Nicholas Chiorazzi

..These and other biology-based indicators of patient clinical course and outcome can be used as starting points from which to understand and treat CLL...

..These results indicate that the enhanced expression of NFkappaB1 mRNA in bone marrow CD34+ cells plays a pivotal role in their abnormal responses to TNF-alpha and, thus, in the pathogenesis of RA...

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..Thus, B-CLL appears to be a disease of B-cell clones that have undergone various types of receptor reconfiguration and yet retain inappropriate antigen-binding properties...

..Therefore, CLL is a disease of both proliferation and accumulation in which a homeostatic balance exists in patients with stable lymphocyte counts or an imbalance exists in patients with rising lymphocyte counts...

..Finally, we discuss current and emerging views of the cellular origin of B-CLL cells and the differentiation pathways down which we believe these cells progress...

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..Finally, the study lays the groundwork for future analyses that might provide a more robust understanding of the development and clonal evolution of this currently incurable disease...

..Taken together, our data indicate that a large proportion of CLL clones emerge from natural antibody-producing cells expressing immunoglobulins that recognize MEACs, and that this reactivity is associated with poor clinical outcome...

..These findings provide an understanding of how BCR-mediated signals impact telomerase modulation in IGHV mutation-based subgroups of B-CLL and normal B cells...

..These similarities and differences between the IgH and IgL V gene repertoires expressed in B-CLL suggest some novel features while also reinforcing concepts derived from studies of the IgH repertoire...

..Our data show that DCs generated from the B-CLL subgroup with unmutated Ig V genes are functionally normal. These results are very promising for the use of DCs from patients with poor prognosis for immunotherapy...

..Binding of CLL mAb to MYHIIA could promote the development, survival, and expansion of these leukemic cells...

..These findings may help explain why high percentages of CD38(+) cells within clones are associated with poor clinical outcome...

..These DC-activating peptides could serve as an adjuvant in immunotherapeutic or vaccine context and the selective activity of these different peptides suggests a means to customize the functional properties of DCs...

..These shared, stereotyped Ig molecules may be valuable probes for antigen identification and important targets for cross-reactive idiotypic therapy...

..These findings indicate the value of multicytokine analyses for prognosis and suggest therapeutic strategies in CLL aimed at reducing CL1 and increasing CL2/CL3 cytokines...

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..In addition, they reinforce the concept that B-CLL is not simply an accumulative disease of slowly dividing B lymphocytes but possibly one of B cells with extensive proliferative histories...

..Furthermore, AID protein was associated with worse patient outcome and adverse cytogenetics. We conclude that the production of fully functional AID protein by U-CLL and M-CLL cells could be involved in clonal evolution of the disease...

..These data suggest that AID-mediated DNA alterations may occur in a variably sized, minor subset of B-CLL cells at any given time...

..It is not clear if this surface membrane expression is a passive consequence of the apoptotic process or an active attempt by the B cell to abort cell death by stabilizing the plasma membrane...

..Our studies suggest immunological mechanisms by which I3C ameliorates SLE in mice and provide a rationale for its use as an adjunctive therapy for human lupus...

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..A correlation between birth rates and disease activity and progression appears to exist, which may help identify patients at risk for worsening disease in advance of clinical deterioration...

..HMGB1 released by necrotic cells may be a signal of tissue or cellular injury that, when sensed by DCs, induces and/or enhances an immune reaction...

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..These results prove that this method identifies infectious agents and provides an experimental methodology to test correlation with disease...

..60; framework region [FR] R/S, 1.72). These results are consistent with the notion that V(H) mutations in B-CLL cells result from canonical SHM and select for altered, structurally sound antigen receptors...

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..Taken together, the results suggest that a PGE(2) feed-forward mechanism for augmenting COX-2 pathway proteins promotes progressively increased levels of AID mRNA, protein, and function...

..The estrogen urinary metabolite ratio of 2- to 16alpha-hydroxyestrone was increased in I3C-fed mice. These findings demonstrate a profound effect of dietary I3C in experimental SLE...

..Once distinct chromatograms were established for each of the SNPs and the nucleotide changes confirmed by sequencing, genotype and haplotype frequencies were tabulated for the groups studied...

..The objective of this study was to quantify blood and tissue levels of Th17 and other interleukin-17-producing cells in patients with this disease and correlate blood levels with clinical outcome...

..These data suggest that CLL may derive from normal B cells whose function is to remove cellular debris, and also to provide a first line of defense against pathogens...

..Thus, nucleotide insertion/deletion can lead to B-cell receptor diversification in B lymphocytes that clonally expand in synovial tissues of patients with rheumatoid arthritis...

..These findings are discussed in the context of available information about the antigen reactivity of CLL B cells and its potential role in clonal survival and drive...

..Since some of these genes have down-regulatory functions in other settings, they may have a regulatory role in DC maturation and immune response generation...

..This (auto)antigen-driven mouse model reliably captures the BCR characteristics of aggressive, treatment-resistant human B-CLL...

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..Our data support the hypothesis that CD137-mediated signaling anergized CD4(+) T cells during priming at the DC interface...

..We concluded that both UM-CLLs and M-CLLs originate from self-reactive B cell precursors and that SHM plays an important role in the development of the disease by altering original BCR autoreactivity...

..B-CLL cells are activated cells and their ZAP-70 expression reflects a normal property of activated B cells populations rather than a neoplastic aberration...

..75 years for FCRL2-low patients. Our studies indicate that FCRL2 has robust predictive value for determining IGHV gene mutation status and clinical progression and thus may further improve prognostic definition in CLL...

..We conclude that CD95 gene mutations play little if any role in the generation of the pool of PB in SLE patients and that mutations in the CD95 gene are rare among autoantibody-producing B cells in SLE and rheumatoid arthritis...

..If the current distinction into B1 and B2 cells has to be maintained also for humans, it is likely that only these CD5-positive cells rather than the FM B cells should be called B1 cells...

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..The difference in the ability to respond to antigen as a full-fledged B-CLL probably accounts for the different biological features and clinical outcomes of the patients in these subgroups...

..It will therefore be important to evaluate drugs that inhibit Cox-2 as potential therapeutic agents in B-CLL in vivo...

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..This has implications for understanding the strong association of humoral autoimmunity with lymphoid neogenesis, which may be associated with deficient censoring of autoreactive cells...

..These data are discussed considering the present views on the origin of B cell subset populations and the relationships between MZ and B1 cells...

..We studied whether cells expressing CD38 and ZAP-70 are more susceptible to stimulation through B-cell receptors than are cells that do not express CD38 and ZAP-70...

..The studies lay the groundwork for future therapies which will target the stimulants or the molecules on the leukemia cells that the stimulants bind. ..

..The Interfacility Transport Division provides transportation of patients from hospital ..

..Hopefully, these differences will provide important basic and clinical insights into this disease and suggest future prognostic and therapeutic approaches to it. ..

..We anticipate that these studies will support a clonal evolution model proceeding from antigenically overexpanded normal aging B cells to a leukemic CCL clone. ..

..The new database will also keep track of education and training information and permit cross-referencing of serious adverse events. ..

..The studies lay the groundwork for future therapies which will target the stimulants or the molecules on the leukemia cells that the stimulants bind. ..