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)

Treatment of the acute promyelocytic (APL) cell line NB4 with interferon alpha (IFN(alpha)), as well as IFN(beta) and gamma, results in an increased expression of the transcripts coding for retinoic-acid receptor type alpha (RAR(alpha)) and the leukemia-specific retinoic acid receptor PML-RAR. Transcriptional induction of the RAR(alpha) and PML-RAR mRNAs is rapid and it is parallelled by an increase in the corresponding proteins. Up-regulation of RAR(alpha) and PML-RAR gene expression by IFN(alpha) is accompanied by a strong potentiation in the induction of 2 retinoid-dependent granulocytic markers, i.e., granulocyte-colony-stimulating factor receptor mRNA and leukocyte alkaline phosphatase. However, IFN(alpha) does not have any effects on the retinoid-dependent regulation of the myeloid surface markers CD11b and CD33. The IFN-dependent increase in RAR(alpha) levels and the enhancing effect of the cytokine on retinoid-dependent granulocytic markers expression may be a characteristic of PML-RAR positive cells, since the phenomena are not observed in HL-60 promyelocytes. Interferons as well as retinoids inhibit the growth of NB4 cells, although the 2 classes of compounds do not significantly interact in terms of anti-proliferative activity. These results suggest the possible use of combinations between IFNs and retinoic acid in the cyto-differentiating treatment of APL patients.
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PMID:Interferons induce normal and aberrant retinoic-acid receptors type alpha in acute promyelocytic leukemia cells: potentiation of the induction of retinoid-dependent differentiation markers. 889 44

Chronic myeloid leukemic (CML) granulocytes exhibit defects in several functions, some of which have been associated with changes in the expression of cell surface molecules, actin reorganization and lowered levels of total cellular actin. In this study, we show by northern blotting that the steady-state level of mRNA for actin is not decreased in the CML granulocyte. Our data suggest that the lowered levels of actin protein in the leukemic granulocyte may be due to altered control at the translational/post-translational step, rather than at the level of transcription/post-transcription, implicated in the regulation of expression of the surface molecules, Fc gamma RII, Fc gamma RIII and alkaline phosphatase.
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PMID:Actin mRNA is not lowered in chronic myeloid leukemic granulocytes. 894 83

The pharmacodynamics of etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ), a water-soluble prodrug of etoposide, was evaluated in 39 patients with solid tumors after a 30-minute intravenous infusion of escalating doses (equivalent to 50 to 175 mg/m2 of etoposide) on a day 1, 3, and 5 schedule of treatment. Serial blood samples were collected at predose and throughout the 32 hours following day 1 of treatment to determine the area under the plasma concentration-time curve (AUC) of etoposide phosphate and etoposide. Hematology profiles and serum chemistries were determined at predose and twice weekly for approximately 3 weeks after each treatment cycle. Both linear and nonlinear pharmacodynamic models were used to evaluate the relationship between hematologic toxicity and etoposide AUC and patient factors (age, gender, performance status, prior radiation therapy, prior chemotherapy, baseline albumin, bilirubin, alkaline phosphatase, creatinine, leukocyte count, granulocyte count). Etoposide phosphate was converted rapidly to etoposide in vivo. The ratio of the etoposide phosphate AUC to that of etoposide was < or = 1.2% indicating that etoposide was the main species in the systemic circulation. Myelosuppression was the dose-limiting toxicity, and significant decreases in white blood cell and granulocyte counts were noted. Hematologic toxicity was best described by a stepwise linear regression model consisting of etoposide AUC, serum albumin, and bilirubin. In summary, hematologic toxicity produced by the intravenous administration of etoposide phosphate correlates significantly with etoposide AUC and patient factors (baseline serum albumin and bilirubin) in cancer patients.
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PMID:A pharmacodynamic evaluation of hematologic toxicity observed with etoposide phosphate in the treatment of cancer patients. 899 71

Leukocyte alkaline phosphatase (LAP) is the product of the gene coding for the liver/bone/kidney-type alkaline phosphatase. In the normal hematopoietic system, the only cell type expressing LAP in basal conditions is the post-mitotic neutrophilic granulocyte. Thus LAP represents a specific and restrictive marker for the terminal maturation of the neutrophilic granulocyte. The study of the factors and the molecular mechanisms responsible for the expression of LAP in cells undergoing granulocytic maturation may shed light on this complex biological process. Acute promyelocytic leukemia (APL) represents a unique biological model in which it is possible to investigate neutrophilic differentiation. APL blasts undergo rapid and irreversible maturation towards cells morphologically and biochemically resembling normal mature granulocytes upon in vivo and in vitro challenge with all-trans retinoic acid (ATRA). In this cellular context, we studied the endogenous factors involved in the expression of LAP. The phosphatase is not synthesized in undifferentiated APL blasts and it is expressed only upon treatment with combinations between ATRA and a second cyto-differentiating signal. The second signal may be given by G-CSF, cAMP analogs, IL-6 and to a lesser extent by IL-1 beta. The molecular mechanisms underlying the induction of LAP by combinations of ATRA and G-CSF or cAMP analogs were studied in detail and are the object of this review.
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PMID:Leukocyte alkaline phosphatase a specific marker for the post-mitotic neutrophilic granulocyte: regulation in acute promyelocytic leukemia. 903 Oct 80

Leucocyte alkaline phosphatase (LAP) is an enzyme expressed on the external aspect of the neutrophilic granulocyte plasma membrane, and represents a specific marker for the fully differentiated granulocyte. In this report we characterize 1B12.1, a monoclonal antibody raised against human bone alkaline phosphatase, by its ability to recognize the LAP protein. As assessed by Western blot analysis, following electrophoresis under non-reducing conditions, the antibody specifically reacts with LAP upon forced expression of the protein in simian COS-7 fibroblasts. In addition, the 1B12.1 antibody recognizes partially purified LAP isolated from peripheral blood granulocytes. With this antibody we developed a quantitative flow-cytometry-based method for the determination of LAP. Double fluorescence flow cytometry demonstrated that the LAP protein was present in relatively high amounts in neutrophilic granulocytes, but not in monocytes, natural killer cells, or B and T lymphocytes of normal individuals. The protein was completely absent in granulocytes obtained from chronic myeloid leukaemia and paroxysmal nocturnal haemoglobinuria patients. Higher than normal levels of LAP protein were evident in neutrophilic granulocytes of patients suffering from polycythaemia vera, essential thrombocythaemia and severe aplastic anaemia. However, the highest amounts of LAP protein were present in the granulocytes of normal individuals treated with G-CSF for the isolation of peripheral blood stem cells.
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PMID:Flow cytometry of leucocyte alkaline phosphatase in normal and pathologic leucocytes. 907 26

Increased susceptibility to infections in patients with myelodysplastic syndromes (MDS) is thought to be due to neutropenia as well as functional abnormalities of neutrophils. In the present study we examined the effect of two different stimulants (fMLP, PMA) and three cytokines (alphaTNF, G-CSF and GM-CSF), both singly and in combination on granulocyte (RB) in 25 MDS patients compared to seven healthy controls. Single fMLP and PMA-stimulation showed similar results for both groups. Preincubation with cytokines enhanced fMLP-stimulated RB in most MDS patients and controls, but in patients to a significantly lesser extent when compared to the control group (p < or = 0,05). Combinations of alphaTNF + GM-CSF and alphaTNF + G-CSF were highly synergistic in priming fMLP-stimulated burst in both groups. But again, as with the single cytokine priming this effect was markedly reduced in MDS patients compared to controls (p < or = 0,05). A specific priming defect for one of the cytokines or a cytokine combination could not be demonstrated. Serum alphaTNF levels were measured in 18 and neutrophil alkaline phosphatase (NAP) index in 23 patients. Results did not correlate with variations of the RB in MDS patients. We conclude that reduced alphaTNF, GM-CSF and G-CSF priming of granulocyte RB is a frequent finding in MDS and may contribute to the enhanced susceptibility to bacterial infections.
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PMID:Cytokine priming of the granulocyte respiratory burst in myelodysplastic syndromes. 937 5

Dermatitis herpetiformis (DH) is a chronic subepidermal blistering disease, in which a perivascular cellular infiltrate, composed mainly of CD4+ T lymphocytes together with a varying number of neutrophils and eosinophils, is thought to be important in the pathogenesis of blister formation. The aim of this study was to investigate the potential role of cytokines such as the interleukins IL-4 and IL-5 and to quantify the distribution of T cells as well as their state of activation using alkaline phosphatase-antialkaline phosphatase and reverse transcriptase-polymerase chain reaction (RT-PCR) procedures in seven patients with typical clinical and histological features of DH. A strong extracellular staining with anti-IL-4 monoclonal antibody was detected in the upper dermis with a prevalent perivascular pattern in perilesional areas, whereas in the dermal-epidermal separation sites there was an intense, scattered distribution. IL-5 was intensely expressed, mainly at the intracellular level, by eosinophils and lymphocytes. Concerning RT-PCR, five DH patients showed a strong positive signal for both IL-4 and IL-5 cytokines while two patients showed a faint signal for both IL-4 and IL-5; these last two cases were histologically poor in inflammatory cells. In view of these results, it can be hypothesized that the recruitment of eosinophils and neutrophils in DH may be induced not only by granulocyte macrophage colony-stimulating factor and IL-8 as previously demonstrated, but also by Th2 cytokines as well.
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PMID:Th2-like cytokine activity in dermatitis herpetiformis. 960 68

Estrogen replacement therapy (ERT) is known to prevent bone loss following the menopause, but the mechanism for this is unclear. Estrogen may suppress the secretion of certain bone-resorbing cytokines. The aim of this study was to assess the effect of ERT on the levels of cytokines measured in peripheral blood. We measured cytokines in 10 postmenopausal women (ages 56-59, 3-9 years since menopause) treated with ERT and 10 age-matched (54-59 years, 4-10 years since menopause) untreated women as controls. Samples of blood were taken and used for mononuclear cell cultures, whole blood (WB) cultures, and the separation of serum. The cultures were treated with lipopolysaccharide (LPS; 500 ng/ml) and hydrocortisone (10(-6) M). The conditioned medium from cultures and the serum were then assayed for interleukin-6 (IL-6), IL-1alpha IL-1beta, IL-1 IL-1ra, tumor necrosis factor alpha (TNF-alpha), and granulocyte macrophage colony stimulating factor (GM-CSF) by enzyme-linked immunosorbent assay. M-CSF and the soluble cytokine receptors soluble IL-6 receptor (sIL-6r) and soluble TNF receptor type 1 (sTNFr1) were also measured in serum and M-CSF in stimulated WB cultures. Measurements were corrected for mononuclear cell count. We also measured serum bone-specific alkaline phosphatase (ibAP) in all subjects. We found that LPS stimulated secretion of all cytokines both in WB and isolated cell cultures, and that this was attenuated by hydrocortisone. A significantly higher ratio of IL-1beta/IL-1ra (p = 0.02) in LPS stimulated WB cultures was seen in the untreated women. Levels of IL-1beta and IL-1alpha measured in WB cultures were lower and IL-1ra was higher in the ERT-treated group but these results were not significant. BAP was higher in the untreated group (p = 0.005) and correlated with IL-alpha/IL-1ra in the whole group (r = 0.49, p = 0.03). Results of other measurements showed no significant differences between groups. We conclude that estrogen may prevent bone loss following the menopause by altering the balance between IL-1beta and IL-1ra.
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PMID:Effects of estrogen therapy of postmenopausal women on cytokines measured in peripheral blood. 978 46

A total of 171 workers with occupational exposure to benzene, toluene, xylene and ethylbenzene, and 37 controls were studied. Hematological parameters were measured using the automated hematology analyzer, (System 190). By routine microscopic methods we investigated the differential distribution of leukocytes and alkaline phosphatase in granulocytes. Of the workers, 95 (55.5%) had deviations of the different blood cells. Hypochromic anemia was found in 50 male workers (29.6%), while leukocytosis with lymphocytosis and neutropenia was found in 20%. In 11 workers (6.4%), dyshematopoiesis, was detected, affecting more than one blood population: anemia in combination with thrombocytopenia or leukocytosis with decreased enzyme activity of the granulocyte alkaline phosphatase. No definite relationship between changes in peripheral blood elements and length of service of the workers was found, but workers with over 20 years' exposure to aromatic hydrocarbons suffered from more severe forms of anemia.
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PMID:Changes in the peripheral blood of workers with occupational exposure to aromatic hydrocarbons. 982 88

Autologous haemopoietic stem cell transplantation (HSCT) represents a potential therapy for severe rheumatoid arthritis (RA). As a prelude to clinical trails, the safety and efficacy of haemopoietic stem cell (HSC) mobilisation required investigation as colony-stimulating factors (CSFs) have been reported to flare RA. A double-blind, randomised placebo-controlled dose escalation study was performed. Two cohorts of eight patients fulfilling strict eligibility criteria for severe active RA (age median 40 years, range 24-60 years; median disease duration 10.5 years, range 2-18 years) received filgrastim (r-Hu-methionyl granulocyte(G)-CSF) at 5 and 10 microg/kg/day, randomised in a 5:3 ratio with placebo. Patients were unblinded on the fifth day of treatment and those randomised to filgrastim underwent cell harvesting (leukapheresis) daily until 2 x 10(6)/kg CD34+ cells (haemopoietic stem and progenitor cells) were obtained. Patients were assessed by clinical and laboratory parameters before, during and after filgrastim administration. RA flare was defined as an increase of 30% or more in two of the following parameters: tender joint count, swollen joint count or pain score. Efficacy was assessed by quantitation of CD34+ cells and CFU-GM. One patient in the 5 microg/kg/day group and two patients in the 10 microg/kg/day group fulfilled criteria for RA flare, although this did not preclude successful stem cell collection. Median changes in swollen and tender joint counts were not supportive of filgrastim consistently causing exacerbation of disease, but administration of filgrastim at 10 microg/kg/day was associated with rises in median C-reactive protein and median rheumatoid factor compared with placebo. Other adverse events were well recognised for filgrastim and included bone pain (80%) and increases in alkaline phosphatase (four-fold) and lactate dehydrogenase (two-fold). With respect to efficacy, filgrastim at 10 microg/kg/day was more efficient with all patients (n = 5) achieving target CD34+ cell counts with a single leukapheresis (median = 2.8, range = 2.3-4.8 x 10(6)/kg, median CFU-GM = 22.1, range = 4.2-102.9 x 10(4)/kg), whereas 1-3 leukaphereses were necessary to achieve the target yield using 5 microg/kg/day. We conclude that filgrastim may be administered to patients with severe active RA for effective stem cell mobilisation. Flare of RA occurs in a minority of patients and is more likely with 10 than 5 microg/kg/day. However, on balance, 10 microg/kg/day remains the dose of choice in view of more efficient CD34+ cell mobilisation.
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PMID:A randomised, blinded, placebo-controlled, dose escalation study of the tolerability and efficacy of filgrastim for haemopoietic stem cell mobilisation in patients with severe active rheumatoid arthritis. 987 64


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