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)

Neutrophil granulocytes are the most important white blood cells in the combat of non-viral infections. Circumstantial evidence indicates that neutrophils in addition modulate the inflammatory process. Production of neutrophils takes place in the bone marrow, and mature cells egress to the circulation. Neutrophils emigrate following activation from the vessels into the tissues (chemotaxis). During this process neutrophils generate reactive oxygen species (respiratory burst) and mobilize intracellular compartments (degranulation). By degranulation, neutrophils exercise influence on nearby cells or bacteria by extracellular release of intragranular proteins (exocytosis), and intensify plasma membrane-related processes, such as chemotaxis and respiratory burst, by translocation of membrane-bound proteins to the surface (upregulation). Ultimately, microorganisms may be killed intracellularly following engulfment (phagocytosis). The thesis presents results of protein-chemical analysis of human neutrophils, based on studies of intact cells and subcellular structures (subcellular fractionation). By fractionation, azurophil granules and specific granules can be disunited from each other and from plasma membrane and secretory vesicles. Only partial separation of plasma membrane and secretory vesicles can be obtained. Subcellular structures are identified by markers, e.g. vitamin B12 binding protein for specific granules, and latent alkaline phosphatase for secretory vesicles. The studies demonstrated tetranectin in neutrophils, localized exclusively in the secretory vesicles. Tetranectin was released by incubation of neutrophils in the presence of weak, inflammatory stimuli and paralleled the upregulation of alkaline phosphatase, but preceded degranulation of specific granules. Alkaline phosphatase has previously been employed as a plasma membrane marker. A novel ELISA for HLA class I antigen was introduced as a new plasma membrane marker. Results obtained by this assay showed upregulation of alkaline phosphatase occurring without a concurrent redistribution of HLA antigen. This indicates that the two proteins are localized in separate compartments. Upregulation of alkaline phosphatase induced by weak stimuli, however, paralleled the translocation of cytochrome b559, anticipated to be the terminal component in the respiratory burst, and known to be localized primarily in the specific granules. The present studies indicate that 15% of cytochrome b is localized in the secretory vesicles. An ELISA was established for quantitation of beta 2-microglobulin, the light chain of HLA class I antigens. The concentration of beta 2-microglobulin in plasma from patients with chronic myeloid leukaemia was found to correlate with the concentration of vitamin B12 binding protein.4+ Measurements in neutrophils demonstrated 65% of the total content of beta 2-microglobulin to be localized in the specific granules, and 20% to be present in secretory vesicles.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Human neutrophil structure and function with special reference to cytochrome b559 and beta 2-microglobulin. 849 95

The Cadmibel Study is a cross-sectional population study, which investigated the hypothesis that environmental exposure of the population to cadmium would result in health effects. The 2,327 participants constituted a random sample of the population of four Belgian districts, chosen to provide a wide range of environmental exposure to cadmium. The urinary cadmium excretion, a measure of lifetime exposure, averaged 9.3 nmol/24h in men (range 0.4-325 nmol/24h) and 7.2 nmol (0.1-71 nmol/24h) in women. The Cadmibel Study refuted the hypothesis that exposure to cadmium would lead to an increase in BP and in the prevalence of hypertension and other cardiovascular diseases. Serum alkaline phosphatase activity and the urinary excretion of calcium correlated significantly and positively with urinary cadmium in both sexes. These findings suggest that the calcium metabolism is gradually affected, as cadmium accumulates in the body. Furthermore, several markers of renal tubular function (urinary excretion of retinol binding protein, N-acetyl-beta-glucosaminidase, beta 2-microglobulin and aminoacids) were significantly and positively associated with urinary cadmium. There was a 10% probability of abnormal values of these markers of tubular function when urinary cadmium exceeded +/- 20 nmol/24h. However, the morbidity associated with the functional changes, observed in the Cadmibel Study, remains presently unknown and requires further investigation, preferably in a longitudinal population studies.
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PMID:Health effects of environmental exposure to cadmium in a population study. 851 95

Serum neural cell adhesion molecule (NCAM) has been described as a prognostic marker in multiple myeloma (MM). Both C-reactive protein (CRP) and beta 2-microglobulin (beta 2M) are established prognostic markers in MM. We tested the diagnostic value of these markers in 212 serum samples of patients with paraproteinemia registered prospectively in a population-based registry. Sixty patients had MM and 152 had other monoclonal gammopathies (hematologic diseases [48], paraneoplastic disease [35], autoimmune disease [15], and monoclonal gammopathy of undetermined significance [56]). CRP and beta 2M had wide and overlapping ranges in all diagnostic categories. However, serum neural cell adhesion molecule (NCAM) was low (< 20 U/mL) in all but 4 of 152 nonmyeloma cases and high (> or = 20 U/mL) in 31 (52%) of the 60 MM cases. Two patients with non-Hodgkin's lymphoma, 1 with chronic lymphatic leukemia, and 1 with autoimmune disease had serum NCAM values between 20 and 30 U/mL. In a discriminant analysis in which serum NCAM, CRP, beta 2M, paraprotein type and concentration, hemoglobin, leukocyte and thrombocyte counts, creatinine, corrected calcium, lactate dehydrogenase, and alkaline phosphatase were included, paraprotein type and concentration and serum NCAM turned out to be the best combination of parameters predicting whether a patient had MM, with 89% of cases being correctly classified. Even without bone marrow and x-ray examinations, serum NCAM, in combination with paraprotein type and concentration, can differentiate between MM and nonmyeloma patients.
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PMID:Serum neural cell adhesion molecule differentiates multiple myeloma from paraproteinemias due to other causes. 855 95

The CadmiBel Study was a cross-sectional population study that investigated the health effects of environmental exposure to cadmium and lead. The 2327 participants constituted a random sample of the population of four Belgian districts, chosen in order to provide a wide range of environmental exposure to cadmium. After adjustment for confounding factors, such as smoking and occupational exposure, the urinary cadmium excretion, a measure of lifetime exposure, was nearly 30% higher in the polluted areas. The CadmiBel Study produced evidence inconsistent with the hypothesis that environmental exposure to cadmium and lead would lead to an increase in blood pressure and to a higher prevalence of hypertension and other cardiovascular diseases. On the other hand, the serum alkaline phosphatase activity and the urinary excretion of calcium were significantly and positively correlated with urinary cadmium in both sexes. These findings suggested that the homeostasis of calcium was gradually affected as cadmium accumulated in the body. Furthermore, several markers of renal tubular dysfunction (urinary excretion of retinol-binding-protein, N-acetyl-beta-glucosaminidase, beta 2-microglobulin and amino acids) were significantly and positively associated with urinary cadmium. Across 10 small areas of which six were polluted with cadmium, an inverse association existed between the creatinine clearance and several indexes of environmental exposure to cadmium (cadmium concentration in the soil, cadmium content of locally grown vegetables, the inhabitants' 24 h urinary cadmium excretion). In the CadmiBel Study, the creatinine clearance was also inversely correlated with the concentrations of lead and zinc protoporphyrin in the blood. Thus, environmental exposure to cadmium and lead was associated with alterations in renal function. The significance in terms of morbidity and mortality of the functional disturbances observed in the CadmiBel Study, and the possible strategies to prevent the transfer of cadmium from the environment to man are under investigation in the prospective PheeCad Study in which half of the Cadmibel participants have been enrolled (participation rate 80%).
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PMID:Public health implications of environmental exposure to cadmium and lead: an overview of epidemiological studies in Belgium. Working Groups. 878 28

Twenty patients with end-stage renal failure on maintenance hemodialysis were studied for the effect of intravenous 1,25(OH)2 vitamin D3 on biochemical bone markers. Active vitamin D, 1,25(OH)2 vitamin D3, was given intravenously after hemodialysis, 1 microgram thrice weekly. Serum ionized calcium, phosphorus, alkaline phosphatase (AKPase), intact parathyroid hormone (PTH), osteocalcin (bone Gla protein), carboxy terminal propeptide of type I procollagen (PICP), cross-linked telopeptide of type I collagen (ICTP) and beta 2-microglobulin were measured before and after 3 and 6 months of treatment with 1,25(OH)2 vitamin D3. The serum ionized calcium and osteocalcin levels were significantly increased at 3 and 6 months after treatment. The serum beta 2-microglobulin level were also increased 6 months after treatment, whereas the serum levels of AKPase and intact PTH decreased after treatment. However, the serum levels of phosphorus, PICP and ICTP did not change significantly after treatment. The decreased levels of serum AKPase and intact PTH suggest reduced bone resorption. Increases of serum osteocalcin levels were caused by stimulation of the osteoblast by 1,25(OH)2 vitamin D3, baseline 20.6 +/- 12.5 micrograms/l, and 36.1 +/- 34.0 and 31.0 +/- 24.6 micrograms/l at 3 and 6 months, respectively (p < 0.01). The lower osteocalcin level at 6 rather than at 3 months may imply reduced bone resorption and/or increased bone mineralization. The meaning of the increase of serum beta 2-microglobulin in uremic patients after calcitriol treatment is unclear. It may indicate reduced deposition and is masked by increased bone resorption from secondary or tertiary hyperparathyroidism. This study did not validate PICP and ICTP measurements as bone markers in uremic patients.
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PMID:Changes of bone markers during long-term intravenous calcitriol therapy in maintenance dialysis patients. 880 25

beta 2-Microglobulin is a constituent of the class I major histocompatibility complex (MHC) molecule and crucial for its normal function in cell recognition. It has also been isolated from bone and shown to regulate bone metabolism and to be altered in various bone diseases. In order to further investigate the role of the immune system in bone metabolism, we studied basic properties of bone physiology in beta 2-microglobulin-deficient mice created by the technique of gene knock-out. Ten week-old male offspring homozygous (non-functional class I MHC molecule) or heterozygous (functional class I MHC molecule) for beta 2-microglobulin knock-out gene did not differ in the following measures of bone turnover: femur length, dry and ash weight and calcium content, serum calcium concentration and alkaline phosphatase activity, total vertebral tissue area, trabecular bone volume, osteid surface, osteoclast surface and mineral apposition rate. These data indicate that the bone turnover in beta 2-microglobulin-deficient mice is appropriate for the stage of their skeletal maturation.
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PMID:Bone turnover in homozygous beta 2-microglobulin knock-out mice does not differ from that of their heterozygous littermates. 884 22

The synthetic polynucleotide polyadenylic-polyuridylic acid (polyA:polyU) has shown antitumor activity in murine studies and human breast cancer. PolyA:polyU was evaluated in 25 cancer patients receiving weekly intravenous doses between 3 and 600 mg/m2. PolyA:polyU was well tolerated up to 600 mg/m2, with no doselimiting toxicity (all < grade 3). Side effects included mild elevation in temperature, fatigue, and mild hyperglycemia. No changes outside of the normal range in hematocrit, WBC count, platelet count, total bilirubin, or alkaline phosphatase were observed. Of 25 patients, 18 completed at least one cycle of 6 weeks, and 5 completed two cycles (median 6 weeks). Four patients had stable disease over 11-13 weeks of treatment, and no clinical responses were observed. At 24 h after the first treatment, there were no significant increases in biologic response (beta 2-microglobulin and neopterin in serum, or 2',5'-oligoadenylate synthetase in peripheral blood mononuclear cells). A small increase in beta 2-microglobulin was observed 24 h after the week 3 treatment (1.1-fold, p < 0.01). By the third week of treatment, 2-5A synthetase levels decreased slightly (to 80% of baseline, p < 0.01). No changes in cytokines IL-6, IL-12, tumor necrosis factor (TNF), or IL-2 receptor in serum were detected after 24 h of treatment. Thus, at these doses, polyA:polyU had no marked modulation on biologic responses in vivo, although this preparation significantly induced 2-5A synthetase in peripheral blood mononuclear cells in vitro. PolyA:polyU was well tolerated. An MTD was not reached but was greater than 600 mg/m2 on this weekly schedule.
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PMID:Phase I/IB study of polyadenylic-polyuridylic acid in patients with advanced malignancies: clinical and biologic effects. 887 34

This study was performed to evaluate the prognostic significance of serum markers of bone and collagen metabolism in multiple myeloma. Serum C-terminal telopeptide of type I collagen (ICTP) reflects degradation of bone, whereas serum osteocalcin, together with serum C-terminal propeptide of procollagen type I (PICP) and serum bone-specific alkaline phosphatase (bAP) reflect synthesis of bone matrix. The N-terminal propeptide of procollagen type III (PIIINP) in serum reflects synthesis of type III collagen. We analysed frozen sera from 109 patients with newly diagnosed multiple myeloma. Serum ICTP was elevated (> 5.0 micrograms/l) in most patients (median 6.6 micrograms/l range 1.4-29.4 micrograms/l). Serum PIIINP was elevated (> 4.2 micrograms/l) in 46% (median 4.0 micrograms/l, range 1.4-20.1 micrograms/l). Serum PICP was generally within the reference limits, whereas serum osteocalcin and serum bAP were elevated in 19% and 37%, respectively. Serum ICTP correlated with serum PIIINP, serum beta 2-microglobulin (beta 2m), serum calcium, performance status, and stage. In univariate analysis, the test variables serum ICTP (P = 0.026) and serum osteocalcin (P = 0.036) were found to be of prognostic value, but PIIINP, PICP, or bAP in serum were not. Serum ICTP and serum beta 2m had a similar prognostic value. In multivariate analysis, serum calcium showed the highest prognostic significance, and serum beta 2m was the only other variable of independent prognostic value. However, in normocalcaemic patients, serum ICTP showed the highest prognostic significance, followed by serum osteocalcin. Thus, the serum levels of ICTP and osteocalcin seem related to bone turnover and calcium metabolism, and provide further information about myeloma activity, particularly in normocalcaemic patients.
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PMID:Serum markers of bone metabolism in multiple myeloma: prognostic value of the carboxy-terminal telopeptide of type I collagen (ICTP). Nordic Myeloma Study Group (NMSG). 901 95

Fifteen patients (13 males and two females; mean age, 63 years; age range, 46-84 years) with multiple myeloma were studied prospectively (range of follow-up period, 2-6 months) to elucidate the diagnostic validity of biochemical markers of bone formation (bone alkaline phosphatase and the C-terminal propeptide of type I procollagen) and bone resorption (urinary excretion of pyridinium cross-links) for monitoring these patients. Eleven of 15 patients received melphalan i.v. and prednisone p.o. every 4 weeks. All patients were given pamidronate i.v. for inhibition of bone resorption. The mean values of the urinary excretion of pyridinium cross-links were significantly higher in the patients fulfilling the criteria of 'progression' or 'relapse' than in those showing 'response' and those in the 'plateau phase' (P < 0.05). In contrast, neither bone alkaline phosphatase nor C-terminal propeptide serum values differed significantly between these two groups (P > 0.05). The concentrations of both bone formation markers were significantly lower in the patients than in the samples obtained from apparently healthy persons (P < 0.001). There was a significant inverse correlation between the number of pamidronate courses and the serum concentrations of bone alkaline phosphatase (P < 0.05). A lack of correlation was observed between the urinary excretion of pyridinium cross-links and all other laboratory parameters measured (serum concentrations of total protein, calcium, creatinine and (beta 2-microglobulin). In conclusion, the urinary excretion of pyridinium cross-links might be a useful parameter for monitoring multiple myeloma patients. Decreased values of bone formation markers may be due to a suppressive effect of the bisphosphonate agents administered or reflect the severity of osteolytic lesions which have been described as being associated with unbalanced bone remodelling.
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PMID:Monitoring of multiple myeloma patients by simultaneously measuring marker substances of bone resorption and formation. 949 1

Gemcitabine is a novel fluorine-substituted cytarabine (Ara-C) analogue with activity against a range of solid tumours. Besides dose-limiting haematological toxicity, renal side-effects were observed from phase I and II studies concerning elevations of serum creatinine, proteinuria and erythrocyturia. The aim of this study was to investigate the effect of gemcitabine on renal function in 11 untreated patients with non-small cell lung cancer (NSCLC). Gemcitabine was given as weekly infusions of 1250 mg/m2 for 3 weeks, followed by 1 week rest. This comprised one cycle (maximum of six cycles). The glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured simultaneously with a constant infusion of 125I-iothalamate and 131I-hippuran, respectively. Tubular damage was monitored by excretion of tubular enzymes (lactic dehydrogenase (LDH), alkaline phosphatase (ALP), gamma-glutamyltransferase (GT) and beta 2-microglobulin); glomerular damage was monitored by excretion of albumin in the urine. In 9 patients, the effect of the first infusion was evaluated. After the first infusion of gemcitabine, no change was observed in renal function. After two, three, and six cycles of treatment, no significant changes in GFR and ERPF were noticed in 9 evaluable patients. However, in 3 patients, a decrease in GFR of > 10% was observed after multiple cycles. In one of them this was accompanied with albuminuria (360 mg/24 h) and erythrocyturia. There were no significant changes in urinary excretion of tubular enzymes or albumin. In conclusion, we did not observe acute renal toxicity with gemcitabine. No significant cumulative effects of gemcitabine on renal function could be detected, although 3 patients, treated with multiple cycles of gemcitabine, showed a moderate decrease in renal function. Glomerular damage might play a role in the development of renal function loss.
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PMID:Effects of gemcitabine on renal function in patients with non-small cell lung cancer. 962 59


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