Gaucher disease is a lysosomal storage disease showing weak genotype-phenotype correlation, with poorly predictable disease severity. Cytopathological alterations are caused not only by the accumulation of the undegraded glycolipid substrate, but also by macrophage activation, displaying serum elevation of various cytokines with important influence to inflammation. Several studies in the literature showed increased incidence of hematological complications in Gaucher patients, including monoclonal and polyclonal gammopathies as well as hematological malignancies, especially multiple myeloma. We had already described a high incidence of immunoglobulin heavy chain gene rearrangements in a cohort of Serbian patients, suggesting that an early occurrence of immune system activation is possible early in the disease course. The object of this study was the analysis of clonal rearrangements of IGH genes and frequencies of alleles of cytokine genes important for inflammation (TNFα, IL-10 and IL-6) as ...

TY - JOUR. T1 - Immunoglobulin heavy chain gene analysis in lymphomas. T2 - A multi-center study demonstrating the heterogeneity of performance of polymerase chain reaction assays. AU - Bagg, Adam. AU - Braziel, Rita M.. AU - Arber, Daniel A.. AU - Bijwaard, Karen E.. AU - Chu, Albert Y.. PY - 2002. Y1 - 2002. N2 - Determination of monoclonality through an evaluation of immunoglobulin heavy chain (IgH) gene rearrangements is a commonly performed and useful diagnostic assay. Many laboratories that perform this assay do so by the polymerase chain reaction (PCR). To evaluate current methods for performing IgH gene testing, 19 different Association of Molecular Pathology (AMP) member laboratories analyzed 29 blinded B cell and T cell lymphoid neoplasm samples of extracted DNA and formalin-fixed, paraffin-embedded (FFPE) tissue and were asked to complete a technical questionnaire. From this study, it is clear that Southern blot analysis remains the diagnostic gold standard, with a 100% diagnostic ...

TY - JOUR. T1 - Clinical significance of monoclonal B cells in cerebrospinal fluid. AU - Nowakowski, Grzegorz S.. AU - Call, Timothy G.. AU - Morice, William G.. AU - Kurtin, Paul J.. AU - Cook, Rachel J.. AU - Zent, Clive S. PY - 2005/1. Y1 - 2005/1. N2 - Background: Morphologically malignant lymphocytes in the cerebrospinal fluid (CSF) are highly suggestive of central nervous system involvement by lymphoid malignancy. Although flow cytometry is increasingly used to detect a monoclonal B-cell population in the CSF, the significance of this finding in the absence of morphologically identifiable malignant cells is unknown. Methods: We reviewed CSF flow cytometric results in 32 patients studied at a single institution over 5 years and identified patients who had monoclonal B-cells in the CSF. Clinical presentation and course were reviewed. Results: Twelve patients had a monoclonal B-cell population in the CSF, but only three had clinical evidence of malignant CNS disease. Of the other nine ...

TY - JOUR. T1 - Determining the repertoire of IGH gene rearrangements to develop molecular markers for minimal residual disease in B-lineage acute lymphoblastic leukemia. AU - Brisco, Michael. AU - Latham, Susan. AU - Sutton, Rosemary. AU - Hughes, Elizabeth. AU - Wilczek, Vicki. AU - van Zanten, Katrina. AU - Budgen, Bradley. AU - Bahar, Anita. AU - Malec, Maria. AU - Sykes, Pamela. AU - Kuss, Bryone. AU - Waters, Keith. AU - Venn, Nicola. AU - Giles, Jodie. AU - Haber, M. AU - Norris, Murray. AU - Marshall, Glenn. AU - Morley, Alexander. PY - 2009. Y1 - 2009. M3 - Article. VL - 11. SP - 194. EP - 200. JO - Journal of Molecular Diagnostics. JF - Journal of Molecular Diagnostics. SN - 1525-1578. IS - 3. ER - ...

Paraffin-embedded tissue; send one tissue block or 4 unstained slides. Ship the specimen at 20° - 25° C. Tissues that are fixed in formalin substitute are unacceptable. Tissue that does not contain lymphocytes is not accepted. Ship all tissue specimens with a cold pack in summer months.. Blood or bone marrow in an EDTA or ACD tube; one 3 mL of blood or 1 mL of bone marrow shipped at 4° C is acceptable. Severely hemolyzed whole blood and/or clotted or frozen whole blood/bone marrow specimens are not accepted.. Fresh tissue that is at least a 5 mm cube, shipped frozen or on ice in RPMI 1640, is accepted.. Cell pellets, at least 10 6-cells shipped at 4° C, are acceptable.. ...

Définitions de 1 2 rearrangement, synonymes, antonymes, dérivés de 1 2 rearrangement, dictionnaire analogique de 1 2 rearrangement (anglais)

Unmutated immunoglobulin heavy chain gene rearrangement Patents must understand and voluntarily sign an informed consent form Able to adhere to the study visit schedule and other protocol requirements Patients must have measurable disease either an absolute lymphocyte counts (ALC) of more than 5,000/ul or measurable lymphadenopathy or organomegaly Eastern Cooperative Oncology Group (ECOG) performance status of =, 2 at study entry Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL 10-14 days prior to and again within 24 hours before starting lenalidomide and must either commit to continue abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual ...

Compaction and looping of the ~2.5-Mb Igh locus during V(D)J rearrangement is essential to allow all V(H) genes to be brought in proximity with D(H)-J(H) segments to create a diverse antibody repertoire, but the proteins directly responsible for this are unknown. Because CCCTC-binding factor (CTCF) has been demonstrated to be involved in long-range chromosomal interactions, we hypothesized that CTCF may promote the contraction of the Igh locus. ChIP sequencing was performed on pro-B cells, revealing colocalization of CTCF and Rad21 binding at ~60 sites throughout the V(H) region and 2 other sites within the Igh locus. These numerous CTCF/cohesin sites potentially form the bases of the multiloop rosette structures at the Igh locus that compact during Ig heavy chain rearrangement. To test whether CTCF was involved in locus compaction, we used 3D-FISH to measure compaction in pro-B cells transduced with CTCF shRNA retroviruses. Reduction of CTCF binding resulted in a decrease in Igh locus ...

The VH gene repertoire of human peripheral B cells was analyzed using PCR analysis of individual blood B cells. Because genomic DNA of single B cells was analyzed, data from both productive and nonproductive VDJ rearrangements were obtained. Nine out of 75 B cells contained both functional and nonfunctional rearrangement products, whereas 62/75 had a single productive VDJ rearrangement. The distribution of VH families was ordered in accordance with the germline complexity, although a bias toward VH3 and some of its members was found. This bias was noted in both the productively and nonproductively rearranged repertoires, indicating that it resulted from molecular and not selective processes. Evidence for negative selection of certain VH3 and VH4 family members was noted in that they were found less often as productive than nonproductive VDJ rearrangements. In addition, evidence for positive selection based on CDR3 was obtained, in that JH6 and DXP1 were found at a higher frequency in the ...

1. Can atypical marginal zone hyperplasia re-grow or relapse? 2. Is PCR for B-cell clonal IGH gene rearrangement necessary to diagnosis pediatric marginal zone lymphoma? 3. Clinically, how to treat atypical marginal zone hyperplasia when complete excision is not possible ...

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The Ireland-Claisen rearrangement is the central step in the synthesis of tubuphenylalanine, a key building block of the highly antitumor-active tubulysins. The rearrangement of substituted β-amino acid allyl esters, in combination with subsequent d

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Puri, J; Ben, neriah Y.; Givol, D; and Lonai, P, Antibodies to immunoglobulin heavy chain variable regions protect helper cells from specific suicide by radiolabeled antigen. (1980). Subject Strain Bibliography 1980. 1413 ...

DNA encoding the rat diversity segment (D), joining segment (JH), and constant (C) region mu, gamma 2a, gamma 1, gamma 2b, epsilon and alpha of the Ig heavy chain has been isolated from a cosmid library. Restriction mapping allowed us to identify two gene clusters: D-JH-C mu and C gamma 1-C gamma 2b-C epsilon-C alpha in addition to a single C gamma 2a gene. Analysis of genomic DNA by Southern blotting permitted identification of the C gamma 2c gene and led to the proposal of the following gene order for the rat Ig heavy chain locus: D-JH-C mu-C delta-(C gamma 2c, C gamma 2a)-C gamma 1-C gamma 2b-C epsilon-C alpha. There is striking homology between the rat and mouse Ig heavy chain loci as regards gene order and distance between CH genes. Partial DNA sequencing confirms this homology and shows that exon sequences are more conserved than are intron sequences. One of the most conserved intron regions between rat and mouse is that spanning the Ig heavy chain enhancer (91% homology). However, the

Describes how B-cell immunoglobulin gene rearrangement tests are used, when they are ordered, and what the results of B-cell immunoglobulin gene rearrangement tests might mean

A convenient web based application for analyzing next-generation sequencing results and reporting IGH gene rearrangements for both repertoire and clonality studies. IGGalaxy has two analysis options one using the built in igBLAST algorithm and the second using output from IMGT; in either case repertoire summaries for the B-cell populations tested are available. IGGalaxy supports multi-sample and multi-replicate input analysis for both igBLAST and IMGT/HIGHV-QUEST. IGGalaxy is built on top of the Galaxy framework (http://galaxyproject.org/) and is distributed as a virtual machine image.

Impaired generation of immature NEMO-deficient Igλ+ B cells in the absence of rearrangements at Igk loci. (a) BM cells from iEκT homozygous mice (iEκT/T)-

概要-σ重排中最基本的反应。该反应是一个平衡反应，1,4-己二烯进行cope重排的话，需要越过140 kJmol-1的能量屏障，这样才能相互变换。

Several genes for the variable region of immunoglobulin heavy chains (VH genes) have been isolated from human fetal liver DNA by using a cDNA plasmid probe containing a mouse VH sequence. The detectable VH genes are separated by 12-16 kilobases of DNA, and hybridization experiments show about 23 hybridizing VH genes in DNA of three different individuals. The complete nucleotide sequence of one of these human VH genes shows that it belongs to the human VHIII subgroup. The VH gene appears to contain an intervening sequence (104 bases in length) within a precursor sequence, between residues -4 and -5. The precursor sequence is itself 19 codons in length. The 3 end of the V gene seems to be at codon 93 or 94, and this is followed by the conserved sequences C-A-C-A-G-T-G and G-A-C-A-C-A-A-A-C-C. The presence of these sequences suggests that similar enzymatic mechanisms are involved in the integration of V genes in both heavy and light chains.

Although it has been assumed that the deregulated bcl-2 expression in t(14;18) cells is mediated in part by the immunoglobulin heavy chain gene regulatory region, this has not been demonstrated, nor was it known which elements of that region were responsible for the deregulation. In these studies, we found that the four DNase I-hypersensitive regions within the IgH 3′ enhancer were able to activate the bcl-2 promoter in the t(14;18) cell line DHL-4. Of those four hypersensitive regions, we demonstrated that HS4 had the most influence on bcl-2 promoter activity. This is similar to the situation in pre-B and plasmacytoma cells, where HS4 is the most active enhancer region. We also showed that the HS1,2 region was capable of activating the promoter independently. By itself, HS3 increased bcl-2 promoter activity by only a minor amount. Other studies of HS3 have shown that it is contains elements that act as negative effectors of the IgH 3′ enhancer (37) , and preliminary studies in our ...

It has been well established that V(D)J recombination of the Ig heavy and light chain genes occur in a sequential manner (1). In this context, the rearrangement of IgH chain genes occurs exclusively in pro-B cells, whereas the rearrangement of IgL chain genes occurs primarily in pre-B cells. Our findings indicate that EμR replacement greatly increases Igk rearrangement in pro-B cells. In addition, the germline transcription of both Vκ and Jκ regions as well as DNA demethylation at the Jκ region are substantially increased in EμR pro-B cells, indicating that Eμ is sufficient to promote the accessibility of these loci to V(D)J recombinase and activate V(D)J recombination in pro-B cells.. To maintain the sequential rearrangement of IgH and IgL chain genes, the rearrangement of IgH loci occurs in pro-B cells but not in pre-B cells. Analysis of B cell development and Igk rearrangement suggests that Igk rearrangement is not efficient in EμR pre-B cells. In further support of this notion, the ...

Conference Paper: A study of clonality of lymphoma of SJL mice using immunoglobulin gene rearrangements and murine leukaemia virus ...

The immunoglobulin heavy-chain (domain. the variable areas of immunoglobulin (Ig) genetics from adjustable (Sixth is v), variety (D), and becoming a member of (M) gene sections during N cell advancement. The recombination of genetics can be firmly managed within the N lymphoid family tree: the Ig heavy-chain (locus are started in lymphoid progenitors adopted by VH-DJH recombination in pro-B cells. The temporary purchase of Sixth is v(G)M recombination can be mainly established by the ease of access of the different Ig gene sections to the Sixth is v(G)M recombinase, which can be managed by multiple epigenetic systems (Jhunjhunwala et al., 2009; Alt and Perlot, 2008). The locus can be made up of the 3 proximal area of 266 kb size consisting of 16 DH, 4 JH, and 8 CH gene sections and of the distal VH gene bunch increasing over a 2.44 Mb area, which contains 195 VH genetics with the largest VH gene family members consisting of 89 VHJ558 genetics (Johnston et al., 2006). VH-DJH recombination at the ...

CloneSelect Imager is a high-throughput automated label-free imaging solution for assurance of monoclonality. Its automatically calculates confluence measurements and generates growth curves, heatmaps, and image montages and helps to increase throughput and productivity because of its ability to image a 96-well plate in 90 seconds.

The CPT codes provided with our Test Descriptions are based on AMA guidelines and are for informational purposes only. Correct CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed.. ...

Browsing NGS databases for TRK gene rearrangements can lead to more profound questions regarding their origin. In our sister website we had only one example of an TRK2 gene rearrangement, QKI-TRK2. The COSMIC database was searched revealing one more TRK2 ...

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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) ...

5,000 CLL-type lymphocytes per mm³). If the diagnosis of CLL is based on the B cell count rather than the total lymphocyte count (which includes both B and T cells), many patients formerly diagnosed with Rai Stage 0 CLL would instead be classified as having MBL. Molecular techniques can detect monoclonal B cell levels as low as 3-5 B cells/microliter (comparable to the amount of stem cells in peripheral blood). The term monoclonal B-cell lymphocytosis was proposed by a consensus committee in 2005 to indicate a monoclonal B cell population in a person with fewer than 5,000 B lymphocytes per microliter (or 5.0 x 109 B lymphocytes/L), no enlarged lymph nodes or enlarged liver and/or spleen or other indications of a lymphoproliferative disorder. MBL has been found in less than 1% of asymptomatic adults under age 40, and in around 5% of adults older than 60. Exact numbers depend on the population studied and the sensitivity of the diagnostic technique. Like CLL, it appears to be more common in ...

Crews, Stephen Thomas (1983) The Structure of Mammalian Genes: (1) Antibody Heavy Chain Variable Region Genes: Organization, Diversity, and Somatic Mutation. (2) Structure and Transcription of the DNA Encompassing the Origin of Replication of Human Mitochondrial DNA. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/4dgr-za66. https://resolver.caltech.edu/CaltechTHESIS:08302019-152439482 ...

Over the last decade, immunogenetic analysis of B-cell receptor immunoglobulins (BcR IG) has proved instrumental in dissecting chronic lymphocytic leukemia (CLL) pathogenesis. Initially, it was the finding that the level of somatic hypermutations in rearranged IG heavy-chain genes could define two C …

In the present study, the case of a 41-year-old man with immunoglobulin (Ig)M multiple myeloma (MM) that presented with an unusually non-aggressive clinical course who has survived for ,9 years to date, is presented. Initial diagnosis of symptomatic MM was established according to the International Myeloma Working Group consensus statement and guidelines. Due to the mild symptoms, no therapy was administered and the patient was closely followed up. Eight years after initial diagnosis, clinical, morphological and genetic progression occurred with the development of hypercalcemia, progressively deteriorating polyneuropathy, clonal expansion of plasma cells up to 50% of hematopoietic cells and demonstration of the typical t(11;14) translocation (Ig heavy chain locus rearrangement ...

Twenty-two B-cell chronic lymphocytic leukemia (CLL) patients were investigated to evaluate residual disease in clinico-hematological remission. Residual disease was determined by monotypy of surface light chain expression and by dual-color staining with CD5 and CD19 markers. Samples were analyzed on flow cytometer. Total CD19+ cells above 25%, the CD5+CD19+/total CD19+ cells ratio above 0.25, clonal excess above 0.4 were considered positive for residual disease. According to these immunological criteria, only four cases achieved phenotypic remission. Our data confirm that dual marker analysis is more sensitive than clonal excess and may predict an early relapse. Ig gene rearrangements were studied by Southern blot analysis using IGHJ and IGKC probes in fifteen cases. All 12 cases that retained a detectable rearrangement displayed a phenotypic residual disease. Conversely, in two cases, DNA analysis failed to detect the residual disease characterized by flow cytometry. In conclusion, this study ...

Chronic lymphocytic leukemia (CLL) is a clonal disease of B lymphocytes manifesting as an absolute lymphocytosis in the blood. However, not all lymphocytoses are leukemic. In addition, first-degree relatives of CLL patients have an ~15 % chance of developing a precursor condition to CLL termed monoclonal B cell lymphocytosis (MBL), and distinguishing CLL and MBL B lymphocytes from normal B cell expansions can be a challenge. Therefore, we selected FMOD, CKAP4, PIK3C2B, LEF1, PFTK1, BCL-2, and GPM6a from a set of genes significantly differentially expressed in microarray analyses that compared CLL cells with normal B lymphocytes and used these to determine whether we could discriminate CLL and MBL cells from B cells of healthy controls. Analysis with receiver operating characteristics and Bayesian relevance determination demonstrated good concordance with all panel genes. Using a random forest classifier, the seven-gene panel reliably distinguished normal polyclonal B cell populations from expression

specific ablation of YY1 in mouse B cells caused a defect in somatic rearrangement in the immunoglobulin heavy-chain (IgH) locus and a block in the progenitor-B-to-precursor-B-cell transition, which was partially rescued by a prerearranged IgH transgene ...

The Cope rearrangement, not to be confused with the Cope elimination, is the conversion of a 1,5-diene to a more stable, constitutionally isomeric (see constitutional isomers) 1,5-diene at a very high temperature.. eg:. ...

What if thermonuclear power was as easy to build as a plasma torch, or rocket engine-- some simple electromechanical assembly (with precise electronic

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Previous studies (20, 36) demonstrated that the downstream Vγ3 gene is preferentially rearranged in the early fetal thymus compared with Vγ2 by a factor of approximately fourfold. Other studies show that the fraction of productive rearrangements is inherently lower for Vγ2 than for rearrangements of other V genes, because Vγ2 uniquely contains an in-frame stop codon near its 3′ end, which must be removed (presumably by endonuclease action) during the recombination process (16). The relative paucity of Vγ2 rearrangements at the fetal stage, coupled with the rarity of productive Vγ2 rearrangements, are critical in ensuring that nearly all TCRγδ+ fetal thymocytes express Vγ3 (or Vγ4) and not Vγ2. The absence of TdT at the fetal stage also plays a role in the process of Vγ3 gene rearrangement. Without TdT and the N nucleotides it adds, the frequency of rearrangements that occur at the site of a dinucleotide homology shared by the Vγ3 and Jγ1 gene segments is increased, thus ensuring ...

With the exception of IGHV mutational status, there was no significant difference in the prognostic markers of cMBL and Rai0-CLL (including chromosomal lesions), although a trend was noticed in the prevalence of unfavorable prognostic factors in Rai0-CLL versus cMBL. The explanation of this phenomenon is difficult, although it could be speculated that the mechanisms inducing clonal expansion (e.g., antigenic stimulation) are already operative in the transition from cMBL to Rai0-CLL (37). This would explain the prevalence of IGHV-UM cases in the Rai0-CLLs and suggest that larger differences could be detected when cMBL are compared to more advanced CLL cases, as indicated by Lanasa and colleagues (38). Moreover, the promoting factors inducing clonal expansion would also facilitate the expression of cellular activation markers (e.g., ZAP-70 and CD38) and the slow accumulation of additional unfavorable lesions (e.g., additional chromosomal abnormalities or NOTCH1 and SF3B1 mutations, appearing late ...

Gene conversion-like events between rearranged IGHV3-23*01 gene sequences and germline VH sequences superimposed by somatic hypermutation (SHM). IGHV3-23*01 mut

The frequency of mitogen-reactive B cells yielding an IgG plaque-forming cell (PFC) response has been determined in vitro by limiting dilution analysis under cu

The related Nametkin rearrangement named after Sergey Namyotkin involves the rearrangement of methyl groups in certain terpenes. In some cases the reaction type is also called a retropinacol rearrangement (see Pinacol ...

IVD IGH Break - The IGH (14q32) break probe is optimized to detect translocations involving the IGH gene region at 14q32 in a dual-color, split assay.

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