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)

Four patients are reported who had Albright's syndrome, hypophosphatemia, and inappropriately low renal tubular reabsorption of phosphate. Three of the patients had radiologic evidence of rickets or osteomalacia, and the fourth had a bone biospy, which showed microradiographic evidence of a previous mineralization defect. Serum parathormone values were elevated before treatment in two patients. Intravenous infusions of calcium in one patient, and of calcium and parathormone in a second patient, showed appropriate target-organ responsiveness. Patients generally showed radiologic improvement of rickets after treatment with large doses of vitamin D, but such treatment failed to restore normal serum values of phosphorus and alkaline phosphatase. It is postulated that a substance elaborated from the dysplastic bone may be interfering with phosphate reabsorption in the renal tubule.
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PMID:Albright's syndrome with rickets. 43 Nov 33

Children with monostotic and polyostotic bone dysplasias often exhibit localized bone overgrowth. We investigated the presence of nuclear estrogen and nuclear progesterone receptors by solid-phase radioimmunoassay, immunocytochemistry, and radioligand binding in osteoblast cell cultures derived from the areas of overgrowth of membranous bone, noninvolved membranous bone, and normal membranous bone from children undergoing elective craniotomy. Membranous bone of normal children had demonstrable levels of nuclear estrogen and progesterone receptors identified by radioimmunoassay and immunocytochemical assay. Two- to threefold increased levels of these receptors (p less than 0.001 versus normals) were found in cultures derived from the involved bone of two children with monostotic fibrous dysplasia and in one patient with polyostotic dysplasia (McCune-Albright syndrome). The noninvolved bone in our patients with fibrous dysplasia exhibited nuclear sex steroid hormone receptor levels similar to those in the normal children. Radioligand binding studies demonstrated increased sex steroid hormone receptors in cultures derived from involved osteoblasts. The presence of an increased level of sex steroid hormone receptor was accompanied by increased alkaline phosphatase activity and increased production of osteocalcin in vitro compared to normal or noninvolved bone. The mechanisms by which sex steroid hormone receptor levels are increased in the ostotic dysplasias remain to be established.
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PMID:Sex steroid hormone receptors in normal and dysplastic bone disorders in children. 236 30

This study of 22 patients with the McCune-Albright syndrome examined the scintigraphic distribution of fibrous dysplasia. The most frequently affected areas were the base of the skull (82% of patients), mandible (50%), facial bones (45%), femora (59%), and legs (64%). The least frequently affected areas included the hands (none), wrists (none), ankles (none), feet (5%), sacrum (5%), and vertebrae (9%). The distribution varied somewhat from idiopathic fibrous dysplasia but generally agreed with the distributions reported in radiographic studies of patients with the McCune-Albright Syndrome. The serum alkaline phosphatase was not an accurate predictor of the extent of fibrous dysplasia.
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PMID:McCune-Albright syndrome: the patterns of scintigraphic abnormalities. 239 15

We studied the osteoblastic abnormalities resulting from activating mutation of the Gs alpha gene in two patients with McCune-Albright syndrome and one patient with monostotic fibrous dysplasia. Histomorphometric analysis of dysplastic lesions showed a low number of differentiated osteoblasts along the bone surface and numerous immature alkaline phosphatase-positive mesenchymal cells actively depositing a woven bone matrix. Osteoblastic cells isolated from dysplastic bone lesions expressed a missense mutation in the Gs alpha gene in position 201 and showed increased intracellular basal cyclic adenosine 3',5'-monophosphate levels compared with normal cells isolated from a noninvolved area in the same patient. Cell proliferation evaluated by DNA synthesis was two-fold to threefold greater in osteoblastic cells expressing the mutation compared with normal cells from the same patient and was greater in cells isolated from more severe than less severe fibrotic lesions. In contrast, the synthesis of osteocalcin, a marker of mature osteoblasts, was lower in osteoblastic cells expressing the Gs alpha mutation compared with normal cells from the same patient and was lower in cells isolated from severe compared with less severe fibrotic lesions, indicating that the increased growth in mutated osteoblastic cells was associated with reduced cell differentiation. The results show that activating mutation of Gs alpha in osteoblastic cells leads to constitutive activation of adenylate cyclase, increased cell proliferation, and inappropriate cell differentiation, resulting in overproduction of a disorganized fibrotic bone matrix in polyostotic and monostotic fibrous dysplasia.
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PMID:Increased proliferation of osteoblastic cells expressing the activating Gs alpha mutation in monostotic and polyostotic fibrous dysplasia. 906 Aug 42

McCune-Albright syndrome is a rare genetic disorder consisting of skin and bone dysplasia and peripheral endocrinopathies. Little data have been collected regarding bisphosphonate treatment of bone fibrous dysplasia in paediatric patients with this syndrome. The aim of our study was to investigate the therapeutic efficacy of pamidronate in these patients. Nine patients with moderate to severe forms of bone fibrous dysplasia were treated with pamidronate intravenously (0.5-1 mg/kg/daily for 2-3 d) at 0.5-1-y intervals. Patients were treated over a time period of 0.5-3.5 y. During treatment no spontaneous fracture occurred. Bone pain and gait abnormality due to pain disappeared after 2-3 therapeutic cycles. Cranial asymmetry and limb length discrepancy remained unchanged. Elevated serum alkaline phosphatase and urine hydroxyproline values were reduced by the treatment, demonstrating drug activity at the lesional level. The effectiveness of pamidronate was also seen at the non-lesional level through an increase in bone density. Radiographic and scintigraphic evidence of lesion healing was not attained. Pamidronate treatment can ameliorate the course of bone fibrous dysplasia in children and adolescents with McCune-Albright syndrome.
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PMID:Pamidronate treatment of bone fibrous dysplasia in nine children with McCune-Albright syndrome. 1070 89

We treated a patient with breast cancer associated with McCune-Albright syndrome. A 40-year-old woman with a history of precocious puberty visited our hospital complaining of a mass in the upper lateral quadrant of the right breast. Although bone scintigraphy revealed multiple high uptake of 99mTc, plain X-ray demonstrated ground-glass appearance, suggesting fibrous dysplasia rather than bone metastases. Serum levels of tumor markers and alkaline phosphatase were within the normal range. Breast cancer associated with McCune-Albright syndrome was diagnosed, and she subsequently underwent breast conserving surgery, excision of abdominal wall myxoma and bone biopsy of the left clavicula. The bone lesion was histologically confirmed as fibrous dysplasia. Although McCune-Albright syndrome isa rare clinical entity, it should be considered as a possible differential diagnosis of bone metastasis in patients with breast cancer. As recent molecular studies have suggested genetic mutations in McCune-Albright syndrome, this syndromemay possibly predispose patients to breast cancer.
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PMID:Breast Cancer in a Patient with McCune-Albright Syndrome. 1109 44

McCune-Albright syndrome (MAS) is sometimes complicated by hypophosphatemia. However, it remains unclear whether a humoral factor is associated with the cause of hypophosphatemia. We isolated cells with mutations of the Gsalpha gene from fibrous bone dysplasia tissues of two MAS patients (MAS cells). Severe combined immunodeficiency (SCID) mice were subjected to experiments using from one of these cells patients. Effects of conditioned media (CM) isolated from MAS cells (MAS-CM) on phosphate transport were investigated by using rat renal slices, the renal cell line OK-B, rat intestinal rings and the human intestinal cell line Caco-2. In addition, the effects of MAS-CM on human sodium-dependent phosphate transporter (NPT2) gene promoter activity expression were investigated in the renal cell line OK-B2400 and were compared with the effects of CM isolated from a patient with oncogenic hypophosphatemic osteomalacia (OHO). MAS cells caused significant hypophosphatemia (P < 0.05) and elevated serum alkaline phosphatase activity (P < 0.05) in SCID mice. The MAS-CM significantly inhibited phosphate uptake in everted intestinal rings (P < 0.01), whereas it had no effect on glucose uptake. The MAS-CM had no effect on either phosphate uptake in the kidney or NPT2 gene promoter activity. In contrast, the CM of the OHO patient significantly inhibited phosphate uptake and NPT2 gene promoter activity. These results indicate that the humoral factor derived from fibrous dysplasia cells of the MAS patient is different to that from OHO patients, because the humoral factor from the MAS patient inhibited phosphate transport not in the kidney but in the intestine.
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PMID:Hypophosphatemic rickets accompanying McCune-Albright syndrome: evidence that a humoral factor causes hypophosphatemia. 1149 30

Thirteen patients with McCune-Albright syndrome (MAS) and bone fibrous dysplasia (BFD) have been treated for 2-6 years with pamidronate, an aminobisphosphonate which inhibits osteoclastic function. MAS is a rare genetic condition caused by constitutive activating mutations of the Gs protein and manifests with skin dysplasia, bone fibrous dysplasia, and multiple endocrinopathies. Raised serum alkaline phosphatase and urinary hydroxyproline have been reported in these patients, indicating bone metabolic hyperactivity. Encouraging therapeutic results have been achieved with pamidronate, mainly in adults. In our study, treatment reduced bone pain, fracture rate and metabolic indices of bone turnover, in particular significantly decreased bone alkaline phosphatase and cross-links (Wilcoxon test; p <0.06), and increased bone mineral density (DEXA). Signs of healing, such as thickening of the cortical bone, were found in some patients. Three patterns of MRI were found: homogeneous hypointense fibrous tissue, 'dotted' hypointense fibrous tissue, and hyperintense cystic images. Pamidronate treatment can be considered a favorable therapeutic option for patients with MAS.
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PMID:Pamidronate treatment in bone fibrous dysplasia in children and adolescents with McCune-Albright syndrome. 1219 52

Bone fibrous dysplasia is one of the main features of McCune-Albright syndrome, a rare genetic condition caused by constitutive activating mutations of Gs-protein and defined by skin dysplasia, bone fibrous dysplasia, and autonomous multiple endocrinopathies. Raised serum alkaline phosphatase (ALP) and urinary hydroxyproline levels indicating bone metabolic hyperactivity have been reported in these patients. Encouraging therapeutic results have been achieved, mainly in adults, with pamidronate, an aminobisphosphonate. In this study we investigate newer bone metabolic indices in a cohort of 11 children and adolescents treated with pamidronate. Tenfold increases of bone ALP and urinary pyridinoline cross-links were found and osteocalcin levels were twofold higher compared with reference values. After treatment, significant decreases in bone ALP and cross-links (Wilcoxon test P < 0.06) were found. Bone mineral density (BMD) significantly increased during treatment. There were signs of radiological healing as thickening of the cortical bone was found in some cases.
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PMID:Bone turnover in children and adolescents with McCune-Albright syndrome treated with pamidronate for bone fibrous dysplasia. 1220 Jun 45

Bone turnover in pregnant women with McCune-Albright syndrome may be affected by both the syndrome and pregnancy. This study evaluated changes in biochemical bone turnover markers in pregnant women with the syndrome. Serum calcium, phosphorus, 1,25-dihydroxyvitamin D (1,25-(OH)2D), intact osteocalcin (I-OC) and alkaline phosphatase (ALP), and urinary pyridinoline (Pyr), deoxypyridinoline (D-Pyr) and hydroxyproline (HPR) were measured during pregnancy and postpartum in 2 women with McCune-Albright syndrome. Serum calcitonin (CT), and plasma intact parathyroid hormone (I-PTH) and parathyroid hormone-related protein (PTHrP) were also measured in 1 patient. Serum corrected Ca levels were normal or low-normal; phosphorus levels were normal, and 1,25-(OH)2D levels increased toward term and decreased thereafter, similar to normal pregnant women. Urinary Pyr, D-Pyr and HPR were elevated during pregnancy compared to normal pregnant women, peaked just after delivery, and decreased thereafter. Serum I-OC and ALP levels were high during pregnancy and postpartum. Intact PTH levels were increased during pregnancy and postpartum compared to normal pregnant women, whereas serum CT and PTHrP levels were not elevated. Both bone formation and absorption appear to be more enhanced during pregnancy and postpartum in women with McCune-Albright syndrome than in normal pregnant women. Additional or amplified cyclic AMP synthesis in bone cells through activation of the alpha subunit of G protein, independent of hormonal control, may explain the high local bone turnover.
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PMID:Accelerated bone turnover in pregnant women with McCune-Albright syndrome. 1586 Sep 20


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