UMLS:C0019829 - FACTA Search

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Query: UMLS:C0019829 (Hodgkin's disease)
30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted an ultrastructural study in 22 cases of B-lymphoproliferative disorders in leukaemic phase bearing the t(11;14) translocation. The features of peripheral blood leukaemic cells in nine cases of mantle cell lymphoma (MCL) were compared to those diagnosed as B-prolymphocytic leukaemia (B-PLL) (five cases), splenic lymphoma with villous lymphocytes (SLVL) (four cases), lymphoplasmocytic lymphoma (LPL) (one case), chronic lymphocytic leukaemia with > 10% prolymphocytes (CLL/ PL) (one case) and unclassified B-non Hodgkin's lymphoma (B-NHL) (two cases). The ultrastructural characteristics were also compared to those present in B-NHL without t(11;14), including cases of follicular centre lymphoma (FCL). This study shows that MCL has distinct ultrastructural features including a cleaved or indented nucleus with an even heterochromatin distribution, an absent or inconspicuous nucleolus, low N/C ratio, abundant mitochondria, a well developed Golgi zone, profiles of endoplasmic reticulum and centrioles. This pattern clearly differs from that found in FCL cells. The nuclear pattern of MCL cells also differed from the cells in the other disorders with t(11;14), but shared an organelle-rich cytoplasm, and features which were not apparent in cases without t(11;14). The cytoplasmic changes observed in cells bearing t(11;14) suggest increased cellular activity which may relate to the chromosome translocation and the resulting over-expression of bcl-1.
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PMID:The ultrastructure of mantle cell lymphoma and other B-cell disorders with translocation t(11;14)(q13;q32). 875 96

Major histocompatibility [correction of histocampatability] complex (MHC) class I-restricted cytotoxic T lymphocytes (CTLs) recognizing Epstein-Barr virus (EBV) latent antigens play a pivotal role in restricting the proliferation of EBV-infected normal B cells. However, it is now well established that most of the EBV-associated malignancies escape this potent CTL response in vivo. This resistance to immune surveillance is not due to an obvious CTL dysfunction but has been partly attributed to the down-regulation of the peptide transporters, TAP-1 and TAP-2, thus restricting the endogenous loading of MHC class I molecules with peptides derived from viral nuclear antigens. In the present study we have explored the possibility that EBV latent membrane protein 2A (LMP2A), which is often expressed in many of the EBV-associated malignancies, such as nasopharyngeal carcinoma and Hodgkin's disease tumors, can be endogenously processed through an alternative, TAP-1- and TAP-2-independent pathway. The data presented in this study clearly demonstrate not only that LMP2A can be processed by a TAP-independent mechanism but also that tumor cells with down-regulated TAP expression can be efficiently recognized by LMP2A-specific T cells following infection with recombinant vaccinia virus encoding this protein. We propose that since LMP2A is a membrane protein, it is directly translocated into the secretory pathway and the processing enzymes present in the endoplasmic reticulum are capable of generating the relevant peptide epitopes for MHC binding. The present finding of TAP-1- and TAP-2-independent presentation of LMP2A epitopes suggests a novel mechanism for immune targeting of EBV-positive malignancies, such as nasopharyngeal carcinoma and Hodgkin's disease tumors.
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PMID:Peptide transporter (TAP-1 and TAP-2)-independent endogenous processing of Epstein-Barr virus (EBV) latent membrane protein 2A: implications for cytotoxic T-lymphocyte control of EBV-associated malignancies. 876 46

We have characterized the conduction and blocking properties of a chloride channel from rough endoplasmic reticulum membranes of rat hepatocytes after incorporation into a planar lipid bilayer. Our experiments revealed the existence of a channel with a mean conductance of 164 +/- 5 pS in symmetrical 200 mm KCl solutions. We determined that the channel was ten times more permeable for Cl- than for K+, calculated from the reversal potential using the Goldman-Hodgkin-Katz equation. The channel was voltage dependent, with an open probability value ranging from 0.9 at -20 mV to 0.4 at +60 mV. In addition to its fully open state, the channel could also enter a flickering state, which appeared to involve rapid transitions to zero current level. Our results showed a decrease of the channel mean open time combined with an increase of the channel mean closed time at positive potentials. An analysis of the dwell time distributions for the open and closed intervals led to the conclusion that the observed fluctuation pattern was compatible with a kinetic scheme containing a single open state and a minimum of three closed states. The permeability sequence for test halides determined from reversal potentials was Br- > Cl- > I- approximately F-. The voltage dependence of the open probability was modified by the presence of halides in trans with a sequence reflecting the permeability sequence, suggesting that permeant anions such as Br- and Cl- have access to an internal site capable of controlling channel gating. Adding NPPB to the cis chamber inhibited the channel activity by increasing fast flickering and generating long silent periods, whereas channel activity was not affected by 50 microM DNDS in trans. The channel was reversibly inhibited by adding phosphate to the trans chamber. The inhibitory effect of phosphate was voltage-dependent and could be reversed by addition of Cl-. Our results suggest that channel block involves the interaction of HPO2-4 with a site located at 70% of the membrane span.
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PMID:Characterization of a chloride-selective channel from rough endoplasmic reticulum membranes of rat hepatocytes: evidence for a block by phosphate. 931 11

Patients with paraneoplastic cerebellar degeneration and Hodgkin's disease develop autoantibodies (Tr-Ab) that immunoreact with the cytoplasm of the Purkinje cells and produce a characteristic punctate pattern in the molecular layer of the cerebellum. In the present study, we analyzed the structures of the adult rat cerebellar cortex identified by Tr-Ab and the expression of the antigen recognized by Tr-Ab in the developing rat brain. By laser confocal microscopy and immunoelectron microscopy, Tr-Ab immunoreactivity was found localized in the cytosol and outer surface of the endoplasmic reticulum of the perikarya of neurons of the molecular layer and the cell body and dendrites of Purkinje cells without a particular concentration in dendritic spines. Tr-Ab reactivity was more widespread in the developing rat brain. Tr-Ab labeling of Purkinje cells was already observed at P0 (day of birth). The staining of the molecular layer followed the development of the dendritic tree. The internal and inner level of the external granule cell layer were labeled with Tr-Ab with a dotted pattern that became almost negative by the 2nd postnatal week. The staining probably corresponded to granule cells as suggested by the positive Tr-Ab labeling of cultures of embryonic granule neurons. The present findings suggest that the antigen recognized by Tr-Ab appears early and is widely expressed in the developing rat brain. In the adult cerebellum, the antigen is localized in the cell body and dendrites of the Purkinje cells but is not concentrated in the dendritic spines.
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PMID:Localization of the neuronal antigen recognized by anti-Tr antibodies from patients with paraneoplastic cerebellar degeneration and Hodgkin's disease in the rat nervous system. 967 7

Epstein-Barr virus (EBV) causes lymphoproliferative diseases in immunocompromised patients and is associated with endemic Burkitt lymphoma, nasopharyngeal carcinoma and some cases of Hodgkin disease. The latent membrane protein 1 (LMP1) of EBV is a transmembrane protein that is essential for the transformation of B lymphocytes. LMP1-mediated up-regulation of Bcl-2 is thought to be an important element in this process. As an approach to explore novel treatments for EBV-associated lymphomas, we constructed a single-chain antibody (sFv) directed against LMP1 to achieve functional inhibition of this oncoprotein in EBV-transformed B lymphocytes. We demonstrated that intracellular expression of an endoplasmic reticulum (ER)-targeted form of this sFv markedly reduced LMP1 protein levels. We also observed a decrease in intracellular level of this protein which correlated with a marked reduction of Bcl-2 expression in EBV-transformed B lymphocytes. We further demonstrated that anti-LMP1 sFv-mediated reduction of Bcl-2 correlated with increased sensitivity of these cells to drug-induced cell death. Therefore, these data suggest that an anti-LMP1 sFv used in combination with conventional chemotherapy may be useful for gene therapy of EBV-associated lymphomas in immunocompromised patients.
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PMID:Phenotypic knock-out of the latent membrane protein 1 of Epstein-Barr virus by an intracellular single-chain antibody. 993 Mar 17

We investigate bursting behaviour generated in an electrophysiological model of pituitary corticotrophs. The active and silent phases of this mode of bursting are generated by moving between two stable oscillatory solutions. The bursting is indirectly driven by slow modulation of the endoplasmic reticulum Ca2+ concentration. The model exhibits different modes of bursting, and we investigate mode transitions and similar modes of bursting in other Hodgkin-Huxley models. Bifurcation analysis and the use of null-surfaces facilitate a geometric interpretation of the model bursting modes and action potential generation, respectively.
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PMID:A Hodgkin-Huxley model exhibiting bursting oscillations. 1093 29

The down-regulation of surface expression of MHC class I molecules has recently been reported in the CD99-deficient lymphoblastoid B cell line displaying the characteristics of Hodgkin's and Reed-Sternberg phenotype. Here, we demonstrate that the reduction of MHC class I molecules on the cell surface is primarily due to a defect in the transport from the Golgi complex to the plasma membrane. Loss of CD99 did not affect the steady-state expression levels of mRNA and protein of MHC class I molecules. In addition, the assembly of MHC class I molecules and the transport from the endoplasmic reticulum to the cis-Golgi occurred normally in the CD99-deficient cells, and no difference was detected between the CD99-deficient and the control cells in the pattern and degree of endocytosis. Instead, the CD99-deficient cells displayed the delayed transport of newly synthesized MHC class I molecules to the plasma membrane, thus causing accumulation of the molecules within the cells. The accumulated MHC class I molecules in the CD99-deficient cells were colocalized with alpha-mannosidase II and gamma-adaptin in the Golgi compartment. These results suggest that CD99 may be associated with the post-Golgi trafficking machinery by regulating the transport to the plasma membrane rather than the endocytosis of surface MHC class I molecules, providing a novel mechanism of MHC class I down-regulation for immune escape.
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PMID:CD99 regulates the transport of MHC class I molecules from the Golgi complex to the cell surface. 1114 51

Mammalian cells are capable of committing "active suicide" or apoptosis in response to specialized pathological mechanisms employing a phylogenetically developed intrinsic program of death, triggered by signal transduction through specific receptors. Changes in cellular structure such as: 1) condensation of the nuclear (chromatin) and cytoplasmic structures (especially the mitochondria); 2) blebbing of the cell membrane; 3) characteristic swelling of the endoplasmic reticulum; and 4) fragmentation of the cells in membrane bound apoptotic bodies, are the dramatic signs of total cell destruction. Apoptosis requires energy in the from of ATP, indicating that programmed cell death (PCD), as opposed to necrosis, is an energy dependent, active physiological and pathophysiological phenomenon. During this immunocytochemical study, we observed the presence of PCD in the prenatal thymus and various human neoplastically transformed tissues. During the intrauterine ontogenesis, in thymocytes or resting T lymphocytes, p53 tumor suppressor protein was identified to be a critical mediator of PCD in response to DNA damage. The cellular interaction of immature, cortical thymocytes (characterized by a double positive CD4+CD8+TCRlow immunophenotype-IP) with thymic RE cells induces positive selection of T lymphocytes that recognize, but are not activated, by self-MHC molecules (tolerance induction). Double positive CD4+CD8+CD3- thymocytes undergo FasL-mediated apoptosis, while CD4+CD8+CD3+ cells use the CD3 mediated pathway of PCD. Two step, apoptotic cell death is mainly restricted to the CD4+CD8+TCR dull thymocyte subpopulation. T-lymphocytes which do not undergo positive selection are killed by apoptosis in response to a number of intrinsic and extrinsic factors, such as chemical toxins, viral infections, X- and UV irradiation, mild hyperthermia, the actions of various hormones, extracellular survival factors, calcium ionophores (such as A23187), various chemotherapeutic drugs (adriamycin, actinomycin D, etc) and antibodies directed to the CD3-TCR (T cell receptor) complex. Immature thymocytes also undergo a second selective process, so-called negative selection, when thymic stromal cells eliminate autoreactive T lymphocytes. As a typical model of embryonal neoplasms, we observed 34 childhood PNET/MED tissues samples. A systematic observation for the presence of apoptosis related markers (especially FasR) and cells in PCD was carried out. A strong expression (intensity of staining: "A"--the highest possible; number of stained neoplastic cells: +++ to ++++, between 50% to 90%) of FasR was detected. We also observed 42 childhood glial tumors, divided as follows: 6 pilocytic ASTRs; 14 low grade ASTRs; 16 anaplastic ASTRs; and 6 GBMs. The GBMs represent an end-stage brain tumor IP dedifferentiation of glial origin. During the immunocytochemical screening of these 42 childhood ASTRs, we detected strong expression (intensity of staining: "A"--the highest possible; number of stained cells: ++ to ++++, between 20% to 90%) of FasR, employing 4 microns thick, formalin fixed, paraffin-wax embedded tissue slides. FasR expression was rated high, 70% to 90% on the tumor cells in pylocytic ASTRs, lowered to 50% to 60% on the neoplastic cells in low grade ASTRs, even lower between 30% to 40% in anaplastic ASTRs and significantly lower, between 20% to 35% on the neoplastically transformed cells of GBM tissues. The presence of apoptotic neoplastic cells was also regularly detected in other human adult neoplasms, such as thyroid, pancreatic, hepatocellular, gastric, colon, breast, ovarian, prostata, and renal cell carcinomas, as well as, in Hodgkin and non-Hodgkin lymphomas and some sarcomas. The expression of apoptosis related cell surface molecules on the surface of both neoplastically transformed cells and on tumor cell specific, cytotoxic T lymphocyte (CTL) surfaces (FasR-FasL system) raises a distinct possibility of active PCD induction in CTL by tumor cells. Juxtacrine interactions between CTL and neoplastically transformed cells, coupled with observations that tumor cells can modulate the intracellular, signaling domains of cell surface receptors to elicit responses quite often contrary to the expected, may even provide a way for CTL to enhance the proliferation and dedifferentiation of cancer cells. Adoptive cellular immunotherapies employing CTL raised against autologous neoplastically transformed cells in vitro should be employed in the control of minimal residual disease following surgical resection of the primary malignant growth.
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PMID:The role of apoptosis in normal ontogenesis and solid human neoplasms. 1120 98

Jaw1, also known as lymphoid-restricted membrane protein (LRMP), is an endoplasmic reticulum-associated protein. High levels of Jaw1/LRMP mRNA have been found in germinal centre B-cells and in diffuse large B-cell lymphomas of 'germinal centre' subtype. This paper documents Jaw1/LRMP expression at the protein level in human tissues by immunohistochemical and western blotting analysis using an antibody reactive with paraffin-embedded tissues. Jaw1/LRMP was highly expressed in germinal centre B-cells (in keeping with gene expression data), in 'monocytoid B-cells', and in splenic marginal zone B-cells. It was absent, or present at only low levels, in mature T-cells, although cortical thymocytes were weakly positive. Among lymphoid neoplasms, Jaw1/LRMP was found in germinal centre-derived lymphomas (follicle centre lymphoma, Burkitt's lymphoma, lymphocyte-predominant Hodgkin's disease) but not in T-cell neoplasms (with the exception of a single T lymphoblastic lymphoma). Classical Hodgkin's disease and myeloma lacked Jaw1/LRMP but many cases of chronic lymphocytic leukaemia (but not mantle zone lymphoma) were Jaw1/LRMP-positive. Approximately half of the marginal zone lymphomas were Jaw1/LRMP-positive. In diffuse large B-cell lymphomas, Jaw1/LRMP was found in three-quarters (24/32) of the cases classified phenotypically as being of 'germinal centre' type, but it was also expressed in almost half (13/28) of the 'non-germinal centre' cases. A similar proportion of 'non-germinal centre' cases were positive for the protein products of two other genes expressed highly in germinal centre cells (HGAL/GCET2 and PAG). The fact that all three of these proteins are expressed in a significant proportion of diffuse large B-cell lymphomas assigned to the 'non-germinal centre' category indicates that the immunophenotypic categorization of diffuse large B-cell lymphoma according to cellular origin may be more complicated than currently understood. Finally, the expression of Jaw1/LRMP in other types of lymphoma and in non-lymphoid tissues/tumours may be of interest in differential diagnosis and research.
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PMID:Jaw1/LRMP, a germinal centre-associated marker for the immunohistological study of B-cell lymphomas. 1673 14

Plasmablastic lymphoma was originally described in 1997 by Delecluse et al. and is an aggressive variant of diffuse large B-cell non-Hodgkin lymphoma seen predominantly in a setting of acquired immunodeficiency syndrome and nearly always in extranodal sites. The authors have seen 10 cases in their department between 2001 and 2005. The patients' ages ranged from 24 to 39 years and there were 7 females and 3 males. In 7 cases where human immunodeficiency virus had been tested it was positive. Eight cases were extranodal and 2 cases involved lymph nodes. Five cases were followed up and 4 were confirmed dead within 5 months of diagnosis, verifying the aggressive nature of this condition. Histology showed large, polygonal tumor cells some of which had a slightly plasmacytic appearance. Six cases had a "starry sky" background. Immunohistochemical stains were negative in 1 case, while the other 9 cases were positive for CD138. Electron microscopy showed concentrically arranged rough endoplasmic reticulum in the cytoplasm in 9 cases. In 1 case the cells were too degenerate for evaluation. This study shows that the ultrastructural features are well developed and can help in distinguishing plasmablastic lymphoma from other light microscopically undifferentiated tumors.
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PMID:The ultrastructural features of plasmablastic lymphoma. 1718 35

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