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)

Fifteen prepubertal short stature children (10 girls, 5 boys), mean age 9.6 years (range 5.2-12.7 years), with normal response to growth hormone stimulation tests (group A) or partial growth hormone deficiency (GHD) of idiopathic nature (group B) were included in a controlled longitudinal study for evaluation of predictive parameters for the long-term growth response after administration of biosynthetic human growth hormone (B-hGH). The average knee-heel length velocity for the first 3 months was significantly correlated to total body height velocity during the following 9 months (p less than 0.0008). By contrast, this association could not be found for height velocity during the same period. The increase in serum values of alkaline phosphatase and insulin-like growth factor I (IGF-1) during the first month of treatment was not significantly correlated to height velocity during the first year. During one year of treatment with B-hGH the mean height velocity for groups A and B increased from 4.4 cm/year (range 2.5-6.5) to 7.6 cm/year (range 4.7-10.6). Bone age advanced by 1.08 +/- 0.60 per chronological year. The ratio between total height and knee-heel length prior to treatment was 3.34 +/- 0.10 and after one year 3.33 +/- 0.10, suggesting a proportional linear growth. An inverse relationship was observed between the ratio and chronological age. In conclusion, early knee-heel measurement may be a useful non-invasive predictor of long-term linear growth in children during treatment with growth hormone, and the ratio of total height to lower leg length may be of importance in detecting dysproportional growth.
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PMID:Predicting and monitoring of growth in children with short stature during the first year of growth hormone treatment. 178 87

Ten children with isolated growth hormone deficiency were treated for 1 year with 0.5 UI/kg week with Somatrem (recombinant human growth hormone), given as intramuscular injections three times weekly. Before treatment the children had a chronological age of 7-12.4 years (mean 10.4 years), with a bone age at least 25% below the chronological age. There was no radiological evidence of an intra or suprasellar mass in any child, and no response to provocative growth hormone tests (with exercise or arginine-insulin injection). Informed written consent for treatment was obtained from the parents of each child. Clinical signs were registered every month; triiodothyronine, thyroxine, thyrotropine, glucose, urea, creatinine, blood cells count, and hemoglobine, glycosylated hemoglobine, glutamic-piruvic and glutamic-oxalacetic transaminases, alkaline phosphatase, anti-human growth hormone and, E. coli antibodies, insulin like growth factor 1, and bone age were assessed every 3 months. The mean height velocity was 0.27 +/- 0.1 cm/month before treatment, and increased throughout treatment to a value of 0.62 +/- 0.16 cm/month after 12 months. Within the first year eight of the 10 children had a height increase of 8.4 +/- 0.98 cm. The other two children showed no significant difference; one of them with a very low socioeconomic status, and the other developed typhoid fever. All of the children showed an advance in bone age, but none reached a bone age appropriate for their chronological age; without modifications in the laboratory parameters. Insulin like growth factor 1 increased in 9 children. Pain at the injection site was the only side effect reported.
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PMID:[Clinical and biochemical evaluation of the administration of growth hormone]. 225 92

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

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

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

To evaluate the osteoblastic function in patients with multiple pituitary hormone deficiencies (M-PHD) and with isolated growth hormone deficiency (I-GHD), bone cells were cultured and the effects of 10(-8) M 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) on parameters of cell proliferation, osteoblastic differentiation, and local paracrine regulation were measured. Three days of 1,25(OH)2D3 treatment increased alkaline phosphatase activity and osteocalcin release but inhibited [3H]thymidine incorporation in all cell cultures from patients as well as from controls. In addition, 1,25(OH)2D3 increased the release of both total and active transforming growth factor-beta (TGF-beta) in bone cells from controls by, respectively, 4.9- and 3.2-fold and in bone cells from I-GHD by 5.1- and 1.5-fold, respectively. However, in bone cells from M-PHD, the stimulation of total TGF-beta release was significantly lower (1.3-fold) than in control and I-GHD cells, and active TGF-beta release was not stimulated at all. One year of supplementation with human growth hormone did not improve this deficient TGF-beta release in bone cells from M-PHD. We conclude that cultured bone cells from I-GHD and M-PHD show a normal response to 1,25(OH)2D3 regarding cell proliferation and osteoblastic differentiation, which implicates a normal 1,25(OH)2D3-receptor function. In cells from controls and I-GHD, 1,25(OH)2D3 enhanced both total and active TGF-beta release. However, bone cells from M-PHD showed a deficient TGF-beta response to 1,25(OH)2D3. These results suggest that the regulation of TGF-beta production is a major paracrine factor involved in hypopituitarism.
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PMID:1,25-dihydroxyvitamin D3-mediated transforming growth factor-beta release is impaired in cultured osteoblasts from patients with multiple pituitary hormone deficiencies. 885 47

Administration of growth hormone (GH) to patients with growth hormone deficiency (GHD) has beneficial effects, but so far has been employed only empirically. We have, therefore, investigated the dose-dependent effect of GH on target tissue by studying biochemical markers of bone and collagen turnover in GHD. Then patients with GHD (nine males and one female aged 21-43 years, mean age 28 years) participated in the study. Growth hormone deficiency was defined as a peak serum GH response of less than 15 mU/l in two provocation tests. After a 4-week run-in period, the study population received increasing doses of GH at 4-week intervals (1, 2 and 4 U/m2). Blood samples were collected in the fasting state at 7.00 h on the last day of each period and assayed for serum levels of osteocalcin (S-BGP), bone alkaline phosphatase (B-ALP), C-terminal propeptide of type I collagen (S-PICP), carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (S-ICTP) and N-terminal propeptide of type III collagen (S-PIIINP). Following replacement therapy, serum insulin-like growth factor I and insulin-like growth factor binding protein 3 increased sequentially with time (p < 0.001 and p < 0.001, MANOVA) and the values were elevated significantly over baseline levels after treatment with 1 U/m2. Serum BGP values were below normal at the start of the study and increased gradually following GH treatment to levels in the low-normal range. Baseline values for serum bone alkaline phosphatase (B-ALP), PICP and PIIINP were within the normal range. The collagen parameters increased with GH replacement (p < 0.001, MANOVA) to levels above normal, whereas B-ALP stayed within normal limits. Serum ICTP values were elevated above the normal range at baseline, indicating increased bone resorption in GHD. A linear increase in values was observed with GH treatment (p < 0.001, MANOVA). Serum ICTP did not correlate significantly with the bone formative parameters but was correlated positively to PIIINP. The sensitivity of S-ICTP as a bone resorptive marker is thus questioned. In conclusion, a dose-dependent increase in markers of growth hormone metabolism and in biochemical markers of both bone and non-bone collagen synthesis was seen following incremental doses of GH in GHD.
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PMID:Dose-dependent effects of recombinant human growth hormone on biochemical markers of bone and collagen metabolism in adult growth hormone deficiency. 902 10

In Duchenne muscular dystrophy (DMD), short stature is a feature of unknown cause. This cross-sectional study of 34 male patients (mean age 8.0 y, age range 1.2-13.7 y) was conducted to examine the relationship between auxological parameters, markers of growth and the extent of muscular weakness. Weight and length at birth (SDS +/- SD; 0.0 +/- 1.2; 0.2 +/- 1.5) and target height SDS (-0.2 +/- 0.7) were normal. Height (HT) SDS (-1.0 +/- 1.1) was lower than the normal population (p < 0.001) and did not correlate with age. Body mass index SDS (-0.1 +/- 1.6) was normal. Tests of insulin-like growth factor-I SDS (-0.6 +/- 1.2) and insulin-like growth factor binding protein-3 SDS (0.1 +/- 1.3) ruled out a severe derangement in the GH-IGF-axis. The carboxy-terminal propeptide of type I procollagen (PICP) SDS (0.6 +/- 1.5) was normal, but bone-specific alkaline phosphatase (BAP) SDS (-1.7 +/- 0.8) was low (p <0.001). HT SDS did not correlate with BAP SDS. The Vignos scale, a grading of muscular function (score: 0 = unaffected; 11 = confined to bed) (median (range): 3 (0-9)) correlated strongly with age (r = 0.77, p < 0.0001), but did not correlate with HT SDS, PICP SDS or BAP SDS. In conclusion, DMD patients are significantly shorter than the normal population, though the HT SDS does not change with age. Growth hormone deficiency does not seem to be the cause of short stature in DMD. Significantly low BAP levels are probably the result of the reduced muscle mass, which leads to a lower biomechanical load on the bone and thus a reduction in bone turnover. The short stature observed in our study is unlikely to be the result of muscular weakness.
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PMID:Short stature in Duchenne muscular dystrophy: a study of 34 patients. 1009 May 50

Biochemical measurements of bone turnover are helpful in the study of the pathophysiology of skeletal metabolism and growth. However, interpretation of their results is difficult because they depend on age, pubertal stage, growth velocity, mineral accrual, hormonal regulation, nutritional status, circadian variation, day-to-day variation, method of expression of results of urinary markers, specificity for bone tissue, sensitivity and specificity of assays. Three markers of bone formation have been described including their bone specificity and age-related changes: osteocalcin, alkaline phosphatase and its skeletal isoenzyme, procollagen I extension peptides. Bone resorption markers (hydroxyproline; deoxypyridinoline; pyridinoline; peptides containing these crosslinks such as N-telopeptide to helix in urine (NTX), C-telopeptide-1 to helix in serum (ICTP) and C-telopeptide-2 in urine and serum (CTX); tartrate-resistant acid phosphatase; hydroxylysine and its glycosides) are described with special attention to methodologic issues, mainly ways of expression of their results. Changes of bone turnover during growth are described during four periods: infancy, prepubertal period, puberty and the postpubertal period. Pubertal changes of bone markers are described with special attention to gender differences and hormonal mechanisms of the growth spurt which determine differences related to the pubertal stage. Disturbances of bone turnover in four conditions are described to illustrate the impact of such diseases on growth and formation of peak bone mass: prematurity, malnutrition, growth hormone deficiency and corticosteroid-treated bronchial asthma. Available data suggest biochemical markers of bone remodeling may be useful in the clinical investigation of bone turnover in children in health and disease. However, their use in everyday clinical practice is not advised at present.
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PMID:Biochemical measurements of bone turnover in children and adolescents. 1092 17

Human growth hormone (hGH) is frequently used clinically for growth abnormalities in children and also in adults with growth hormone deficiency. The hormone is usually administered to the individuals by frequent injections. In the present study we investigated the potential of bone marrow stromal cells as vehicles to deliver the GH in vivo by infusion of cells transduced with hGH cDNA into mice femurs. The effect of the hormone on the transduced cells in vitro was also assessed. Bone marrow stromal cells established from a mouse model of human osteogenesis imperfecta mice (oim) were transduced with a retrovirus containing hGH and neomycin resistance genes. The hGH-expressing cells were selected in a medium containing G418 and were then assessed for the hGH expression in vitro. The selected cells synthesized 15 ng/10(6) cells of hGH per 24 h in vitro and exhibited alkaline phosphatase activity when they were treated with the human recombinant bone morphogenetic protein 2 (rhBMP-2). The transduced cells also proliferated faster than the LacZ transduced cells but they did not exhibit a higher rate of matrix synthesis. When 2 x 10(6) hGH+ cells were injected into the femurs of mice, hGH was detected in the serum of the recipient mice up to 10 days after injection. The highest level of growth hormone expression, 750 pg/ml, was detected in the serum of the recipient mice I day after injection of the transduced cells. hGH was also detected in the medium conditioned by cells that were flushed from the femurs of the recipient mice at 1, 3, and 6 days after cell injection. These data indicate that bone marrow stromal cells could potentially be used therapeutically for the delivery of GH or any other therapeutic proteins targeted for bone. The data also suggest that GH may exert its effects on bone marrow stromal cells by increasing their rate of proliferation.
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PMID:In vivo expression of human growth hormone by genetically modified murine bone marrow stromal cells and its effect on the cells in vitro. 1097 31


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