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)

Osteomalacia is characterized by large osteoid seams and a preserved volume of bone trabeculae. The mineralization of newly formed bone requires adequate concentrations of calcium and phosphate: the Ca.P product has been regarded as a useful, empirical diagnostic test of osteomalacia. It decreases in patients with osteomalacia mainly because they have very low plasma phosphate levels. At present total body bone mineral and total body bone density can be directly measured by whole body absorptiometry, which indicates the lowest total mineral content of the skeleton which can increase quickly after adequate treatment. The main symptoms of osteomalacia are: bone pain; muscular weakness (commonly as pelvic girdle myopathy); Looser-Milkman pseudofractures or more often a pattern of generalized demineralization at X-ray. The main biochemical parameters in osteomalacia include: defective calcium absorption with hypocalcemia and hypocalciuria; defective intestinal phosphate absorption with hypophosphatemia; there is often increased renal phosphate clearance due to hypocalcemia and secondary hyperparathyroidism; elevated alkaline phosphatase and osteocalcin levels; high bone turnover confirmed by kinetic studies carried out with radiocalcium or 99mTc-MDP. An etiological classification of the osteomalacias includes: 1) nutritional osteomalacia: a) inadequate exposure to sunlight and/or insufficient vitamin D intake; b) defective intestinal absorption of vitamin D because of malabsorption syndromes (e.g. jejuno-ileal bypass for obesity).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The osteomalacias. 166 41

Subcellular fractionation of pig kidney cortex revealed that aminoacylase I (EC 3.5.1.14, N-acyl-L-amino-acid aminohydrolase) is predominantly a soluble enzyme with only 0.5% of the total activity being recovered in the membrane fraction. The aminoacylase I activity associated with the membrane preparations displayed neither rapid release following incubation with phosphatidylinositol-specific phospholipase C from Bacillus thuringiensis nor the distinctive differential pattern of detergent solubilization which was seen with glycosyl-phosphatidylinositol-anchored proteins (renal dipeptidase, alkaline phosphatase). When fractionated by phase separation in Triton X-114, integral membrane proteins of kidney microvillar membranes partitioned predominantly (greater than 90%) into the detergent-rich phase. In contrast, only 3.7% of aminoacylase I activity associated with microvillar membranes partitioned into the detergent-rich phase. Aminoacylase I activity of pig kidney would therefore appear to be a hydrophilic protein in nature and is not, as suggested previously, a G-PI-anchored integral membrane protein.
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PMID:Aminoacylase I is not a glycolipid-anchored ectoenzyme in pig kidney. 182 88

The effectiveness of the 24-hour whole body retention of Tc-99m MDP in monitoring disease activity was evaluated in 58 patients with Paget's disease of bone. Patients had baseline 24-hour retention studies, bone scans, radionuclide bone blood-flow studies, and alkaline phosphatase and OH-Proline level measurements. Increased retention of Tc-99m MDP was present in 88% (51/58) of individuals while alkaline phosphatase and OH-Proline were respectively elevated in 100% (58/58) and 64% (35/55) of patients. Forty-seven examinations were further obtained to evaluate changes in retention with therapy. Retention correctly reflected response to treatment in 89.3% of follow-ups versus 85.1% with alkaline phosphatase (n = 47). It was accurate in 90.9% of patients versus 75% for OH-Proline (n = 44). We conclude that the retention study, while not absolutely correlative with Pagetic activity, still is useful in grading the condition. It is a simple additional step that monitors the global severity of lesions localized on bone scans.
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PMID:Whole body retention of Tc-99m phosphate in Paget's disease of bone. 186 58

This retrospective study aimed to assess the usefulness and clinical importance of current, commonly used, diagnostic staging procedures in breast cancer. The analysis comprises all 398 women clinically staged I-III (UICC criteria), and irradiated with radical intent in the Professorial Unit of Radiotherapy at the Middlesex Hospital over a ten-year period (1978-1987). The routine initial screening in this institution included the following staging investigations within 4 weeks of referral: 99mTc MDP bone scan; chest X-ray; liver function tests (including serum alkaline phosphatase) and liver ultrasound scan. Further enquiry and examination of the patient, clear progression of disease, additional radiographs or a recommended repeat interval scan provided sufficient additional information to confirm metastatic disease. The overall rate of detection of metastatic disease at three months was 29/389 (7.4%) for skeletal scintigraphy, 10/386 (2.6%) for chest radiographs, 8/271 (2.9%) for liver ultrasound and 3/347 (0.8%) for serum alkaline phosphatase. In total 37/398 (9.3%) of patients were confirmed to have metastatic disease by three months. Skeletal scintigraphy alone appears to identify 78% (29/37) of those with detectable metastatic disease at 3 months. Skeletal scintigraphy and liver ultrasound will identify 95% (35/37).
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PMID:How far investigations for occult metastases in breast cancer aid the clinician. 203 84

The reproducibility and diagnostic value of local bone to soft tissue uptake ratio of 99mTc(Sn)-MDP as a bone tracer was examined in a prospective study in 35 patients who were under investigation and/or treatment for postmenopausal osteoporosis. The ratio of tracer uptake in the second lumbar vertebra (L2) and both femoral shafts was calculated from the number of counts in suitable regions of interest. Results obtained with settings and calculations in the routine practice were compared to the results obtained by revision of all raw data in one run by one person. The results were compared to the serum alkaline phosphatase activity (AP) and to local bone mineral mass as determined by dual photon absorptiometry (DPA). In 15 patients serial measurements during fluoride therapy were also compared to serum osteocalcin values and to bone histomorphometric data. The precision error of the calculation of uptake ratios from raw counts (including selection of region of interest) was 13.9% for the femoral shaft and 14.7% for L2. The mean difference between left and right femoral shaft in individuals was not significant and its variance was small P greater than 0.1). There was a weak but significant linear correlation between local uptake ratio in the spine and AP in the total material (r = 0.328 P less than 0.01). However, changes in local uptake ratio during therapy with fluoride in 15 patients were too small to be of any value and did not correlate with changes in alkaline phosphatase or osteocalcin or trabecular surface covered with osteoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The value of local 99mTc(Sn)-MDP bone to soft tissue uptake ratio in osteoporosis, before and during fluoride therapy. 236 58

Dietary hexachlorocyclohexane (HCH) and gamma-isomer of HCH produced significant increase in liver weights of mice. Elevated levels of alanine and aspartate aminotransferases and of alkaline phosphatase in the blood of these animals suggested hepatotoxicity. Hepatic soluble enzymes--aspartate aminotransferase and lactate dehydrogenase--were markedly lowered. Among the hepatic lysosomal enzymes, acid phosphatase and acid cathepsin were increased in the experimental animals. Hepatic glucose-6-phosphatase was lowered by HCH while aldolase activity was increased. Hydrolytic enzymes in small intestine, viz., disaccharidases, lipase, amylase, dipeptidase and phosphatases, were also affected by dietary HCH and gamma-HCH. The results suggested cellular toxicity in hepatocytes of HCH and gamma-HCH fed animals, and also interference in gastrointestinal absorption.
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PMID:Biochemical toxicity of hexachlorocyclohexane and its gamma-isomer in albino mice. 248 47

We have used 99Tcm-MDP to develop a measure of overall skeletal activity for use in renal disease. The method utilizes the relative clearances of 99Tcm-MDP and 51Cr-EDTA from the blood after simultaneous injection. This is expressed as a ratio and the upper limit in normals is 1.4. This ratio has been evaluated in 42 patients with chronic renal failure and compared with appearances of left-hand radiographs. The ratio was elevated in these patients and the level corresponded to the degree of severity of the subperiosteal resorption. Similarly, there was a close correlation between the ratio values and the serum alkaline phosphatase measurements and parathyroid hormone values. Thirty-three patients had sequential studies performed at intervals of up to 2 years. Twenty-one patients showed no change on clinical, biochemical or bone scan evaluation. Of these, only one patient showed a change in ratio value of greater than 20%. Twelve patients showed evidence of change based either on clinical, biochemical or bone scan alteration and all 12 patients showed changes in ratio values greater than 20%. The 51Cr-EDTA/99Tcm-MDP ratio appears to offer not only a single plasma sample method for the detection and evaluation of renal bone disease, but our results also suggest that it may be valuable in the follow-up of these patients.
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PMID:51Cr-EDTA/99Tcm-MDP ratio: a simple non-invasive method for assessing renal osteodystrophy. 249 84

Renal dipeptidase (dehydropeptidase-I, EC 3.4.13.11) was released from pig kidney membrane preparations by treatment with phosphatidylinositol-specific phospholipase C from Staphylococcus aureus and Bacillus thuringiensis and a phospholipase C preparation from Bacillus cereus to a similar extent as alkaline phosphatase. Endopeptidase-24.11 and aminopeptidase N were not released by this treatment. After treatment of the membrane fraction with the S. aureus phospholipase C the dipeptidase was converted from an amphipathic to a hydrophilic form, as deduced from phase-separation experiments in Triton X-114. It is concluded that renal dipeptidase is anchored to the microvillar membrane by covalently attached phosphatidylinositol.
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PMID:Renal dipeptidase is one of the membrane proteins released by phosphatidylinositol-specific phospholipase C. 282 7

The aim of this study was to detect early renal changes in the rat. Female Wistar rats received oral doses of cyclosporine (12.5, 25 or 50 mg/kg daily). The duration of the experiment was 1, 2, and 3 weeks. Controls received the vehicle only (olive oil). The following alterations were seen by light microscopy: Hypertrophy of the juxtaglomerular apparatus (PAS stain). Cytoplasmic droplets of neutral fat (Oil Red 0) in clusters of cortical tubules, probably belonging to the same nephron. Both the above phenomena increased with dosage and duration of treatment and were absent in controls. In the fat containing tubulus (FCT) brush border staining (alkaline phosphatase) was decreased or absent. Since after PAS the brush border was visualized in many FCT, it is concluded that many FCT were proximal tubulus (PT) of which the brush border has been damaged. In FCT mitochondrial staining (Cytochrome oxidase activity) was strongly decreased or absent. Mean lysosomal volume (acid phosphatase and dipeptidase II) is increased in the PT; in some cyclosporine animals, lysosomes were enlarged, while in others they were comparable to controls. Electron microscopy showed in some PT cells an increased number of empty vacuoles and focal alteration of mitochondria. Normal mitochondria were present next to grossly altered mitochondria. Autophagocytosis of mitochondria was clearly present. The lysosomes appeared swollen and contained electron dense material, not organised in the typical 50 A pattern of myeloid figures. These morphological changes suggest a defect of mitochondrial metabolism, leading to lipid deposition in PT. The mitochondrial metabolism can be disturbed by a direct toxic effect of cyclosporine or indirectly via ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cyclosporine nephrotoxicity: comparative cytochemical study of rat kidney and human allograft biopsies. 301 37

To improve the understanding of diphosphonate affinity to metabolically active bone, the underlying diphosphonate kinetics have been evaluated and compared to Cr-EDTA kinetics. MDP binds to plasma proteins, varying from 25% initially to approximately 70% after 24 h. The renal clearance of diphosphonate is found to be equal to Cr-EDTA clearance. Using simultaneous bolus injection of 99Tc-MDP and 51Cr-EDTA, it has been possible to obtain a coarse estimate of bone uptake of MDP. This uptake is found to correlate well with s-alkaline phosphatase, but since MDP binding to bone is reversible, the plasma elimination curve is not monoexponential. Therefore it has not been possible to describe the uptake of MDP in bone mathematically.
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PMID:Studies on diphosphonate kinetics. Part I: Evaluation of plasma elimination curves during 24 h. 310 90


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