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)

A 76-year-old man had progressive low back pain, leg weakness, and sensory loss. Radiology showed changes consistent with wide-spread Paget's disease, but no cord compression or involvement of nerve roots was detected by myelography or computerised axial tomography. His symptoms were relieved within 12 days of starting 100 MRC units of subcutaneous salmon calcitonin and recurred when calcitonin was discontinued for 5 days. The improvement continued on calcitonin treatment for 1 year, with falls in serum alkaline phosphatase and urinary hydroxyproline excretion. It is suggested that calcitonin treatment, in reducing the abnormally high metabolic activity of the diseased bone, and hence its vascular perfusion, allows more blood to reach the spinal cord.
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PMID:Spinal-cord syndrome due to non-compressive Paget's disease of bone: a spinal-artery steal phenomenon reversible with calcitonin. 610 24

Dichloromethylene diphosphonate (Cl2MDP), a powerful inhibitor of bone resorption, was given (daily dose: 500 mg i.v. for 2 months and then 1600 mg p.o.) to five patients with Paget's disease after 8 months treatment with 50-100 MRC u/day of human calcitonin (CT). During treatment with CT plasma alkaline phosphatase (ALP) and urinary hydroxyproline (HOP) levels fell to about 60% of pretreatment values within the first 2 months in all the patients. Cl2MDP therapy resulted in a further drop of urinary HOP to 20% of baseline values, while serum ALP rose impressively during the first 2 weeks of therapy and then slowly fell to 25% of baseline values. We conclude that Cl2MDP can induce a further biochemical response after the so-called plateau phenomenon to CT and that it may represent the therapy of choice for severe Paget's disease.
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PMID:Sequential treatment of Paget's disease with human calcitonin and dichloromethylene diphosphonate (Cl2MDP). 623 18

Subcutaneous injections for two days of 100 MRC units each of synthetic salmon calcitonin were administered to 40 out of 77 patients with Paget's disease of bone. Chemical pathology (alkaline serum phosphatase, hydroxyprolinuria) showed an initially satisfactory response of all patients to this treatment. Resistance developed in 6 out of 8 patients on long term treatment with recurrence of increased serum alkaline phosphatase, occurring after 4 months at the earliest and 24 months at the latest. Human calcitonin may be an alternative of treatment in these cases of secondary resistance. Treatment with calcitonin is nearly risk-free and represents a definite progress in comparison with earlier forms of treatment.
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PMID:[Treatment of Paget's disease of bone with salmon calcitonin (author's transl)]. 730 2

It has been suggested that the intensity of hypocalcemic response to administration of calcitonin may reflect the magnitude of osteoclastic activity. To determine whether this hypothesis is correct or not, I performed a calcitonin-loading test in twenty dialysis patients with secondary hyperparathyroidism. The test involved the intravenous injection of 120 MRC units of synthetic eel calcitonin analogue for 3 hours. Serum calcium concentration fell from 9.6 +/- 0.9 mg/dl to 8.7 +/- 0.9 mg/dl following calcitonin administration (p < 0.001). There was a statistically significant correlation between the fall in serum calcium concentration and the baseline intact parathyroid hormone levels (r = 0.661, p < 0.002), as well as the fall in serum calcium concentration and baseline serum alkaline phosphatase activity (r = 0.817, p < 0.001), respectively. From these findings, it was concluded that calcitonin lowers serum calcium concentration in proportional to the activity of osteoclastic bone resorption. To determine whether the effect of calcitonin on calcium concentration related to PTH secretion, same test was performed before and after parathyroidectomy (PTX) in 9 patients with severe secondary hyperparathyroidism required surgery. The fall in serum calcium concentration during calcitonin administration before PTX was significantly greater than that of after PTX (p < 0.05). Thus, it is concluded that calcitonin-loading test is clinically usefull index to estimate osteoclastic activity in patients with secondary hyperparathyroidism.
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PMID:[Changes in serum calcium concentration following eel calcitonin analogue administration as an index of osteoclastic bone resorption in patients with secondary hyperparathyroidism]. 760 28

An ELISA-based micro-neutralization (Nt) test in MRC-5 cells for titration of neutralizing antibodies against human cytomegalovirus (CMV) in human plasma and preparations of immune globulins was developed to eliminate microscopic reading of cytopathic effect (CPE), a process that is subjective and time consuming. Un-neutralized CMV from the Nt reaction and grown in MRC-5 cells as per the standard micro-Nt test was coated in the same plates by various methods and CMV antigen was quantified by polyclonal or monoclonal CMV antibodies. Optimal coating of plates with CMV antigen (100 TCID50 of virus grown on MRC-5 cells for 7 days) was obtained by freezing/thawing of virus infected MRC-5 cells in phosphate buffered saline, ph 7.2. The CMV antigen treated sequentially with CMV monoclonal antibody to late nuclear protein antigen, goat anti-mouse IgG3 alkaline phosphatase conjugate and phosphatase substrate gave an absorbance of 1 at 410 nm wavelength whereas uninfected MRC-5 cells treated under similar conditions did not show any absorbance. The optimal Nt reaction occurred at 37 degrees C for 1-2 h and was unaffected by complement. At 4 degrees C, CMV was inactivated in 1-2 h. The antibody titres were affected by the virus dose used in the Nt test over a range of 20 to 798 TCID50. When the titre was determined against a reference serum, the effect of virus dose on the Nt titre was reduced. Complete neutralization virus read microscopically correlated with ELISA absorbance of < 0.1. CPE produced by approximately 1 TCID50 of CMV showed an absorbance of 0.1 or more. The correlation coefficient (r) between Nt titres and CMV IgG antibodies determined by ELISA was 0.69 (P < 0.001) for 257 human plasma samples and 0.85 (P < 0.001) for 50 immune globulin preparations.
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PMID:An enzyme immunoassay based micro-neutralization test for titration of antibodies to human cytomegalovirus (CMV) and its correlation with direct ELISA measuring CMV IgG antibodies. 873

Carbocalcitonin spray administered for 12 months at a daily dosage of 80 U MRC according to five schedules has been tested on 150 normal spontaneous postmenopausal women for its influence on bone mineral density (BMD), bone metabolism and osteoarticular pain. BMD was monitored before and at the end of treatment in comparison with BMD of untreated control women. Metabolic markers (serum alkaline phosphatase, serum osteocalcin and urinary hydroxyproline) were also evaluated before and during treatment (at the 9th or 10th month of treatment). Osteoarticular pain was assessed by an analogic visual scale. Intranasal carbocalcitonin, administered according to cyclic schedules at a high frequency dosage, was able to maintain bone mass only in the earlier postmenopausal women. BMD percent increase after 12 months of treatment was 1.10 and 1.31 in women with low (< 0.870 mg/cm2) and high baseline BMD (> or = 0.870 mg/cm2), respectively. In advanced menopause the maintaining effect of carbocalcitonin on BMD seemed evident only if the baseline bone mass was lower than the BMD of the age matched control group. At least six months of treatment/year is necessary for effective therapy. Both systemic and local tolerance were optimal. No significant side-effects were detected.
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PMID:Effects of cyclic therapy with intranasal carbocalcitonin in healthy spontaneous postmenopausal women. 873 20

The present study systematically investigated the expression and distribution of the major histocompatibility complex (MHC) classes I and II in the rat. About 150 native tissue probes from eight adult Lewis rats were taken, representative for most organs, tissues, and the vascular system. MHC expression was analyzed by two monoclonal antibodies (mAb) generated against the non-polymorphic determinants of rat MHC class I (Ox-18) and class II (Ox-6). Immunoreactivities were compared to those of different endothelial (HIS52, TLD-3A12, Ox-43, REHA-1 antigen), histiocytic (ED1, ED2), B-cell (RLN-9D3), and T-cell (MRC Ox-52) markers. A nonspecific mAb (MR12/53) served as a negative control. Pretested concentrations on various tissues and the alkaline phosphatase-anti-alkaline phosphatase technique allowed semiquantitative evaluation of serial cryostat tissue sections. MHC class I expression was detected on most immunocompetent cells. Endothelial cells were stained heterogeneously along the vascular system and the organ-specific microcirculation. Furthermore, some organs showed staining of parenchymal cells. MHC class II was found on all immunocompetent cells positive for the B-cell marker and about 15% of cells positive for the histiocytic markers. Besides the well-known expression of MHC class II in the outer zone of the renal proximal tubule, further organ-specific cell forms were found positive. In conclusion, the present study outlines tissue-specific distribution of MHC I/ II and implies that each organ carries a variable immunologic burden that needs to be considered for any transplantation model.
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PMID:Organ-specific distribution of major histocompatibility antigens in rats. 1089 31

In this study we demonstrate, for the first time, that dexamethasone and BMP-2 stimulated alkaline phosphatase (ALP) activity in MRC-5 fibroblasts, a cell line derived from human fetal lung. Previously we reported that the water-soluble matrix (WSM) of nacre obtained from the inner shell layer of the oyster Pinctada maxima, promoted an increase in ALP activity that was dose-dependent. In this work, we show that the effect of WSM is also time-dependent. As a comparison, the effect of WSM was also tested in bone marrow stromal cells because marrow and other bone surface-derived osteoblast stem cells have the inherent direct potential for osteogenesis. WSM promotes cell proliferation and ALP activity when tested with bone marrow cells in concentrations between 135 and 540 microg protein/mL. The effect of WSM on ALP activity of bone marrow stromal cells is similar to that obtained by dexamethasone. These results imply that MRC-5 fibroblasts respond to differentiating factors that promote osteoblastic phenotype in bone-derived cell cultures.
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PMID:Comparative effects of nacre water-soluble matrix and dexamethasone on the alkaline phosphatase activity of MRC-5 fibroblasts. 1148 95

Fotemustine (Muphoran, S10036), a nitrosourea derivative active in the treatment of malignant melanoma and primary brain tumors, was evaluated in combination with the free radicals cytoprotective agent amifostine (Ethyol, WR-2721) and its alkaline phosphatase (AP)-generated active metabolite WR-1065 in four human melanoma (RPMI-7950, SK-MEL2, SK-MEL5 and WM-115) and lung fibroblast (MRC-5) cell lines. No difference in AP activity was found among the melanoma cell lines, but AP was found to be significantly higher in MRC-5. For combination experiments, cell lines were first exposed to amifostine or WR-1065 for 15 min and then exposed to fotemustine for two cell doubling times. Non-cytotoxic amifostine and WR-1065 concentrations used (0.2 and 0.6 and 0.1 and 0.3 mmol/l, respectively) were deduced from clinically achieved plasma values. Interactions were analyzed from the variations in IC(50) of fotemustine induced by pre-exposure of the cells to amifostine or WR-1065. In all melanoma cell lines, amifostine enhanced the cytotoxic activity of fotemustine as a significant decrease in IC(50) was observed. No significant difference was found between synergistic effects achieved with amifostine and WR-1065 given at half concentrations. No differential effect was found in the MRC-5 cell line as compared with the melanoma cell lines. Expression variation of O(6)-methylguanine methyltransferase was not found to be implicated in the interaction. The present results demonstrating that amifostine or its main active metabolite do not impair the cytotoxicity of fotemustine justify an extensive clinical evaluation of this combination in metastatic melanoma.
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PMID:Enhancement of fotemustine (Muphoran) cytotoxicity by amifostine in malignant melanoma cell lines. 1190 6

A novel matrix protein, designated as p10 because of its apparent molecular mass of 10 kDa, was isolated from the nacreous layer of pearl oyster (Pinctada fucata) by reverse-phase high-performance liquid chromatography. In vitro crystallization experiments showed that p10 could accelerate the nucleation of calcium carbonate crystals and induce aragonite formation, suggesting that it might play a key role in nacre biomineralization. As nacre is known to contain osteogenic factors, two mineralogenic cell lines, MRC-5 fibroblasts and MC3T3-E1 preosteoblasts, were used to investigate the biological activity of p10. The results showed that p10 could increase alkaline phosphatase activity, an early marker of osteoblast differentiation, while the viability of MRC-5 and MC3T3-E1 remained unchanged after treatment of p10. Taken together, the findings led to identification of a novel matrix protein from the nacre of P. fucata that plays a role in both the mineral phase and in the differentiation of the cells involved in biomineralization.
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PMID:A novel matrix protein p10 from the nacre of pearl oyster (Pinctada fucata) and its effects on both CaCO3 crystal formation and mineralogenic cells. 1697 40


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