CLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 4 2007
Mingbing Zeng PhD MD
Abstract Background:, Higher-order aberrations and contrast sensitivity were evaluated in patients who underwent phacoemulsification cataract extraction followed by implantation of aspherical, monofocal or multifocal intraocular lens (IOL) replacements. Methods:, In this comparative trial, 124 patients with an average age of 66.8 ± 5.2 years and their 124 eyes were randomly divided into three surgical implantation groups to receive one of three types of IOLs in replacement of cataract lenses. The patients of group 1 were given an aspherical IOL Z9001 (AMO, Santa Ana, CA, USA) replacement, and group 2 was implanted a monofocal IOL SA60AT (Alcon, Fort Worth, TX, USA) and group 3 the multifocal IOL SA40N (AMO). Post-surgical best-corrected visual acuity, corneal aberrations, total ocular aberrations, pupil diameters, capsulorhexsis sizes and contrast sensitivity were measured and compared. Results:, There was no statistical difference for mean best-corrected visual acuity, pupil diameter, curvilinear capsulorhexis size and corneal aberration among the three groups. For the spherical aberration, fourth-order higher-order aberration and total ocular higher-order aberration, the SA40N group was higher than the SA60AT group and the SA60AT group was higher than the Z9001 group, and the differences between the three groups were statistically significant for these measurements. Contrast sensitivity was higher for the Z9001 group than the SA60AT group and the SA60AT group was higher than the SA40N group, and the difference was statistically significant in all the spatial frequencies of 3, 6, 12 and 18. Conclusions:, Although the multifocal IOL can provide near vision, it can increase higher-order aberration and negatively influence contrast sensitivity. However, the aspherical IOL can reduce aberration and improve contrast sensitivity as compared with the monofocal IOL. [source]

Definitive molecular cytogenetic characterization of 15 colorectal cancer cell lines,

GENES, CHROMOSOMES AND CANCER, Issue 3 2010
Turid Knutsen
In defining the genetic profiles in cancer, cytogenetically aberrant cell lines derived from primary tumors are important tools for the study of carcinogenesis. Here, we present the results of a comprehensive investigation of 15 established colorectal cancer cell lines using spectral karyotyping (SKY), fluorescence in situ hybridization, and comparative genomic hybridization (CGH). Detailed karyotypic analysis by SKY on five of the lines (P53HCT116, T84, NCI-H508, NCI-H716, and SK-CO-1) is described here for the first time. The five lines with karyotypes in the diploid range and that are characterized by defects in DNA mismatch repair had a mean of 4.8 chromosomal abnormalities per line, whereas the 10 aneuploid lines exhibited complex karyotypes and a mean of 30 chromosomal abnormalities. Of the 150 clonal translocations, only eight were balanced and none were recurrent among the lines. We also reviewed the karyotypes of 345 cases of adenocarcinoma of the large intestine listed in the Mitelman Database of Chromosome Aberrations in Cancer. The types of abnormalities observed in the cell lines reflected those seen in primary tumors: there were no recurrent translocations in either tumors or cell lines; isochromosomes were the most common recurrent abnormalities; and breakpoints occurred most frequently at the centromeric/pericentromeric and telomere regions. Of the genomic imbalances detected by array CGH, 87% correlated with chromosome aberrations observed in the SKY studies. The fact that chromosome abnormalities predominantly result in copy number changes rather than specific chromosome or gene fusions suggests that this may be the major mechanism leading to carcinogenesis in colorectal cancer. Published 2009 Wiley-Liss, Inc. [source]

Sequencing of intron 3 of HMGA2 uncovers the existence of a novel exon

GENES, CHROMOSOMES AND CANCER, Issue 1 2002
Sven Hauke
Aberrations affecting the gene encoding the high mobility group protein HMGA2 (formerly HMGIC) have been found in a variety of human tumors, e.g., uterine leiomyomas, lipomas, and pulmonary chondroid hamartomas. These aberrations lead to fusion genes, transcriptional up-regulation, or aberrant transcripts of HMGA2. In the latter case, truncated transcripts consisting of exons 1 to 3 of HMGA2, encoding the three DNA-binding domains, and ectopic sequences derived from chromosome 12 are frequent. There are several lines of evidence indicating that the biological and tumorigenic features of truncated HMGA2 derivatives, i.e., those composed of the DNA-binding domains and a shortened acidic tail, clearly differ from those of the normal protein consisting of three DNA-binding domains and one large acidic tail. By sequencing the complete 112 kb third intron of HMGA2, we were able to detect several of the ectopic sequences, known as fused to HMGA2. Expression studies revealed co-expression of one of these transcripts with the normal transcript in tumors with 12q14-15 aberrations as well as in other tumors, and in normal tissues. Thus, this transcript (HMGA2b) is flanked by an alternative terminal exon of HMGA2. Due to the loss of the part encoding the acidic tail, the expression of the latter transcript may have more striking effects than the "wild type" HMGA2 (HMGA2a) in terms of tumorigenesis. This finding clearly indicates that functional studies also should address the role of the HMGA2b transcript. © 2002 Wiley-Liss, Inc. [source]

Molecular-cytogenetic comparison of mucosa-associated marginal zone B-cell lymphoma and large B-cell lymphoma arising in the gastro-intestinal tract

GENES, CHROMOSOMES AND CANCER, Issue 4 2001
Thomas F.E. Barth
Extranodal B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type may represent a model of lymphoma progression, because a small cell component frequently occurs in the large cell variants. We studied 52 extranodal B-cell lymphomas: 18 extranodal marginal zone B-cell lymphomas of MALT type (MZBL,MT), 7 MZBL,MT of the gastro-intestinal tract with a diffuse large B-cell component (giMZBLplusLBCL), and 27 diffuse large B-cell lymphomas of the gastro-intestinal tract without small cell component (giLBCL). Analytical techniques were comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). The translocation t(11;18) was found as the sole aberration in two MZBL,MT only. In contrast to this, t(11;18)-negative MZBL,MT were characterized by frequent gains on chromosome 3 and DNA amplifications on 2p13,p15. Furthermore, we found a clonal lymphoma progression from the small to the large cell component with accumulation of gains and losses of chromosomal material in the large cell component in giMZBLplusLBCL. Aberrations overlapping with MZBL,MT and giMZBLplusLBCL included losses on chromosome 13, amplifications of the REL proto-oncogene, or gains on chromosome 12. In addition, the large cell component revealed gains on 8q24, including amplifications of the MYC proto-oncogene, and losses on 2q. The giLBCL had frequent gains on chromosomes 12 and 9, as well as on 11q, and losses on 6q. We conclude that, based on the distinctive and partly overlapping patterns of genetic aberrations, MALT lymphomas can be divided into different genetic subgroups. © 2001 Wiley-Liss, Inc. [source]

Basaloid in contrast to nonbasaloid head and neck squamous cell carcinomas display aberrations especially in cell cycle control genes

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 11 2003
Micaela Poetsch PhD
Abstract Background. At present, the differences between head and neck basaloid squamous cell carcinoma (BSCC) and nonbasaloid squamous cell carcinoma (SCC) are mostly on the basis of histologic and immunohistologic findings. Methods. In this study, we investigated 8 BSCCs and 59 SCCs for loss of heterozygosity (LOH) at chromosomes 5q, 9p, 9q, 10q, 11q, 13p, 17p, and 18q. In addition, we analyzed p16, PTEN, and CCND1 (cyclin D1) and investigated the HPV status. Immunohistochemically, the expression of MIB-1, p16, p53, and cyclin D1 was determined. Results. Aberrations in the BSCCs were especially frequent at 9p and in the CCND1 gene. In contrast, alterations at 10q occurred almost exclusively in conventional SCCs. Obvious differences could be determined concerning the HPV status: HPV-DNA was detected in all BSCCs but only in 17% of conventional SCCs. Conclusions. Although the number of investigated BSCCs is rather low and did not allow statistical conclusions, our results focus on certain differences between the molecular pathogenesis of BSCCs and SCCs. © 2003 Wiley Periodicals, Inc. Head and Neck 25: 000,000, 2003 [source]

Genetic Aberrations in Chernobyl-Related Thyroid Cancers: Implications for Possible Future Nuclear Accidents or Nuclear Attacks

IUBMB LIFE, Issue 12 2003
Gennady Ermak
Abstract Cases of thyroid cancer among children in Belarus represent a unique model system in which the cause of the cancer is known - radiation. Although other sources of radiation-induced cancers are diminishing (survivors of Hiroshima and Nagasaki, and individuals exposed to diagnostic or therapeutic radiation) fears of radiation exposure from accidents and terrorism are increasing. Our analysis of current data reveals that Chernobyl-related cancer cases might have a specific pattern of genetic aberrations. These data strongly confirm the hypothesis that radiation-induced cancers might arise as a result of specific gene aberrations that are distinct from those in sporadic cancers, suggesting that methods of prevention and treatment of radiation-induced cancers might require a different approach. Understanding of the molecular mechanisms of Chernobyl-related papillary thyroid carcinomas will help to identify mechanisms by which radiation causes aberrations and oncogenic cell transformation. Thus, in turn, it will be important in the development of new treatments or technologies to minimize the effects of radiation damage from nuclear accidents or nuclear attacks. IUBMB Life, 55: 637-641, 2003 [source]

Areca nut extract-treated gingival fibroblasts modulate the invasiveness of polymorphonuclear leukocytes via the production of MMP-2

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2009
Hsuan-Hsuan Lu
Background:, Areca nut chewing is associated with an increase in the incidence of oral neoplastic or inflammatory diseases. Aberrations in matrix metalloprotease (MMP) expression are associated with the pathogenesis of oral diseases. This study investigated the potential effects of areca nut extract (ANE) on human gingival fibroblasts and the consequential impacts on inflammatory pathogenesis. Methods:, Analyses of senescence marker, cell viability, changes of the cell cycle, and cell granularity in gingival fibroblasts together with an assessment of the invasiveness of polymorphonuclear (PMN) leukocytes after treatment with the supernatant of ANE-treated gingival fibroblasts were performed to characterize the phenotypic impacts. Western blotting and gelatin zymography were used to assay the expression and activity of MMP-2. Results:, Chronic subtoxic (<10 ,g/ml) ANE treatment resulted in premature growth arrest, appearance of senescence-associated ,-galactosidase activity and various other senescence-associated phenotypes in gingival fibroblasts. Gingival fibroblasts established from older individuals had a higher propensity to become ANE-induced senescent gingival fibroblasts. An activation of MMP-2 was identified in senescent cells. PMN leukocytes treated with the supernatant of ANE-induced senescent cells exhibited a significant increase in invasiveness, which was abrogated by both a MMP-2 blocker and a MMP-2 nullifying antibody. Conclusions:, This study provides evidence whereby MMP-2 secreted from ANE-induced senescent gingival fibroblasts would facilitate the invasiveness of PMN leukocytes, which could be associated with the oral inflammatory process in areca chewers. [source]

Areca nut extract represses migration and differentiation while activating matrix metalloproteinase-9 of normal gingival epithelial cells

JOURNAL OF PERIODONTAL RESEARCH, Issue 5 2008
Y-H Tseng
Background and Objective:, Areca (betel) chewing is associated with an increase in the incidence of periodontal diseases. Aberrations in matrix metalloproteinase (MMP) expression have been reported to be associated with periodontal disease. This study investigated the effects of areca nut extract on MMP activity and the phenotype of human gingival epithelial cells. Material and Methods:, Reverse transcription-polymerase chain reaction, western blotting and gelatin zymography were used to assay MMPs. Cell viability, mobility and detachment assays were performed to characterize the phenotypic impact. Confocal microscopy was employed to evaluate cell aggregation and the distribution of E-cadherin and F-actin. Results:, Treatment of gingival epithelial cells with 10 µg/mL of areca nut extract reduced its cell viability. Treatment with 5 and 10 µg/mL of areca nut extract for 24 h activated MMP-9 but not MMP-2 in gingival epithelial cells. This activation could be nuclear factor-,B dependent and was abrogated by 10 µm curcumin. Areca nut extract also reduced the migration and detachment of gingival epithelial cells. The differentiated cell,cell contact of gingival epithelial cells was markedly impaired by areca nut extract. This was accompanied by a disruption of distribution of E-cadherin and F-actin. Conclusion:, The areca nut extract-mediated activation of MMP-9 in gingival epithelial cells could signify a potential periodontal pathogenesis in areca chewers. The areca nut extract-mediated inhibition of cell viability and migration, together with the changed aggregation in gingival epithelial cells, suggests that impairment of the re-epithelization underlies the process and this, in turn, might exacerbate gingival inflammation. [source]

Quantitative characterization of hemodynamic properties and vasculature dysfunction of high-grade gliomas

NMR IN BIOMEDICINE, Issue 6 2007
Vijaya Nagesh
Abstract Aberrations in tumor and peritumoral vasculature may not be distinguishable by cerebral blood flow (CBF) or cerebral blood volume (CBV) alone. The relationships between CBF and CBV were examined to estimate vasculature-specific hemodynamic characteristics. Twenty glioma patients were studied with dynamic susceptibility T2*-weighted MRI [(dynamic contrast-enhanced magnetic resonance imaging (DSC-MRI)] before and during week 1 and 3 of radiotherapy (RT). CBF and CBV were calculated from DSC-MRI, and relationships between the two were evaluated: the physiological measure of mean transit time (MTT),=,CBV/CBF; empirical fitting using the power law CBV,=,constant,×,(CBF),. Three different tissue types were assessed: the Gd-enhancing tumor volume (GEV); non-enhanced abnormal tissue located beyond GEV but within the abnormal hyperintense region on FLAIR images (NEV); normal tissue in the hemisphere contralateral to the tumor (CNT). The effects of tissue types, CBV magnitudes (low, medium and high), before and during RT, on MTT and , were analyzed by analysis of variance (ANOVA). The MTT and , for the three tissue types were significantly different (p,<,0.009). MTT increased from CNT (1.60,s) to NEV (1.93,s) to GEV (2.28,s) (p,<,0.0005). , was significantly greater in GEV (1.079) and NEV (1.070) than in CNT (1.025). , increased with increasing CBV magnitude while MTT was independent of CBV magnitude. There was a significant decrease in MTT of NEV and GEV during week 3 of RT compared with pre-RT values for all CBV magnitudes. There was a significant increase in , during RT in the tumor and peritumor. Progressive abnormalities in vasculature and hemodynamic characteristics of the vascular bed were delineated, with significant disorder in the tumor but mild abnormality in peritumoral tissue. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Detecting Genomic Aberrations Using Products in a Multiscale Analysis

BIOMETRICS, Issue 3 2010
Xuesong Yu
Summary Genomic instability, such as copy-number losses and gains, occurs in many genetic diseases. Recent technology developments enable researchers to measure copy numbers at tens of thousands of markers simultaneously. In this article, we propose a nonparametric approach for detecting the locations of copy-number changes and provide a measure of significance for each change point. The proposed test is based on seeking scale-based changes in the sequence of copy numbers, which is ordered by the marker locations along the chromosome. The method leads to a natural way to estimate the null distribution for the test of a change point and adjusted,p -values for the significance of a change point using a step-down maxT permutation algorithm to control the family-wise error rate. A simulation study investigates the finite sample performance of the proposed method and compares it with a more standard sequential testing method. The method is illustrated using two real data sets. [source]

A pooled analysis of karyotypic patterns, breakpoints and imbalances in 783 cytogenetically abnormal multiple myelomas reveals frequently involved chromosome segments as well as significant age- and sex-related differences

BRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2003
Thérèse Nilsson
Summary. The cytogenetic features (ploidy, complexity, breakpoints, imbalances) were ascertained in 783 abnormal multiple myeloma (MM) cases to identify frequently involved chromosomal regions as well as a possible impact of age/sex. The series included MM patients from the Mitelman Database of Chromosome Aberrations in Cancer and from our own laboratory. Hyperdiploidy was most common, followed by hypodiploidy, pseudodiploidy and tri-/tetraploidy. Most cases were complex, with a median of eight changes per patient. The distribution of modal numbers differed between younger and older patients, but was not related to sex. No sex- or age-related differences regarding the number of anomalies were found. The most frequent genomic breakpoints were 14q32, 11q13, 1q10, 8q24, 1p11, 1q21, 22q11, 1p13, 1q11, 19q13, 1p22, 6q21 and 17p11. Breaks in 1p13, 6q21 and 11q13 were more common in the younger age group. The most frequent imbalances were +,9, ,,13, +,15, +,19, +,11 and ,,Y. Trisomy 11 and monosomy 16 were more common among men, while ,X was more frequent among women. Loss of Y as the sole change and +,5 were more common in elderly patients, and ,,14 was more frequent in the younger age group. The present findings strongly suggest that some karyotypic features of MM are influenced by endogenous and/or exogenous factors. [source]

Molecular mechanisms of pancreatic carcinogenesis

CANCER SCIENCE, Issue 1 2006
Toru Furukawa
Pancreatic ductal adenocarcinoma is one of the most fatal malignancies. Intensive investigation of molecular pathogenesis might lead to identifying useful molecules for diagnosis and treatment of the disease. Pancreatic ductal adenocarcinoma harbors complicated aberrations of alleles including losses of 1p, 6q, 9p, 12q, 17p, 18q, and 21q, and gains of 8q and 20q. Pancreatic cancer is usually initiated by mutation of KRAS and aberrant expression of SHH. Overexpression of AURKA mapping on 20q13.2 may significantly enhance overt tumorigenesity. Aberrations of tumor suppressor genes synergistically accelerate progression of the carcinogenic pathway through pancreatic intraepithelial neoplasia (PanIN) to invasive ductal adenocarcinoma. Abrogation of CDKN2A occurs in low-grade/early PanIN, whereas aberrations of TP53 and SMAD4 occur in high-grade/late PanIN. SMAD4 may play suppressive roles in tumorigenesis by inhibition of angiogenesis. Loss of 18q precedes SMAD4 inactivation, and restoration of chromosome 18 in pancreatic cancer cells results in tumor suppressive phenotypes regardless of SMAD4 status, indicating the possible existence of a tumor suppressor gene(s) other than SMAD4 on 18q. DUSP6 at 12q21-q22 is frequently abrogated by loss of expression in invasive ductal adenocarcinomas despite fairly preserved expression in PanIN, which suggests that DUSP6 works as a tumor suppressor in pancreatic carcinogenesis. Restoration of chromosome 12 also suppresses growths of pancreatic cancer cells despite the recovery of expression of DUSP6; the existence of yet another tumor suppressor gene on 12q is strongly suggested. Understanding the molecular mechanisms of pancreatic carcinogenesis will likely provide novel clues for preventing, detecting, and ultimately curing this life-threatening disease. (Cancer Sci 2005) [source]

4432: Comparison of the two domains of visual optics: the aberrometric domain and the straylight domain

ACTA OPHTHALMOLOGICA, Issue 2010
TJTP VAN DEN BERG
Purpose The ocular point-spread-function defines the functional problem originating from optical defects in the eye. Aberrations as well as scatter degrade the psf. How do these two types of defect differ with respect to their effect on the psf, and on functional measures? Methods Literature models for different aspects of the optical irregularities in the eye media, in particular Thibos et al. JOSA A 2002 for the aberration structure and Van den Berg et al. VR 1999 for small particle scattering, were used to delineate their effects on the psf. The Thibos et al. model was extrapolated to allow inclusion of the high orders of aberration not normally included in aberrometry, but potentially visible with double pass. With respect to the visual function counterparts, straylight (C-Quant from Oculus) outcomes were compared to visual acuity and contrast sensitivity in 2400 subjects. Results As a reference the full scale psf standard model of Vos et al. CIE 1999 was used. The modeled aberration structures of the eye proved to predict the central part of the psf up till about 0.3 degrees if extreme high orders were included. For angles >1 degree predicted values were far below the actual values of the psf. Small particle scattering was essential to predict the psf for angles above 1 degree. Conclusion In the assessment of disturbances to the optical media two domains must be discriminated: the aberration domain and the small particle domain, with corresponding parts (small angle vs large angle) to the psf. Straylight typically originates from irregularities of size 10 micrometer and below, as opposed to aberrations originating from refractile humps and bumps extending over 100 micrometer and more. Straylight has independent value. [source]

Principle of adaptive optics

ACTA OPHTHALMOLOGICA, Issue 2009
PG SÖDERBERG
Purpose To provide an overview of adaptive optics imaging of the retina. Methods In ophthalmoscopical imaging, the two dimensional spatial radiance variation of the back scattered light from the retinal surface is measured. Perfect imaging would require that light backscattered from one point on the retina examined is refocused to one point on the detector. Due to diffraction, light scattering and aberrations, some of the light, injected into the eye examined and some of the light back scatted from the retina examined, are deviated. This leads to loss of contrast. Aberrations induced are, for each individual, specific to the optics of the eye examined. In AOSLO, in addition to confocal illumination and light detection, aberrations induced by the optics of the eye examined are individually measured by wave front sensing and corrected for. Results In the AOSLO, a wave front sensor is introduced between the light source and the eye examined. The information from the wave front sensor is fed back to a deformable mirror, also placed in between the light source and the eye examined. The deformable mirror corrects the wave front aberrations induced by the optics of the eye examined. This allows the injected light to form a point on the retinal surface and simultaneously, the backscattered light from the retina of the eye examined to be focused to a point on a detector. An x-y scanner in front of the eye allows sequential illumination and capturing of aberration minimized back scattered light from an x-y matrix of the retinal surface of the eye examined. The relative radiances measured in the x-y matrix represent the image. Conclusion Adaptive optics in ophthalmoscopy improves contrast in the image of the retina examined by correcting for aberrations induced by the optics of the eye examined. [source]

High Order Aberrations of the eye implanted the Verisyse® iris-claw intraocular lens

ACTA OPHTHALMOLOGICA, Issue 2007
JJ GICQUEL
Purpose: To investigate the influence of the secondary implantation site of the Verisyse® iris-claw intraocular lens (IOL) on high order aberrations (HOAs) using wavefront analysis in aphakic patients. Methods: Twenty aphakic patients (20 eyes) who had complicated phacoemulsification, leaving no capsular support, but good iris support and clear unwounded cornea implantated with the aphakic Verisyse®(AMO) intraocular lens site either implanted retropupilarely or over the iris. Wavefront aberrations were measured using the IRX3 Hartmann-Shack aberrometer at 4 mm pupil aperture diameter. Results: Nine patients were implanted in the anterior chamber versus 11 who had the IOL clipped behind the iris. Best corrected visual acuity was significantly higher and HOAs were significantly lower in the retropupilarely implanted group. Conclusions: In addition to being atraumatic, the Verisyse® intraocular lens implanted behind the iris may restore vision in the absence of capsular support in a more physiological way than when fixated over the iris. [source]

Gli3 -deficient mice exhibit cleft palate associated with abnormal tongue development

DEVELOPMENTAL DYNAMICS, Issue 10 2008
Xi Huang
Abstract Palatogenesis depends on appropriate growth, elevation, and fusion of the palatal shelves and aberration in these processes can lead to palatal clefting. We observed a high incidence of palate clefting in mice deficient in Gli3, known for its role as a repressor in the absence of Shh signaling. In contrast with several current mouse models of cleft palate, Meckel's cartilage extension, cranial neural crest migration, palatal shelf proliferation, apoptosis, and key signaling components mediated by Shh, Bmp, Fgf, and Tgf,, appeared unaffected in Gli3,/, mice. Palatal clefting in Gli3,/, mice was consistently associated with tongue abnormalities such as failure to flatten and improper positioning, implicating a critical role of Gli3 and normal tongue morphogenesis for timely palatal shelf elevation and joining. Furthermore, Gli3,/, palatal shelves grown in roller cultures without tongue can fuse suggesting that the abnormal tongue is likely an impediment for palatal shelf joining in Gli3,/, mutants. Developmental Dynamics 237:3079,3087, 2008. © 2008 Wiley-Liss, Inc. [source]

Searching PubMed for molecular epidemiology studies: The case of chromosome aberrations

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2006
Donatella Ugolini
Abstract The available tools for searching literature in the field of Molecular Epidemiology are largely unsatisfactory. To identify major problems in retrieving information on this discipline, we comment here on the results of a literature search on cytogenetic biomarkers in children exposed to environmental pollutants. The search, done on the PubMed/MedLine database, was based on a strategy combining descriptors listed in the PubMed Medical Subject Headings (MeSH) Thesaurus and other available tools (free text or phrase search tools). 178 articles were retrieved by searching the period from January 1, 1980 to November 30, 2004. Only 2 of the 178 articles were indexed by the MeSH term "Epidemiology, molecular" (introduced in 1994) and 30 of 178 by the MeSH term "Biological markers" (introduced in 1989). The case of chromosome aberration (CA) was emblematic of the problem: 44 of 78 articles (56.4%) were not pertinent to the search. The reasons for this poor performance are reported and discussed. Authors and indexers may be able to improve the efficiency of article retrieval in the field of molecular epidemiology by using relevant terms in the title and abstract. This may suggest appropriate MeSH terms to the indexers for the indexing process. As regards the difficulty in identifiyng population studies using CA, the introduction of a specific MeSH term for chromosome aberrations when used as a biomarker would improve the search process. Environ. Mol. Mutagen., 2006. © 2006 Wiley-Liss, Inc. [source]

Genotoxicity of nitrosulfonic acids, nitrobenzoic acids, and nitrobenzylalcohols, pollutants commonly found in ground water near ammunition facilities

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2006
Tamara Grummt
Abstract 2-Amino-4,6-dinitrobenzoic acid (2-A-4,6-DNBA), 4-amino-2,6-dinitrobenzoic acid (4-A-2,6-DNBA), 2,4,6-trinitrobenzoic acid (2,4,6-TNBA), 2-amino-4, 6-dinitrobenzylalcohol (2-A-4,6-DNBAlc), 4-amino-2,6-dinitrobenzylalcohol (4-A-2,6-DNBAlc), 2,4-dinitrotoluol-5-sulfonic acid (2,4-DNT-5-SA), 2,4-dinitrotoluol-3-sulfonic acid (2,4-DNT-3-SA), and 2, 4-dinitrobenzoic acid (2,4-DNBA) are derivatives of nitro-explosives that have been detected in groundwater close to munitions facilities. In the present study, the genotoxicity of these compounds was evaluated in Salmonella/microsome assays (in strains TA100 and TA98, with and without S9 and in TA98NR without S9), in chromosomal aberration (CA) tests with Chinese hamster fibroblasts (V79), and in micronucleus (MN) assays with human hepatoma (HepG2) cells. All compounds except the sulfonic acids were positive in the bacterial mutagenicity tests, with 2,4,6-TNBA producing the strongest response (8023 revertants/,mol in TA98 without S9 activation). 2-A-4,6-DNBA was a direct acting mutagen in TA98, but negative in TA100. The other positive compounds were ,1,3 orders of magnitude less mutagenic than 2,4,6-TNBA in TA98 and in TA100; relatively strong effects (,50,400 revertants/,mol) were produced by the benzylacohols in the two indicator strains. With the exception of 2,4-DNBA, the mutagenic responses were lower in the nitroreductase-deficient strain TA98NR than in the parental strain. 2,4-DNBA produced a marginally positive response in the V79-cell CA assay; the other substances were devoid of activity. Only the benzoic acids were tested for MN induction in HepG2 cells, and all produced positive responses. As in the bacterial assays, the strongest effect was seen with 2,4,6-TNBA (significant induction at ,1.9 ,M). 4-A-2,6-DNBA was positive at 432 ,M; the weakest effect was observed with 2,4,-DNBA (positive at ,920 ,M). The differences in the sensitivity of the indicator cells to these agents can be explained by differences in the activities of enzymes involved in the activation of the compounds. The strong responses produced by some of the compounds in the human-derived cells suggest that environmental exposure to these breakdown products of nitro-explosives may pose a cancer risk in man. Environ. Mol. Mutagen., 2006. © 2005 Wiley-Liss, Inc. [source]

Gender differences in genetic damage induced by the tobacco-specific nitrosamine NNK and the influence of the Thr241Met polymorphism in the XRCC3 gene

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2005
Courtney E. Hill
Abstract The rapid increase in adenocarcinoma of the lung and mortality amongst women strongly suggests that gender differences exist in sensitivity to certain tobacco carcinogens. In the current study, we performed the mutagen-sensitivity assay, with the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), to test the hypothesis that women are more sensitive to the genotoxic effects of NNK than men. Chromosome aberration (CA) frequencies in peripheral blood lymphocytes (PBLs) from 99 patients were evaluated before and after in vitro exposure to NNK. Because the Thr241Met polymorphism in the DNA-repair gene XRCC3 is associated with increased risk of tobacco-related cancers, especially among women, we also tested the hypothesis that individuals who inherit the homozygous variant 241Met allele are more sensitive to the genotoxic effects of NNK. CA frequency was significantly higher 1 hr after NNK treatment in women, compared with men (P = 0.02). When smoking and gender were considered together, a significant interaction was observed. PBLs from female smokers had significantly higher frequencies of NNK-induced CA, compared with female nonsmokers 1 hr after treatment (P = 0.02). We observed no overall effect of the Thr241Met polymorphism on NNK-induced CA in men, women, smokers, or nonsmokers. Overall, our data indicate that women are more sensitive to the genotoxic effects of NNK than men. Because in past years smoking among women has increased, and in view of the close correlation between NNK exposure and adenocarcinoma of the lung, our data provide a plausible explanation for the recent increase in the incidence of this cancer among women. Environ. Mol. Mutagen., 2005. © 2005 Wiley-Liss, Inc. [source]

Differential mutagen sensitivity of peripheral blood lymphocytes from smokers and nonsmokers: Effect of human cytomegalovirus infection

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3 2004
Thomas Albrecht
Abstract We used the mutagen sensitivity assay to test the hypothesis that human cytomegalovirus (HCMV) infection modifies the sensitivity of cells to genetic damage from genotoxic agents. Chromosome aberration (CA) frequency in peripheral blood lymphocytes (PBLs) from 20 smokers who were matched with 20 nonsmokers by age (± 5 years), sex, and ethnicity was evaluated following in vitro exposure to bleomycin and/or HCMV infection. Bleomycin induced significant (P < 0.05) concentration-dependent increases in the frequency of aberrant cells, chromatid-type damage (breaks), and chromosome-type aberrations (deletions, rearrangements) in PBLs. The baseline (background) CA frequency was similar in both smokers and nonsmokers. Significantly higher frequencies of aberrant cells (P < 0.05) were observed in PBLs from smokers compared to nonsmokers at all bleomycin concentrations tested (10, 30 and 100 ,g/ml). Infection of PBLs with HCMV induced a significant (P < 0.05) twofold increase in the frequency of CA (primarily chromatid breaks) in PBLs, regardless of the smoking status. PBLs from smokers and nonsmokers infected with HCMV prior to challenge with bleomycin demonstrated significant (P < 0.05) concentration-dependent increases in the levels of aberrant cells, chromatid-type damage (breaks), and chromosome-type aberrations (deletions, rearrangements) compared to noninfected cells challenged with bleomycin. The frequency of induced CA was consistently higher for PBLs derived from smokers relative to nonsmokers (P = 0.06 and 0.002). These data indicate that, individually, both smoking and HCMV infection significantly enhance the sensitivity of PBLs to bleomycin-induced genetic damage. More importantly, the data also suggest that smoking and HCMV infection interact synergistically to enhance the sensitivity of PBLs to such damage. Environ. Mol. Mutagen. 43:169,178, 2004. © 2004 Wiley-Liss, Inc. [source]

Mutagenicity and disinfection by-products in surface drinking water disinfected with peracetic acid

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2002
Silvano Monarca
Abstract The aims of this research were to study the influence of peracetic acid (PAA) on the formation of mutagens in surface waters used for human consumption and to assess its potential application for the disinfection of drinking water. The results obtained using PAA were compared to those found with sodium hypochlorite (NaClO) and chlorine dioxide (ClO2). The Ames test, root anaphase aberration assay, and root/micronuclei assay in Allium cepa and Tradescantia/micronuclei test were used to evaluate the mutagenicity of disinfected samples. Microbiological tests were also performed, and disinfection by-products (DBPs) were identified using gas chromatography/mass spectrometry (GC/MS). A slight bacterial mutagenicity was found in raw lake and river water, and similar activity was detected in disinfected samples. A plant test revealed genotoxicity in raw river water, and microbiological analysis showed that PAA has bactericidal activity but lower than that of the other disinfectants. The DBPs produced by PAA were mainly carboxylic acids, which are not recognized as mutagenic, whereas the waters treated with the other disinfectants showed the presence of mutagenic/carcinogenic halogenated DBPs. However, additional experiments should be performed with higher concentrations of PAA and using water with higher organic carbon content to better evaluate this disinfectant. [source]

The prognostic significance of cytogenetic aberrations in childhood acute myeloid leukaemia.

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2007
A study of the Swiss Paediatric Oncology Group (SPOG)
Abstract In childhood-onset acute myeloid leukaemia (AML) the clinical value of karyotypic aberrations is now acknowledged, although there is still debate concerning the prognostic significance of some events. To add to this knowledge, cytogenetic analysis was performed on a consecutive series of 84 childhood AML patients diagnosed in Switzerland. A result was obtained for all patients, with 69 (82%) showing a clonal karyotypic aberration. In the remaining 15 (18%), no karyotypic aberration was seen by either conventional or fluorescence in situ hybridisation analyses. The most frequent aberrations observed were t(11q23) (19% of all patients), t(8;21) (12%) and +8 (11%). Except for cytogenetics, no clinical parameter was shown to be significantly associated with outcome. The analysis of individual cytogenetic subgroups demonstrated that aberrations involving chromosome 16q were the strongest predictor of a good prognosis, while +8 and complex karyotypes represented the strongest predictors of a poor prognosis. It was also noteworthy that patients with the rare aberrations of del(11q) (n = 4) and t(16;21)(p11;q22) (n = 3) had a poor outcome. The results support the importance of cytogenetic analysis in childhood AML, but show that further work is required in the classification of the poor prognosis aberrations. [source]

Splicing site mutations in dentin sialophosphoprotein causing dentinogenesis imperfecta type II

EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 5 2006
Heidi Holappa
Dentinogenesis imperfecta (DGI) type II (OMIM # 125490) is an inherited disorder affecting dentin. Defective dentin formation results in discolored teeth that are prone to attrition and fracture. To date, several mutations have been described in the dentin sialophosphoprotein (DSPP) gene, causing DGI types II and III and dentin dysplasia type II. DSPP encodes two proteins: dentin sialoprotein (DSP) and dentin phosphoprotein (DPP). Here, we describe a mutational analysis of DSPP in seven Finnish families with DGI type II. We report two mutations and five single nucleotide polymorphisms. In one family we found a mutation that has been described earlier in families with different ethnicity, while in six families we found a novel g.1194C>A (IVS2-3) transversion. Bioinformatic analysis of known DSPP mutations suggests that DGI type II is usually caused by aberration of normal splicing. [source]

Acute leukemias with ETV6/ABL1 (TEL/ABL) fusion: Poor prognosis and prenatal origin

GENES, CHROMOSOMES AND CANCER, Issue 10 2010
Jan Zuna
The ETV6/ABL1 (TEL/ABL) fusion gene is a rare aberration in malignant disorders. Only 19 cases of ETV6/ABL1 -positive hematological malignancy have been published, diagnosed with chronic myeloid leukemia, other types of chronic myeloproliferative neoplasm, acute myeloid leukemia or acute lymphoblastic leukemia (ALL). This study reports three new cases (aged 8 months, 5 years, and 33 years) of ALL with the ETV6/ABL1 fusion found by screening 392 newly diagnosed ALL patients (335 children and 57 adults). A thorough review of the literature and an analysis of all published data, including the three new cases, suggest poor prognosis of ETV6/ABL1 -positive acute leukemias. The course of the disease in the two pediatric patients is characterized by minimal residual disease monitoring, using quantification of both the ETV6/ABL1 transcript and immunoreceptor gene rearrangements. Eosinophilia could not be confirmed as a hallmark of the ETV6/ABL1 -positive disease. Studies of neonatal blood spots demonstrated that, in the child diagnosed at five years, the ETV6/ABL1 fusion initiating the ALL originated prenatally. © 2010 Wiley-Liss, Inc. [source]

DNA repair polymorphisms associated with cytogenetic subgroups in B-cell chronic lymphocytic leukemia,

GENES, CHROMOSOMES AND CANCER, Issue 9 2009
Christina Ganster
Genetic polymorphisms in DNA repair genes can affect the risk of developing different forms of cancer. Therefore, we have studied the putative association of seven single nucleotide polymorphisms (SNPs) in five DNA repair genes with the incidence of chronic lymphocytic leukemia (CLL). We included 461 CLL patients and the same number of age- and sex-matched controls. As chromosomal aberrations are important prognostic markers in CLL, we additionally correlated the SNPs with the occurrence of favorable and unfavorable cytogenetic aberrations in CLL patients. Patients with del(13q) as a sole aberration were allocated to the favorable cytogenetic risk group, and patients with del(17p) and/or del(11q) to the unfavorable cytogenetic risk group. All investigated SNPs were equally distributed between patients with the favorable cytogenetic aberration and controls. However, differences were observed in the distribution of rs13181 in ERCC2 between all CLL patients and controls. Moreover, the clearest differences were found for rs13181 in ERCC2 and rs25487 in XRCC1 between CLL patients with unfavorable cytogenetic aberrations and controls. These data suggest that inborn genetic polymorphisms may predict the outcome of CLL. © 2009 Wiley-Liss, Inc. [source]

PAX5/IGH rearrangement is a recurrent finding in a subset of aggressive B-NHL with complex chromosomal rearrangements,

GENES, CHROMOSOMES AND CANCER, Issue 2 2005
Bruce Poppe
We present an extensive characterization of 10 B-cell lymphomas with a t(9;14)(p13;q32). The presence of the PAX5/IGH gene rearrangement was demonstrated by fluorescence in situ hybridization (FISH) using a validated probe set, whereas complex karyotypic changes were reassessed by multiplex-FISH (M-FISH). Pathologic and clinical review revealed the presence of this rearrangement in 4 histiocyte-rich, T-cell-rich B-cell lymphomas (HRTR-BCLs) and 2 posttransplantation diffuse large B-cell lymphomas (PTLD-DLBCLs). In contrast to initial observations describing this translocation in lymphoplasmacytic lymphoma (LPL) and LPL-derived large B-cell lymphoma, our data showed a wide morphologic and clinical spectrum associated with the PAX5/IGH rearrangement, pointing to an association between this aberration and a subset of de novo DLBCLs presenting with advanced disease and adverse prognosis. In addition, the recurrent incidence of this rearrangement in both HRTR-BCL (4 cases) and PTLD-DLBCL (2 cases) was previously unrecognized and is intriguing. © 2005 Wiley-Liss, Inc. [source]

Distinct sequences on 11q13.5 and 11q23,24 are frequently coamplified with MLL in complexly organized 11q amplicons in AML/MDS patients

GENES, CHROMOSOMES AND CANCER, Issue 4 2004
Andrea Zatkova
Amplification within chromosome arm 11q involving the mixed-lineage leukemia gene (MLL) locus is a rare but recurrent aberration in acute myeloid leukemia and myelodysplastic syndrome (AML/MDS). We and others have observed that 11q amplifications in most AML/MDS cases have not been restricted to the chromosomal region surrounding the MLL gene. Therefore, we implemented a strategy to characterize comprehensively 11q amplicons in a series of 13 AML/MDS patients with MLL amplification. Analysis of 4 of the 13 cases by restriction landmark genomic scanning in combination with virtual genome scan and by matrix-based comparative genomic hybridization demonstrated that the 11q amplicon in these four cases consisted of at least three discontinuous sequences derived from different regions of the long arm of chromosome 11. We defined a maximally 700-kb sequence around the MLL gene that was amplified in all cases. Apart from the core MLL amplicon, we detected two additional 11q regions that were coamplified. Using fluorescence in situ hybridization (FISH) analysis, we demonstrated that sequences in 11q13.5 and 11q23,24 were amplified in 8 of 13 and 10 of 12 AML/MDS cases, respectively. Both regions harbor a number of potentially oncogenic genes. In all 13 cases, either one or both of these regions were coamplified with the MLL amplicon. Thus, we demonstrated that 11q amplicons in AML/MDS patients display a complex organization and have provided evidence for coamplification of two additional regions on the long arm of chromosome 11 that may harbor candidate target genes. © 2004 Wiley-Liss, Inc. [source]

Molecular-cytogenetic comparison of mucosa-associated marginal zone B-cell lymphoma and large B-cell lymphoma arising in the gastro-intestinal tract

A genetic polymorphism in the coding region of the gastric intrinsic factor gene (GIF) is associated with congenital intrinsic factor deficiency,

HUMAN MUTATION, Issue 1 2004
Marilyn M. Gordon
Abstract Congenital intrinsic factor (IF) deficiency is a disorder characterized by megaloblastic anemia due to the absence of gastric IF (GIF, GenBank NM_005142) and GIF antibodies, with probable autosomal recessive inheritance. Most of the reported patients are isolated cases without genetic studies of the parents or siblings. Complete exonic sequences were determined from the PCR products generated from genomic DNA of five affected individuals. All probands had the identical variant (g.68A>G) in the second position of the fifth codon in the coding sequence of the gene that introduces a restriction enzyme site for Msp I and predicts a change in the mature protein from glutamine5 (CAG) to arginine5 (CGG). Three subjects were homozygous for this base exchange and two subjects were heterozygous, one of which was apparently a compound heterozygote at positions 1 and 2 of the fifth codon ([g.67C>G] + [g.68A>G]). The other patient, heterozygous for position 2, had one heterozygous unaffected parent. Most parents were heterozygous for this base exchange, confirming the pattern of autosomal recessive inheritance for congenital IF deficiency. cDNA encoding GIF was mutated at base pair g.68 (A>G) and expressed in COS-7 cells. The apparent size, secretion rate, and sensitivity to pepsin hydrolysis of the expressed IF were similar to native IF. The allelic frequency of g.68A>G was 0.067 and 0.038 in two control populations. This sequence aberration is not the cause of the phenotype, but is associated with the genotype of congenital IF deficiency and could serve as a marker for inheritance of this disorder. Hum Mutat 23:85,91, 2004. © 2003 Wiley-Liss, Inc. [source]

Design of a Singlet Lens and the Corresponding Aberration Correction Approaches for Cell Phone Camera

IEEJ TRANSACTIONS ON ELECTRICAL AND ELECTRONIC ENGINEERING, Issue 4 2010
Yupeng Zhang Member
Abstract A singlet lens model that is designed for future cell phone camera is discussed. The proposed lens model unavoidably introduces significant optical aberration because of its high field angle (maximum field angle 48°). To correct the aberrations, traditional paraxial aberration and third-order Seidel aberration are no longer applicable because the accuracy will decline dramatically when the field angle reaches a high value. In this paper, the main objective is to find an improved first-order aberration equation and an improved third-order Seidel aberration equation using field-dependent coefficients to correct lateral chromatic aberration (LAT) and distortion, respectively, for a high-field-angle singlet lens. The simulation results suggest that improved higher order aberration equations are more accurate to represent real aberrations than the lower order case. However, the chromatic aberration is still visible in the resultant images even though LAT is corrected, because of the differences of blur between different colors caused by axial chromatic aberration (AX) and other monochromatic aberrations such as field curvature. This poses a new research topic as our future work. Copyright © 2010 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc. [source]