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Immunology of Scleroderma
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
The centromere comprised of the kinetochore, which is a trilaminar disc-shaped structure, serves as the attachment site for the spindle microtubules. The microtubules facilitate the alignment and separation of the chromosome during mitosis.184,185 The prevalence of ACA in SSc varies but has been found to be strongly associated with the lcSSc.134 ACA has also been identified in normal individuals186 and patients with Raynaud’s,166,186 SLE,186 primary biliary cirrhosis,187 and morphea.187 ACA comprises at least 6 centromere polypeptides (CENP): CENP-A to CENP-F More than 90% of ACA-positive sera from SSc patients reacts with CENP-A, -B, and -C188 and studies have demonstrated that these antibodies are capable of disrupting mitosis.189 CENP-A is a protein that is very similar to histone H3 of the H3/H4 nucleosomal core and is approximately 18 kD in size. It copurifies with H3/H4, but it has a centromere specific binding domain and is therefore distinct from H3 and H4.190,191 CENP-B is a DNA binding protein of 80kD and can be identified in 100% of all ACA-positive sera. It is distributed throughout the centromeric alpha-satellite heterochromatin below the kinetochore.192 CENP-C is a 140 kD protein that is a component of the kinetochore plate, which is essential for normal centromere function.193
Practical Approach to Molecular Biology in Hematopathology
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Anwar Mikhael, Harold R. Schumacher
The technique requires the availability of DNA probes specific for the chromosomal aberrations seen in leukemias. These probes can be: Chromosome-specific, hybridizing to satellite DNA sequences present at the centromere. These are especially applicable to cases with numerical abnormalities.Hybridizable to multiple sequences from a single chromosome (chromosome painting). These are particularly suitable for structural rearrangements (translocation). Examples include Philadelphia chromosome translocation t(9;22) of CML, the t(8;14), t(2;8) and t(8;22) seen in Burkitt’s and 11q23 seen in ALL.Specific to a unique sequence.
Molecular Biology
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Michael Kuo, Richard M. Irving, Eric K. Parkinson
Each DNA molecule is packaged into a chromosome by complex folding of the DNA around proteins. Diploid human cells contain 22 pairs of autosomes (1 to 22) and a pair of sex chromosomes (XX or XY) that determines the sex of the organism. One of each pair of chromosomes is maternally inherited and the other is paternally inherited. Each chromosome has a distinctive shape, size and banding pattern, but have the common appearance of two arms apparently separated by a constriction. The centromere is microscopically recognizable as the central constriction separating the chromosome into a long arm (q for queue) and a short arm (p for petit), but its biological role lies in anchoring the chromosome to the mitotic spindle for segregation during cell division. The ends of the chromosomes are capped by telomeres, which are specialized structures containing unique simple repetitive sequences. They maintain the structural integrity of the chromosome and provide a solution for complete replication of the extreme ends of the chromosome. The conventional nomenclature for chromosomal locus assignment is given by the chromosome number, followed by the arm and finally the position on the arm, for example, 3p21 indicates position 21(two-one) on the short arm of chromosome three.
An intercomparison exercise to compare scoring criteria and develop image databank for biodosimetry in South Korea
Published in International Journal of Radiation Biology, 2021
Yang Hee Lee, Younghyun Lee, Hyo Jin Yoon, Su San Yang, Hae Mi Joo, Ji Young Kim, Seong-Jun Cho, Wol Soon Jo, Soo Kyung Jeong, Su Jung Oh, Yeong-Rok Kang, Ki Moon Seong
Differences in scoring criteria were investigated in depth through a technical workshop. Table 3 shows a summary of the scoring discrepancies. During selecting metaphase spreads, the number of centromeres in metaphases used for DCA was somewhat different between participating laboratories. In order to obtain more scorable metaphase spreads, laboratories selected metaphases containing 45 centromeres as well as complete metaphases (i.e. 46 centromeres), in which case only one missing chromosome is unlikely to affect dicentric frequency. Of them, two laboratories additionally selected metaphase even with more than 46 centromeres, taking into account the occurrence of numerical chromosomal abnormalities (e.g. Turner syndrome, Klinefelter syndrome, Down syndrome) (Roizen and Patterson 2003; Lanfranco et al. 2004; Sybert and McCauley 2004).
Mutant ATRX: uncovering a new therapeutic target for glioma
Published in Expert Opinion on Therapeutic Targets, 2018
Santiago Haase, María Belén Garcia-Fabiani, Stephen Carney, David Altshuler, Felipe J. Núñez, Flor M. Méndez, Fernando Núñez, Pedro R. Lowenstein, Maria G. Castro
The role of ATRX in the resolution of G4 and other non-B DNA secondary structures is essential in preserving genomic stability. Consequently, the accumulation of G4 and other secondary structures in ATRX-mutated cells may be a major contributor to genomic instability. ATRX appears to play a critical role in genomic stability preservation and contributes to chromosome dynamics during mitosis [60]. A study performed in HeLa cells shows that ATRX downregulation by siRNA results in abnormal chromosome congression during mitosis [108]. RNAi knock down of ATRX in mouse ES cells also induces a telomere-dysfunction phenotype and reduces chromobox homolog 5 (CBX5) enrichment at telomeres, suggesting that ATRX participates in telomere chromatin integrity maintenance [109]. In addition, studies in transgenic mice show that ATRX contributes to regulation of pericentric heterochromatin structure [110–112]. This is an essential mechanism that coordinates sister centromere cohesion and appropriate separation of chromatids during mitosis. The loss of this mechanism results in centromere instability and aneuploidy [106,113].
Vinorelbine’s anti-tumor actions may depend on the mitotic apoptosis, autophagy and inflammation: hypotheses with implications for chemo-immunotherapy of advanced cancers and pediatric gliomas
Published in Journal of Chemotherapy, 2018
Meric A. Altinoz, Aysel Ozpinar, Ebru Emekli Alturfan, Ilhan Elmaci
Vinorelbine is a semi-synthetic vinca alkaloid and similar to other vinca alkaloids, arrests the tumor cells in G2 and metaphase of the cell cycle by inhibiting tubulin depolymerization and mitotic spindle formation.1 Vinorelbine’s anti-tumor effects are summarized in Table 1. Vinorelbine has a modified catharantine nucleus; and therefore acts lesser on neuronal axonal tubules causing lower neurotoxicity.1 Further, the substitution on the catharanthine instead of the vindole moiety provides enhanced lipophilicity, enhancing the drug penetration into cancer cells.2Vinca alkaloid’s suppression of microtubules mediates their ability to block mitosis. After nuclear envelope breakdown in mitosis, the microtubules originating from opposite spindle poles become attached at their plus ends to the centromeres at the kinetochores. Kinetochore-microtubules and associated motor proteins are responsible for the chromosomal movement. In U2OS (human osteosarcoma cells) vinorelbine suppressed cell growth by 50% at an IC50 of 5.7 nM. At concentrations approximating the IC50s for mitotic accumulation (7.3 nM), vinorelbine decreased centromere dynamicity by 25% and increased the time centromeres spent in a paused state by 52%.3