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)

The Golgi apparatus and alkaline and acid phosphatase and nonspecific esterase activities were studied in the jejunal epithelium of adult male albino mice (Mus musculus) under normal conditions and after MTX treatment. In the control, the Golgi apparatus took the form of rods, spheres and crescents occupying the supranuclear region. After MTX, the Golgi apparatus, in most of the cells, was hypertrophied. In the control cells, alkaline and acid phosphatase and nonspecific esterase activities were moderate and localized supranuclearly, but were intense in the brush border and basement membrane. After MTX, all three enzyme activities increased, with a marked reaction in the brush border and basement membrane. The increase in alkaline phosphatase may mean that more phosphate transport is needed in the active phosphorylation process or in the transfer of MTX macromolecules across the cell membrane, or it may be due to MTX-induced disorganization of metabolism. The increase in acid phosphatase activity denotes an increase in catabolic processes resulting from imbalance of lysosomal function, while the rise in nonspecific esterase activity could be related to fatty acid metabolism, or it might be due to the detoxicant function of esterases. In all control and MTX-treated specimens, the supranuclear concentration of these enzymes coincided with the localization of the Golgi apparatus.
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PMID:The effect of methotrexate (MTX) on the small intestine of the mouse. IV. The Golgi apparatus, phosphatases and esterases. 133 5

The rationale of preoperative chemotherapy for osteosarcoma requires: eradication of microscopic metastatic foci which have already occurred in many patients with osteosarcoma, determination of a more effective form of postoperative adjuvant chemotherapy and easier and safer limb-salvage procedures through clearer marginal definition with reduction of primary lesions. In this paper, chemotherapeutic effects on the 5-year survival rate were analyzed for 49 patients with primary non-metastatic osteosarcoma of the extremities treated with radical surgery. The efficacy of preoperative chemotherapy was assessed in 11 cases of osteosarcomas treated with systemic chemotherapy as a preliminary study. As to the 5-year cumulative survival rate, the systemic group (20 cases) showed a level of 56.7%, which was significantly higher (p less than 0.05) than the figure of 13.8% in a historical retrospective group (29 cases). In assessing the effective tumor response to preoperative chemotherapy, a close correlation between the tumor necrotic ratio and the ratio of decrease of serum alkaline phosphatase was revealed. Seven (63.6%) of 11 cases showed correlation of the tumor necrotic ratio with the ratio of decrease of serum alkaline phosphatase. The tumor necrotic ratios calculated were relatively definite (50-60%) in the CDDP group (3 cases), varied (10-70%) in the HDMTX group (4 cases), and low (less than 40%) in the ADR group (4 cases), regarded as a control group in further studies.
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PMID:[Rationale of preoperative chemotherapy of osteosarcoma]. 347 75

Methotrexate-loaded glutaraldehyde-treated canine carrier erythrocytes were used to deliver a 1.6-mg/kg dosage of drug. About 90% of the drug-loaded cells disappeared from circulation within 1 h. Approximately 11 mg of drug reached the liver, and a substantial portion of the methotrexate entered the enterohepatic bile salt circulation. Biochemical tests of liver function, such as alkaline phosphatase and serum glutamine pyruvate transaminase, indicated mild hepatocellular necrosis which was attributed to the action of methotrexate on the hepatocytes. Bilirubin levels were unchanged during and following drug treatment. The plasma half-life of the drug was extended 2.4-fold in the first 24 h following injection.
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PMID:Hepatic pharmacokinetics of glutaraldehyde-treated methotrexate-loaded carrier erythrocytes in dogs. 641 45

Forty-three patients, ranging in age from 7 to 30 years (median age, 17 yr), with primary osteogenic sarcoma (OS), confirmed by biopsies and with no evidence of metastatic disease at the time of diagnosis, received T-7 chemotherapy for an average of 4 months before surgery, including high-dose methotrexate (HDMTX) and citrovorum factor rescue (CFR) (median, 7 courses), and 1 course each of bleomycin, cyclophosphamide, and dactinomycin, and adriamycin. At the time of definitive surgery, the surgical specimen showed a good histologic response to chemotherapy (grade III or IV response) in 29 (67%) of 43 patients and a poor histologic response (grade I or II response) in 14 (33%) of 43 patients. Among those who responded well, no patient relapsed, as all received a complete course of preoperative and postoperative chemotherapy for more than 5 to over 28 months after the initiation of treatment (medium, 13 mo). Among those who responded poorly, 6 of 14 patients relapsed with pulmonary metastases (a thoracotomy was beneficial to 1), 4 of 6 patients are alive with disease, and 1 patient died of progressive disease. On retrospective analysis, we observed that good and poor responders did not differ in the distribution of sex, age, race, primary site of disease, or histologic subtype of OS. An elevated alkaline phosphatase level that returned to normal under preoperative chemotherapy indicated a good response. Neither the 24-, 48-, and 72-hour serum MTX levels nor the fluid intake and urinary output during 3 days that followed HDMTX with CFR correlated significantly with tumor response. Based on our studies with this form of therapy, we concluded that the response of OS to preoperative chemotherapy is of prognostic value.
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PMID:Prognostic factors in the response of primary osteogenic sarcoma to preoperative chemotherapy (high-dose methotrexate with citrovorum factor). 697 39

A 49 year-old man was admitted to our hospital in May 1989, with a cervical tumor and leukocytosis. He had been pointed out leukocytosis for last two years. Peripheral blood examinations demonstrated an increase of leukocytes (39,500/microliters) with low neutrophil alkaline phosphatase, eosinophilia and immature cells. Examination of bone marrow revealed normoplasia with 5.6% eosinophils, 1.4% myeloblasts, 2.6% promyelocytes and 250/microliters megakaryocytes. Cytogenetic analysis disclosed 46, XY, t (12;13) (p13;q12). Southern blot analysis showed no BCR rearrangement. The tumor cells had infiltrated the lymph nodes. Pathological finding agreed with the specimen of the lymph node as in the clot section of bone marrow. He was diagnosed as having a chronic myeloproliferative disorder with tumor formation and was treated with anti-leukemia drugs, including BH-AC, THP, VDS, MTX, VP-16, BUS, 6MP and uvenimex. He showed hematological remission, temporary, but he did not reach cytogenetical remission and died in April 1990. Further study in a large series is necessary to define whether the abnormality of the chromosome with t(12;13) (p13;q12) is characteristic in cases with tumor formation.
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PMID:[Atypical chronic myeloproliferative disorder with translocation (12;13) (p13;q12) and tumor formation]. 786 15

Methotrexate (2.5 mg/day) was used in addition to ursodeoxycholic acid (10-15 mg/kg per day) in 8 female patients with primary biliary cirrhosis. All patients had undergone ursodeoxycholic acid treatment for more than 6 months preceding this study and their serum alkaline phosphatase remained constant at more than 300 U/l for more than 2 months. One patient showed histologic stage I, three stage II, two stage III and two stage IV disease. Within 6 months, fatigue and itching disappeared in all symptomatic patients. Serum alkaline phosphatase activities improved dramatically (621 +/- 299 to 378 +/- 258, mean +/- S.D.) in all but one patient and normalized in four. Serum gamma-glutamyltransferase activities (180 +/- 99 U/l vs. 150 +/- 125 U/l) and immunoglobulin M concentrations (616 +/- 424 vs. 362 +/- 195 mg/dl) also improved. Adverse effects of methotrexate therapy were only regularly observed within the first 2-6 weeks, such as fatigue and transient enhancement of transaminases and serum bile acid concentrations. We conclude that methotrexate may be a highly effective drug for the treatment of primary biliary cirrhosis in patients whose symptoms and/or laboratory liver function tests are not improved enough by ursodeoxycholic acid alone. However, its influence on histology and the natural history of the disease needs to be established.
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PMID:Positive responses to methotrexate and ursodeoxycholic acid in patients with primary biliary cirrhosis responding insufficiently to ursodeoxycholic acid alone. 810 53

Methotrexate (MTX) has become an important drug in the treatment of rheumatoid arthritis (RA). The American College of Rheumatology convened a committee to assess the risks of development of clinically significant liver disease (CSLD) during MTX treatment, to evaluate the risk and role of surveillance liver biopsies, and to provide recommendations about monitoring patients for liver toxicity. The committee recommends obtaining liver blood tests (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase, albumin, bilirubin), hepatitis B and C serologic studies, and other standard tests including complete blood cell count and serum creatinine tests prior to starting treatment with MTX. A pretreatment liver biopsy should be considered only for patients with a history of prior excessive alcohol consumption, persistently abnormal baseline AST values, or chronic hepatitis B or C infection. At intervals of every 4-8 weeks the AST, ALT, and albumin levels should be monitored. Routine surveillance liver biopsies are not recommended for RA patients receiving traditional doses of MTX. However, a biopsy should be performed if a patient develops persistent abnormalities on liver blood tests. These are defined as elevations (above the upper limit of laboratory normal) in the AST in 5 of 9 determinations within a given 12-month interval (6 of 12 if tests are performed monthly) or a decrease in serum albumin below the normal range. The recommendations for monitoring and selection of patients for liver biopsy identify patients at potential risk for CSLD, and thus significantly reduce the number or patients who would be exposed to this procedure. Close monitoring is essential to reduce the risk of unrecognized serious liver disease. These recommendations should be revised as necessary to reflect new and compelling information.
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PMID:Methotrexate for rheumatoid arthritis. Suggested guidelines for monitoring liver toxicity. American College of Rheumatology. 798 33

The relationship between the serum concentration of methotrexate and the prognosis has been studied in 108 patients with osteosarcoma of the extremities treated from September 1986 to December 1989 at the Chemotherapy Department of Rizzoli Hospital. The protocol of neoadjuvant chemotherapy included high doses of methotrexate (HDMTX) adriamycin, cisplatinum, ifosfamide and VP-16. After a median follow-up of 40.4 months (range 24-62), 84 (77.7%) of the patients studied remained continuously disease-free (CDF) and 24 relapsed. Significantly higher mean serum MTX concentrations were observed in the patients who remained CDF (669.5 mumol/l) than in the patients who relapsed (571.9 mumol/l) (p < .004). The breaking point of prognostic significance for the serum MTX levels seems to be 700 mumol/l. In fact, according to the mean MTX concentrations, the patients with less than 700 mumol/l showed a significantly lower disease-free survival than the patients with higher mean MTX concentrations (68.12% vs 94.87% p < .0013). The distribution of prognostic variables between the two groups was the same in terms of site and histological type of tumor and alkaline phosphatase serum levels at diagnosis. In the group which had more than 700 mumol/l MTX, a higher percentage of good histological response after primary chemotherapy was observed. This is probably independent from the MTX because no significant preoperative MTX serum levels between good and partially responding patients were observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum methotrexate (MTX) concentrations and prognosis in patients with osteosarcoma of the extremities treated with a multidrug neoadjuvant regimen. 851 97

In the treatment of patients with primary biliary cirrhosis (PBC), methotrexate (MTX) and ursodeoxycholic acid (UDCA) have both been associated with clinical, biochemical, and histologic improvement. Studies with methotrexate have only been performed in uncontrolled conditions. We conducted a prospective controlled study on the combined treatment with methotrexate and ursodeoxycholic acid, comparing the clinical, biochemical, and histologic evolution in six untreated patients with that in eight patients treated with MTX 15 mg/week in association with UDCA 500 mg/day. All patients had noncirrhotic PBC and were followed up for two years. A significant decrease of alkaline phosphatase, glutamic pyruvic transaminase, and gamma-glutamyltranspeptidase was found in the methotrexate/ursodeoxycholic acid treated-group, as compared to the control group. The clinical and histologic evolution, however, was not significantly different in the two groups. Methotrexate toxicity consisted of interstitial pneumonitis in one, of a transient rise of transaminases at three months in five, and of a significant decrease of blood platelets and white blood cells after two years of treatment. In controlled conditions, a two-year treatment with methotrexate and ursodeoxycholic acid does not produce a significant clinical or histologic benefit. Based on this experience, and taking into account the possible risks associated with this therapy, the empiric use of methotrexate cannot be recommended in patients with non-cirrhotic PBC.
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PMID:Combined treatment with methotrexate and ursodeoxycholic acid in non-cirrhotic primary biliary cirrhosis. 866 66

Juvenile Rheumatoid Arthritis (JRA) is frequently associated with osteoporosis. In order to determine if JRA osteoporosis is related to reduced formation or to increased bone resorption or both, serum levels of calcium (Ca), phosphorus (PO4), magnesium (Mg), alkaline phosphatase (ALP), parathormone (PTHi), 25-hydroxyvitamin D3 (25-OHD) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D), osteocalcin (OT), carboxyterminal propeptide (P-coll-1-c), and carboxyterminal telopeptide of type I collagen (ICTP) were evaluated in 47 JRA children, 33 with active disease and 14 in remission. The therapy consisted of nonsteroidal antiinflammatory (NSAIDs) drugs in pauciarticular subset, NSAIDs and Methotrexate (MTX) in polyarticular, NSAIDs and steroids in systemic onset. OT reflects bone formation, P-coll-1-c reflects collagen production and bone formation, ICTP, marker of collagen degradation in bone, indicates bone destruction. Serum levels of Ca, PO4, Mg, ALP, PTHi 25-OHD and 1,25-(OH)2D were comparable in JRA children and in controls. OT (8.7 +/- 3.7 ng/ml vs 9.6 +/- 5.1), P-coll-1-c (301.2 +/- 118.4 ng/ml vs 264.1 +/- 100.1) and ICTP (15.7 +/- 5.7 ng/ml vs 16.1 +/- 6.1) did not differ statistically in the whole group of JRA children vs controls. OT (8.0 +/- 3.5 vs 10.4 +/- 3.8) and ICTP (14.4 +/- 5.4 vs 18.8 +/- 5.4) were significantly lower in active than inactive group. In polyarticular and systemic onset OT and ICTP were significantly lower than in pauciarticular. No difference was found in active patients treated with steroids vs active patients treated with NSAIDS and NSAIDs plus MTX. The lower serum levels of OT and ICTP in active disease support the hypothesis that both bone formation and resorption are reduced in JRA bone turnover.
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PMID:Bone turnover is reduced in children with juvenile rheumatoid arthritis. 963 20


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