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

A female presenting multiple osteoma cutis lesions without underlying endocrinological disturbance was studied. Histologically, lesions revealed true bone formation with multiple osteoblastic cells. This was confirmed by demonstrating high alkaline phosphatase activity and osteonectin expression in osteoma cutis lesions. Interestingly, tenascin and type III procollagen were in close association to bony lesions, indicating that these matrix proteins may be somehow involved in bone formation. In situ hybridization revealed fibroblastic cells around bony lesions, which actively deposited type I collagen and osteonectin. One of the activators of bone formation, TGF beta, was also present in some osteoblastic cells. The results thus indicate that in osteoma cutis, fibroblasts have the ability to differentiate into osteoblastic cells, which have some properties of osteoblasts, such as high alkaline phosphatase activity and a high expression of osteonectin.
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PMID:A study of bone formation in osteoma cutis employing biochemical, histochemical and in situ hybridization techniques. 135 50

Among the noninvasive methods proposed for the study of collagen metabolism as an of fibrosis and inflammation, the most widely accepted method is quantitation in serum of the N-terminal peptide of type III procollagen (P-III-Ps). We measured this variable in 87 subjects classified into five study groups: 19 controls (C), 18 alcoholics (E), 15 patients diagnosed as liver cirrhosis (CH), 11 chronic liver disease (HC) and 24 pregnant women (EMB). In our environment, the serum level of P-III-P in the healthy population was 9.12-12.8 ng/ml. In 27.77% of the alcoholics studied (5 cases) the mean value exceeded this level, 19.35 +/- 3.05 ng/ml. Forty percent of the cirrhotics (6 cases) presented the highest values, 26.54 +/- 11.45 ng/ml, while 83.33% of the patients with chronic active hepatitis presented a mean value of 18.53 +/- 3.8 ng/ml. Of the 24 pregnant women, 95.83% (23 cases) had higher than normal values, and concentrations roses in the last trimester of gestation with respect to the previous trimesters. Analysis of the correlations of all the biochemical parameters of liver function with P-III-Ps disclosed a relationship between P-III-Ps and alkaline phosphatase in the groups of cirrhotics and chronic persistent hepatitis (p less than 0.05). We conclude that the N-terminal peptide of type III procollagen is a useful marker of active fibrosis.
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PMID:[Serum determination of N-terminal peptide of type III procollagen as a marker of fibrotic activity]. 273 69

Bone metastases are very frequent. Some are sensitive to the action of anticancer drugs. However, there is as yet an unsolved methodological problem in the evaluation of response to these drugs. The uniquely radiological UICC criteria are quite insufficient, in as much as they appear with a long delay and sometimes give erroneous results. In this work we give a brief review of biological and clinical knowledge about bone metastases, and we attempt to give an array of the possible evaluation criteria and their respective value. We propose as a working hypothesis a classification of responses taking into account the criteria: the urinary hydroxyproline to urinary creatinine ratio, the serum dosage of bone isoenzyme of alkaline phosphatase and propeptide of type III procollagen (P III NP), and as an essential element, an analysis of all available imaging techniques. A visual study of bone scintillation scans must precede that of radiographs and, when possible, it must be associated to computerized scintillation scanning. When metastasis are located to the pelvis, the vertebral column, or the sternum, a CT scan or better, a nuclear magnetic resonance study (IRM), is indispensable in order to have a direct measure of the tumor extension to soft tissues. Furthermore, in the case of isolated metastases, one of these imaging techniques allows a diagnostic biopsy. Finally an analysis of response at the bone level will always be associated with a measure of their duration and an evaluation of metastases to other sites.
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PMID:[Response of bone metastases to medical treatment: definition of evaluation criteria and classification trials]. 273 14

The prognostic value of the aminoterminal propeptide of type III procollagen (P3NP) was investigated in 63 patients with primary biliary cirrhosis (PBC) followed for up to 87 months. No patient with an initially normal serum P3NP level died during the study; survival was significantly worse with increasing serum P3NP levels. Cox multivariate analysis confirmed that serum P3NP was an independent prognostic variable. Positive correlations were found between serum P3NP and histological stage, pericellular fibrosis, piecemeal necrosis, and serum concentrations of alanine aminotransferase and aspartate aminotransferase. Raised P3NP levels also correlated with the degree of cholestasis as evaluated by serum bilirubin, serum alkaline phosphatase, and copper binding protein deposition in the liver. Serum P3NP is of prognostic value because it reflects the major pathophysiological features of PBC.
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PMID:Type III procollagen peptide: a marker of disease activity and prognosis in primary biliary cirrhosis. 289 70

Inasmuch as recombinant human growth hormone is now more generally available for the treatment of different types of short stature, there is a need for better short-term indicators of treatment success. In healthy children, serum concentrations of antigens related to the aminoterminal propeptide of type III procollagen (P-III-NP) closely follow the growth velocity curve. P-III-NP was measured longitudinally in 20 children with growth hormone deficiency during 6 months of human growth hormone substitution therapy. Two different radioimmunoassay systems were used; one recognizes predominantly the intact propeptide showing a lesser affinity to a smaller monomeric peptide (RIAgnost assay), while the other assay detects both forms equally (FAB assay). These results were compared to the growth response [median 5.6 (0.4 to 13.9) cm in 6 months] and to other established growth correlated parameters (somatomedin C, alkaline phosphatase). A relatively better growth response correlated significantly with high pretreatment P-III-NP (RIAgnost assay) values (r = 0.56) and delayed bone age (r = -0.70). A combination of these parameters in multiple regression analysis increased the cumulative prediction value to above 60% (r2 = 0.61). On the other hand, P-III-NP (FAB assay) values proved to be best in monitoring treatment, correlating with the individual growth rate during the first 3 months (r = 0.40; p less than 0.05), during the consecutive 3 months (r = 0.66; p less than 0.001), and during the total 6-month period (r = 0.46; p less than 0.05). All other parameters showed associations to growth only during some treatment periods.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term monitoring of treatment with recombinant human growth hormone by serial determinations of type III procollagen-related antigens in serum. 335 59

We measured bone mineral density (BMD) using dual-energy x-ray absorptiometry in 20 patients with Cushing's syndrome (CS) (14 pre- and 2 postmenopausal women, 4 men) before and in 18 of them also at regular intervals after surgical cure (median duration of follow-up, 36 months). In addition, in the premenopausal women with CS, fasting blood samples and 2-h fasting urine samples for measurement of biochemical parameters of bone and collagen metabolism were collected before and in 9 of them also at regular intervals during the first 2 yr after surgery. Marked osteopenia was present in most patients with active CS (Z-scores: lumbar spine -1.45 +/- 1.44 and femoral neck -1.50 +/- 1.02; mean +/- SD). No consistent change in BMD was observed at 3 and 6 months after surgery. Thereafter BMD increased considerably in almost all patients. For the 15 patients with a follow-up of at least 1 yr, Z-scores at the last evaluation were -0.65 +/- 1.27 for the lumbar spine and -0.98 +/- 1.02 for the femoral neck (both P < 0.002 compared with pretreatment values). In the premenopausal patients, the increase in BMD both in the lumbar spine and in the femoral neck at 24 months was inversely correlated with age (r = -0.733, P < 0.03, and r = -0.667, P < 0.05, respectively). Serum levels of osteocalcin, bone alkaline phosphatase, carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen, and the cross-linked telopeptide of type I collagen were not significantly different between the group of 14 premenopausal patients with active CS and a control group of 18 age-matched healthy premenopausal women. However, the urinary hydroxyproline/creatinine ratio was significantly higher in patients with CS (24.6 +/- 9.6 vs. 16.2 +/- 3.5 mumol/mmol, P < 0.01). In all 9 premenopausal patients, serum levels of osteocalcin increased considerably between 0 and 3 months (from 1.04 +/- 0.20 to 3.82 +/- 0.30 nmol/L) (mean +/- SEM, P < 0.0001), indicating a prompt increase of osteoblast activity. Also serum levels of carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen, and cross-linked telopeptide of type I collagen, and the urinary hydroxyproline/creatinine ratio increased significantly between 0 and 3 months. Thereafter these levels decreased gradually. We conclude that marked osteopenia in the lumbar spine and femoral neck is present in most patients with active Cushing's syndrome.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Bone mineral density and bone turnover before and after surgical cure of Cushing's syndrome. 755 64

The preliminary results of a prospective double-blind controlled trial of colchicine in 100 patients with hepatitis B virus-related cirrhosis are reported. The patients, 94 males and 6 females, aged 32-80, were assigned to receive either 1 mg of colchicine or an identical placebo orally on a daily basis. The duration of the follow up ranged from 15 to 51 months (median 26 months). Seventy percent had histological proof of cirrhosis. On entry, 80 patients were in Child-Pugh class A, 19 were in class B, and one was in class C. Compared to the placebo group, there was no improvement in the colchicine group after a 24-month follow up in any of the biochemistry data, for example, serum albumin, alkaline phosphatase, alanine and aspartate aminotransferase, bilirubin, and prothrombin time. The difference in the cumulative survival rates at 51 months did not reach statistical significance (p = 0.8) in either group. There was no histological improvement in 30 patients who were willing to undergo repeated liver biopsies. No trend toward improvement of the hepatic pressure gradient was observed in these patients. The serum levels of aminopropeptide of type III procollagen increased significantly in patients in both groups after 24 months of therapy (1.07 +/- 0.06 vs. 1.36 +/- 0.06 U/ml in the colchicine group, 0.93 +/- 0.09 vs. 1.25 +/- 0.07 U/ml in the placebo group; p < 0.05). In addition, neither the clinical deterioration of cirrhosis nor death was prevented in patients receiving colchicine therapy. This report indicates that colchicine has no effect in the treatment of HBV-related postnecrotic cirrhosis.
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PMID:A double-blind randomized controlled trial of colchicine in patients with hepatitis B virus-related postnecrotic cirrhosis. 789 Sep 5

Serum bone Gla protein (BGP) and bone alkaline phosphatase (B-AP), markers of bone formation, carboxyterminal cross-linked telopeptide of type I collagen (ICTP), marker of bone resorption, and aminoterminal propeptide of type III procollagen (PIIINP) levels, index of collagen synthesis, were determined in 8 adults (mean age +/- SE: 29.6 +/- 1.2 yr) with childhood onset GHD before and after 3 and 6 months of recombinant GH treatment (0.5 IU/kg/week). Before treatment, mean BGP (3.8 +/- .5 ng/ml) and B-AP (44.9 +/- 6.9 IU/L) were significantly (P < 0.001 and p < 0.05, respectively) lower than those recorded in normals (5.4 +/- 0.1 ng/ml and 61.8 +/- 1.9 IU/L, respectively), while serum ICTP and PIIINP levels were similar to those found in controls (ICTP: 4.7 +/- 0.8 vs 4.1 +/- 0.3 ng/ml; PIIINP: 3.7 +/- 0.6 vs 3.2 +/- 0.2 ng/ml). BGP and ICTP levels significantly (p < 0.005) increased after 3 (28.4 +/- 5.3 ng/ml and 17.5 +/- 2.8 ng/ml, respectively) and 6 months (25.1 +/- 5.0 ng/ml and 15.0 +/- 1.9 ng/ml, respectively) of recombinant GH treatment. B-AP levels significantly (p < 0.01) increased during the treatment (basal: 44.9 +/- 6.9 IU/L, 3rd month: 173.6 +/- 40 IU/L, 6th month: 194.4 +/- 40 IU/L), while non B-AP levels remained similar to those recorded in basal condition. Serum PIIINP levels significantly (p < 0.0001) rose up after 3 (12.5 +/- 1.4 ng/ml) and 6 months (10.2 +/- 0.8 ng/ml). Serum BGP and ICTP levels were directly (r = 0.85, p < 0.001; r = 0.53, p < 0.01) correlated with serum IGF-I levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone treatment in adults with GH deficiency: effects on new biochemical markers of bone and collagen turnover. 814 66

To evaluate the effect of ursodeoxycholic acid (UDCA) treatment according to the severity of primary biliary cirrhosis, a long-term prospective open trial in 54 consecutive PBC patients, 19 with histological stage I-II, 24 stage III, and 11 stage IV was carried out. UDCA was administered at a dosage of 250 mg twice a day. Clinical and biochemical assessment (AST, ALT, alkaline phosphatase, GGT, bilirubin) were done initially and every six months. Serum hyaluronate (HY) and type III procollagen amino propeptide (PIIIP) were also evaluated, as they are considered markers of fibrosis and prognosis. All patients were followed-up for at least two years (24-36 months); results were analyzed at 24 months after treatment. The composite pruritus score failed to show significant changes during UDCA treatment, while intensity score demonstrated a significant reduction from the 6th month. Patients with histological stage I-II disease had a significant decrease of liver enzymes (AST, ALT, alkaline phosphatase, GGT) after six months and maintained the levels up to 24 months. The patients with histological stage III disease showed a significant decrease of AST, ALT, alkaline phosphatase (but not GGT) up to month 18; subsequently AST and ALT serum levels increased, reaching values comparable to baseline by 24 months. In patients with histological stage IV disease no significant change in liver enzymes was observed during the follow-up. HY and PIIIP serum levels failed to show significant changes during UDCA treatment in the three groups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Different response to ursodeoxycholic acid (UDCA) in primary biliary cirrhosis according to severity of disease. 828 73

Serum bone Gla protein (BGP), a marker of osteoblastic function, serum carboxyterminal cross-linked telopeptide of type I collagen (ICTP), a marker of bone resorption, and serum aminoterminal propeptide of type III procollagen (PIIINP) levels, an index of collagen synthesis, were determined in seven children and eight adults with congenital growth hormone deficiency (GHD). In children with GHD, serum BGP (mean +/- s.e.: 12.9 +/- 0.7 ng/ml), ICTP (8.3 +/- 1.3 ng/ml) and PIINP (3.5 +/- 0.5 ng/ml) levels were significantly lower (P < 0.001) than those recorded in normal children (BGP 18.9 +/- 0.8 ng/ml, ICTP 14.4 +/- 0.5 ng/ml and PIIINP 6.7 +/- 0.7 ng/ml). Total alkaline phosphatase (184.7 +/- 13.4 IU/l) and bone alkaline phosphatase (77.8 +/- 4.1 IU/l) levels were also significantly lower (P < 0.0001) than in controls (338.1 +/- 14.9 IU/l and 181.0 +/- 7.8 IU/l, respectively). Serum BGP, ICTP and PIIINP levels were not significantly correlated with height velocity values. In adults with GHD, mean BGP levels (3.8 +/- 0.3 ng/ml) were significantly lower (P < 0.0001) than those recorded in normals (5.4 +/- 0.1 ng/ml). On the contrary, serum ICTP levels were similar to those found in controls (patients: 4.7 +/- 0.8 ng/ml vs normals: 4.1 +/- 0.3 ng/ml), suggesting the presence of a normal resorption activity associated with a reduced osteoblastic function. This finding was also confirmed by the presence of reduced bone alkaline phosphatase levels (GHD: 44.9 +/- 6.9 IU/I vs controls: 58.3 +/- 2.0 IU/I; P<0.02), while the less specific total alkaline phosphatase levels (119.5 +/- 14.8 IU/I) were similar to those recorded in normal subjects (122.3 +/- 4.0 IU/I). Serum PIIINP levels (3.7 +/- 0.6 ng/ml) were similar to those recorded in normals (3.2 +/- 0.2 ng/ml), suggesting that in adulthood the collagen turnover is not negatively influenced by the chronic GHD. No significant correlations were found between BGP/ICTP/PIIINP and IGF-I levels. In conclusion, our data show that in children with GHD the lack of GH insulin-like growth factor-I (IGF-I) effects on bone and collagen turnover is associated with a significant reduction of bone turnover (low bone formation plus low bone resoRption) and collagen synthesis. On the contrary, adult GHD seems to exert less relevant effects on bone and collagen turnover, probably due to the fact that in adult life further hormones or local factors might partially counteract the negative consequences of chronic GH-IGF-I deficiency.
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PMID:New markers of bone and collagen turnover in children and adults with growth hormone deficiency. 829 Apr 28


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