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A. Di Palma - One of the best experts on this subject based on the ideXlab platform.
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Bone Alkaline Phosphatase Isoenzyme in renal osteodystrophy.
Nephrology dialysis transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 1996Co-Authors: Carlos Jarava, J R Armas, M Salgueira, A. Di PalmaAbstract:Serum total Alkaline Phosphatase is the most commonly used biochemical marker of bone disease in renal patients, but Alkaline Phosphatase originates from different organs and sometimes lacks specificity. Bone Isoenzyme measurement is considered superior to total Alkaline Phosphatase for the assessment of bone metabolism. We have studied the value of bone Isoenzyme, determined by a new. IRMA (Tandem-R-Ostase), in haemodialysis patients with secondary hyperparathyroidism and renal osteodystrophy. Fifty-six haemodialysis patients were studied. Intact parathyroid hormone (PTH), osteocalcin, total Alkaline Phosphatase and bone Alkaline Phosphatase were determined. A transiliac bone biopsy was performed in 20 of the 56 patients after double tetracycline labelling. There was a significant correlation between bone Alkaline Phosphatase and PTH (r = 0.79, P < 0.001) and between bone and total Alkaline Phosphatase (r = 0.84, P < 0.001) in all patients. The patients who underwent a bone biopsy showed osteitis fibrosa in 17, mixed lesion in one, adynamic bone disease in one and normal bone in one. Bone Alkaline Phosphatase showed a significant correlation with static and dynamic histomorphometric indices similar to that obtained with PTH and better than those of total Alkaline Phosphatase and osteocalcin. It is concluded that bone Alkaline Phosphatase (ostase) seems to be a useful non-invasive marker of bone metabolism in patients on haemodialysis with high turnover bone disease. More studies are necessary to know its value in low turnover bone disease.
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Bone Alkaline Phosphatase Isoenzyme in renal osteodystrophy
Nephrology Dialysis Transplantation, 1996Co-Authors: Carlos Jarava, J R Armas, M Salgueira, A. Di PalmaAbstract:Serum total Alkaline Phosphatase is the most commonly used biochemical marker of bone disease in renal patients, but Alkaline Phosphatase originates from different organs and sometimes lacks specificity. Bone Isoenzyme measurement is considered superior to total Alkaline Phosphatase for the assessment of bone metabolism. We have studied the value of bone Isoenzyme, determined by a new IRMA (Tandem-R-Ostase), in haemodialysis patients with secondary hyperparathyroidism and renal osteodystrophy. Fifty-six haemodialysis patients were studied. Intact parathyroid hormone (PTH), osteocalcin, total Alkaline Phosphatase and bone Alkaline Phosphatase were determined. A transiliac bone biopsy was performed in 20 of the 56 patients after double tetracycline labelling. There was a significant correlation between bone Alkaline Phosphatase and PTH (r=0.79, P
Michael P. Whyte - One of the best experts on this subject based on the ideXlab platform.
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denaturing gradient gel electrophoresis analysis of the tissue nonspecific Alkaline Phosphatase Isoenzyme gene in hypophosphatasia
Molecular Genetics and Metabolism, 2002Co-Authors: Paula S. Henthorn, Michael P. Whyte, Steven Mumm, Jonathan Jones, Patrick M Finnegan, Michelle N PodgornikAbstract:Hypophosphatasia, a heritable form of rickets/osteomalacia, was first described in 1948. The biochemical hallmark, subnormal Alkaline Phosphatase (ALP) activity in serum, reflects a generalized disturbance involving the tissue-nonspecific Isoenzyme of ALP (TNSALP). Deactivating mutations in the gene that encodes TNSALP have been reported in patients worldwide. Nevertheless, hypophosphatasia manifests an extraordinary range of clinical severity spanning death in utero to merely premature loss of adult teeth. There is no known medical treatment. To delineate the molecular pathology which explains the disease variability and to clarify the pattern(s) of inheritance for mild cases of hypophosphatasia, we developed comprehensive mutational analysis of TNSALP. High efficiency of mutation detection was possible by denaturing gradient gel electrophoresis (DGGE). Primers and conditions were established for all TNSALP coding exons (2-12) and adjacent splice sites so that the amplicons incorporated a GC clamp on one end. For each amplicon, the optimum percentage denaturant was determined by perpendicular DGGE. In 19 severely affected pediatric subjects (having perinatal or infantile hypophosphatasia or early presentation during childhood) from among our large patient population, we detected 2 TNSALP mutations each in 16 patients (84%) as expected for autosomal recessive disease. For 2 patients (11%), only 1 TNSALP mutation was detected by DGGE. However, one subject (who died from perinatal hypophosphatasia) had a large deletion as the second mutation. In the other (with infantile hypophosphatasia), no additional mutation was detected by DNA sequencing of all protein-coding exons. Possibly, she too has a deletion. For the final patient, with unclassifiable hypophosphatasia (5%), we detected only a single mutation which has been reported to cause relatively mild autosomal dominant disease; the other allele appeared to be intact. Hence, DGGE analysis was 100% efficient in detecting mutations in the coding exons and adjacent splice sites of TNSALP in this group of severely affected patients but, as expected, failed to detect a large deletion. To date, at least 78 different TNSALP mutations (in about 70 hypophosphatasia patients) have been reported globally. In our large subset of severely affected patients, we identified 8 novel TNSALP mutations (Ala34Ser, Val111Met, Delta G392, Thr117His, Arg206Gln, Gly322Arg, Leu397Met, and Gly409Asp) and 1 new TNSALP polymorphism (Arg135His) furthering the considerable genotypic variability of hypophosphatasia.
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infantile hypophosphatasia successful prenatal assessment by testing for tissue non specific Alkaline Phosphatase Isoenzyme gene mutations
Prenatal Diagnosis, 1995Co-Authors: Paula S. Henthorn, Michael P. WhyteAbstract:We successfully assessed a fetus at risk for lethal infantile hypophosphatasia using amniocyte DNA and allele-specific oligonucleotide (ASO) probes for two missense mutations in the tissue-non-specific Alkaline Phosphatase Isoenzyme (TNSALP) gene. The nucleotide changes had been discovered in a sister who died at 8 months of age from this inborn error of metabolism. The mother was known to carry the 747 (cDNA) G-->A transition, whereas her husband and 5-year-old daughter, who were also healthy, carried the 1309 A-->T transversion. Amniocytes, obtained at 16 weeks' gestation, provided genomic DNA for polymerase chain reaction (PCR) amplification of the appropriate TNSALP gene exons. ASO hybridization revealed absence of the 747A mutation and presence of the 1309T base changes in the fetus, indicating a carrier for hypophosphatasia. At 8 months of age, the offspring was in excellent health and without any radiological evidence of skeletal disease. His serum ALP activity and plasma pyridoxal 5'-phosphate level were decreased and increased, respectively, at levels consistent with the prenatal assessment. The ASO studies were confirmed postnatally using peripheral blood leukocyte DNA. This is the first application of direct mutational analysis to assess a fetus at risk for hypophosphatasia.
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Infantile hypophosphatasia: Successful prenatal assessment by testing for tissue‐non‐specific Alkaline Phosphatase Isoenzyme gene mutations
Prenatal diagnosis, 1995Co-Authors: Paula S. Henthorn, Michael P. WhyteAbstract:We successfully assessed a fetus at risk for lethal infantile hypophosphatasia using amniocyte DNA and allele-specific oligonucleotide (ASO) probes for two missense mutations in the tissue-non-specific Alkaline Phosphatase Isoenzyme (TNSALP) gene. The nucleotide changes had been discovered in a sister who died at 8 months of age from this inborn error of metabolism. The mother was known to carry the 747 (cDNA) G-->A transition, whereas her husband and 5-year-old daughter, who were also healthy, carried the 1309 A-->T transversion. Amniocytes, obtained at 16 weeks' gestation, provided genomic DNA for polymerase chain reaction (PCR) amplification of the appropriate TNSALP gene exons. ASO hybridization revealed absence of the 747A mutation and presence of the 1309T base changes in the fetus, indicating a carrier for hypophosphatasia. At 8 months of age, the offspring was in excellent health and without any radiological evidence of skeletal disease. His serum ALP activity and plasma pyridoxal 5'-phosphate level were decreased and increased, respectively, at levels consistent with the prenatal assessment. The ASO studies were confirmed postnatally using peripheral blood leukocyte DNA. This is the first application of direct mutational analysis to assess a fetus at risk for hypophosphatasia.
Yoshiki Seino - One of the best experts on this subject based on the ideXlab platform.
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serum bone Alkaline Phosphatase Isoenzyme levels in normal children and children with growth hormone gh deficiency a potential marker for bone formation and response to gh therapy
The Journal of Clinical Endocrinology and Metabolism, 1997Co-Authors: Hitoshi Tobiume, Taeko Ono, Susumu Kanzaki, Shigeki Hida, Tadashi Moriwake, Shigeki Yamauchi, Hiroyuki Tanaka, Yoshiki SeinoAbstract:Serum bone Alkaline Phosphatase (B-ALP) has been considered to be a good marker for bone formation. Recently, a specific immunoradiometric assay for serum B-ALP has been developed. Using this system, we measured the serum levels of B-ALP in 363 normal children (207 males and 156 females, age 0-18 yr) and in 20 GH-deficient children (age 5-13 yr) who showed significant bone growth during GH therapy. We found the following results. 1) There were no significant circadian variations in serum B-ALP levels (coefficients of variation: 2.10-9.66%). 2) In normal children, serum B-ALP levels were high in infants and gradually declined and increased again during puberty. During the pubertal period, the highest serum B-ALP values were observed at midpuberty (stage 3 of breast and pubic hair development and 4-12 mL of testicular volume). 3) Serum B-ALP levels were significantly correlated with levels of the carboxy-terminal propeptide of type 1 procollagen (r = 0.447, P < 0.0001) and osteocalcin (r = 0.433, P < 0.0001). 4) After beginning GH therapy, serum B-ALP levels increased significantly; a 26% increase in serum B-ALP level was observed after 3 months of GH therapy. 5) The ratio between serum B-ALP level after 3 months of GH therapy and before GH therapy was positively correlated with the GH-induced improvement in the height SD score (height SD score after 1 yr of GH therapy minus that before GH therapy) and improvement in the height velocity SD score (height velocity SD score during GH therapy minus before GH therapy) (r = 0.531, P < 0.05 and r = 0.608, P < 0.01, respectively). 6) The increment of SD score in serum B-ALP level after 1 yr of GH treatment was also significantly correlated with that for bone mineral density after 1 yr of GH therapy (r = 0.663, P < 0.005). These results show that B-ALP levels are a useful marker for bone formation because B-ALP levels increased when the growth rate accelerated. Serum B-ALP is a potential predictor of the effectiveness of GH therapy, because the serum level after 3 months of GH therapy reflects the outcome of 1 yr of GH therapy.
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Growth hormone (GH) treatment of GH-deficient children increases serum levels of insulin-like growth factors (IGFs), IGF-binding protein-3 and -5, and bone Alkaline Phosphatase Isoenzyme.
The Journal of clinical endocrinology and metabolism, 1996Co-Authors: Taeko Ono, Susumu Kanzaki, Yoshiki Seino, D J Baylink, S MohanAbstract:To investigate the contribution of the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) to the regulation of bone growth in 10 GH-deficient Japanese children receiving recombinant GH therapy, we determined the percent increase from pretreatment levels of serum IGF-I, IGF-II, IGFBP-3, IGFBP-5, and bone-specific Alkaline Phosphatase Isoenzyme (B-ALP). For 10 children between 6-13 yr of age, serum IGF-I and IGF-II were increased after 1 month of treatment by 53% and 7%, respectively; after 12 months of therapy, IGF levels remained elevated at 51% and 17%, respectively. Serum IGFBP-3 and IGFBP-5 were also increased after 1 month of GH therapy by 17% and 13% respectively; after 12 months of therapy, they remained elevated at 22% and 15%, respectively. After 12 months of treatment, the bone formation marker B-ALP was also elevated to 23% greater than pretreatment levels. The elevation of IGF-I induced by GH was significantly correlated with the increases in IGFBP-3 (r = 0.735; P < 0.0001) ...
Carlos Jarava - One of the best experts on this subject based on the ideXlab platform.
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Bone Alkaline Phosphatase Isoenzyme in renal osteodystrophy.
Nephrology dialysis transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 1996Co-Authors: Carlos Jarava, J R Armas, M Salgueira, A. Di PalmaAbstract:Serum total Alkaline Phosphatase is the most commonly used biochemical marker of bone disease in renal patients, but Alkaline Phosphatase originates from different organs and sometimes lacks specificity. Bone Isoenzyme measurement is considered superior to total Alkaline Phosphatase for the assessment of bone metabolism. We have studied the value of bone Isoenzyme, determined by a new. IRMA (Tandem-R-Ostase), in haemodialysis patients with secondary hyperparathyroidism and renal osteodystrophy. Fifty-six haemodialysis patients were studied. Intact parathyroid hormone (PTH), osteocalcin, total Alkaline Phosphatase and bone Alkaline Phosphatase were determined. A transiliac bone biopsy was performed in 20 of the 56 patients after double tetracycline labelling. There was a significant correlation between bone Alkaline Phosphatase and PTH (r = 0.79, P < 0.001) and between bone and total Alkaline Phosphatase (r = 0.84, P < 0.001) in all patients. The patients who underwent a bone biopsy showed osteitis fibrosa in 17, mixed lesion in one, adynamic bone disease in one and normal bone in one. Bone Alkaline Phosphatase showed a significant correlation with static and dynamic histomorphometric indices similar to that obtained with PTH and better than those of total Alkaline Phosphatase and osteocalcin. It is concluded that bone Alkaline Phosphatase (ostase) seems to be a useful non-invasive marker of bone metabolism in patients on haemodialysis with high turnover bone disease. More studies are necessary to know its value in low turnover bone disease.
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Bone Alkaline Phosphatase Isoenzyme in renal osteodystrophy
Nephrology Dialysis Transplantation, 1996Co-Authors: Carlos Jarava, J R Armas, M Salgueira, A. Di PalmaAbstract:Serum total Alkaline Phosphatase is the most commonly used biochemical marker of bone disease in renal patients, but Alkaline Phosphatase originates from different organs and sometimes lacks specificity. Bone Isoenzyme measurement is considered superior to total Alkaline Phosphatase for the assessment of bone metabolism. We have studied the value of bone Isoenzyme, determined by a new IRMA (Tandem-R-Ostase), in haemodialysis patients with secondary hyperparathyroidism and renal osteodystrophy. Fifty-six haemodialysis patients were studied. Intact parathyroid hormone (PTH), osteocalcin, total Alkaline Phosphatase and bone Alkaline Phosphatase were determined. A transiliac bone biopsy was performed in 20 of the 56 patients after double tetracycline labelling. There was a significant correlation between bone Alkaline Phosphatase and PTH (r=0.79, P
Taeko Ono - One of the best experts on this subject based on the ideXlab platform.
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serum bone Alkaline Phosphatase Isoenzyme levels in normal children and children with growth hormone gh deficiency a potential marker for bone formation and response to gh therapy
The Journal of Clinical Endocrinology and Metabolism, 1997Co-Authors: Hitoshi Tobiume, Taeko Ono, Susumu Kanzaki, Shigeki Hida, Tadashi Moriwake, Shigeki Yamauchi, Hiroyuki Tanaka, Yoshiki SeinoAbstract:Serum bone Alkaline Phosphatase (B-ALP) has been considered to be a good marker for bone formation. Recently, a specific immunoradiometric assay for serum B-ALP has been developed. Using this system, we measured the serum levels of B-ALP in 363 normal children (207 males and 156 females, age 0-18 yr) and in 20 GH-deficient children (age 5-13 yr) who showed significant bone growth during GH therapy. We found the following results. 1) There were no significant circadian variations in serum B-ALP levels (coefficients of variation: 2.10-9.66%). 2) In normal children, serum B-ALP levels were high in infants and gradually declined and increased again during puberty. During the pubertal period, the highest serum B-ALP values were observed at midpuberty (stage 3 of breast and pubic hair development and 4-12 mL of testicular volume). 3) Serum B-ALP levels were significantly correlated with levels of the carboxy-terminal propeptide of type 1 procollagen (r = 0.447, P < 0.0001) and osteocalcin (r = 0.433, P < 0.0001). 4) After beginning GH therapy, serum B-ALP levels increased significantly; a 26% increase in serum B-ALP level was observed after 3 months of GH therapy. 5) The ratio between serum B-ALP level after 3 months of GH therapy and before GH therapy was positively correlated with the GH-induced improvement in the height SD score (height SD score after 1 yr of GH therapy minus that before GH therapy) and improvement in the height velocity SD score (height velocity SD score during GH therapy minus before GH therapy) (r = 0.531, P < 0.05 and r = 0.608, P < 0.01, respectively). 6) The increment of SD score in serum B-ALP level after 1 yr of GH treatment was also significantly correlated with that for bone mineral density after 1 yr of GH therapy (r = 0.663, P < 0.005). These results show that B-ALP levels are a useful marker for bone formation because B-ALP levels increased when the growth rate accelerated. Serum B-ALP is a potential predictor of the effectiveness of GH therapy, because the serum level after 3 months of GH therapy reflects the outcome of 1 yr of GH therapy.
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Growth hormone (GH) treatment of GH-deficient children increases serum levels of insulin-like growth factors (IGFs), IGF-binding protein-3 and -5, and bone Alkaline Phosphatase Isoenzyme.
The Journal of clinical endocrinology and metabolism, 1996Co-Authors: Taeko Ono, Susumu Kanzaki, Yoshiki Seino, D J Baylink, S MohanAbstract:To investigate the contribution of the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) to the regulation of bone growth in 10 GH-deficient Japanese children receiving recombinant GH therapy, we determined the percent increase from pretreatment levels of serum IGF-I, IGF-II, IGFBP-3, IGFBP-5, and bone-specific Alkaline Phosphatase Isoenzyme (B-ALP). For 10 children between 6-13 yr of age, serum IGF-I and IGF-II were increased after 1 month of treatment by 53% and 7%, respectively; after 12 months of therapy, IGF levels remained elevated at 51% and 17%, respectively. Serum IGFBP-3 and IGFBP-5 were also increased after 1 month of GH therapy by 17% and 13% respectively; after 12 months of therapy, they remained elevated at 22% and 15%, respectively. After 12 months of treatment, the bone formation marker B-ALP was also elevated to 23% greater than pretreatment levels. The elevation of IGF-I induced by GH was significantly correlated with the increases in IGFBP-3 (r = 0.735; P < 0.0001) ...
