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)

Severe hepatitis C virus (HCV)-related fibrosing cholestatic hepatitis leading to early liver failure has been reported only exceptionally. Of 259 HCV-infected renal transplant (RT) patients in one hospital unit, four (1.5%) are described, representing the first series of this particular post-RT disease. Patient mean age was 55.7 yr. Three were men. All had pretransplant, hepatitis B surface antigen-negative and were anti-HCV antibodies positive. Three of them showed pretransplant mild liver enzyme abnormalities, and all received kidneys from HCV-negative donors. All were on steroids, cyclosporine, and azathioprine (AZA). The clinical pattern appeared early after RT (mean, 11.5 mo). In three patients, hyperbilirubinemia (6.5 to 20 mg/dl) and high alkaline phosphatase levels (428 to 859 IU/L) were observed. Also, in all subjects, high gamma glutamyl transpeptidase levels (639 to 4270 IU/L), mild aspartate aminotransferase and alanine aminotransferase abnormalities, and serum HCV RNA were observed. Liver biopsy revealed diffuse fibrosis, leukocyte infiltrates, and different degrees of cholestasis, with typical signs of HCV hepatitis in only one patient. Two patients developed subfulminant liver failure and died 2 and 3 mo after biopsy, respectively. One patient also suffered hepatic failure, receiving a liver transplant. The fourth is alive on dialysis awaiting a combined kidney and liver transplant. It is concluded that fibrosing cholestatic hepatitis is a new, early, and severe complication after RT in HCV(+) patients, which appears in patients with ongoing HCV infection under AZA therapy, despite a nonaggressive immunosuppressive protocol. Both HCV and AZA could play a concurrent role in the pathogenesis of this severe complication after RT.
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PMID:Fibrosing cholestatic hepatitis in hepatitis C virus-infected renal transplant recipients. 962 Dec 97

9-(2-phosphonylmethoxyethyl)adenine (PMEA) and its closely related structural analogue (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) are potent inhibitors of retroviruses and hepatitis B virus. In its oral prodrug form (adefovir dipivoxil), PMEA is currently the subject of advanced phase II/III clinical trials for the treatment of HIV infections. PMEA has also been shown to be a potent differentiation-inducing agent. In the present study, PMEA was found to have a strong differentiation-inducing effect on rat choriocarcinoma (RCHO) cells, comparable to that of methotrexate, which is the drug of choice for the chemotherapy of choriocarcinoma in humans. PMEA induced differentiation of choriocarcinoma trophoblast cells in a concentration-dependent manner within the 2- to 50-microM concentration range, as ascertained by giant cell formation, alkaline phosphatase induction, progesterone secretion, and the disappearance of a cytotrophoblast-specific surface antigen. PMEA had to be exposed to the rat choriocarcinoma cell cultures for at least 2-3 days to achieve optimal growth inhibition and differentiation of the tumor cells. Unlike PMEA, (R)-9-(2-phosphonylmethoxypropyl)adenine failed to induce differentiation of proliferating cytotrophoblasts into nonproliferating, hormonally active giant cells. This points to the specificity of PMEA as an inducer of choriocarcinoma cell differentiation.
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PMID:Potent differentiation-inducing properties of the antiretroviral agent 9-(2-phosphonylmethoxyethyl) adenine (PMEA) in the rat choriocarcinoma (RCHO) tumor cell model. 977 47

Clinical course in hepatocellular carcinoma may be very different. We prospectively evaluated 96 patients with hepatocellular carcinoma unsuitable for radical therapy to investigate factors that could influence survival. Clinical, pathologic, and molecular data of patients were analyzed by univariate and multivariate analysis. The overall actuarial probability of survival at year 1, 2, 3, 4, 5, and 6 was 72%, 41%, 38%, 24%, 20%, and 9%. At univariate analysis, alpha-fetoprotein (AFP) (P =.0082); alkaline phosphatase (P =.0281); bilirubin (P =.0076); etiology (P =.0001); increment of tumor mass at month 3 (P =.0051); type of estrogen receptor (ER) in the tumor (P =.0000); prothrombin time (P =.0003); and portal vein thrombosis (P =.0000) had prognostic significance. At multivariate analysis, only type of ER (P =.0000) and bilirubin (P =.0030) showed independent predictive value for mortality. Survival was significantly longer in patients with wild-type estrogen receptors (P =.0000). Cumulative probability of survival at year 1, 2, 3, 4, 5, and 6 was 94%, 66%, 52%, 43%, 35%, and 18% for wild-type and 51%, 21%, 16%, and 9% for variant estrogen receptors (no patients alive after 4 years). Hepatitis B surface antigen (HBsAg)-positive patients with variant ERs had a median survival of 8 months versus 45 months in anti-hepatitis C virus-positive patients with wild-type ERs (P =.0001). In conclusion, (1) the presence of variant liver ER transcripts in the tumor was the strongest negative predictor of survival in inoperable hepatocellular carcinoma; (2) their presence was associated with spontaneous survival significantly worse than in patients with wild-type estrogen receptors; and (3) HBsAg-positive patients with variant receptors were characterized by the worst survival.
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PMID:Natural history of inoperable hepatocellular carcinoma: estrogen receptors' status in the tumor is the strongest prognostic factor for survival. 1091 29

We have performed immunophenotypical (IP) analyses of tumor infiltrating leukocytes (TIL) in both childhood brain tumors (medulloblastomas[MEDs]/primitive neuroectodermal tumors [PNETs] and astrocytomas [ASTRs]) and malignant melanomas (both primary and metastatic) employing a well-characterized library of monoclonal antibodies (MoABs) directed against leukocyte differentiation/activation associated antigens. The antigens were detected by an indirect, biotinstreptavidin conjugated alkaline phosphatase (AP) immunocytochemical technique. Our systematic cell-surface antigen expression profile analysis of 76 primary childhood brain tumors (34 MEDs/PNETs and 42 ASTRs) identified CD8+ CTL in 58/76 brain tumors. CD4+, MHC class II restricted helper lymphocytes were present in 65/76 brain tumors and represented 1-10% of the observed cells. Macrophages were present in 74/76 childhood brain tumor cases observed by us. Leukocyte common antigen (LCA) expression was demonstrated in all 76 brain tumors studied. MoAB UJ 308 detected the presence of premyelocytes and mature granulocytes in 60/76 brain tumors. They were localized perivascularly, within the tumor tissue, or close to necrotic regions. Natural killer (NK) cells were not defined in the childhood brain tumors observed in this study. The IP characteristics of the heterogeneous leukocytic infiltrate of 30 primary (PMs) and 10 metastatic melanomas (MMs) was also investigated by us. We established the presence of some type of melanoma infiltrating host's immunological effector cells in all 40 observed melanoma cases. More specifically, we found NK cells, macrophages and granulocytes in 30/30 PMs and 10/10 MMs. These effector cells represented the vast majority (> 80%) of the melanoma infiltrating immunocompetent cells. T lymphocytes were observed in 20/30 PMs and 6/10 MMs, but their numbers represented only between 5% to 10% of the heterogeneous leukocytic infiltrate. B cells were found in 22/30 PMs and 8/10 MMs, their numbers representing less than 5%. Presence of cells of the dendritic reticulum, involved in antigen presentation was not determined in any of the observed PMs and MMs. The notion that infiltration of the neoplastically transformed mass of cells by TIL is always a prognostically positive phenomenon has changed in recent years as research on extracellular matrix remodeling and angiogenesis have identified numerous secreted factors which are common to both neoplastically transformed cells and infiltrating leukocytes.
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PMID:Controversies on the prognostic significance of tumor infiltrating leukocytes in solid human tumors. 1092 5

The aim of this study was to evaluate the prognostic factors at presentation and survival in Italian patients with hepatocellular carcinoma (HCC). Clinical and demographic data of 176 patients consecutively observed from 1993 to 1997 were evaluated by univariate and multivariate analyses. Overall median survival was 18 months. At univariate analysis, low albumin, high bilirubin, high alkaline phosphatase, high alpha-fetoprotein (AFP); high platelet count, hepatitis B surface antigen (HBsAg)-positivity, the presence of ascites, of encephalopathy, of portal vein thrombosis (PVT), male sex, no treatment, poor differentiation, untreatable tumours and incidental diagnosis were each associated with shorter survival. HBsAg-positive subjects more often presented with untreatable lesions or diffuse tumours (P=0.001 and P=0.007, respectively) and had significantly worse survival (P=0.0057). By multiple regression analysis, low albumin, high bilirubin, abnormal AFP, presence of PVT and of untreatable lesions were independent risk factors for worse survival. Thus, the most important factors influencing survival are the degree of functional impairment of the liver, the presence of hepatitis B viral (HBV) infection, the type of diagnosis and the aggressiveness of the tumour.
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PMID:Prognostic features and survival of hepatocellular carcinoma in Italy: impact of stage of disease. 1116 52

A descriptive and cross sectional study was conducted to determine whether hepatic function changes in workers occupationally exposed to a mixture of organic solvents, were due to the exposure or confusing factors. A non random sample of 77 workers, operators and supervisors of the Olefin Plant I and II of a petrochemical industry in Maracaibo, Venezuela, was used. Their mean age was 29 +/- 7 years, and had at least one year of exposure to the solvents. This sample was compared with a group of employees of the administrative offices or control panel workers, with a mean age of 36 +/- 8 year and with similar anthropometric characteristics. Workers with a known history of liver disease, blood transfusions and diabetes mellitus were excluded of the study. In addition to a complete occupational disease medical history and a physical examination, serum samples were obtained to determine the activity of the aspartato aminotransferase (AST), alanin aminotransferase (ALT), gamma glutamiltransferase (GGT), alkaline phosphatase (AF), the concentration of the total bile acids (BAS), the surface antigen of hepatitis B(HbsAg) and the hepatitis A virus antibodies: AntiHAV-IgG and the AntiHAV-IgM. An urine sample was taken and analyzed by standard methodology to determine urinary phenols. The air concentrations of benzene, ethylbenzene, toluene and xylene were analyzed by gas chromathography. The serum activities of the liver enzymes, the concentration of bile acids and urinary phenols were not influenced by the exposure to the solvents. The increase of the activity of GGT was associated with obesity and alcohol consumption. The antibodies of the surface antigen of hepatitis A-IgM were normal in both groups and the antibodies for the antigen of hepatitis A-IgG presented a prevalence of 6% in the exposed group and 9% in the non exposed not being associated with liver abnormalities. The individual air concentrations of the solvents were below the environmentally permissible concentrations, except one sample of benzene (1, 14 ppm) that was over the allowed limit. The total maximum concentration of the mixture of organic solvents, resulting of the sum of fractions of each organic solvent, was within the allowed limits. In conclusion, obesity and alcohol consumption, and not the occupational factors, seem to be responsible for the alteration in GGT in workers of these Olefin Plants.
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PMID:[Liver function of workers occupationally exposed to mixed organic solvents in a petrochemical industry]. 1141 82

During systematic cell-surface antigen expression profile analyses of 76 primary childhood brain tumors [34 medulloblastomas (MED)/primitive neuroectodermal tumors (PNETs) and 42 astrocytomas (ASTR)], a library of monoclonal antibodies (MoABs) directed against various leukocyte-associated, lymphocyte cell-line differentiation antigens in childhood brain tumors was utilized. The antigens were detected employing an indirect, biotin-streptavidin conjugated alkaline phosphatase (AP) immunocytochemical technique. Major histocompatibility complex (MHC) class I restricted, tumor-associated antigen (TAA) specific, CD8(+) cytotoxic T lymphocytes (CTL) were identified in 58/76 (76.32%) brain tumors, and usually represented 1-10% of all cells, but in some cases 30-44% of the cells were CD8(+). CD4(+), MHC class II restricted helper lymphocytes were present in 65/76 (85.53%) brain tumors, and accounted for 1-10% of the observed cells. Macrophages were present in 74/76 (97.37%) brain tumors, and their number also represented 1-10% of all observed cells in the brain tumor frozen sections. Leukocyte common antigen (LCA) expression was detected in all 76 (100%) brain tumors studied. MoAB UJ 308 detected the presence of premyelocytes and mature granulocytes in 60/76 (78.95%) brain tumors. Natural killer (NK) cells were not defined in the observed brain tumors. The great majority of childhood glial tumors, particularly ASTRs express Fas (APO-1/CD95) receptor whereas normal cells in the central nervous system (CNS) do not. FasR is a transmembrane glycoprotein which belongs to the nerve growth factor/tumor necrosis factor (NGF/TNF) receptor superfamily. As part of our screening, the 42 childhood ASTRs were also investigated for expression of CD95. We detected strong expression (strong intensity of staining, number of stained cells 50-100%) of FasR, employing formalin fixed, paraffin-wax embedded tissue slides. Brain tumors and melanomas have been shown to produce their autocrine FasL, and are even capable of switching CD95-related signal transduction from the PCD pathway to a proliferative pathway. In view of our results, we conclude that: (1) the tumor infiltrating leukocytes in MEDs/PNETs and ASTRs represent a very diverse population and are present in a great majority of the cases studied; (2) the strong expression of FasR in ASTRs provides a manner in which T lymphocytes may exert their anti-tumor effects, but may also represent yet another way that tumors may evade the immune response; and (3) further observations of the expression of various antigens involved in juxtacrine, in situ growth control are necessary for the refinement of cellular immunotherapeutical approaches in the treatment of human malignancies.
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PMID:Immunocytochemical detection of leukocyte-associated and apoptosis-related antigen expression in childhood brain tumors. 1141 97

Mouse infection with murine cytomegalovirus (MCMV) is an established model for studying human cytomegalovirus infection. In this study, the relationship was analyzed between MCMV activity in organs of infected mice and the presence of infectious virus (viremia), viral genomes (DNAemia), or secreted virus-encoded proteins in the blood. For the latter, 2 recombinant viruses were constructed that encode for the hepatitis B virus surface antigen and the secreted alkaline phosphatase, respectively, as secreted marker proteins. The secreted markers correlated better with the infection in organs than DNAemia and viremia. The marker protein assays can serve as practical and sensitive tools for longitudinal monitoring of MCMV infection in individual mice.
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PMID:Secreted virus-encoded proteins reflect murine cytomegalovirus productivity in organs. 1167 22

We have analysed the surface antigen phenotype of a human embryonic stem (hES) cell line (H7) and the changes that occur upon differentiation induced by retinoic acid, hexamethylene bisacetamide and dimethylsulphoxide. The undifferentiated stem cells expressed Stage Specific Embryonic Antigen-3 (SSEA3), SSEA4, TRA-1-60, and TRA-1-8 but not SSEA1. In these characteristics they closely resemble human embryonal carcinoma (EC) cells derived from testicular teratocarcinomas, and are distinct from murine EC and ES cells. The undifferentiated cells also expressed the liver/bone/kidney isozyme of alkaline phosphatase detected by antibody TRA-2-54, the class 1 major histocompatability antigens, HLA-ABC, and the human Thy1 antigen. Differentiation of hES cells was induced by retinoic acid, HMBA and DMSO with the appearance of various cell types including neurons and muscle cells. The surface antigens characteristically expressed by hES cells were down-regulated following induction of differentiation and other antigens appeared, notably several ganglioside glycolipids detected by antibodies VIN-IS-56 (GD3 and GD2), VIN-2PB-22 (GD2), A2B5 (GT3) and ME311 (9-O-acetyl-GD3). Whereas the expression of HLA was slightly down-regulated upon differentiation, its expression was strongly induced by interferon-y in both the undifferentiated and the differentiated cells, although the induction in the differentiated cultures was considerably stronger than in the stem cells. In all of these features the human ES cells, and their pattern of differentiation, resembled the pluripotent human EC cell line NTERA-2 although clearly the range of cells generated by the hES cells was considerably greater.
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PMID:Surface antigens of human embryonic stem cells: changes upon differentiation in culture. 1203 29

Hepatitis C virus (HCV) infection is a common cause of liver disease in thalassemia major patients in Western, especially Mediterranean, countries. Its significance in thalassemic patients from Southeast Asia has not been critically evaluated. In this report, we describe our study of the prevalence of HCV infection among Thai patients with thalassemia. The relationships of the infection to blood transfusion and the infection's effects on liver function have also been determined. Of the 104 patients studied, 21 (20.2%) tested positively by enzyme immunoassay for anti-HCV antibody, whereas only 2 patients (2%) had the hepatitis B surface antigen. There was no significant relationship between the presence of anti-HCV antibodies and the number and frequency of blood transfusions. In fact, 2 patients (10%) who tested positive for anti-HCV antibodies had never received transfusions. Patients with anti-HCV antibodies had significantly abnormal liver functions, such as higher levels of serum aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) and lower levels of serum albumin, compared with patients without anti-HCV antibodies (P = .021, .017, and .004, respectively). However, there were also significant correlations between iron status as indicated by transferrin saturation or serum ferritin levels and SGOT, SGPT, and gamma-glutamyltransferase (GGT) levels. Moreover, abnormal liver function as represented by elevated levels of SGOT, SGPT, GGT, and serum alkaline phosphatase was observed more frequently in patients with iron overload than in patients with a lower degree of iron burden. The presence of HCV did not alter the effects of iron overload on liver function. The findings suggest that both HCV and iron overload are the main causes of abnormal liver function in Thai patients with thalassemia. The treatment of both problems, if coexisting in patients with thalassemia, is required to prevent progression to chronic liver disease.
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PMID:Prevalence and clinical significance of hepatitis C virus infection in Thai patients with thalassemia. 1468 98


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