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:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The following 10 enzymes were assayed in 187 amniotic fluid and maternal serum samples at 15-42 weeks of gestation: alkaline phosphatase, heat-stable alkaline phosphatase (only in amniotic fluid), acid phosphatase, alanine aminotransferase, aspartate aminotransferase, alpha-amylase, gamma-glutamyltransferase, creatine kinase, lactate dehydrogenase, and lysozyme. The normal reference ranges are reported for amniotic fluid and maternal serum enzymes, together with the abnormal values accompanying neural tube defects and EPH-gestosis. The determination of gamma-glutamyltransferase, heat-stable alkaline phosphatase and creatine kinase was found to be of appreciable diagnostic significance in clinical practice.
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PMID:Variation in some enzymes in amniotic fluid and maternal serum during pregnancy. 256 24

For 7 working days running the ethyleneoxide (EtO) concentration has been determined in a medium sized sterilization plant of a medical endoscopy department. Sampling was taken from passive collectors of 3 M. The concentrations were 4 times (= 57% of the whole measured values) under the detection limit of 0.25 ppm = 0.46 mg/m3 in accordance with an eight hour shift; the EtO-level of 1.5, 2.1 and 9.2 ppm stayed for the remaining cases. Consequently the present valid TRK-value of 3 ppm was exceeded only one time. The exposition duration was between 0.6 and 13 years (median 5.5 years) for these 7 participants with a mean age of 33.4 (median 5.5 years). On the occasion of routine laboratory checks which included the analysis of important hematological, hepatological, nephrological and immunological values, no EtO-exposure has been found which was in causal connection with pathological findings. The search for specific RAST-IgE-antibodies against EtO in serum passed negatively. The enzyme activities of the gamma-GT correlated approximately with the anamnestic mentioned alcohol quantity, consumed daily.
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PMID:[Occupational medicine studies of 7 ethylene oxide-exposed endoscopy nursing professionals]. 312 77

A cell line, GBM, was established from a human malignant glioblastoma and was characterized with particular reference to its response to conventional drugs. The GBM cell line exhibited a 73 +/- 7 h doubling time in monolayer cultures. Expression of glial fibrillary acidic and S-100 proteins was observed. Karyotype analysis of GBM cells at early passages revealed the presence of two near-triploid clones (A and B) with multiple chromosome rearrangements; a 100% frequency for clone B was observed in the established cell line. GBM cells had tumorigenic properties, since the s.c. injection of cultured cells into nude mice gave rise to slowly growing tumors. The morphology of GBM cells was retained during in vitro and in vivo passages, as judged by light microscopy. GBM cells were relatively resistant to most conventional drugs; among the tested drugs, only taxol exhibited a marked cytotoxic effect comparable to that found in cells of a different tumor type. GBM cells were found positive for the epidermal growth factor receptor, HER2-neu and P-glycoprotein by flow cytometry of cells labelled with monoclonal antibodies. In spite of the expression of relatively high gamma-glutamyltransferase activity, the intracellular glutathione level was comparable to that of other chemosensitive tumor cells. This glioblastoma cell line is a suitable model for the identification and preclinical studies of new agents and provides an additional system to explore the molecular basis of the intrinsic drug resistance of glioblastoma.
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PMID:Characterization of an established human, malignant, glioblastoma cell line (GBM) and its response to conventional drugs. 792 29

Organ Weight, hematologic and blood chemistry values were determined to establish reference values in the female ferret. Organ weight per kg body weight was calculated for various organs. Body surface area (BSA) was also determined by the direct method, and K values (constant) were calculated. The K value was 3.48 in the Dubois and Dubois equation, and 9.69 in the Meeh-Rubner equation. Blood samples were used to record 10 hematologic and 57 serum (plasma) chemistry values, and 7 immunological parameters. Among hematologic values, values whose coefficient of variation (cv) exceeded 30% were RBC, WBC and PLT. In blood chemistry, the CV of gamma-G, UA, ZTT, GPT, gamma-GTP, MAO, ALD and IgG exceeded 30%. In the total amino acid analysis, only the CV of TAU exceeded 30%. Electrophoretograms of amylase and CPK isozyme were quite different from those of humans. Although 1-MEHIS, 3-MEHIS and CAR have not been detected or are present in trace amounts in human plasma, concrete values were detected in female ferret plasma. Hematologic and serum chemistry values were in general agreement with normal values seen in cats and dogs. However, the alpha 1-G percentage, and ALP and amylase activities were lower than the corresponding values in cats and dogs. The RBC count, RET-C percentage and LDH activities were higher than in cats and dogs. Since there have been no comprehensive articles on reference values for the female ferret, the present report contributes to studies that involve this animal as an experimental model.
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PMID:Reference values for organ weight, hematology and serum chemistry in the female ferret (Mustela putrius furo). 851 87

The carcinogenic and metastatic processes are thought to consist of a sequence of steps, and animal models featuring highly metastatic lesions are clearly necessary to allow analysis of the whole process of transformation from preneoplastic changes to high grade metastatic tumors, and to access effectiveness of therapeutic treatments of advanced cancers in vivo. The purpose of the present study was to establish a model and to screen for reported genetic alterations in induced lesions. In the present study, it was confirmed that lung metastasis of hepatocellular carcinomas (HCCs) induced in male F344 rats by N-nitrosomorpholine (NNM), given in the drinking water at a dose of 120 ppm for 24 weeks, was significantly enhanced by additional carcinogenic pretreatments and that a single i.p. injection of 100 mg/kg body weight N-diethylnitrosamine (DEN) alone was sufficient for that purpose. Molecular biological analyses of the induced lesions revealed point mutations in the p53 gene in 60.9% of HCCs, and elevated expression of mRNAs for p53, c-myc, c-fos, TGF-alpha, TGF-beta1, alpha-fetoprotein, GST-P, and GGT, and decreased mRNA expression of EGF and EGFR in HCCs when compared to controls. No obvious association of gene alterations with metastatic potential of primary tumors was found except for an increase in the incidence of p53 mutations. Since the process of metastasis is thought to be sequential and selective, further comparative analysis of metastatic and primary lesions should clarify the mechanisms involved in the multi-step process of metastasis.
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PMID:Highly metastatic hepatocellular carcinomas induced in male F344 rats treated with N-nitrosomorpholine in combination with other hepatocarcinogens show a high incidence of p53 gene mutations along with altered mRNA expression of tumor-related genes. 902 67

Our previous studies in the hamster pancreatic cancer model have indicated that pancreatic ductal adenocarcinomas derive not only from ductal/ductular cells but also from islets. To verify the presence of carcinogen-responsive cells within islets, we tested the effect of the pancreatic carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) on recently established continuous hamster pancreatic islet culture. Isolated pure pancreatic islets of hamsters were treated in vitro with BOP at a concentration of 0.25 mM three times a week for 19 weeks. Each treatment week was designed as a stage. The growth of these cells, designated KL5B, was compared with untreated cultured islets, designated KL5N. As in our previous study, between 14 and 21 days of culture, exocrine and intermediary cells developed within both KL5N and KL5B islets, which were then replaced by undifferentiated cells. No differences were found in the growth patterns of KL5N and KL5B until stage 4, when KL5B cells showed accelerated cell growth and cell pleomorphism, which increased gradually at later stages of treatment. Anchorage-independent and in vivo growth did not appear until stage 19. Mutation of c-Ki-ras at codon 12 (GGT-->GAT) was detected in KL5B cells but not in KL5N cells. In vivo KL5B cells formed anaplastic invasive cancer with areas of glandular formation, overexpressed TGF-alpha and EGFR, expressed cytokeratin, vimentin, laminin and alpha-1 antitrypsin and reacted strongly with L-phytohemagglutinin and tomato lectin. Some cells within islets are responsive to the carcinogenic effects of BOP. Whether these cells represent islet cell precursors (stem cells) or malignant transdifferentiated islet cells remains to be seen.
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PMID:Induction of adenocarcinoma from hamster pancreatic islet cells treated with N-nitrosobis(2-oxopropyl)amine in vitro. 1006 71

The cell surface aminopeptidase N (APN/CD13), overexpressed in tumor cells, plays a critical role in angiogenesis. However, potent, selective, and, particularly, noncytotoxic inhibitors ot this protein are lacking, and the present work was undertaken with the aim of developing a new generation of noncytotoxic inhibitors that bind to APN/CD13. In this context, we have synthesized a series of novel flavone-8-acetic acid derivatives. Among the herein described and evaluated compounds, the 2',3-dinitroflavone-8-acetic acid (19b) proved to be the most efficient and exhibited an IC(50) of 25 microM which is 2.5 times higher than that of bestatin (1), the natural known inhibitor of APN/CD13. However, in contrast to bestatin (1), the dinitroflavone 19b did not induce any cytotoxicity to cultured human model cells. The presence of other substituents such as NO(2) or OCH(3) groups at the 3'- or 4'-position of the B phenyl group, or the existence of steric constraints (compounds 24 and 29), did not improve selectivity and potency. The flavone 19b affinity for APN/CD13 is not recovered with other proteases such as matrix metalloproteinase-9 (MMP-9), angiotensin converting enzyme (ACE/CD143), neutral endopeptidase (NEP/CD10), gamma-glutamyl transpeptidase (CD224), or the serine proteases dipeptidyl peptidase IV (DPPIV/CD26) or cathepsin G.
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PMID:Synthesis and biological evaluation of novel flavone-8-acetic acid derivatives as reversible inhibitors of aminopeptidase N/CD13. 1293 Jan 51

A real-time PCR technique with automated computerized analysis (TaqMan ) was tested to detect K-ras mutations in 66 patients suffering from NSCLC. This technology is characterized by high reproducibility of data and a time-saving analysis procedure. In 11% (7/66) of the tumour specimens and 2% (1/58) of adjacent tumour-free lung specimens a K-ras codon 12 mutation was detected. In adenocarcinomas containing > or =40% tumour cells, however, K-ras mutations were seen in 25% of the cases. The point mutations detected in tumours were GGT right curved arrow TGT in five cases and GGT right curved arrow GTT in two cases. As compared with immunohistochemical parameters, the K-ras mutated group was characterized by a c-erbB-2 negativity (p=0.04) and a smaller number of c-erbB-3 (p=0.02) positive cases. EGFR, bcl-2, p53, Ki-67 and p120 expression did not differ significantly. Determination of the K-ras point mutations by automated TaqMan PCR in NSCLC tumour specimens is feasable and highly specific. Due to its high throughput capacity this method represents a valuable tool for routine screening.
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PMID:Automated real-time PCR to determine K-ras codon 12 mutations in non-small cell lung cancer: comparison with immunohistochemistry and clinico-pathological features. 1296 94

Forty free-ranging elk (Cervus elaphus manitobensis) were captured by net gun in Riding Mountain National Park (Manitoba, Canada) during February 2002 and were administered either saline (control) or xylazine by the intranasal route, to evaluate the efficacy and benefit of intranasal xylazine to reduce stress. Elk that received xylazine had higher relaxation scores than control elk, and the onset of sedation occurred quickly, often <1 min. Serum concentrations of cortisol, creatine kinase, and gamma-glutamyltransferase were lower in elk that received xylazine than in control elk. At the conclusion of handling, the intravenous administration of yohimbine quickly abolished the sedative effect of xylazine, which allowed elk to be released without concern of physical injury due to ataxia. The intranasal administration of xylazine can be used to reduce stress in wild animals under situations where they are being handled while physically restrained.
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PMID:Intranasal administration of xylazine to reduce stress in elk captured by net gun. 1546 26

Activating mutations of Ras gene families have been found in a variety of human malignancies, including lung cancer, suggesting their dominant role in tumorigenesis. Many studies have showed that the Kras gene is activated by point mutations in approximately 15-20% of non-small cell lung cancers (NSCLCs), however, there are only a few reports on Nras mutations in NSCLC. We have genotyped Nras mutation status (n=195) and Kras mutation status (n=190) in surgically treated lung adenocarcinoma cases. The presence or absence of Nras and Kras mutations was analyzed by real-time quantitative polymerase chain reaction (PCR) with mutation-specific sensor and anchor probes. EGFR mutation status at kinase domain has already been reported. Nras mutation was found in 1 of 195 patients. This mutation was a G-to-T transversion, involving the substitution of the normal glycine (GGT) with cystein (TGT) and thought to be a somatic mutation. The patient was male and a smoker. Kras mutant patients (11.1%; 21/190) had a significantly worse prognosis than wild-type patients (p=0.0013). Eighty-two EGFR mutations at kinase domain had exclusively Nras or Kras mutations. Although Nras gene mutation might be one of the mechanisms of oncogenesis of lung adenocarcinoma, this was a very rare event. Further studies are needed to confirm the mechanisms of Nras mutations for the sensitivity of molecular target therapy for lung cancer.
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PMID:Nras and Kras mutation in Japanese lung cancer patients: Genotyping analysis using LightCycler. 1767 10


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