Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Factor I (FI) is a regulatory serine protease of the complement system which cleaves three peptide bonds in the alpha-chain of C3b and two bonds in the alpha-chain of C4b thereby inactivating these proteins. The human protein and the recently characterized mouse factor I are heterodimers of about 88,000 MW which consist of a non-catalytic heavy chain of 50,000 MW which is linked to a catalytic light chain of 38,000 MW by a disulphide bond. For the screening of a rat liver cDNA library we used a hybridization probe produced by polymerase chain reaction (PCR) using degenerated primers which corresponded to conserved parts of the human and the murine factor I nucleotide sequences. One of the identified sequences, which had a length of 2243 base pairs (bp), contained the complete coding region and the whole 3' untranslated region. The length of the coding region in rat consisted of 1812 bp followed by a 3' untranslated region of 207 bp including the polyadenylation signal and the beginning of the poly A tail. Comparison of the rat cDNA-derived coding sequence revealed identities of 87% to the mouse and of 78% to the human FI nucleotide sequence. The translation product of rat FI mRNA was 604 amino acid residues (aa) in length with an identity of 85% to the mouse (603 aa) and 69% to the human protein (583 aa). The comparison of the molecular mass predicted by the primary structure and derived from rat FI isolated from rat serum as detected in immunoblot analyses suggested a glycosylation of more than 20% of the total mass of the FI protein. Expression studies using reverse transcription (RT)-PCR assays indicated that FI-specific mRNA could neither be identified in B cells, nor in T cells, monocytes or granulocytes from rat and human peripheral blood nor in rat peritoneal macrophages. These data were in agreement with the results of RT-PCR obtained with several human lymphoma cell lines (Jurkat, MOLT-4, HUT102, Wil 2-NS, Ramos, Raji, U937) all of which were devoid of FI-specific mRNA. In accord with our data from two rat hepatoma cell lines (FAO and H4IIE) and one from man (HepG2) only isolated rat hepatocytes (HC) but neither Kupffer cells (KC), hepatic stellate cells (HSC; Ito cells) nor sinusoidal endothelial cells (SEC) expressed FI-specific mRNA. FI mRNA was also detected in human umbilical vein endothelial cells (HUVEC) and in the uterus and small intestine of the rat. Spleen and lymph nodes did not contain any detectable FI-specific mRNA.
 ...
PMID:Rat complement factor I: molecular cloning, sequencing and expression in tissues and isolated cells. 1058 9

The transduction of exogenous hepatocyte growth factor (HGF) genes to spleen T lymphocytes and the immune effects of syngeneic spleen graft on spleen lymphoma cells were studied in LEW/Sea rats. Three different systems were designed. (1) Six female rats and six male rats received irradiated spleen graft and were followed for 7 months. (2) Five female rats and six male rats received intra-peritoneal (i.p.) injections of the Lewis red cells incorporated 20-bp HGF genes and anti-interleukin-6 (IL-6) antibody (Ab) with spleen graft and were followed for 5.5 months. (3) Four females and five males received i.p. injections of the Lewis red cells incorporated 20-bp HGF genes and anti-IL-6 Ab without spleen graft and were followed for 5.5 months. Hemato-pathological analyses, flow cytometer analyses of gamma-delta (gammadelta) T-cell receptor (TCR)-positive lymphocytes and reverse-transcription-polymerase chain reaction (RT-PCR) of TCRgamma gene, TCRValpha3 gene and apoptotic genes were performed. Results showed that one of the six females received irradiated spleen graft developed nodal gamma-delta (gammadelta) T-cell pre-lymphoma with 100% of gammadelta TCR+ lymphocytes in the mesenteric lymph nodes. One female injected with the HGF genes and anti-IL-6 Ab and grafted spleen died of advanced hepatosplenic gammadelta T-cell lymphoma at 3.5 month observation. All the five males injected with the HGF genes and anti-IL-6 Ab without spleen graft developed early hepatosplenic gammadelta T-cell lymphoma at 5.5 month observation. In two rats with spleen graft and the two rats without spleen graft, which were injected with the HGF genes and anti-IL-6 Ab, the lymphoma was suspected uncertainly with activated TCRValpha3 mRNA. The i.p. injections of HGF genes, which were incorporated in the red blood cells, triggered hapatosplenic gammadelta T-cell lymphoma. Surviving spleen graft rejected the lymphoma cells, but not in rats rejected the graft. Spleen graft was a good organ transplantation to expect graft versus lymphoma effects.
Leuk Lymphoma 2003 Jan
PMID:A type of rat hepatosplenic gamma-delta (gammadalta) T-cell lymphoma developed after injections with hepatocyte growth factor (HGF) oligonucleotides, which was rejected by surviving syngeneic spleen graft. 1269 Nov 60

IgM antibodies to gangliosides, sialic acid-containing glycosphingolipids, have been shown to mediate anti-tumor effects in cancer patients with melanoma and neuroblastoma and to correlate with survival. Mechanisms by which the antibodies induce tumor suppression, however, have not been systematically studied. To investigate this point, we produced and characterized C57BL/6 mice transgenic for IgM antibody to ganglioside GD2. The transgenic (TG) mice showed high IgM, but not IgG antibody titers against GD2 in their sera. No significant clinical symptoms were observed. When EL4 cells, syngeneic T lymphoma that express ganglioside GD2, were injected into TG mice, prolonged survival was observed. Complement-dependent cytotoxicity (CDC) of EL4 cells was mediated with TG mice sera. Neither antibody-dependent cellular cytotoxicity with their sera nor cytotoxic T lymphocyte activity to EL4 cells was shown in TG mice. Spleen lymphocytes from TG mice had increased numbers of natural killer (NK) cells, but not T cells, B cells, or macrophages compared with wild-type mice. Depletion of NK cells with anti-asialo GM1 rabbit serum reduced or abrogated the observed anti-tumor effects, suggesting that NK cells play a major role in tumor eradication or suppression. NK cell activity in TG mice was much higher than wild-type mice. Moreover, TG mice showed prolonged survival after injection with syngeneic B16 melanoma cells, which express GM3, but not GD2 or GD3. Taking these results together, our studies demonstrate that the TG mice have significant anti-tumor characteristics, probably due to CDC and NK cell expansion and activation with anti-ganglioside GD2 antibody.
 ...
PMID:Expansion of natural killer cells in mice transgenic for IgM antibody to ganglioside GD2: demonstration of prolonged survival after challenge with syngeneic tumor cells. 1285 87

Spleen is surgically removed for both non-neoplastic and neoplastic pathologies. A significant proportion of splenectomy specimens require distinguishing between reactive and neoplastic conditions (eg lymphoma). To establish a 'normal' reference range for the spleen lymphocyte subsets, fresh samples of benign, reactive spleens obtained from adult patients (N=12) and samples of normal spleen obtained from cadaveric transplant donors (N=14) were analyzed using three- and four-color flow cytometry. Study of pan-B, -T, and -NK marker expression revealed that the frequency of T cells is higher and that of B cells is lower in reactive (non-neoplastic) compared to normal (cadaveric) spleen. Furthermore, our study established a frame of reference for cell markers commonly used for immunophenotyping of lymphoma, and identified discrete lymphocyte subsets, such as early plasma cells and T cells carrying the phenotype of the NK/T subset. These results will facilitate an accurate interpretation of the flow cytometric analysis of human spleen lymphocytes.
 ...
PMID:Flow cytometric analysis of normal and reactive spleen. 1526 9

Although anti-CD20 immunotherapy effectively treats human lymphoma and autoimmune disease, the in vivo effect of immunotherapy on tissue B cells and their subsets is generally unknown. To address this, anti-mouse CD20 mAbs were used in a mouse model in which the extent and kinetics of tissue B cell depletion could be assessed in vivo. CD20 mAb treatment depleted most mature B cells within 2 days, with 95-98% of B cells in the bone marrow, blood, spleen, lymph nodes, and gut-associated lymphoid tissues depleted by day 7, including marginal zone and follicular B cells. The few spleen B cells remaining after CD20 mAb treatment included pre-B, immature, transitional, and some B1 B cells that expressed CD20 at low levels. By contrast, peritoneal cavity B cells expressed normal CD20 densities and were coated with CD20 mAb, but only 30-43% of B1 cells and 43-78% of B2 cells were depleted by day 7. Spleen B cells adoptively transferred into the peritoneal cavity were similarly resistant to mAb-induced depletion, while transferred B cells that had migrated to the spleen were depleted. However, peritoneal B1 and B2 cells were effectively depleted in mAb-treated wild-type and C3-deficient mice by thioglycolate-induced monocyte migration into this otherwise privileged niche. Inflammation-elicited effector cells did not promote peritoneal cavity B cell depletion in FcR-deficient mice treated with CD20 mAb. Thus, the majority of CD20(+) cells and B cell subsets within lymphoid tissues and the peritoneum could be depleted efficiently in vivo through Fc-dependent, but C-independent pathways during anti-CD20 immunotherapy.
 ...
PMID:The peritoneal cavity provides a protective niche for B1 and conventional B lymphocytes during anti-CD20 immunotherapy in mice. 1577 4

Combination therapy using reovirus type 3 and the chemo-therapeutic agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) is sufficient to cure approximately 80% of EL-4 lymphoma tumor-bearing BD2F1 male mice. Cured animals can be challenged with the EL-4 tumor, in the absence of the therapy, to yield 100% survival, whereas those challenged with heterologous tumor produce 0% survival. These results strongly suggest that a host-immune response is responsible for the observed therapeutic effect. Reovirus, a double-stranded RNA virus, is an efficient inducer of type I interferon. In an effort to determine the role of virus in this therapy, we substituted interferon-alpha (IFN-alpha) for reovirus in the therapy. Doses of IFN-alpha from 1000-10,000 U were capable of replacing reovirus to produce cure rates similar to reovirus. Spleen cells isolated from therapy-treated animals demonstrated high levels of cytotoxicity against the natural killer cell-sensitive cell line YAC-1, but not against EL-4 tumor. In vitro stimulation of isolated spleen cells by IFN-alpha resulted in a high level of natural killer cell activity, but no cytotoxicity against the EL-4 tumor. A significant antiproliferative effect against the EL-4 tumor in cell culture was demonstrated by IFN-alpha. Finally, therapy-treated, tumor-bearing mice that were injected with anti-IFN-alpha + -beta antibodies had similar survival levels as control mice, indicating that other cytokines might also play a role in promoting tumor killing. These investigations suggest that IFN-alpha may be a mediator of antitumor activity in the reovirus therapy system.
 ...
PMID:The role of interferon-alpha in a successful murine tumor therapy. 1598 24

This is a case report of a patient who presented with acute pancreatitis without the common causes. A pancreatic biopsy revealed large B cell lymphoma. Spleen lymphoma with pancreatic involvement inducing acute pancreatitis, which is a rare disorder, was diagnosed. Here we also review the few similar cases reported in the literature.
 ...
PMID:Malignant lymphoma of spleen presenting as acute pancreatitis: a case report. 1765 47

The presence of circulating villous lymphocytes (VLs) in lymphoma patients usually points to splenic marginal zone B-cell lymphoma (SMZL), even if the VLs can be found occasionally in other small B-cell lymphomas. However, those cells are variably described, and detailed cytologic characterization is often lacking. We identified lymphoma cases with numerous basophilic VLs among the large group of splenic lymphoma with VLs, and for further delineation, 37 cases with this particular cytology were analyzed. Patients, predominantly older men, presented with moderate lymphocytosis and splenomegaly without pancytopenia. The monoclonal B cells expressed IgM + D, IgM + G, IgM or IgG, as well as CD76 and CD11c, frequently CD103, and rarely CD123. Spleen sections were peculiar, with atrophic white pulp and a monomorphic diffuse lymphoma infiltration in a congested red pulp. Bone marrow infiltration was interstitial and intrasinusoidal without extensive fibrosis. Cytogenetic analysis showed a frequent absence of clonal aberrations (68%). Most cases (79%) were IgH mutated, with an overrepresentation of V(H)3 and V(H)4 gene families. These results, as well as the clinical evolution, show that those lymphoma cases represent a homogeneous group distinct from SMZL and reminiscent of hairy cell leukemia variant, perhaps corresponding to a separate lymphoma entity.
 ...
PMID:Splenic red pulp lymphoma with numerous basophilic villous lymphocytes: a distinct clinicopathologic and molecular entity? 1804 95

Patients with autoimmune lymphoproliferative syndrome (ALPS) have defective lymphocyte apoptosis with increased risk for lymphoid malignancies. Herein, we report a patient with ALPS who developed histiocytic sarcoma in a background of sinus histiocytosis and massive lymphadenopathy or Rosai- Dorfman disease. This patient had documented ALPS type Ia with a germline missense mutation in exon 9 of the TNFRSF6 gene (973 A>T, D244V) encoding Fas (CD95/Apo-1). He presented at 10 months with hepatosplenomegaly and autoimmune hemolytic anemia and was diagnosed with ALPS. At the age of 6 (1/2) years, he developed classic Hodgkin lymphoma which was treated using standard chemotherapy. Two years later, a biopsy of a positron emission tomography-positive axillary node showed features of ALPS and focal involvement by sinus histiocytosis and massive lymphadenopathy. Thereafter, the patient continued to have continued lymphadenopathy and progressive splenomegaly, leading to exploratory surgery at the age of 13 years for suspicion of lymphoma. Para-abdominal nodes revealed sheets of malignant- looking histiocytes with increased mitotic activity and areas of necrosis, indicative of histiocytic sarcoma. Spleen and lymph nodes also showed involvement by Rosai-Dorfman disease. Both components had an identical phenotype of S-100+/CD68+/ CD163+. The occurrence of malignancies involving 2 separate hematopoietic lineages in ALPS has not been reported earlier. Given the central role of defective Fas signaling in ALPS, histiocytes may be yet another lineage at risk for neoplastic transformation secondary to a block in apoptosis.
 ...
PMID:Development of disseminated histiocytic sarcoma in a patient with autoimmune lymphoproliferative syndrome and associated Rosai-Dorfman disease. 2021 76

3Recombinant ret oncogene products in complete Freund's adjuvant were injected into normal mice and ret oncogene transgenic mice. Spleen cells from the mice immunized with ret proteins were highly proliferated in vitro by the stimulation of ret proteins. The proliferating T cells have CD4(+) phenotype and secreated CTLL-2 reactive interleukins. The peritoneal exudate cells from ret protein-immunized mice suppressed ret-2 lymphoma, which was derived from ret lymphoma transgenic mice. The peritoneal exudate cells from ret melanoma transgenic mice did not suppress ret-2 lymphoma, when they were immunized with ret proteins.
 ...
PMID:Recombinant ret oncogene products induce T-lymphocyte proliferation, and suppress lymphoma derived from ret transgenic mice. 2155 28


<< Previous 1 2 3 4 5 6 7 8 9 Next >>