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)

Acute toxic hepatic necrosis is common and may be fatal. Predicting clinical outcome may be aided by following serum markers that could indicate recovery or may signify massive (substantial) destruction of functional liver mass. Previously, in a published case of chloroform poisoning, we serially assayed serum biomarkers of hepatocellular necrosis (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase) and markers of hepatocellular regeneration (alpha-fetoprotein, retinol-binding protein, gamma-glutamyl transferase, and des-gamma-carboxyprothrombin). We noted a decline in necrotic markers and a synchronous elevation in regenerative markers, which could be suggestive of a favorable outcome in similar cases. We now report 6 Amanita mushroom poisonings with favorable outcome and 2 fatal acetaminophen poisonings in which the same markers were observed. Our results further support our hypothesis that a sustained decline in serum markers of hepatocyte necrosis with a concurrent elevation in regenerative markers could aid in prediction of favorable outcome in patients with acute liver injury.
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PMID:Biomarkers of liver regeneration allow early prediction of hepatic recovery after acute necrosis. 1047 40

Most urologists perform adjuvant radiation therapy for stage 1 (TxN0M0) testicular seminoma after orchiectomy, although the majority of patients with clinical stage 1 seminoma do not have occult metastases and therefore do not require elective nodal irradiation. However, there are currently no clinical or histological parameters that can be used to distinguish patients who need radiation therapy from those who do not. We reported previously that estimates of volume-weighted mean nuclear volume (MNV) were a better predictor of the prognosis of prostate cancer and renal cell carcinoma than subjective histological grading. Here, we examined the usefulness of estimation of MNV for predicting the prognosis of primary testicular seminoma. A retrospective study of 57 patients with testicular seminoma diagnosed between April 1981 and March 1997 at Kobe City General Hospital was performed. Unbiased estimates of MNV data were compared for prognostic value with the level of beta-human chorionic gonadotropin (beta-HCG), alpha-fetoprotein (AFP), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH). Fifty patients were stage 1 (TxNoMo), and 7 patients were stage 2 (TxN1-2M0). All patients received orchiectomy, followed by radiation therapy. Estimates of MNV of stage 2 patients were significantly larger than that of stage 1 patients (P = 0.0142). Although the LDH level was also significantly higher in stage 2 (P = 0.001), there were no significant differences between stages 1 and 2 with respect to beta-HCG (P = 0.997), ALP (P = 0.226), and AFP (P = 0.467). Multivariate logistic regression analysis revealed that the estimate of MNV was the only variable predicting lymph node metastasis (P = 0.0315). In stage 1 patients, only the estimate of MNV was significantly correlated with progression-free survival (P = 0.0118). These findings indicate that the estimate of MNV may be an important prognostic indicator for testicular seminoma. Estimates of MNV may also be useful for excluding patients from surveillance protocols.
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PMID:Prognosis of primary testicular seminoma: a report on 57 new cases. 1078 78

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

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

Seminoma arising in patients with Klinefelter's syndrome is extremely rare; to our knowledge, only three cases have been reported in the English language literature. We report a case of intrapelvic seminoma in a 39-year-old man with Klinefelter's syndrome. Gross examination revealed that the tumor was a solid and irregular mass measuring 90 mm in diameter. The cut surfaces of this ill-defined tumor were yellow-white with necrotic foci. Histologically, the tumor cells were separated into lobules by branching, fibrous septa containing lymphocytes. In some parts of the tumor, a cord-like arrangement of tumor cells was present. Immunohistochemically, the tumor cells were strongly and diffusely positive for antiplacental alkaline phosphatase antibody along their cytoplasmic membranes, but negative for both chorionic gonadotrophin and alpha-fetoprotein. Based on these findings, we diagnosed this tumor as a seminoma. The testes when examined were found to be atrophic bilaterally, but with no tumor lesions. Chromosomal analysis yielded a 47XXY karyotype, compatible with Klinefelter's syndrome. These findings indicate a case of primary intrapelvic seminoma in Klinefelter's syndrome. The patient underwent intensive radiation therapy postoperatively, and he demonstrated no evidence of recurrence or metastasis during the 13-month period following surgery.
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PMID:Primary intrapelvic seminoma in Klinefelter's syndrome. 1156 17

Hepatocellular carcinoma is a primary tumor complicating liver disease, associated with cirrhosis in 80-90% of the cases. A kidney transplant recipient with chronic B and C viral hepatitis was admitted because of general malaise, renal function impairment and positive AST, ALT and alkaline phosphatase tests, and very high alpha-fetoprotein levels. Ascites, spontaneous bacterial peritonitis and renal failure developed. A CT showed multiple liver masses. Renal failure required hemodialysis. The patient died 17 days after the initial symptoms with hepatic encephalopathy. A postmortem liver biopsy confirmed the diagnosis of cirrhosis and hepatocellular carcinoma (HCC). This report, as well as a few others, shows the accelerated evolution of chronic viral hepatitis in kidney transplant patients and questions the convenience of kidney transplantation and the adequate follow up in chronic viral hepatitis.
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PMID:[Fatal acute hepatic failure with hepatocarcinoma presentation in a patient with renal transplant with asymptomatic chronic B and C hepatitis]. 1172 27

Primary intrahepatic rhabdomyosarcoma is extremely rare in children. We describe a case of pleomorphic rhabdomyosarcoma originating from the liver in an eight-year-old boy presenting with abdominal pain, spiking fever and a rapidly growing abdominal mass for one week. Preoperative imaging studies revealed a large solid tumor in the right lobe of the liver without any tumor elsewhere in the body. Serological study was negative for HBsAg and positive for anti-HBs. Biochemical tests including serum glutamic-oxalacetic and glutamic-pyruvic transaminase, alkaline phosphatase, bilirubin and alpha-fetoprotein were all within normal limits. The tumor was removed by an extended right hepatectomy. Histological and immunohistochemical examination confirmed a pleomorphic rhabdomyosarcoma. The patient eventually succumbed to tumor recurrence with massive internal hemorrhage two months after resection of the tumor. This is the first report of primary pleomorphic rhabdomyosarcoma of the liver in children. Abdominal ultrasonography, computed tomography scan and angiography are valuable for preoperative planning but the imaging findings are non-specific. Pathological examination with immunohistochemical stains remains the most important method in arriving at the exact diagnosis. The poor prognosis and early death of most previously reported cases imply the need for investigation of a more effective treatment method of this uncommon tumor.
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PMID:Primary pleomorphic rhabdomyosarcoma of the liver: a case report. 1262 94

Fetal blood was obtained in 35 normal pregnancies undergoing termination for psychosocial reasons between 11 and 17 weeks of gestation. Biochemical and endocrinological analyses were performed on each sample including concentrations of urea, creatinine, beta-microglobulin total protein, electrolytes, enzymes, alpha-fetoprotein (AFP), human chorionic gonadotrophin (HCG), thyroid stimulating hormone (TSH), thyroxin binding globulin (TBG), total thyroxin (TT4) and free thyroxin (FT4). The results were compared with values in maternal serum obtained at the same time. Fetal serum contained significantly higher concentrations of iron, beta-microglobulin, alkaline phosphatase (ALP), aspartate amniotransferase (AST), AFP, HCG and TSH and lower concentration of total protein, TBG and TT4 than maternal serum. Significant positive linear relationships were found between gestational age and the concentration of fetal serum total protein, ALP, TBG and FT4. Significant negative linear relationships were observed between gestational age and fetal serum beta-microglobulin and iron concentration. There were no significant correlations between fetal and maternal values. These data indicate that fetal blood biochemistry is not directly related to placental transfer and that the proteins and enzymes found inside the gestational sac are essentially of feto-placental origin with minimal contribution from the maternal protein metabolism. The comparison of coelomic fluid composition at 10-13 weeks with that of fetal serum at 11-17 weeks suggests that the anatomical changes in the human materno-fetal interface architecture between the early and late pregnancy periods could have a direct impact on materno-fetal transfer pathways.
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PMID:Blood biochemistry and endocrinology in the human fetus between 11 and 17 weeks of gestation. 1280 97

The in vitro differentiation of mouse embryonic stem cells into different somatic cell types such as neurons, endothelial cells, or myocytes is a well-established procedure. Long-term culture of rat embryonic stem cells is known to be hazardous, and attempts to differentiate these cells in vitro so far have been unsuccessful. We herein describe stable long-term culture of an alkaline phosphatase-positive rat embryonic stem cell-like cell line (RESC) and its differentiation into neuronal, endothelial, and hepatic lineages. RESCs were characterized by typical growth in single cells as well as in embryoid bodies when cultured in the presence of leukemia inhibitory factor. RESC expressed stage-specific-embryonic antigen-1 and the major histocompatibility complex class I molecule. For neuronal differentiation, cells were incubated with medium containing 10(-6) M retinoic acid for 14 days. For endothelial differentiation, RESCs were grown on Matrigel for 14 days, and for induction of hepatocyte-specific antigen expression, RESCs were grown in medium supplemented with fibroblast growth factor-4. Differentiated cells exhibited typical morphological changes and expressed neuronal (nestin, mitogen-activated protein-2, synaptophysin), glial (S100, glial fibrillary acid protein), endothelial (panendothelial antibody, CD31) and hepatocyte-specific (alpha-fetoprotein [alphaFP], albumin, alpha-1-antitrypsin, CK18) antigens. In addition, expression of hepatocyte-specific genes (alphaFP, transthyretin, carbamoyl-phosphate synthetase, and coagulation factor-2) was detected by reverse transcription polymerase chain reaction. We were able to culture RESCs under stable, long-term conditions and to initiate programmed differentiation of RESCs to endothelial, neuronal, glial, and hepatic lineages in the rat species.
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PMID:Long-term culture and differentiation of rat embryonic stem cell-like cells into neuronal, glial, endothelial, and hepatic lineages. 1283 96

We previously reported that the HS-4 insulator, derived from the chicken beta-globin locus, was able to shield a downstream inducible promoter from viral enhancers or silencers present in the genome of adenovirus vectors. In this study, we constructed two recombinant adenoviruses (Ad) that express an alkaline phosphatase (AP) reporter gene driven by an alpha-fetoprotein (AFP) enhancer/promoter with and without HS-4 insulator (Ad.HS4.AFP-AP and Ad.AFP-AP). The insulated vector, Ad.HS4.AFP-AP, conferred significantly higher AP expression than Ad.AFP-AP in all AFP-producing hepatocellular carcinoma cell lines (HepG2, Hep3B, and HuH7) examined. AP expression from Ad.HS4.AFP-AP was specific to hepatoma cells and barely detectable in AFP-negative tumor cell lines and normal human cells, including human hepatocytes. Intravenous infusion of viral vectors into mice with liver metastasis derived from Hep3B hepatoma cells resulted in AP expression exclusively localized to tumor cells. The number of tumor cells with detectable AP expression was significantly higher in mice infused with Ad.HS4.AFP-AP than in mice that received the non-insulated vector. This study demonstrates that the HS-4 insulator in the context of an Ad vector can increase the activity of the AFP promoter, while maintaining its tumor-specificity in vitro and in vivo. Considering that the anti-tumor activity of oncolytic vectors often depends on the level of pro-apoptotic or suicide gene expression, insulators might be a useful tool to improve the efficacy and specificity of these vectors.
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PMID:Insulation from viral transcriptional regulatory elements enables improvement to hepatoma-specific gene expression from adenovirus vectors. 1287 74


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