bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cotreatment with a novel phosphoinositide analogue inhibitor and carmustine enhances chemotherapeutic efficacy by attenuating AKT activity in gliomas
Authors: Van Meter Timothy E. , Broaddus William C. , Cash Dana , Fillmore Helen 
Published: October 2006

AbstractBACKGROUND.Heightened activity of the AKT signaling pathway is prominent in malignant gliomas and has been suggested to play a role in treatment resistance. Selective targeting of AKT, therefore, may increase chemosensitivity. Recently, a novel class of AKT‐selective inhibitors has been described, including SH‐6, a phosphatidylinositol analogue.METHODS.The effects of SH‐6 on AKT signaling were tested in glioma cells, and the putative role of AKT signaling in chemoresistance was tested by attenuating AKT signaling pharmacologically and genetically. The initial characterization of SH‐6 included treatment of glioma cells with increasing doses of SH‐6 (0.30–30 μM) and examining the effects on AKT signaling proteins by Western blot analyses and in kinase assays with immunoprecipitated AKT1. Dose‐response studies with SH‐6 administered to glioma cell lines were performed using a luminescent cell‐viability assay (0.1–30 μM). Studies examining the effect of carmustine, either alone or in combination with either the phosphatidylinositol 3‐kinase inhibitor LY294002 or SH‐6, were performed by cell viability assays and clonogenic survival assays. The effect of carmustine on AKT activity as a response to treatment also was examined. Caspase assays were used to examine the potential role of apoptosis in SH‐6/ carmustine ‐elicited cell death. Finally, the induction of a dominant‐negative AKT1 transgene was used in combination with carmustine to demonstrate the role of AKT1 in carmustine chemoresistance.RESULTS.Serum‐stimulated phosphorylation of AKT1 was inhibited by SH‐6 at doses ≥10 μM (>70% decrease in Threonine 308 and Serine 473 phosphorylation of AKT1). In adenosine triphosphate assays, 72 hours of treatment with SH‐6 led to 50% lethal doses near 10 μM for 2 cell lines tested. SH‐6 enhancement of carmustine‐mediated cell death led to synergistic increases in Caspase 3/Capsase 7 activity, implicating apoptosis as the cell death mechanism. In clonogenic assays, SH‐6 cotreatment with carmustine significantly decreased the number of colonies at 10 μM (P < .05) compared with carmustine alone. No decrease was observed in cells that were treated with SH‐6 alone (10 μM). LY294002 (10 μM) was also able to enhance the effects of carmustine significantly in both cell lines.CONCLUSIONS.In the current study, the authors characterized the efficacy of a new class of adjuvant chemotherapeutics that show promise in enhancing the efficacy of standard chemotherapy regimens in gliomas. Cancer 2006. © 2006 American Cancer Society.
Age‐dependent decreases in mitogen‐stimulation level and RNA content in peripheral blood mononuclear cells of down syndrome patients
Authors: Hamurcu Zuhal , Demirtas Halil , Patiroglu Turkan , Kumandas Sefer , Imamoglu Nalan , Ozkul Yusuf , Donmez‐Altuntas Hamiyet 
Published: October 2006

AbstractObjective:The aim of the present study was to determine whether or not the phytohemagglutinin (PHA)‐activated proliferation and average RNA content in peripheral blood mononuclear cells (PBMC) of Down syndrome (DS) patients change with age.Method:Stimulated portion of PBMC and total RNA levels in these cells after 72 h of PHA stimulation from 38 DS patients were compared with 28 age‐matched healthy controls using flow cytometric measurement.Results:Decreased ratio of PBMC from DS patients undergoes mitogenic stimulation with age (r = −0.84, P = 0.000). This decrease is not observed in the cells of control individuals (r = 0.03, P = 0.869). Stimulated PBMC in infants with DS have higher level of RNA contents compared to controls (Z = 2.227, P = 0.026). While RNA content in mitogen‐stimulated PBMC of DS decreased progressively and significantly with age (r = −0.70, P = 0.000), no significant age‐related change in RNA content was found among the cells of healthy individuals in the range of 0–27 year old (r = 0.275, P = 0.157, P > 0.05).Conclusion:Age‐dependent decreases in mitogen‐activated proliferation ratio and average RNA content of PBMC from DS patients appear as regular events. These results may contribute to the explanation of the immune deficiency seen in DS patients since the PHA‐stimulated cells are principally T‐lymphocytes. This is the first report on the decrease in PHA‐stimulated proliferation ratio (stimulability) and RNA level in PBMC of DS patients in relation to age. © 2006 International Society for Analytical Cytology
Behavior of enteric neural crest‐derived cells varies with respect to the migratory wavefront
Authors: Druckenbrod Noah R. , Epstein Miles L. 
Published: October 2006

AbstractNeural crest‐derived cells colonize the entire gastrointestinal tract. The migration of these enteric neural crest‐derived cells (ENCCs) occurs by their formation of cellular strands that extend into the intestinal mesenchyme. We have studied the behavior of crest cells that underlies the formation and extension of these strands by time‐lapse microscopy. ENCCs expressing fluorescent marker molecules were visualized in situ in the embryonic mouse and chick gut. The major contributor to strand extension is from cells located within a region approximately 300 μm behind (rostral to) the most caudal cells in the migratory wavefront. Cells in the region immediately behind the leading cell of the strand either move intermittently in parallel with the leading cell, or advance caudally toward the wavefront over other ENCCs. Another addition to the strands arises from isolated cells located caudal to the wavefront. These cells showed a range of behavior including attachment and separation from the strands. The extending strands converged to form nodes, and then diverged along independent paths to form new strands, a behavior suggestive of attraction and repulsion. This behavior is probably responsible for the unique reticulated arrangement of ganglia in the enteric nervous system. As cells become positioned farther behind the wavefront, they exhibit more restricted movement and varied trajectories. We conclude that ENCCs exhibit different behaviors, depending on their position with respect to the wavefront. These different behaviors suggest a critical role for cell–cell interaction in the migratory process. Developmental Dynamics 236:84–92, 2007. © 2006 Wiley‐Liss, Inc.
Cross‐presentation of antigens from apoptotic tumor cells by liver sinusoidal endothelial cells leads to tumor‐specific CD8+ T cell tolerance
Authors: Berg Martina , Wingender Gerhard , Djandji Dominik , Hegenbarth Silke , Momburg Frank , Hämmerling Günter , Limmer Andreas , Knolle Percy 
Published: October 2006

AbstractDevelopment of tumor‐specific T cell tolerance contributes to the failure of the immune system to eliminate tumor cells. Here we report that hematogenous dissemination of tumor cells followed by their elimination and local removal of apoptotic tumor cells in the liver leads to subsequent development of T cell tolerance towards antigens associated with apoptotic tumor cells. We provide evidence that liver sinusoidal endothelial cells (LSEC) remove apoptotic cell fragments generated by induction of tumor cell apoptosis through hepatic NK1.1+ cells. Antigen associated with apoptotic cell material is processed and cross‐presented by LSEC to CD8+ T cells, leading to induction of CD8+ T cell tolerance. Adoptive transfer of LSEC isolated from mice challenged previously with tumor cells promotes development of CD8+ T cell tolerance towards tumor‐associated antigen in vivo. Our results indicate that hematogenous dissemination of tumor cells, followed by hepatic tumor cell elimination and local cross‐presentation of apoptotic tumor cells by LSEC and subsequent CD8+ T cell tolerance induction, represents a novel mechanism operative in tumor immune escape.
Unrelated medical care in life years gained and the cost utility of primary prevention: in search of a ‘perfect’ cost–utility ratio
Authors: van Baal Pieter H. M. , Feenstra Talitha L. , Hoogenveen Rudolf T. , Ardine de Wit G. , Brouwer Werner B. F. 
Published: October 2006

AbstractAn important subject of debate in cost–utility analysis of health care programmes is whether to include costs of unrelated medical care in life years gained. The inclusion of such costs is likely to be of consequence in the case of primary prevention. This paper presents different strategies regarding the inclusion not only of the costs, but also of the health effects of unrelated medical care in economic evaluations. Four different cost–utility ratios are presented and related to the criterion of internal consistency. In addition, the possibility to relate the ratios to a well‐posed decision problem is analysed. An example computes the different ratios for smoking cessation interventions in different age groups. Including health care costs of unrelated medical care in life years gained increases cost utility ratios, but excluding unrelated medical costs favours smoking cessation interventions targeted at older smokers over those at younger smokers. We conclude that for primary prevention only a cost utility ratio that includes both the costs and effects of unrelated medical care meets the criterion of internal consistency and is related to a meaningful decision problem. Therefore, this type of cost–utility ratio should be preferred even if the data requirements may be substantial. Copyright © 2006 John Wiley & Sons, Ltd.
Reduction and methylation of sodium arsenate in the rat
Authors: Rowland Ian R. , Davies Margaret J. 
Published: October 2006

AbstractAfter a single oral dose of sodium [74As] arsenate to male Wistar rats, arsenic was rapidly absorbed and accumulated in the blood and to a lesser extent in the liver, kidneys, lungs and spleen. Within 1 h of dosing, arsenic was present in the blood, liver and spleen predominantly in the methylated forms (methylarsonic acid and dimethylarsinic acid), whereas in the lung and kidneys, approximately 50% was in the inorganic form. Intravenous injection of sodium [74As] arsenate resulted in a pattern of arsenic species in the blood and kidneys similar to that seen after oral administration, suggesting that the gut flora does not contribute significantly to biotransformation of arsenic in vivo. Analysis of the forms of arsenic in portal blood after administration of arsenate via the small intestine revealed a rapid reduction of arsenate to arsenite, followed by linear rates of production of methylarsonic acid and dimethylarsinic acid.
Subchronic feeding study in rats of immobilized lactase following in utero exposure
Authors: Becci Peter J. , Gephart Larry A. , Re Thomas A. 
Published: October 2006

AbstractThe effect of subchronic feeding of immobilized lactase composite following in utero exposure was studied in Sprague‐Dawley rats. The dose levels of immobilized lactase composite that were used were 25, 100 and 400 mg per kg body weight per day. Reproduction performance, body weight gain and food consumption, organ weight, hematological and clinical chemical data, and ophthalmic, gross and histopathological examinations were used to study possible toxicological or pathological effects. No treatment‐related effects were observed in either male or female rats exposed to immobilized lactase composite at any dose level.
Influence of experimental hepatic impairment on the toxicokinetics and the anticholinesterase activity of carbaryl in the rat
Authors: Falzon M. , Fernandez Y. , Cambon‐Gros C. , Mitjavila S. 
Published: October 2006

AbstractThe blood kinetics of carbaryl were followed over 24h after oral administration of 14C‐carbaryl at 20 mg kg (0.17 μCi mg−1) in control animals and in animals with an altered liver function (70% hepatectomy or tranylcypromine treatment). The variations in the primary toxicity of carbaryl were assessed by measuring the inhibition of the plasma and erythrocyte cholinesterases and by evaluation of the lethal doses. The 14C radioactivity in the blood and, in parallel, cholinesterase inhibition were maintained at a higher level in animals with an altered hepatic function. A study of acute toxicity also showed a decrease of the LD50 (91 mg kg−1 with tranylcypromine, 342 mg kg−1 in the hepatectomized group) in the treated animals, with respect to the controls (585 mg kg−1). In all cases, tranylcypromine had a greater effect on blood kinetics, cholinesterase inhibition and LD50 than did 70% hepatectomy.
Susceptibility of lipids to mercurials
Authors: Nakada Susumu , Imura Nobumasa 
Published: October 2006

AbstractAffinity of mercury compounds to various phospholipids and fatty acids were examined. Inorganic mercury showed a higher affinity to lipids containing unsaturated fatty acids than to those composed of saturated fatty acids. This suggests that inorganic mercury may easily act on the double bonds of fatty acid residues in phospholipids which are major components of the biomembrane. On the other hand, methylmercury was almost inert to these lipids regardless of the presence or absence of unsaturated bonds.
Oxidation of mercury by catalase and peroxidase in homogeneous solution
Authors: Wigfield Donald C. , Perkins Sherry L. 
Published: October 2006

AbstractExperiments in homogenous solution confirm previous findings that catalase is an effective oxidant for Hg°→Hg2+. Peroxidase also effects the oxidation, and in both oxidations the co‐substrate hydrogen peroxide is not essential for mercury oxidation, although the oxidation is enhanced by the presence of hydrogen peroxide.
Reactivity, SCE induction and mutagenicity of benzyl chloride derivatives
Authors: Hemminki K. , Falck K. , Linnainmaa K. 
Published: October 2006

AbstractBenzyl chloride, benzyl bromide, p‐methylbenzyl chloride, and p‐nitrobenzyl chloride were used to study chemical reactivity with 4‐(p‐nitrobenzyl)‐pyridine (NBP), and with guanosine in vitro, in relation to mutagenic potency in S. typhimurium and sister chromatid exchange (SCE) induction in CHO cells. Benzyl bromide was found to be the most reactive compound, followed by p‐methylbenzyl chloride, benzyl chloride and p‐nitrobenzyl chloride. The order of mutagenicity was p‐nitrobenzyl chloride ≫ benzyl bromide > benzyl chloride ∽ p‐methylbenzyl chloride. The compounds tested caused base‐pair mutations only. The order of SCE‐inducing ability decreased as follows: benzyl bromide > benzyl chloride ∽ p‐nitrobenzyl chloride ∽ p‐methylbenzyl chloride. The particularly high mutagenicity of p‐nitrobenzyl chloride in bacteria may be due to reactions other than direct aralkylation, or it may react particularly actively with DNA. Among the other compounds, benzyl bromide was the most active aralkylating compound, mutagen and SCE inducer. The results suggested that reaction of N2 of guanine, as compared with N‐7 of guanine, failed to show any remarkable mutagenicity or SCE induction, since p‐methylbenzyl chloride, reacting preferentially at N2 of guanosine, failed to show unexceptional potency.
Dose‐dependent induction and suppression of liver mixed‐function oxidase system in chlorinated hydrocarbon solvent metabolism
Authors: Koizumi Akio , Kumai Miho , Ikeda Masayuki 
Published: October 2006

AbstractThe effect of continuous exposure to trichloroethylene (TRI), tetrachloroethylene (TETRA) or methyl‐chloroform (MC) on the hepatic mixed‐function oxidase system (MFOS) was studied in rats by using 10000 × g supernatant fraction. Exposure to TETRA for 240 h at 200, 100 and 50 ppm enhanced oxidative conversion from TETRA to trichloroacetic acid. When the animals were exposed for 240 h to 200, 400 and 800 ppm, oxidative conversion from MC to trichloroethanol was elevated. However, elevation was less remarkable with the increase of exposure intensities from 400 to 800 ppm. With TRI, MFOS activities were more critically assessed as a function of duration and dose because the variable response in MFOS activity was observed in preliminary studies when rats were exposed to 400 ppm for 240 h. The MFOS activities in rats exposed to TRI at 50, 400 or 800 ppm for 48 h, 72 h, 168 h and 240 h were measured. The MFOS activities were all suppressed after 48‐h exposure irrespective of the exposure concentration. After 72–240 h, suppression was superseded by activation at 50 ppm, while continuity of suppressive state was observed at 800 ppm and transitional state was the case of the exposure at 400 ppm. The possibility that epoxide hydratase would be involved in the metabolism of TRI, but not in those of other two chemicals, was also presented. Based on these findings, mathematical models for TRI and TETRA metabolism were established, which can explain hepatotoxicity appearing only after exposure to TRI at 800 ppm for 168 h or more.
Efficiency of a composite treatment for mixed fission products in rats
Authors: Kostial Krista , Kargačin Biserka , Šimonović Ivan 
Published: October 2006

AbstractThe effect of a composite antidotal treatment — consisting of a mixture of calcium alginate, ferrihexacyanoferrate(II) and potassium iodide — administered in diet and/or Na3(CaDTPA) administered intraperitoneally on the absorption and the removal of radioactive strontium, caesium, iodine and cerium was investigated in 7‐week‐old female rats. The animals were on respective treatments for 3 days. The retention of 141Ce, 85Sr, 137Cs and 131I was determined in the whole body, carcass, gut, liver, kidneys and respective critical organs (femur, muscle, thyroid) 6 days after their oral or intraperitoneal administration. In animals which received the antidotal mixture or Na3(CaDTPA) alone, the radionuclide retention was practically the same as in rats which were given the composite treatment [mixture + Na3(CaDTPA)]. This indicates that the efficiency of one treatment was not increased by the other. For 141Ce, Na3(CaDTPA) was an effective antidote, while 85Sr, 137Cs and 131I were reduced by the mixture. It is concluded that the composite treatment might be a quick treatment for choice for reducing mixed fission products retention, especially in cases when identification of exposure is difficult or impossible to make.
An investigation of fibrogenic and other toxic effects of arc‐welding fume particles deposited in the rat lung
Authors: Hicks R. , Al‐Shamma K. J. , Lam H. F. , Hewitt P. J. 
Published: October 2006

AbstractLung burdens of deposited particles from fumes generated by arc‐welding were established in rats by single inhalation exposures, repeated intermittent exposure or by intratracheal injection. Fumes from manual metal arc‐welding using flux‐coated mild‐steel rods (MMA‐MS) were compared with those from metal inert‐gas welding with stainless steel wire (MIG‐SS). After initial rapid clearance of deposited material from the lungs, persistent residual deposits remained. Such residues resulting from single inhalation were small and confined mainly to peribronchial accumulations in macrophage clusters. Deposits remaining after repeated inhalation were larger and more widespread. Intratracheal administration (50 mg) established massive residual deposits, giving nodular accumulations in peribronchial, subpleural and perivascular sites, with substantial alveolar parenchymal involvement. Deposits from both types of fumes contained predominantly iron. Particles from stainless steel also contained chromium, but concentrations of this element were low in deposits from MMA‐MS fumes. MMA‐MS deposits contained silica, probably amorphous. Long‐term studies (up to 450 days) attempted to detect evidence of fibrosis resulting from particle burdens. Low‐grade collagen fibre layers developed at margins of MMA‐MS nodules. Diffuse reticulin fibre networks occurred within MIG‐SS aggregates. Tissue hydroxyproline levels were increased (doubled) in lungs with intratracheal burdens of MMA‐MS particles, but no significant increases resulted from MIG‐SS. The major lesions were nodular aggregates of particle‐laden macrophages with giant‐cell formation, and alveolar epithelial thickening with atelectasis.
The genetic activity of anthramycin, tomaymycin and sibiromycin in bacterial forward‐ and reverse‐mutation assays and in the mouse bone‐marrow micronucleus test
Authors: Gairola C. , Thomas H. , Szeinbach S. L. , Lubawy W. C. 
Published: October 2006

AbstractThe genetic activity of the structurally similar antitumor antibiotics anthramycin, tomaymycin and sibiromycin was evaluated in the standard Ames Salmonella/microsome mutagenicity assay, a Salmonella typhimurium forward‐mutation assay and the micronucleus test. None of the test drugs showed any significant genetic activity in forward or reverse Salmonella mutation assays. The ability of mouse‐liver enzymes to produce mutagens from the drugs was examined in the Salmonella reverse‐mutation assay and was generally negative. As the concentrations of sibiromycin increased, some activity was detected in the presence of liver S‐9 fractions from Aroclor‐induced mice. This observation could not be verified at higher concentrations in the reverse‐mutation assay due to cytotoxicity, and in the forward‐mutation assay due to interference with the selection process by S‐9. Cytogenetic evaluation of anthramycin and tomaymycin in the micronucleus test also gave negative results. However, significant increases in the frequency of micronucleated polychromatic erythrocytes were observed in the bone marrow of sibiromycin‐treated mice. The results suggest that, except for some possible activity of sibiromycin, these drugs are generally devoid of any marked genetic activity in the test systems employed.
Use of the hamster embryo cell transformation assay to detect metabolic activation of N‐2‐acetylaminofluorene by intact organ cells
Authors: Poiley Judith A. , Ernst Mary K. , Cavanaugh Dorothy M. , Raineri Ronald 
Published: October 2006

AbstractN‐2‐Acetylaminofluorene (AAF), a potent carcinogen in a variety of animal species and organs, was used to determine the metabolic capabilities of isolated organ cells in transformation as well as biochemical studies. Cells isolated from liver, lung, small intestine, kidney and bladder were compared with hamster embryo fibroblasts (target cells in the transformation studies) and rat mammary fibroblasts in all studies. In addition to studying AAF activation by the cells, we also determined the levels of whole‐cell binding. Liver, kidney, small intestine and lung cells from hamsters, and liver, kidney and lung cells from rats showed high levels of AAF metabolism to 2‐aminofluorene and N‐hydroxy‐2‐acetylaminofluorene. The highest levels of covalent binding to intact cells were seen with the same cell types. These cells were also effective in activating AAF to a form which transformed hamster embryo cells. Cells isolated from a variety of organs can activate AAF as evidenced by the metabolites which are formed and by the levels of whole cell binding. Furthermore, hamster embryo cells are transformed when co‐incubated with a variety of organ cells and AAF.