The p53 tumour suppressor gene Steele, R. J. C.; Thompson, A. M.; Hall, P. A. ...
British journal of surgery,
November 1998, Volume:
85, Issue:
11
Journal Article, Conference Proceeding
Micronuclei (MN) are routinely enumerated in mouse peripheral blood to index genotoxicity. Recent data from the Collaborative Study Group for the Micronucleus Test (CSGMT) CSGMT (The Collaborative ...Study Group for the Micronucleus Test), Evaluation of the rat micronucleus test with bone marrow and peripheral blood: summary of the 9th collaborative study by CSGMT/JEMS MMS, Environ. Mol. Mutagen. 32 (1998) 84–100 suggest that rat peripheral blood may also be appropriate for the enumeration of MN, if scoring is limited to the youngest fraction of reticulocytes. The experiments described herein were designed to test whether modifications to a flow cytometric scoring procedure for measuring micronucleated reticulocytes (MN-RET) in mouse peripheral blood could be extended to accurately enumerate MN in rat peripheral blood. Rats were treated with saline or one of three genotoxic agents (6-mercaptopurine, ethyl methanesulfonate or propane sultone) in an acute dosing protocol. Peripheral blood samples were subsequently collected for both microscopic and flow cytometric analysis. Micronucleus frequencies were scored in the youngest fraction of reticulocytes: scoring by microscopy was restricted to the types I and II reticulocytes based on RNA content utilizing acridine orange supravital staining; flow cytometric measurements were restricted to the youngest fraction of reticulocytes based on transferrin receptor (CD71) staining. A statistically significant dose-related increase in the incidence of MN was observed, irrespective of scoring method. A higher level of statistical discrimination between control and genotoxin-treated groups was observed for the flow cytometric data and can most likely be explained by the increased number of cells scored (10× more than microscopy) and the lower scoring variability. Together, these data suggest that (i) rat peripheral blood represents an appropriate compartment for evaluating genotoxin-induced MN when the analysis is restricted to young reticulocytes, and (ii) the measurement of MN in rat peripheral blood reticulocytes benefits from the high throughput methodology of flow cytometry.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To evaluate whether p21 (WAF-1/CIP1) should be considered a potential candidate for human bladder cancer gene therapy, we determined: (1) the basal level of p21 expression in bladder cancer cell ...lines, (2) the response of bladder cancer cells to increased p21 expression following p21 adenovirus infection, and (3) the mechanism of growth inhibition produced by p21 overexpression.
Five established human bladder cancer cell lines and one primary culture derived from an invasive transitional cell carcinoma were used in this study. To examine the effect of p21 protein on the growth of human bladder cancer cells, a recombinant adenovirus vector system containing p21 cDNA, under the control of cytomegalovirus promoter, was constructed. A control virus containing p21 in an antisense orientation was used to eliminate potential artifacts caused by viral toxicity.
Human bladder cancer cell lines exhibit variable endogenous p21 levels which correlate with the in vitro growth status. Significant, but highly variable increases in the steady-state level of p21 were detected in p21 adenovirus infected cells. Human bladder cancer cell lines responded heterogeneously to p21 adenovirus infection. Growth of the WH cell line was substantially inhibited in a dose and time-course dependent fashion. The mechanism of p21 growth inhibition was found to be due to G
0/G
1 arrest and not the induction of apoptosis. In contrast, p21 adenovirus failed to inhibit the growth of T24 bladder cancer cells because T24 cells were resistant to viral infection. The 253J bladder cancer cells exhibited marked sensitivity to adenovirus; substantial growth inhibition was seen with both sense and antisense p21 very early in the time course of infection.
We found significant variation in the basal level of p21 protein expression in several human bladder cancer cell lines. Increased p21 expression as a result of adenoviral infection may be a potent growth suppressor in some human bladder cancer because it elicits cell cycle arrest in G
0/G
1 stage, but not the induction of apoptosis. Bladder cancer cells exhibit a wide spectrum of sensitivity to adenoviral infection that may be caused by the presence of viral receptor heterogeneity. This wide spectrum of sensitivity has significant basic scientific and clinical implications and warrants further study.
Obligatory exercise
is a compulsive behavior pattern in which exercise dominates daily life at the expense of other activities and lack of exercise produces withdrawal symptoms. This study examined ...the hypothesis that obligatory exercise is motivated similarly to eating disorders (cf.
S. P. Coen & B. M. Ogles, 1993
) and would be predicted by appearance-related imagery. Obligatory exercise (
J. K. Thompson & L. Pasman, 1991
) and exercise imagery (
H. A. Hausenblas, C. R. Hall, W. M. Rodgers, & K. J. Munroe, 1999
) were assessed before and after a 10-week exercise program in 243 adult exercisers. Regression analyses revealed that imagery accounted for 20% of the variance in obligatory exercise. Appearance-related imagery did not predict significantly obligatory exercise. Energy-related imagery was the strongest predictor. Obligatory exercise may not be as associated with appearance-related concerns as eating disorders, suggesting different motivational bases for these 2 behavioral patterns.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Energy dispersive X-ray fluorescence (EDXRF) was used to nondestructively determine the elemental composition of current-size $10 United States Federal Reserve Notes (FRN) from series 1928 to series ...2003. The X-ray spectra from all the bank notes were cataloged into a digital spectral library for searching and comparisons of questioned bank notes. Paper and different color printing inks were analyzed to determine elemental composition. One of the components of the green ink on the back of the early issues was identified as being the compound pigment Pigment Green 15, also known as chrome green (PbSO4·xPbCrO4·yFe4Fe(CN)6) precipitated onto a base of baryte (BaSO4) and Paris white (CaCO3). Our data show that the concentrations of Pb in the green ink have declined since the first issue of Series 1928 and ended with Series 1988. EDXRF is an excellent analytical method for rapid nondestructive elemental analysis of bank notes. This elemental characterization is useful for authenticating bank notes for the numismatist and for the forensic scientist. The method described can also be used for quality control in the manufacture of bank notes and for evaluating how circulating bank notes deteriorate.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Many studies have looked at the economically optimum N application rate (cost of N vs. increased yield) for cool-season forage grasses, but few of these studies have also addressed the effect of N ...fertilization on livestock or environmental health. The objective of this study was to determine the N application rate to cool-season grass species that optimizes economic return without elevating herbage or soil NO3–N levels. Four N rates were applied in split applications to established stands of orchardgrass (Dactylis glomerata L.), smooth bromegrass (Bromus inermis Leyss.), tall fescue (Festuca arundinacea Schreb.), and timothy (Phleum pratense L.) near State College, PA, on a Murrill silt loam (fine-loamy, mixed, mesic Typic Hapludults) soil. Harvest treatments of three and four times per year were imposed on each Grass × N treatment. Economically optimum N rates (EONR) were 284, 368, and 299 kg N ha−1 or 26, 32, and 29 kg N Mg−1 of forage harvested for orchardgrass, tall fescue, and timothy, respectively. Smooth bromegrass did not reach an economic plateau at the highest (402 kg ha−1) N rate. At EONR, NO3–N concentration exceeded 1000 mg kg−1 in forage from early season harvests when four harvests per year were taken but not when three harvests per year were taken. Soil NO3–N concentration generally was not elevated above background levels when EONR was applied to orchardgrass or tall fescue. Our results, in conjunction with results from New York, indicate that the EONR for the cool-season grasses and harvest systems evaluated is 5 to 10 kg N Mg−1 of dry forage greater than current recommendations in New York and Pennsylvania. However, continued research is needed in a wider range of climates and soil types using various N sources.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The optimal evaluation and management of patients with atrial fibrillation who suffer an acute ischemic stroke remains controversial. MethodsMedical records of 171 consecutive patients with atrial ...fibrillation and acute stroke at six U.S. university hospitals were reviewed. Data collected included the use of antithrombotic therapy, brain and cardiac imaging, bleeding complications, stroke risk factors, and contraindications to anticoagulation. ResultsMean age was 75.4 years. Cardiovascular risk factors associated with increased stroke risk were present in 87%; 35% had at least one contraindication to anticoagulation. Half of the patients with stroke risk factors and no contraindications to anticoagulation were not receiving any antithrombotic therapy at the time of admission. Of the 22 patients who were treated with warfarin, and had INR values on admission, 16 had levels of <2.0; only six had INR values between 2.0 and 3.0. Transthoracic echocardiography was performed in 107 patients (63%); intracardiac thrombi were visualized in only 5%. Initial brain imaging revealed hemorrhagic transformation in nine. Heparin was used in 93 patients (54%), usually within 48 hours of stroke onset. Patients who received delayed heparin typically did not have repeat brain imaging prior to starting heparin. One patient had a delayed symptomatic cerebral hemorrhage. Of the survivors, 47% were discharged and treated with warfarin (or warfarin plus aspirin), 28% with ASA, 7% with other antithrombotic therapies, and 18% with no antithrombotic therapy. ConclusionAntithrombotic therapy was underutilized and inadequately monitored in atrial fibrillation patients prior to stroke onset. After hospital admission, a wide range of diagnostic and management strategies, which often did not follow current recommendations, were employed.
Acyl-, aroyl-, and heteroaroyl-acetic esters 6a−f and 8a−l are prepared by reactions of 1-acylbenzotriazoles 1a−k with acetoacetic esters 5 or 7a,b in the presence of sodium hydride followed by ...regioselective deacetylation. Similar C-acylation/deacetylation of acetylacetone and benzoylacetone affords β-diketones 10a−d and 13a−c, respectively.
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IJS, KILJ, NUK, PNG, UL, UM
A prospective clinical study of 20 initially asymptomatic HTLV-I-seropositive carriers was commenced in 1991 to determine the natural history of the infection in relation to HTLV-I proviral load, ...immune responses, and lymphocyte phenotype. Proviral load varied widely between carriers but was relatively constant within an individual over time. The lymphocyte phenotype and prevalence of activated lymphocytes were not predictive of disease and the magnitude of the cytotoxic T-lymphocyte response to HTLV-I was independent of proviral load. Incident conditions, some related to HTLV-I infection, including a case of HTLV-I-associated myelopathy (HAM), were documented in 9 carriers. Development of myelopathy and uveitis was associated with high peripheral blood HTLV-I proviral load that predated symptoms. Persistently high proviral load appears to predate the development of HTLV-I-associated inflammation in neuro-ophthalmic tissue.
Multiple IgA subclasses have been identified in humans, primates and lagomorphs, whereas in mice, cattle and dogs only a single subclass has been identified. The two human subclasses (IgA1 and IgA2) ...are defined by a difference in the length of the hinge region of the alpha chains between the CH1 and CH2 domains. The single IgA subclass so far identified in dogs has an alpha-chain hinge region with a predicted amino-acid sequence similar to that of the human alpha1 chain. Allelic variants that differ in the coding sequence of the hinge region have been identified in mice and pigs. In order to investigate whether allelic variants are present in dogs, a portion of the IGHA gene from eight individual dogs was cloned and sequenced. Four sequence variants were identified, and these differed in the coding region of their hinge. A major difference between the variants was the presence of a base polymorphism in the splice acceptor site for the second exon, which resulted in shortening of the hinge in two of the variants. Individuals expressed one or two of the variants identified, suggesting they may be heterozygous or homozygous. Further work is required to determine the effect of the variation on the biological activity of dog IgA and any relationship to susceptibility to mucosal disease.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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