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11.
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13.
Thrombospondin mediates the cytoadherence of Plasmodium falciparum- infected red cells to vascular endothelium in shear flow conditions 总被引:3,自引:0,他引:3
Rock EP; Roth EF Jr; Rojas-Corona RR; Sherwood JA; Nagel RL; Howard RJ; Kaul DK 《Blood》1988,71(1):71-75
Cerebral malaria is thought to involve specific attachment of Plasmodium falciparum-infected knobby red cells to venular endothelium. The nature of surface ligands on host endothelial cells that may mediate cytoadherence is poorly understood. We have investigated the effects of soluble thrombospondin, rabbit antiserum raised against thrombospondin, and human immune serum on cytoadherence of parasitized erythrocytes in ex vivo mesocecum vasculature. Preincubation of infected red cells with soluble thrombospondin or human immune serum inhibits binding of infected red cells to rat venular endothelium. Infusion of the microcirculatory preparation with rabbit antithrombospondin antibodies before perfusion of parasitized erythrocytes also resulted in decreased cytoadherence. In addition, incubation of infected cells with human immune sera obtained from malaria patients significantly inhibited the observed cytoadherence. Our results indicate that thrombospondin mediates binding of infected red cells to venular endothelium and may thus be involved in the pathogenesis of cerebral malaria. 相似文献
14.
The role of IL-10 in the regulation of ocular autoimmune disease was
studied in experimental autoimmune uveoretinitis (EAU) elicited in mice by
immunization with the retinal antigen interphotoreceptor retinoid binding
protein. IL-10-deficient mice were susceptible to EAU, indicating that
pathogenesis can occur without presence of IL-10. Treatment of normal mice
with IL-10 for 5 days after uveitogenic immunization ameliorated subsequent
EAU scores, and down-regulated antigen-specific production of tumor
necrosis factor-alpha and IFN- gamma. A concomitant treatment with IL-4
further reduced disease, and resulted in emergence of antigen-specific IL-4
and IL-10 production, as well as in enhancement of the IgG1 antibody
isotype. IL-4 by itself was not protective. Only IL-10, but not IL-4, was
able to inhibit the function of differentiated uveitogenic T cells in
culture. Expression of mRNA for Th1 and Th2 cytokines in the eye during the
course of EAU showed that while a Th1 pattern predominated early, IL-10
mRNA expression coincided with down-regulation of the Th1 response and
resolution of EAU. Systemic neutralization of IL-10 during the expression
phase of EAU resulted in elevated disease scores. Our results suggest that
endogenous IL-10 limits expression of EAU and may play a role in the
natural resolution of disease. The data further suggest that exogenous
IL-10 may be useful in therapeutic control of autoimmune uveitis. While
IL-10 by itself is sufficient to suppress Th1 effector development and
function, a concomitant administration of IL-4 is required to shift the
autoimmune response towards a non-pathogenic Th2 pathway.
相似文献
15.
Monocytoid B-cell lymphoma: its evolution and relationship to other low- grade B-cell neoplasms 总被引:3,自引:0,他引:3
Monocytoid B-cell lymphoma (MBCL) is a newly recognized B-cell neoplasm of uncertain histogenesis. The cytologic features of the neoplastic monocytoid B lymphocytes are virtually identical to those of hairy cell leukemia (HCL). As with HCL, progression of MBCL to a higher histologic grade is very unusual. However, whereas circulating leukemic cells are a characteristic feature of HCL, peripheral blood involvement has not been reported in MBCL. We recently studied a patient with MBCL of the spleen and axillary lymph nodes who developed peripheral blood involvement by MBCL cells. Unlike the cells of HCL, the circulating MBCL cells exhibited strong acid phosphatase activity that was tartrate sensitive. The leukemic cells had the antigenic phenotype IgM lambda, CD20+, CD11c+, CD5-, CD25(TAC)-, and PCA-1-. Immunogenetic studies of both lymph node and peripheral blood cells revealed identical immunoglobulin heavy-chain gene rearrangements. When compared with a series of HCL, the immunophenotype was similar except for the absence of PCA-1 and TAC. Progression of the MBCL to a large cell lymphoma, also expressing IgM lambda, was documented in an abdominal lymph node of this patient. Therefore, although rare, peripheral blood involvement by lymphoma cells may occur during the course of MBCL and should be distinguished from HCL with cytochemical and immunophenotypic studies. In addition, comparison of the clinical, pathologic, and immunologic features of MBCL with those of other low-grade B-cell neoplasms suggests that a close lineage relationship exists between MBCL and HCL. 相似文献
16.
Human MSH2 binds to trinucleotide repeat DNA structures associated with neurodegenerative diseases 总被引:5,自引:5,他引:5
The expansion of trinucleotide repeat sequences is associated with several
neurodegenerative diseases. The mechanism of this expansion is unknown but
may involve slipped-strand structures where adjacent rather than perfect
complementary sequences of a trinucleotide repeat become paired. Here, we
have studied the interaction of the human mismatch repair protein MSH2 with
slipped-strand structures formed from a triplet repeat sequence in order to
address the possible role of MSH2 in trinucleotide expansion. Genomic
clones of the myotonic dystrophy locus containing disease-relevant lengths
of (CTG)n x (CAG)n triplet repeats were examined. We have constructed two
types of slipped-strand structures by annealing complementary strands of
DNA containing: (i) equal numbers of trinucleotide repeats (homoduplex
slipped structures or S-DNA) or (ii) different numbers of repeats
(heteroduplex slipped intermediates or SI-DNA). SI-DNAs having an excess of
either CTG or CAG repeats were structurally distinct and could be separated
electrophoretically and studied individually. Using a band-shift assay, the
MSH2 was shown to bind to both S-DNA and SI-DNA in a structure- specific
manner. The affinity of MSH2 increased with the length of the repeat
sequence. Furthermore, MSH2 bound preferentially to looped-out CAG repeat
sequences, implicating a strand asymmetry in MSH2 recognition. Our results
are consistent with the idea that MSH2 may participate in trinucleotide
repeat expansion via its role in repair and/or recombination.
相似文献
17.
18.
M. MICHAELA OTT ANITA HELBING GERMAN OTT JIRI BARTEK LARS FISCHER ALEXANDER DÜRR HANS KREIPE HANS K. MÜLLER-HERMELINK 《The Journal of pathology》1996,179(3):238-242
Centrocytic lymphoma, or mantle cell lymphoma (MCL), is characterized by a chromosomal translocation t(11;14) (q13;q32) involving the bcl-1 locus on chromosome 11. Cyclin D1 is a cell-cycle regulatory protein essential for G1–S transition and has been identified as a potential transforming gene affected by the translocation. In this study, 32 cases of MCL were analysed for the bcl-1 rearrangement and cyclin D1 protein expression. In 17 cases, a rearrangement at the major translocation cluster of bcl-1 could be detected. Twenty-four cases exhibited nuclear cyclin D1 expression that was not detectable in other B-cell lymphomas ( n =40) or in normal B-cells. In nine MCL samples, cyclin D1 was expressed without a detectable bcl-1 rearrangement. The detection of a t(11;14) by means of classical cytogenetics in one of these cases, however, may suggest that this discrepancy could be due to chromosomal breakages outside the typical translocation cluster region. In two cases, a bcl-1 rearrangement was not accompanied by cyclin D1 expression. This study provides further evidence that cyclin D1 is involved in the pathogenesis of MCL and can be exploited as a diagnostic marker in the differential diagnosis of B-cell lymphomas and in the identification of MCL. 相似文献
19.
20.
Flair J Carrilho Cleusa R Moraes João RR Pinho Isabel MVGC Mello Dennis A Bertolini Marcílio F Lemos Regina C Moreira Leda C Bassit Rita A Cardoso Gabriela Ribeiro-dos-Santos Luiz C Da Silva 《BMC public health》2004,4(1):1-11