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Serum Alkaline Phosphatase Level (serum + alkaline_phosphatase_level)
Selected AbstractsPhenotypic Characterization of Early Onset Paget's Disease of Bone Caused by a 27-bp Duplication in the TNFRSF11A Gene,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2003Kiyoshi Nakatsuka Abstract Three different insertion mutations in the TNFRSF11A gene affecting the signal peptide of RANK have been described. An 18-bp duplication at position 84 (84dup18) is associated with the clinical syndrome of familial expansile osteolysis (FEO), whereas a 15-bp duplication at the same site (84dup15) causes the syndrome of expansile skeletal hyperphosphatasia (ESH). Here we report the phenotype of patients harboring a 27-bp duplication at position 75 (75dup27) in RANK. Affected individuals had hearing impairment and tooth loss beginning in the second or third decade. Radiographs of affected bones showed lytic and sclerotic lesions with bony enlargement and deformity. Serum alkaline phosphatase levels were elevated between 2 and 17 times above the normal range. Most patients had pelvic and skull involvement, and all had involvement of the mandible and maxilla. Most patients also had bony enlargement of the small joints of the hands, and one developed hypercalcemia during a period of immobilization. We conclude that the 75dup27 mutation of RANK causes a Paget's disease of bone-like phenotype that is distinct from, but which overlaps with, FEO and ESH. A particularly striking feature was involvement of the mandible and maxilla, but it remains to be seen if this is a specific feature of the 75dup27 mutation until further kindreds with this mutation are reported. [source] Carcinoma of the gall-bladder associated with primary sclerosing cholangitis and ulcerative colitisDIGESTIVE ENDOSCOPY, Issue 1 2000Mitsuru Seo A 64-year-old Japanese male was admitted to Fukuoka University Hospital to undergo further examination for an elevated ,-glutamyltransferase (,-GTP) level. Endoscopic retrograde cholangiography (ERC) showed dilatation of the intrahepatic bile duct and stenosis of the proximal portion of the common bile duct. No abnormality was found in the gall-bladder. Since the fecal occult blood test was positive, sigmoidoscopy and a barium enema were performed. Sigmoidoscopy showed a hyperemic and hemorrhagic mucosa in the rectum, but a barium enema study did not show any abnormal findings in the entire colon. We diagnosed the patient to have primary sclerosing cholangitis (PSC) and ulcerative proctitis based on these radiological and endoscopic findings. Bloody stool and fever occurred 4 months after the first admission. The patient's colitis extended to the entire colon. Because of the failure of corticosteroid therapy, a subtotal colectomy was performed. Given that a mass was intraoperatively palpable in the gall-bladder, a cholecystectomy was simultaneously performed. In the whole resected colon, diffuse ulcerations and mucosal islands were found. Grossly, a flat polypoid lesion, measuring 2 cm in diameter, was found in the fundus of the resected gall-bladder. Sections of this lesion in the gall-bladder revealed cystic atypical glands and some atypical cell clusters invading the subserosa. The present case suggests that careful observations are needed for patients with ulcerative colitis who have an elevated ,-GTP level even if the colitis is limited to the distal colon and the serum alkaline phosphatase level is normal. [source] The value of magnetic resonance cholangiopancreatography in predicting common bile duct stones in patients with gallstone disease,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 1 2003B. Topal Background: The application of available predictive scoring systems for the detection of common bile duct (CBD) stones has not reduced the number of patients who undergo unnecessary endoscopic retrograde cholangiopancreatography. The aim of this study was to create a predictive model for CBD stones and to assess the value of magnetic resonance cholangiopancreatography (MRCP) in prediction. Methods: In 1998, 366 patients with gallstone disease (118 males, 248 females; mean age 57 (range 8,84) years) underwent cholecystectomy. Statistical analysis was performed on patient data obtained at the time of first presentation. Results: CBD stones were demonstrated in 43 (12 per cent) of 366 patients. The predictive model for common duct stones included ultrasonography showing CBD stones or bile duct dilatation, age greater than 60 years, fever, serum alkaline phosphatase level above 670 units/l and serum amylase level above 95 units/l. In patients with a predicted probability greater than 5 per cent, CBD stones were present in 11 per cent, compared with 1 per cent in patients with a probability of 5 per cent or less. MRCP had an observed sensitivity of 95 per cent, specificity of 100 per cent, positive predictive value of 100 per cent and negative predictive value of 98 per cent. Conclusion: In patients with a predicted probability for CBD stones of more than 5 per cent, MRCP is recommended in order to confirm the presence or absence of stones and as guidance in further management. Copyright © 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd [source] Molecular basis of perinatal hypophosphatasia with tissue-nonspecific alkaline phosphatase bearing a conservative replacement of valine by alanine at position 406FEBS JOURNAL, Issue 11 2008Structural importance of the crown domain Hypophosphatasia, a congenital metabolic disease related to the tissue-nonspecific alkaline phosphatase gene (TNSALP), is characterized by reduced serum alkaline phosphatase levels and defective mineralization of hard tissues. A replacement of valine with alanine at position 406, located in the crown domain of TNSALP, was reported in a perinatal form of hypophosphatasia. To understand the molecular defect of the TNSALP (V406A) molecule, we examined this missense mutant protein in transiently transfected COS-1 cells and in stable CHO-K1 Tet-On cells. Compared with the wild-type enzyme, the mutant protein showed a markedly reduced alkaline phosphatase activity. This was not the result of defective transport and resultant degradation of TNSALP (V406A) in the endoplasmic reticulum, as the majority of newly synthesized TNSALP (V406A) was conveyed to the Golgi apparatus and incorporated into a cold detergent insoluble fraction (raft) at a rate similar to that of the wild-type TNSALP. TNSALP (V406A) consisted of a dimer, as judged by sucrose gradient centrifugation, suggestive of its proper folding and correct assembly, although this mutant showed increased susceptibility to digestion by trypsin or proteinase K. When purified as a glycosylphosphatidylinositol-anchorless soluble form, the mutant protein exhibited a remarkably lower Kcat/Km value compared with that of the wild-type TNSALP. Interestingly, leucine and isoleucine, but not phenylalanine, were able to substitute for valine, pointing to the indispensable role of residues with a longer aliphatic side chain at position 406 of TNSALP. Taken together, this particular mutation highlights the structural importance of the crown domain with respect to the catalytic function of TNSALP. [source] | ||||||||||