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)

6-Mercaptopurine (6MP) metabolism was quantitatively determined in L5178Y murine lymphoma. Cells grown in time-course incubates with [35S]-6MP were extracted with cold perchloric acid, and the buffered extracts were subjected to high-performance liquid cation-exchange chromatography prior to and after hydrolysis with alkaline phosphatase. Free sulfate, 6-thiouric acid, 6-thioxanthosine, 6-thioguanosine, 6-thioinosine, free 6MP, and 6-methylthioinosine were separated from each other; identified in the radiochromatograms by elution volume, UV spectroscopic data, and enzymatic peak-shifting analyses with purine nucleoside phosphorylase; and quantitatively determined by means of 35S radioactivity. Gross intracellular 35S concentrations remained constant at 5 x 10(-5) M after 1 hr of incubation. 6MP metabolism in L5178Y cells was distinguished into an early phase (to 1 hr of incubation) in which 6MP was predominantly catabolized to 6-thiouric acid and free sulfate, into an intermediate phase (to 8 hr) in which substantial amounts of free 6MP and of ribonucleotides of 6-thioxanthosine and 6-thioguanosine were present while the concentrations of nonnucleotide oxidation products sharply decreased, and into a late phase (to 24 hr) in which the ribonucleotides of 6MP, of 6-thioguanosine and, in particular, of 6-methylthioinosine were the most abundant metabolites.
Cancer Res 1979 Sep
PMID:Quantitation of intracellular metabolites of [35S]-6-mercaptopurine in L5178Y cells grown in time-course incubates. 47 98

The effects of phosphate restriction and of 1 alpha OH D3 administration were investigated in patients with advanced chronic renal failure. Few modifications of the various biochemical parameters in the patients were achieved with the restriction of dietary phosphate while better results were obtained with 1 alpha OH D3 administration. In dialyzed patients the treatment with this drug resulted in a normalization in serum calcium and alkaline phosphatase levels and in a remarkable significant decline in plasma parathyroid hormone and a reduction in the bone disease associated with uremia. This treatment in dialyzed uremic patients could avoid the employment of higher dialysate calcium concentration potentially dangerous for postdialysis hypercalcemia with the risk of metastatic calcifications.
Int J Artif Organs 1979 Sep
PMID:Effects of 1-alpha OH D3 therapy in uremic patients in conservative or dialytic treatment. 47 81

Investigation of the kindred of a 58-year-old woman with all of the features of "adult" hypophosphatasia revealed 12 individuals in 3 generations with subnormal circulating total alkaline phosphatase (AP) activity. The pattern of inheritance suggested autosomal dominant transmission, with incomplete penetrance of the trait particularly in the young males. Hypophosphatasic individuals other than the proposita were clinically well but had loss of permanent teeth, showing that dental abnormalities could be the only clinical manifestation of the disorder. Radiographic investigation of the proposita revealed that completion of stress fractures was necessary for healing; maturation of incomplete fractures resulted in stable Looser zones. Skeletal survey and radionuclide bone imaging were unremarkable in hypophosphatasic individuals without fracture. Subclinical osteopenia was found in several affected women by metacarpal cortical width and bone densitometric measurements. Laboratory studies showed increased plasma and urinary phosphoethanolamine levels in affected individuals. Phosphoethanolamine and phosphoserine appeared to be natural subtrates for AP since a negative correlation existed between each substrate and circulating total AP activity. Phosphoethanolamine and phosphoserine levels were greatest in the clinically affected proposita; furthermore, only she showed absence of leukocyte AP activity. Heat fractionation of her total circulating AP activity suggested severe reduction in the bone isoenzyme. Hypophosphatasic children had higher levels of total circulating AP than affected adults; the increase was apparently secondary to increased bone isoenzyme. Iliac crest bone biopsies showed greater abnormality in affected women. Osteoidosis was particularly pronounced in the proposita's younger affected sister and hypophosphatasic daughter. Histomorphometric analyses of the biopsies revealed a paucity of osteoblasts despite increased quantities of unmineralized matrix. The finding that hypophosphatasic children in this kindred had higher circulating total AP activity than adults and were able to model their skeleton normally, together with observations that the bone biopsy in adults had a paucity of osteoblasts, suggests that some factor(s) during growth is able to induce both AP activity and osteoblast function, or, that this disorder is an "abiotrophy" with deficient osteoblastic formation and/or accelerated destruction in adult life.
Medicine (Baltimore) 1979 Sep
PMID:Adult hypophosphatasia. Clinical, laboratory, and genetic investigation of a large kindred with review of the literature. 48 Nov 94

3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase, E.C. 1.1.1.34), the major rate-limiting enzyme of the sterol biosynthetic pathway, was studied in ileal epithelial cells isolated in a villus-to-crypt gradient according to Weiser (Weiser, M. M. 1973. J. Biol. Chem, 248:2536-2541). Alkaline phosphatase (E.C. 3.1.3.1) served as a marker for the mature villus cells. Protease effects on activity determinations were negligible. The intracellular location of HMG-CoA reductase could not be precisely determined. The activity of ileal reductase was predominantly associated with the less differentiated lower villus and crypt cells, while the reverse gradient occurred with alkaline phosphatase. This distribution of enzymes persisted in both fed and fasted rats injected with control saline-phosphate, although fasting decreased total reductase units in the ileum by 86% in 72 hr. Treatment with cholestyramine and with 4-aminopyrazolo[3,4-d]pyrimidine (APP) enhanced reductase activity in ileal cells. The percent stimulation in both cases was higher in the upper villus cells than in the crypt cells, leading to abolition of the gradient in enzyme activity. However, APP treatment caused a 98% loss in total alkaline phosphatase units and a 55% loss in total epithelial cell protein in 72 hr. Thus, there was no increase in total reductase units. These data show that APP affects ileal cell metabolism directly. Furthermore, it appears that the regulation of sterol synthesis in the intestinal mucosa, via HMG-CoA reductase, involves a complex interplay of the effects exerted by the level of alimentation, the enterohepatic circulation of bile, and the levels of plasma lipoproteins.
J Lipid Res 1979 Sep
PMID:Distribution of 3-hydroxy-3-methylglutaryl coenzyme A reductase and alkaline phosphatase activities in isolated ileal epithelial cells of fed, fasted, cholestyramine-fed, and 4-aminopyrazolo[3,4-d]pyrimidine-treated rats. 49 57

Tetramisole and its analogues are potent inhibitors of alkaline phosphatase, including isoenzymes of Sarcoma 180/TG which appear to be involved in the mechanism of resistance of this neoplastic cell line to the 6-thiopurines. To determine the requirement for the thiazole ring system of tetramisole for inhibitor potency, 2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b]oxazole, 2,3-dihydro-6-phenylimidazo[2,1-b]oxazole, and 2,3,5,6-phenylimidazo[2,1-a]imidazole were synthesized and tested for inhibitory activity against alkaline phosphatase isolated from Sarcoma 180/TG. The results indicate that 2,3,5,6-tetrahydro-6-phenylimidazo[2,1-b]oxazole caused 50% inhibition at 0.21 mM, while the other synthesized compounds were inactive at a concentration of 1 mM; in contrast, tetramisole required only 0.045 mM for 50% inhibition of alkaline phosphatase activity. The findings support the concept that the thiazole ring system of the tetramisole structure is required for maximum inhibitory potency of this series against alkaline phosphatase.
J Med Chem 1979 Sep
PMID:Synthesis and biological evaluation of tetramisole analogues as inhibitors of alkaline phosphatase of the 6-thiopurine-resistant tumor sarcoma 180/TG. 49 May 46

Oesophageal biopsies were obtained from 74 patinets undergoing upper gastrointestinal fibreoptic endoscopy. Thirteen patients with histological evidence of inflammation had a raised alkaline phosphatase activity (2.7 +/- 1.6 nmol/mg protein/min) compared with 49 normal controls (1.2 +/- 0.68 nmol/mg protein/min: P less than 0.001). The acid phosphatase level was lower (8.4+/- 4.0 vs. 5.8 +/- 2.2 nmol/mg protein/min: P less than 0.05) and the glucuronidase activity raised (0.44 +/- 0.17 vs 0.81 +/- 0.32 nmol/mg protein/min: P less than 0.001) and their ratio declined (24.0 +/- 1.9 nmol/mg protein/min: P less than 0.001) in patients with oesophagitis. This may be due to differential secretion of membrane coating granules, a form of lysosome found isophagitis--was assessed by point counting. The volume density rose from 10.9 +/- 4.25% in normal biopsies to 46.4+/-12.5% (P less than 0.001) in oesophagitis. These results show a consistent pattern that possibly indicates an intermediate stage between the clinically, histologically, and biochemically normal oesophagus and one that is inflamed on endoscopy.
Gut 1979 Sep
PMID:Changes in enzyme activity in normal and histologically inflamed oesophageal epithelium. 49 16

Three methods were compared in human serum for determining the activity of the placental isoenzyme of alkaline phosphatase: 1. Heat inactivation at 65 degrees C for 10 minutes, 2. Differential inactivation with L-p-Bromotetramisole, and 3. an immunological precipation test. A good comparison between the three methods was found (correlation coefficient between 0.973 and 0.982). For long series or screening determinations for "Regan-isoenzyme" the differential inactivation with L-p-Bromotetramisole is preferred because of the short analysis time and the possibility of simple mechanisation.
J Clin Chem Clin Biochem 1979 Sep
PMID:[Measuring the activity of the placental isoenzyme of alkaline phosphatase: 3 methods compared (author's transl)]. 50 8

A patient with liver abscess in association with regional enteritis is reported. Liver abscess should be suspected in patients with regional enteritis who present with fever, elevated serum alkaline phosphatase, liver tenderness, right upper quadrant pain or hepatomegaly.
Am J Gastroenterol 1979 Sep
PMID:Liver abscess. A complication of regional enteritis. 50 33

Ceforanide, a new cephalosporin antibiotic with a long half-life (3 h), can be administered twice daily. We evaluated its antimicrobial activity, pharmacology, and clinical efficacy. Twenty-seven patients with infections due to susceptible organisms received ceforanide, 0.5, 1, or 2 g, intramuscularly or intravenously every 12 h for 6 to 28 days. In vitro studies with the clinical isolates from 27 patients treated plus 263 additional isolates showed that ceforanide was active against cephalothin-susceptible gram-positive and gram-negative microorganisms. In addition, ceforanide inhibited 65% of cephalothin-resistant Escherichia coli and 65% of Enterobacter spp. at </=12.5 mug/ml. After a single 1-g intramuscular dose, the mean peak plasma concentration at 1 h was 48.9 mug/ml and that at 12 h was 4.7 mug/ml. Plasma accumulation occurred in some patients. The infections included 10 pneumonias, 3 with bacteremia and 1 with empyema; 11 soft tissue infections, 4 with abscesses and 3 with sepsis; and 3 urinary tract infections. One case each of endocarditis, osteomyelitis, and septic thrombophlebitis, all due to Staphylococcus aureus, were treated. Clinical response was satisfactory in all patients; bacteriological response was satisfactory in 26 of 27 patients. Ceforanide was well tolerated. Three patients developed mild increases in liver enzymes, and one developed slight eosinophilia. In another case, the antibiotic was discontinued because of a fivefold rise in serum glutamic-oxalacetic transaminase (aspartate aminotransferase) and serum glutamic-pyruvic transaminase (alanine aminotransferase) and a twofold rise in lactic acid dehydrogenase and alkaline phosphatase.
Antimicrob Agents Chemother 1979 Sep
PMID:Ceforanide: in vitro and clinical evaluation. 50 95

The isolation of plasma membranes is often accompanied with a loss of sensitivity to stimulatory agents (e.g. mitogens). Changes in the structure of the cell membranes after cell breakage have also been reported. Concerning this problem, "mild" cell disruption conditions were tested by using osmotic shock. Different membrane fractions were isolated, resulting in an enrichment of plasma membranes in one fraction. All fractions were characterized by plasma membrane marker enzymes (alkaline phosphatase, gamma-glutamyltransferases), the amount of cholesterol, the molar ratio of cholesterol and phospholipid, by dodecyl sulfate-gelectrophoresis and by electronmicroscopy. Total balance sheets of the fraction were made for each of the different biochemical parameters. The enriched plasma membranes resulting by using the described method had also lost the sensitivity to the stimulatory effect caused by mitogens such as Concanavalin A.
Hoppe Seylers Z Physiol Chem 1979 Sep
PMID:Preparation and fractionation of membrane vesicles of thymocytes after osmotic cell disruption. 51 Nov 18


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