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Selected AbstractsA single amino acid exchange shifts the serological reactivity of the novel HLA-B*4442 allele product from HLA-B44 to HLA-B21INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2006F. Mrazek Summary A novel HLA-B (human leukocyte antigen-B) allele, HLA-B*4442, was identified both in a Czech patient with leukaemia and in his mother. The presence of a novel allele was initially suspected because conflicting results were obtained by serological and DNA typing techniques. The HLA typing using the polymerase chain reaction,sequence-specific primers (PCR,SSP) at the two-digit level indicated an allele belonging to the HLA-B*44 group, whereas serological typing indicated HLA-B21. Typing with PCR,sequence-specific oligonucleotides (PCR,SSO) resulted in a unique reaction pattern that could not be assigned to a known allele, PCR,SSP typing at the four-digit level did not match any known B*44 allele, either. The sequencing-based typing of the HLA-B locus then revealed the novel B*4442 allele that is identical with B*4405 except a single C,G nucleotide exchange at position 572. This exchange results in an amino acid substitution from serine to tryptophan at position 167 of the expressed HLA-B protein. The B21 serological reactivity of the novel B*4442 allele product was confirmed by employing an additional serological panel of typing sera. Our findings support previous reports claiming that serine at the position 167 in the alpha-2 domain of the HLA-B protein is a major determinant of the HLA-B44(12) serological epitope. [source] Oncogene expression profiles in K6/ODC mouse skin and papillomas following a chronic exposure to monomethylarsonous acid,JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 6 2009Don A. Delker Abstract We have previously observed that a chronic drinking water exposure to monomethylarsonous acid [MMA(III)], a cellular metabolite of inorganic arsenic, increases tumor frequency in the skin of keratin VI/ornithine decarboxylase (K6/ODC) transgenic mice. To characterize gene expression profiles predictive of MMA(III) exposure and mode of action of carcinogenesis, skin and papilloma RNA was isolated from K6/ODC mice administered 0, 10, 50, and 100 ppm MMA(III) in their drinking water for 26 weeks. Following RNA processing, the resulting cRNA samples were hybridized to Affymetrix Mouse Genome 430A 2.0 GeneChips®. Micoarray data were normalized using MAS 5.0 software, and statistically significant genes were determined using a regularized t -test. Significant changes in bZIP transcription factors, MAP kinase signaling, chromatin remodeling, and lipid metabolism gene transcripts were observed following MMA(III) exposure as determined using the Database for Annotation, Visualization and Integrated Discovery 2.1 (DAVID) (Dennis et al., Genome Biol 2003;4(5):P3). MMA(III) also caused dose-dependent changes in multiple Rho guanine nucleotide triphosphatase (GTPase) and cell cycle related genes as determined by linear regression analyses. Observed increases in transcript abundance of Fosl1, Myc, and Rac1 oncogenes in mouse skin support previous reports on the inducibility of these oncogenes in response to arsenic and support the relevance of these genomic changes in skin tumor induction in the K6/ODC mouse model. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:406,418, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20304 [source] Recruitment of Additional Brain Regions to Accomplish Simple Motor Tasks in Chronic Alcohol-Dependent PatientsALCOHOLISM, Issue 6 2010Mitchell H. Parks Background:, Chronic alcohol-dependent patients (ALC) exhibit neurocognitive impairments attributed to alcohol-induced fronto-cerebellar damage. Deficits are typically found in complex task performance, whereas simple tasks may not be significantly compromised, perhaps because of little understood compensatory changes. Methods:, We compared finger tapping with either hand at externally paced (EP) or maximal self-paced (SP) rates and concomitant brain activation in ten pairs of right-hand dominant, age-, and gender-matched, severe, uncomplicated ALC and normal controls (NC) using functional magnetic resonance imaging (fMRI). Results:, Mean tapping rates were not significantly different in ALC and NC for either task, but SP tapping variances were greater in ALC for both hands. SP tapping was more rapid with dominant hand (DH) than non-dominant hand (NDH) for both groups. EP and SP tapping with the non-dominant hand demonstrated significantly more activation in ALC than NC in the pre and postcentral gyri, inferior frontal gyrus, inferior parietal lobule, and the middle temporal gyrus. Areas activated only by ALC (not at all by NC) during NDH tapping included the inferior frontal gyrus, middle temporal gyrus, and postcentral gyrus. There were no significant group activation differences with DH tapping. No brain regions activated more in NC than ALC. SP tapping in contrast to EP activated fronto-cerebellar networks in NC, including postcentral gyrus, anterior cingulate, and the anterior lobe and vermis of the cerebellum, but only parietal precuneus in ALC. Conclusions:, These findings with NDH finger tapping support previous reports of neurocognitive inefficiencies in ALC. Inferior frontal activation with EP in ALC, but not in NC, suggests engagement of regions needed for planning, organization, and impulse regulation; greater contralateral parietal lobe activation with SP in ALC may reflect right hemispheric impairments in visuospatial performance. Contrasting brain activation during SP and EP suggests that ALC may not have enlisted a fronto-cerebellar network as did NC but rather employed a higher order planning mode by recruiting parietal lobe functions to attain normal mean finger tapping rates. Elucidation of the compensatory neural mechanisms that allow near normal performance by ALC on simple tasks can inform functional rehabilitation of patients in recovery. [source] Characterization of Hepatitis B Virus Surface Antigen and Polymerase Mutations in Liver Transplant Recipients Pre- and Post-TransplantAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2003Jeffrey J. Germer We evaluated serum samples from 18 chronic hepatitis B virus (HBV) patients who underwent liver transplantation for the presence of HBV polymerase and S gene mutations and HBV genotype using a new commercially available sequencing assay. All three patients with hepatitis B immune globulin (HBIG) treatment failure followed by nucleoside analogue treatment failure were infected with HBV genotype C; a pre-existing HBV S antigen (HBsAg) mutation (sD144A) was identified in one patient pretransplant, while sG145R mutations emerged in the other two patients post-transplant. These HBsAg mutations persisted for the duration of the study (5,6 years), despite the absence of HBIG administration for a 4,5-year period. Significant viral polymerase mutations (rtL180M and rtM204I/V) also emerged in all of these patients following treatment with lamivudine and/or famciclovir. Four of six patients with HBIG breakthrough without nucleoside analogue treatment failure yielded potentially significant HBsAg mutations post transplant. These data do not support previous reports highlighting the disappearance of HBsAg mutants in liver transplant recipients after discontinuation of HBIG. Determination of HBV genotype, as well as identification of HBV polymerase and S gene mutations in liver transplant candidates may be warranted to optimize HBV management strategies post transplant. [source] Increased nasal mucosal swelling in subjects with asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2002J. Hellgren Objective The objective of this study was to evaluate nasal mucosal swelling with acoustic rhinometry in subjects with asthma and in healthy controls. Methods We examined 184 individuals with asthma and compared with 156 randomly selected controls outside the pollen season, where 144 subjects in the asthma group and 80 controls had a previous history of non-infectious rhinitis (NIR). Nasal mucosal swelling was assessed with acoustic rhinometry before and after nasal decongestion with oxymetazoline and was analysed for the cross-sectional area (4 cm from the nostril) and the volume between 3.3 and 4 cm from the nostril. Symptom scores for nasal blockage, secretion, itching and sneezing were assessed on a 0,10 visual analogue scale as well as peak nasal inspiratory flow and spirometry. Results Before decongestion there was a decrease in the cross-sectional area at 4 cm (1.32 cm2 vs. 1.59 cm2, mean left + right P = 0.04) and in the volume (1.70 vs. 1.91 cm3P = 0.03) in the asthma group compared with healthy controls. After decongestion there were no significant differences in cross-sectional area at 4 cm (1.66 vs. 1.73 cm2P = 0.32) or volume (2.12 vs. 2.24 cm3P = 0.32). Combined nasal symptom scores were higher in the asthma group (1.8 vs. 0.8, P = 0.0001) and peak nasal inspiratory flow was lower (119 vs. 124 L/min, P = 0.38) than the healthy controls. FEV1 (% predicted) was also lower in asthma group (84 vs. 93%P < 0.0001). Conclusion We have been able to demonstrate an increased nasal mucosal swelling in a population sample of persons with asthma compared to healthy controls. These data support previous reports of a generalized airway inflammation in patients with asthma and suggest that acoustic rhinometry can be used to monitor the nasal mucosal swelling in these patients. [source] | ||||||||||