Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 53-year-old woman was admitted to our hospital on Nov. 16, 1987, because of general fatigue. On admission, she had hepatosplenomegaly and her peripheral blood profile showed a white blood cell count (WBC) of 309 x 10(3)/microliters with immature neutrophils, a hemoglobin level (Hb) of 7.6 g/dl, platelet count (PLT) of 536 x 10(3)/microliters, neutrophilic alkaline phosphatase (NAP) score of 44. Both Vitamin B12 and LDH levels were high. The bone marrow showed marked myeloid hyperplasia. In a cytogenetic study, Ph1 was found in 3 of 8 metaphases and Ph1 with an additional abnormality of 8 trisomy was noted in 5 of 8 metaphases. She was diagnosed as having chronic myelogenous leukemia (CML) and treated by i.m. injection of interferon (IFN)-alpha at a daily dose of 6 x 10(6) U. Administration of IFN-alpha induced fever for a few days. WBC, PLT count and LDH level gradually decreased, and the NAP score and hepatosplenomegaly improved. She achieved remission in February, 1988. Administration of IFN-alpha was stopped in April, 1988, when the bone marrow showed hypocellularity and normal karyotype. She was treated with 20 mg of prednisolone daily from May until August, because of progressive pancytopenia. She had received no treatment until July, 1989. In May, 1989, the bone marrow again showed myeloid hyperplasia and Ph1 was found in all cells analyzed. Therefore, we resumed IFN-alpha treatment. It is interesting that remission of CML continues for more than one year after discontinuation of IFN-alpha in this case.
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PMID:[One-year remission of chronic myelogenous leukemia (CML) after discontinuation of interferon-alpha]. 221 81

Primary cultures of defined populations of mouse trophoblast, isolated from mature placentas, were analyzed for their MHC antigen expression and for the modulatory effect of interferon (IFN) by antibody- and complement-mediated cytotoxicity and flow cytofluorometry. The cells were obtained from placentas by enzymatic digestion, followed by Percoll gradient fractionation, and are large, fetally derived epithelial cells, which we previously characterized and identified as trophoblast cells. After 2 days in culture, a significant proportion of the trophoblast cells were susceptible to antibody- and complement-mediated lysis by anti-paternal strain alloantisera (40%) and, to a lesser degree, by an anti-class I monoclonal antibody (20%). Flow cytofluorometric analysis indicated that 20 to 50% of the cultured trophoblast cells expressed low levels of paternal strain class I antigens as compared to L cell fibroblasts. After culture for 48 hr with IFN-alpha/beta or IFN-gamma, the percent of class I-positive cells was increased to 68 to 76%, as was the mean fluorescence intensity, which correlated with the increased percent of antibody- and complement-mediated specific lysis (73%). No expression of class II MHC antigen by the cultured trophoblast cells was detected, even after culture in the presence of IFN-gamma. The cultured trophoblast cells, when tested for alkaline phosphatase (AP) activity, were composed of strongly positive and weakly positive subpopulations. An inverse correlation between strength of AP activity and the expression of H-2 was observed by double staining. These results indicate that trophoblast cells cultured in vitro are able to express paternal strain class I but not class II MHC antigens, as has been reported in vivo, and that this expression can be modulated by IFN. Further study of these cells should provide important clues for the understanding of materno-fetal coexistence in the face of MHC antigen differences.
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PMID:Expression of MHC antigens on murine trophoblast and their modulation by interferon. 242 87

K562 is a human leukemic cell line used as model of hematopoietic differentiation. A variety of differentiation-inducing agents was used in this study, and the expression of surface membrane antigens associated with specific lineages of differentiation and changes in the cytochemistry of the induced cells were monitored. Sodium butyrate, hemin, retinoic acid, dimethyl sulfoxide (DMSO), phorbol myristate acetate (PMA), and interferon induced unique alterations in the binding of monoclonal antibodies specific for erythroid, granulocytic, monocytic, and megakaryocytic lineages. Hemoglobinization, Sudan Black B, glycogen content, nonspecific esterase, alkaline phosphatase, and 5'-nucleotidase staining were also altered. K562 cells were terminally differentiated with PMA to nitroblue tetrazolium-(NBT) positive macrophages. Expression of 3-fucosyl-N-acetyl lactosamine, previously thought to be myeloid specific but found on all early hematopoietic progenitors, was modulated during differentiation to nonmyeloid lineages. Lineage infidelity was noted during functional differentiation along all hematopoietic lineages. The presence of multiple lineage surface markers and cytoplasmic characteristics in leukemic cells is not indicative of lack of potential to differentiate. K562 cells cannot be compared to any normal stage of hematopoietic differentiation, but they do have the capacity to differentiate along erythroid, macrophage, and megakaryocytic lineages.
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PMID:Differentiation of K562 leukemia cells along erythroid, macrophage, and megakaryocyte lineages. 242 57

The concomitant presence of B antigens and of the antigen recognized by the monoclonal antibody Leu-M5 (CD11c) on neoplastic lymphoid cells has been reported to be largely restricted to hairy cell leukemia (HCL). The authors studied Leu-M5 reactivity of neoplastic cells from 59 patients whose specimens were referred with a stated diagnosis of HCL by using the alkaline phosphatase anti-alkaline phosphatase technique on peripheral blood (PB) and bone marrow (BM) specimens. Tartrate-resistant acid phosphatase (AcP-T) activity was also studied. In 49 patients, HCL had been confirmed previously by BM biopsy, and specimens were evaluated for disease status during or after therapy with interferon (IFN) or 2'-deoxycoformycin. The remaining ten patients were newly referred for confirmation of the diagnosis of HCL before therapy. In all 55 patients in whom the BM biopsy demonstrated HCL, virtually every leukemic cell was Leu-M5 reactive, and the reaction proved, in some cases, to be helpful in the detection of small numbers of hairy cells in PB or BM preparations. AcP-T reactivity was demonstrated in the neoplastic cells of 52 of these 55 patients, including all but 3 of those receiving IFN, and was helpful in confirming persistent leukemia when interpretation of BM biopsy sections was difficult because the numbers of hairy cells were small. However, in four of the ten newly referred patients, BM biopsy showed features of splenic lymphoma with villous lymphocytes, rather than HCL. The neoplastic cells of these four patients were of B-cell origin and in three were Leu-M5 reactive. The authors' study indicates that Leu-M5 is present in nearly all hairy cells, but its presence in conjunction with other B-cell markers is not specific for HCL.
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PMID:Evaluation of Leu-M5 (CD11c) in hairy cell leukemia by the alkaline phosphatase anti-alkaline phosphatase technique. 245 31

Two stable hybridoma cell lines secreting specific antibodies against human gamma interferon (HuIFN-gamma) were established. Both monoclonal antibodies (designated as MD-1 and MD-2) belong to the IgG1/kappa subclass and neutralize the antiviral activity of natural and recombinant DNA derived HuIFN-gamma (nHuIFN-gamma and rHuIFN-gamma respectively), although MD-1 is far more effective than MD-2. MD-1 and MD-2 recognize different epitopes and do not compete with each other in binding to HuIFN-gamma as concluded from competition assays. In a 'Western' blot, both antibodies reacted with the 20 kDa and 25 kDa polypeptides present in nHuIFN-gamma preparations. A sandwich enzyme immunoassay using microtiter plates coated with unlabeled MD-2 was developed. Biotinylated MD-1 was used as the second antibody. Bound MD-1 was detected by an avidin/alkaline phosphatase enzyme reaction. This immunoassay is highly specific and as sensitive as a bioassay. A radioimmunoassay using MD-2 coated on polystyrene balls and 125I-labeled MD-1 as the second antibody showed a sensitivity comparable to that of the enzyme immunoassay.
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PMID:Monoclonal antibodies to human immune interferon and their use in a sensitive solid-phase ELISA. 258 59

The present report describes a comparative study in dwarf goats on human IFN-alpha 2a (0.5 x 10(6) IU kg-1 body weight IM), poly I: poly C (an interferon inducer; 30 micrograms kg-1 b.w. IV), and Escherichia coli endotoxin (an I1-1 inducer; 0.1 micrograms kg-1 b.w. IV). Although IFNs are considered to be species specific, human IFN-alpha 2a was very potent in dwarf goats. All 3 stimuli induced the 'acute phase response'. Among the varied physiological alterations, which together produce this response, are fever and depression, inhibition of gastric function, tachycardia, a decrease in serum alkaline phosphatase activity, leukopenia, lymphopenia and neutropenia followed by neutrophilic leukocytosis, hypoferraemia and hypozincaemia. The results suggest that, apart from I1-1, IFN-alpha also seems to mediate the systemic 'acute phase response' to certain exogenous stimuli.
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PMID:Comparative observations of fever and associated clinical, haematological and blood biochemical changes after parenteral administration of poly I: poly C, interferon-alpha 2a and Escherichia coli endotoxin in goats. 265 64

The activity of the enzyme ornithine decarboxylase (ODC) is increased in confluent culture of two breast cancer cell lines (T47D and MCF-7) following a change of medium. The increase in activity is maximum at 12 hours and this level is reduced in cells treated with high concentrations of HuIFN-alpha. However, the increased level of ODC activity seen in the first few hours after medium change can be stimulated by low concentrations of interferon (10-100 units per ml). The activity of the acidic and alkaline phosphatase of the above cell lines are affected by HuIFN-alpha similar to ODC. In stimulating levels of ODC and phosphatases, interferon is acting similar to mitogens, and in T47D and MCF-7 cells this stimulatory effect precedes the inhibitory effect more commonly seen in interferon-treated cells.
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PMID:Ornithine decarboxylase and phosphatase activity can be stimulated by low concentrations of interferon in human breast cancer cell lines. 285 Oct 88

A case of complete remission of adult T-cell leukemia (ATL) induced by beta-interferon is reported. A 46-year-old male was diagnosed as ATL because of the increased number of ATL cells with deeply indented and lobulated nuclei in the peripheral blood, accompanied by elevated values of the lactic dehydrogenase, the alkaline phosphatase, and the calcium in the serum. The result of the cell surface marker analysis of peripheral blood lymphocytes was compatible with ATL and anti-ATL associated antibody (ATLA) was positive. The integration of proviral deoxyribonucleic acid (DNA) of human T-cell leukemia virus type I(HTLV-I) was proved in the peripheral blood lymphocytes using Southern blot hybridization. Since an ordinal chemotherapy was not so effective for this patient, he was treated with 1.8 X 10(7) units of recombinant beta-interferon (beta-IFN) per day for 7 days as one course. After 5 courses of treatment, a markedly favorable response was recognized, and he achieved complete remission. A lower dose of beta-IFN (9 X 10(6) units per day for 3 days as one course, one or two courses per month) has been continued and he has still been in a complete remission state for 10 months. It is concluded that beta-IFN should be used to treat ATL.
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PMID:A first case of complete remission of beta-interferon sensitive adult T-cell leukemia. 289 May 36

The unique curability of gestational trophoblastic tumors may in part be attributable to a host immunologic response. The occurrence of rapidly progressive and fatal choriocarcinoma may be favored by histocompatibility between patients and their partners. However, histocompatibility is not a prerequisite for the development and persistence of gestational choriocarcinoma. The expression of HLA by choriocarcinoma cells in culture is enhanced following incubation with gamma-interferon and this may be of both biologic and clinical significance. Complete molar pregnancy is a complete allograft because all molar chromosomes are of paternal origin. Patients with complete mole are sensitized to paternal HLA antigen which is expressed in molar tissue. Other polymorphic antigen systems including trophoblast-leukocyte common antigens and placental-type alkaline phosphatase are also expressed in molar tissue. We have studied the immunopathology of the molar implantation site to investigate possible humoral and cellular immune responses. The relationships among normal placenta, complete mole and choriocarcinoma are not clearly understood. The pattern of expression of oncofetal antigens in these three gestational tissues may be used to assess trophoblastic differentiation. In studies to date, molar trophoblast has the same pattern of expression of oncofetal antigens as normal placental trophoblast. We will review recent advances in our understanding of the immunobiology of gestational trophoblastic disease and suggest new directions for further research.
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PMID:Immunobiology of complete molar pregnancy and gestational trophoblastic tumor. 303 May 77

Sixty-nine patients with hairy-cell leukemia (HCL) were treated with interferon alfa-2b (IFN) in a single-institution study. The dose used was 2 x 10(6) U/m2 self-administered subcutaneously three times weekly, for a planned treatment duration of 12 to 18 months. Of the 68 evaluable patients, the major response rate was 75%, with 13% complete responses (CRs) and 62% partial responses (PRs). An additional eleven patients (16%) had minor responses (MRs). Duration of response was denoted as failure-free survival (FFS), defined as the time from the end of IFN therapy to a need for further antileukemic therapy. Of the 60 responding patients followed after discontinuation of IFN, 27 have relapsed, requiring further therapy. The median actuarial FFS for these 60 patients is 25.4 months. All but five patients are alive, and the actuarial overall survival for the 69 patients is 91% +/- 4% at 4 years from the start of IFN. The best indicators of relapse were the neutrophil alkaline phosphatase (NAP) score and degree of residual bone marrow hairy cells (%HCL) at the completion of therapy. Patients with NAP less than 30 (n = 21) had the best prognosis (median FFS, 30.4 months), while those with NAP greater than or equal to 30 and %HCL less than or equal to 30 (n = 21) or %HCL greater than 30 (n = 16) had intermediate and poor prognoses, respectively (median FFS, 23.5 and 12.4 months) (P = .0005). Fourteen of the relapsing patients are evaluable for response to a second course of IFN, with seven PRs and four MRs. Stratified randomized trials are indicated to determine the role of maintenance therapy for responding patients.
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PMID:Relapse after interferon alfa-2b therapy for hairy-cell leukemia: analysis of prognostic variables. 305 3


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