogen-treated postmenopausal with baseline determination of body mass index (BMI), calcium intake, biochemical measurements, and serial bone densitometry over 3 years. Serum assays included bone Gla protein (BGP), total and bone-specific alkaline phosphatase (AP, BSAP), carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase (TRAP). Urine assays included hydroxyproline (OHP), calcium, total pyridinoline, and total deoxypyridinoline. Individual biochemical markers and calcium intake were modestly correlated with bone density changes but were inconsistent regarding the spine versus the hip. All of the formation variables were significantly correlated to spine density change (r = -0.24 to -0.49) whereas the only resorption variable that correlated was urine OHp/Cr (r = -0.31). The only formation variable that correlated with hip density change was serum PICP whereas all of the resorption variables except serum TRAP were correlated (r = -0.23 to -0.35). "High turnover" individuals were defined at those with levels of biochemical variables at least 1 SD above the mean young normal for each variable. Higher bone loss rates were seen in this group for several of the turnover markers compared with bone loss rates in all other individuals. However, the sensitivity of this "high turnover" status for identifying high bone losers did not exceed 60% for any of the variables. In untreated postmenopausal women, a model using urine OHp, serum ICTP, serum BSAP, and calcium intake was able to predict 42% of the variance of change in BMD of the lumbar spine. A model using BMI, serum ICTP, and serum BGP could predict 32% of the variance of change in BMD of the femoral neck. No combination of markers could predict variance in bone density change at either site in estrogenized women (premenopausal and estrogen-treated postmenopausal). We conclude that measuring individual serum and urine markers of bone turnover cannot accurately predict bone loss rates in the spine and hip; however, combinations of demographic and biochemical variables could predict some of the variance in untreated postmenopausal women. Biochemical markers cannot replace serial bone densitometry for accurate determination of change in bone mass at the most clinically relevant sites.
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PMID:Bone density change and biochemical indices of skeletal turnover. 866 54


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