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Combined Loss (combined + loss)

Distribution by Scientific Domains

Medical Sciences	71%

Selected Abstracts

Combined loss of orphan receptors PXR and CAR heightens sensitivity to toxic bile acids in mice,

HEPATOLOGY, Issue 1 2005
Hirdesh Uppal
Efficient detoxification of bile acids is necessary to avoid pathological conditions such as cholestatic liver damage and colon cancer. The orphan nuclear receptors PXR and CAR have been proposed to play an important role in the detoxification of xeno- and endo-biotics by regulating the expression of detoxifying enzymes and transporters. In this report, we showed that the combined loss of PXR and CAR resulted in a significantly heightened sensitivity to bile acid toxicity in a sex-sensitive manner. A regimen of lithocholic acid treatment, which was tolerated by wild-type and PXR null mice, caused a marked accumulation of serum bile acids and histological liver damage as well as an increased hepatic lipid deposition in double knockout males. The increased sensitivity in males was associated with genotype-specific suppression of bile acid transporters and loss of bile acid,mediated downregulation of small heterodimer partner, whereas the transporter suppression was modest or absent in females. The double knockout mice also exhibited gene- and tissue-specific dysregulation of PXR and CAR target genes in response to PXR and CAR agonists. In conclusion, although the cross-regulation of target genes by PXR and CAR has been proposed, the current study represents in vivo evidence of the combined loss of both receptors causing a unique pattern of gene regulation that can be translated into physiological events such as sensitivity to toxic bile acids. (HEPATOLOGY 2005;41:168,176.) [source]

Chromosome 1p and 19q status and p53 and p16 expression patterns as prognostic indicators of oligodendroglial tumors: A clinicopathological study using fluorescence in situ hybridization

NEUROPATHOLOGY, Issue 1 2007
Yoon Kyung Jeon
To verify the prognostic implications of the statuses of chromosome 1p and 19q and the expressions of p53, p16 and GFAP in oligodendrogliomas, we investigated these parameters and correlated the results with patient outcome. Twenty-seven cases of low-grade oligodendroglioma (LO) and 29 cases of anaplastic oligodendroglioma (AO) were analyzed by FISH for 1p and 19q status and by immunohistochemistry for p53, p16, and GFAP expression using a tissue microarray. Direct sequencing of the p53 gene was also performed. 1p deletion was observed in 39 of 56 patients (69.9%), and 19q deletion in 41 of 56 (73.2%). Combined loss of 1p and 19q was found in 38 of 56 (67.9%) and exhibited distinct concomitant deletion (P = 0.000). p53 overexpression was observed in 17 cases (30.3%), GFAP expression in 18 cases (32.1%), and p16 loss in 40 cases (74%) of oligodendrogliomas. The expressions of p53 and GFAP were more frequent in AO than in LO (P = 0.015 and 0.001). In contrast, p53 expression was more common in oligodendrogliomas with an intact 19q (P = 0.029), or an intact 1p (P = 0.071). Only five of 14 patients with p53 expression showed TP53 mutation, which was inversely correlated with 1p deletion (P = 0.036). Patients with combined loss of 1p and 19q exhibited better overall survival (P = 0.045). Patients with p53 expression without combined 1p and 19q loss showed poor overall survival (P < 0.000). However, TP53 mutation along with 1p and 19q status could not predict patient outcome. Patients with p16 loss without combined 1p and 9q loss showed poor overall survival (P = 0.011). Therefore, in oligodendrogliomas, the absence of the combined deletion of 1p and 19q and the aberrant expression of p53 or loss of p16 could be used as poor prognostic markers. [source]

Combined loss of orphan receptors PXR and CAR heightens sensitivity to toxic bile acids in mice,

Chromosome 1p and 19q status and p53 and p16 expression patterns as prognostic indicators of oligodendroglial tumors: A clinicopathological study using fluorescence in situ hybridization

Role of 2-oxo and 2-thioxo modifications on the proton affinity of histidine and fragmentation reactions of protonated histidine,

RAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 17 2010
Adrian K. Y. Lam
A combination of electrospray ionisation (ESI), multistage and high-resolution mass spectrometry experiments was used to compare the gas-phase chemistry of the amino acids histidine (1), 2-oxo-histidine (2), and 2-thioxo-histidine (3). Collision-induced dissociation (CID) of all three different proton-bound heterodimers of these amino acids led to the relative gas-phase proton affinity order of: histidine >2-thioxo-histidine >2-oxo-histidine. Density functional theory (DFT) calculations confirm this order, with the lower proton affinities of the oxidised histidine derivatives arising from their ability to adopt the more stable keto/thioketo tautomeric forms. All protonated amino acids predominately fragment via the combined loss of H2O and CO to yield a1 ions. Protonated 2 and 3 also undergo other small molecule losses including NH3 and the imine HN=CHCO2H. The observed differences in the fragmentation pathways are rationalised through DFT calculations, which reveal that while modification of histidine via the introduction of the oxygen atom in 2 or the sulfur atom in 3 does not affect the barriers against the loss of H2O+CO, barriers against the losses of NH3 and HN=CHCO2H are lowered relative to protonated histidine. Copyright © 2010 John Wiley & Sons, Ltd. [source]

Chromosomal anomalies in oligodendroglial tumors are correlated with clinical features

CANCER, Issue 5 2003
M.D., Martin J. van den Bent Ph.D.
Abstract BACKGROUND Patients who have oligodendrogliomas (OD) that demonstrate loss of both 1p and 19q appear to have a better prognosis after they receive chemotherapy and radiotherapy compared with patients who have OD without these characteristics. It is unclear whether this improvement in outcome is due only to a better response to treatment. The authors investigated the correlation between genetic and clinical characteristics of OD in 33 patients who received chemotherapy with procarbazine, lomustine, and vincristine for recurrent disease after receiving radiotherapy. METHODS The initial presentation, prior treatments, overall survival, and response to chemotherapy were assessed. The 1p and 19q status in OD lesions was determined with fluorescence in situ hybridization on paraffin embedded, archival material using locus specific probes. P53 mutations were assessed by polymerase chain reaction,single-strand conformation polymorphism analysis and immunohistochemistry for P53; the proliferation index was assessed with the MIB-1 antibody. RESULTS Patients who had OD lesions with a combined loss of 1p and 19q typically presented with low-grade tumors that manifested with seizures of long-standing duration. In contrast, patients who had OD lesions without a combined loss of 1p and 19q usually presented with focal deficits that required immediate treatment. Both the response rate to chemotherapy and the time to disease progression after chemotherapy were significantly better in patients who had a combined loss of 1p and 19. Tumors with classic OD morphology more often had a combined loss of 1p and 19q, although the genotype was better at identifying patients with chemoresponsive tumors. P53 mutations were observed in three tumors, none of which had a combined loss of 1p and 19q. CONCLUSIONS OD lesions with combined a loss of 1p and 19q have a more indolent nature compared with OD lesions that do not have these losses. Virtually all patients with these tumors present with low-grade tumors accompanied by seizures and remain stable for prolonged periods. Future trials must keep these tumor types apart. Cancer 2003;97:1276,84. © 2003 American Cancer Society. DOI 10.1002/cncr.11187 [source]

Autumn sowing increases severity of pasmo (Mycosphaerella linicola) on linseed in the UK

ANNALS OF APPLIED BIOLOGY, Issue 1 2009
S.A.M Perryman
Abstract Surveys and field experiments showed pasmo to be the most serious disease affecting UK winter linseed in the 1997,98, 1998,99 and 1999,2000 growing seasons. Survey data indicated that pasmo was widespread in England and Scotland, causing extensive loss of leaves and stem and capsule symptoms, on both winter and spring linseed crops. In winter linseed experiments at ADAS Boxworth and Rothamsted, when severe epidemics occurred (1997,98 and 1999,2000), control of pasmo with one or two MBC fungicide sprays increased yield. In experiments when severe pasmo epidemics did not occur (1998,99), fungicide applications did not increase yield. In all three growing seasons, large numbers of air-borne Mycosphaerella linicola ascospores were collected in the summer months. At the time when the winter linseed crop was emerging and becoming established in October/November, there were more air-borne M. linicola ascospores in 1999 than in 1998. April/May rainfall was much greater in 1998 (135 mm) and 2000 (223 mm), when severe pasmo epidemics developed by July, than in 1999 (68 mm) when disease severity in July was less. Regression analyses suggested that yield decreased as percentage area affected by pasmo on leaves or stems in July increased. The formulae relating yield loss to pasmo severity, derived from these experiments, were combined with disease survey data to estimate, retrospectively, the UK national losses from pasmo. Estimated national losses from pasmo on winter linseed, although >50% of crops were sprayed with fungicide, were approximately £2.9M in 1998, £1.6M in 1999 and £0.37M in 2000 (when the area of winter linseed had decreased greatly). Estimated combined losses on winter and spring linseed were approximately £14.8M in 1998, £34.9M in 1999 and £11.0M in 2000. [source]