Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High sequence variability in the envelope gene of human immunodeficiency virus has provoked interest in nonenvelope antigens as potential immunogens against retrovirus infection. However, the role of core protein antigens encoded by the gag gene in protective immunity against retroviruses is unclear. By using recombinant vaccinia viruses expressing the Friend murine leukemia helper virus (F-MuLV) gag gene, we could prime CD4+ T-helper cells and protectively immunize susceptible strains of mice against Friend retrovirus infection. Recovery from leukemic splenomegaly developed more slowly after immunization with vaccinia virus-F-MuLV gag than with vaccinia virus-F-MuLV env; however, genetic nonresponders to the envelope protein could be partially protected with Gag vaccines. Class switching of F-MuLV-neutralizing antibodies from immunoglobulin M to immunoglobulin G after challenge with Friend virus complex was facilitated in mice immunized with the Gag antigen. Sequential deletion of the gag gene revealed that the major protective epitope was located on the N-terminal hydrophobic protein p15.
 ...
PMID:Protection against Friend retrovirus-induced leukemia by recombinant vaccinia viruses expressing the gag gene. 153 53

Two distinct clones of Friend spleen focus-forming virus (SFFV), differing in their erythroleukemic potential, are described. These isolates have been cloned free of their associated helper viruses and shown to be replication-defective. Both SFFV isolates have been rescued from rat fibroblast nonproducer cell clones with cloned replication-competent viruses, F-MuLVA and F-MuLVP, obtained from the anemia- or polycythemia-inducing isolates of Friend virus complex, respectively. These rescued viruses induce a rapid proliferative disease associated with the appearance of macroscopic spleen foci and splenomegaly. In addition, each is subject to regulation by the W, Steel (Sl), and Fv-2 host gene loci. These two isolates of SFFV can, however, be distinguished by both biological and molecular criteria. Friend SFFVP induces a rapid polycythemia associated with the appearance of large numbers of erythropoietin (EPO)-independent erythroid colony-forming cells in the marrow and spleen. In contrast, SFFVA induces a rapid anemia associated with a progressive decrease in the number of EPO-dependent erythroid colony-forming cells in marrow, and a rapid increase in the number of EPO-dependent erythroid colony-forming cells in spleen. Furthermore, the nature of the disease induced by the two isolates of SFFV is independent of the Friend helper virus: SFFVP, rescued from a nonproducer cell clone with either F-MuLVA or F0MuLVP, induced a polycythemic transformation, whereas SFFVA, rescued with either F-MuLVA or F-MuLVP, induced an anemic transformation. The two Friend SFFV isolates can also be discriminated on the basis of translational products encoded by their gag and env genes: SFFVP encodes the amino-terminal gag-gene protein p15, whereas SFFVA encodes the gag-gene proteins p15, p12, and p30. In addition, the SFFV isolates encode nonidentical 55,000-mol wt env gene-related proteins that can be distinguished by analysis of their methionine-containing tryptic peptides.
 ...
PMID:Anemia- and polycythemia-inducing isolates of Friend spleen focus-forming virus. Biological and molecular evidence for two distinct viral genomes. 692 80

The chromosome aberration t(7;11)(p15;p15) is uncommon but recurrent in leukemia. We experienced a case of acute leukemia with t(7;11)(p15;p15), the hematological appearance of which mimicked myeloid crisis in chronic myeloid leukemia (CML). This case showed splenomegaly, a decreased neutrophil alkaline phosphatase (NAP) score, increased vitamin B12 value, and cells at all stages of neutrophilic maturation in both bone marrow and peripheral blood. We initially had difficulty differentiating acute myeloid leukemia (AML) M2 with marked myeloid differentiation from myeloid crisis of Philadelphia chromosome (Ph)-negative CML. Immature myeloid cells in the peripheral blood disappeared and cytogenetic analysis indicated that marrow cells changed to the normal karyotype after remission induction therapy. Therefore, this case was thought not to be myeloid crisis but AML M2 subtype. The NUP98/HOXA9 fusion transcript was detected by reverse transcription-polymerase chain reaction (RT-PCR) at exon A but not exon B of NUP98.
 ...
PMID:A case of acute myeloid leukemia with t(7;11)(p15;p15) mimicking myeloid crisis of chronic myelogenous leukemia. 1213 1

Recent studies have demonstrated an essential role of Gag-specific CD4+ T-cell responses for viral control in individuals infected with human immunodeficiency virus type 1. However, little is known about epitope specificities and functional roles of the Gag-specific helper T-cell responses in terms of vaccine-induced protection against a pathogenic retroviral challenge. We have previously demonstrated that immunization with Friend murine leukemia virus (F-MuLV) Gag proteins protects mice against the fatal Friend retrovirus (FV) infection. We report here the structure of a protective T helper cell (Th) epitope, (I)VTWEAIAVDPPP, identified in the p15 (MA) region of F-MuLV Gag. In mice immunized with the Th epitope-harboring peptide or a vaccinia virus-expressed native full-length MA protein, FV-induced early splenomegaly regressed rapidly. In these mice, FV-infected cells were eliminated within 4 weeks and the production of virus-neutralizing antibodies was induced rapidly after FV challenge, resulting in strong protection against the virus infection. Interestingly, mice immunized with the whole MA mounted strong CD4+ T-cell responses to the identified Th epitope, whereas mice immunized with mutant MA proteins that were not bound to the plasma membrane failed to mount efficient CD4+ T-cell responses, despite the presence of the Th epitope. These mutant MA proteins also failed to induce strong protection against FV challenge. These data indicate the importance of the properly processible MA molecule for CD4+ T-cell priming and for the resultant induction of an effective immune response against retrovirus infections.
 ...
PMID:Identification of a protective CD4+ T-cell epitope in p15gag of Friend murine leukemia virus and role of the MA protein targeting the plasma membrane in immunogenicity. 1516 26