Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085110 (SCID)
 11,041 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. In order to study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11-17.5 weeks) human fetal brain or neural retina is transplanted into the anterior chamber of the eye of immunosuppressed adult rats (Epstein et al., 1992; Cvetkovich et al., 1992), and more recently in immunodeficient (SCID) mice. The human xenografts survive for many months, vascularize and form a blood-brain barrier. Immunohistochemistry with PGP 9.5 identified neuronal cell bodies and neuritic processes. Electron microscopy revealed axonal growth cones and synaptic junctions. Infection of these xenografts with cell-free HIV-1 proved difficult, however co-engraftment with HIV-1-infected human monocytes resulted in characteristic pathological changes, including the formation of syncytial giant cells, neuronal loss, and astroglial proliferation, supporting the hypothesis that these cells can mediate neurotoxicity. In other studies, xenografts of human fetal retinal tissue were readily infected with cell-free human cytomegalovirus (HCMV) strain AD169. These grafts contained cells with intracytoplasmic and intranuclear inclusions typical of HCMV infection. Productive infection within these grafts was demonstrated by the presence of immediate early, and late (capsid) HCMV antigens, by recovery of HCMV on human fibroblast cultures, and by serial passage of virus to additional retinal xenografts (DiLoreto et al., 1994).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human neural xenografts: progress in developing an in-vivo model to study human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) infection. 787 92

Persistent infection was established in SCID mice given 10(7) Cryptosporidium parvum oocysts. Nine groups of infected SCID mice were inoculated with 10(6), 10(5), or 10(4) total spleen cells, CD8-depleted spleen cells, or CD4-depleted spleen cells from naive BALB/c donors. Infection was significantly reduced in all treatment groups. The most profound effect occurred with spleen cell preparations containing CD4 T lymphocytes but depleted of CD8 T lymphocytes.
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PMID:Effect of spleen cell populations on resolution of Cryptosporidium parvum infection in SCID mice. 790 81

An adult mouse-Giardia lamblia model was developed and used to study host-parasite interactions, including antigenic variation. The H7/1 clone of isolate GS infected mice consistently and produced infections in 14 mouse strains tested. Infection patterns were mouse strain and Giardia isolate dependent. Antigenic variation occurred in immunocompetent mice but not in mice with severe combined immunodeficiency.
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PMID:Giardia lamblia infections in adult mice. 803 34

Cat fleas (Ctenocephalides felis) from eight commercial flea colonies from various regions of the USA were examined by selective PCR amplification, and subsequent restriction digest analysis and Southern hybridization of PCR products, for the presence of a rickettsia-like organism (ELB agent). These flea colonies were either started with fleas from one supplier (EL Labs), in which ELB agent was first identified, or were started with fleas from stray cats and dogs and later came into contact with ELB-infected fleas. Infection rates in the colonies ranged from 43% to 93%. The successful propagation of ELB agent in these colonies may be due to efficient trans-stadial and transovarial transmission. While ELB agent has recently been identified in blood from human murine typhus cases, attempts to infect mammalian cells and SCID mice with flea isolates were unsuccessful.
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PMID:Molecular identification of rickettsia-like microorganisms associated with colonized cat fleas (Ctenocephalides felis). 806 13

Leukemia cell infiltration and the induction of lethal hematopoietic disease in immune-deficient SCID mice transplanted with human T cell acute lymphoblastic T leukemia (T-ALL) cells occurred only when the cells possessed mutant p53 genes and lacked a wild-type allele or when T-ALL cells lacking p53 protein were infected with specific mutant p53 genes. A series of six mutant p53 genes were cloned from relapse T-ALL-derived cell lines and were constructed into defective retroviral expression vectors. Viruses encoding mutant p53 proteins were used to infect relapse T-ALL cells in a study designed to compare their pathogenic potency. The mutant p53 genes possessed a distinct hierarchy in vivo and in vitro: mutants inducing the greatest increase in proliferation of different T-ALL lines in vitro and colony formation in methylcellulose cultures also induced tissue invasiveness of infected T-ALL cells in vivo. Mutant p53 gene transfer to a cell line lacking p53 protein showed that the more potent p53 mutants possessed a distinctive dominant oncogenic activity in vitro and in vivo. The dominant oncogenic activity of these mutant p53 proteins was not dependent on the presence of and on complex formation with wild-type p53 protein. These "hot" p53 mutations thus represent bona fide gain-of-function mutations. Infection of p53-negative T-ALL cells with viruses encoding gain-of-function mutant p53 genes resulted in the acquisition of metastatic potential and tissue invasiveness. Taken together, our results suggest that specific mutant p53 genes play a role in the generation of lymphohematopoietic metastatic potential and tissue invasiveness as assayed in SCID mice, whereas the expression of wild-type p53 is capable of keeping this metastatic potential in check.
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PMID:Gain-of-function mutations of the p53 gene induce lymphohematopoietic metastatic potential and tissue invasiveness. 808 50

Infection with the human immunodeficiency virus (HIV) results in immunosuppression and depletion of circulating CD4+ T cells. Since the thymus is the primary organ in which T cells mature it is of interest to examine the effects of HIV infection in this tissue. HIV infection has been demonstrated in the thymuses of infected individuals and thymocytes have been previously demonstrated to be susceptible to HIV infection both in vivo, using the SCID-hu mouse, and in vitro. The present study sought to determine which subsets of thymocytes were infected in the SCID-hu mouse model and to evaluate HIV-related alterations in the thymic microenvironment. Using two different primary HIV isolates, infection was found in CD4+/CD8+ double positive thymocytes as well as in both the CD4+ and CD8+ single positive subsets of thymocytes. The kinetics of infection and resulting viral burden differed among the three thymocyte subsets and depended on which HIV isolate was used for infection. Thymic epithelial (TE) cells were also shown to endocytose virus and to often contain copious amounts of viral RNA in the cytoplasm by in situ hybridization, although productive infection of these cells could not be definitively shown. Furthermore, degenerating TE cells were observed even without detection of HIV in the degenerating cells. Two striking morphologic patterns of infection were seen, involving either predominantly thymocyte infection and depletion, or TE cell involvement with detectable cytoplasmic viral RNA and/or TE cell toxicity. Thus, a variety of cells in the human thymus is susceptible to HIV infection, and infection with HIV results in a marked disruption of the thymic microenvironment leading to depletion of thymocytes and degeneration of TE cells.
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PMID:Human immunodeficiency virus infection of the human thymus and disruption of the thymic microenvironment in the SCID-hu mouse. 837 27

We have previously developed an in vivo experimental system for a bovine hemoprotozoan parasite, in which SCID mice were periodically transfused with bovine red blood cells (Bo-RBCs), followed by infection with the parasite. The SCID mice prepared by the original method, however, had both mouse and bovine RBCs in the circulation, and their proportion always fluctuated significantly. In the present study, we aimed to deplete the mouse RBCs circulating in SCID mice and, thereby, to create SCID mice having complete Bo-RBC substitution. An anti-erythropoietin rabbit serum, an anti-mouse RBC rabbit serum and 23 monoclonal anti-mouse RBC rat antibodies were prepared for this purpose. They were examined, after administration into SCID mice, for their ability to decrease hematocrit value and also for any other adverse effect. A monoclonal antibody, clone 2E11, was found to have potent ability to induce clearance of the mouse RBCs in SCID mice without causing toxic effects. SCID mice receiving this antibody together with periodic transfusion of Bo-RBCs had their circulating RBCs completely substituted with Bo-RBCs. Infection of Bo-RBC-SCID mice with bovine hemoprotozoan parasites demonstrated that elimination of the mouse RBCs from Bo-RBC-SCID mice resulted in augmentation of parasite growth.
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PMID:A method for rapid and complete substitution of the circulating erythrocytes in SCID mice with bovine erythrocytes and use of the substituted mice for bovine hemoprotozoa infections. 855 Oct 53

In the search for a suitable vaccine candidate for Lyme borreliosis the principles of protective immunity were studied in a murine model of Borrelia burgdorferi infection. It was found that the spirochetal outer surface protein A (lipOspA) in its native and recombinant lipidated form induces monospecific immune sera, which in passive transfer experiments protect SCID mice against experimental and tick-borne infection and disease. These and similar findings of independent groups led to the development of a vaccine formulation containing lipOspA. When tested in clinical phase I/II safety trials the recombinant lipOspA vaccine was shown to be safe, immunogenic and able to elicit borreliacidal antibodies. At present, clinical phase III efficacy trials are being conducted. B. burgdorferi infection involves the dissemination of the spirochetes from the site of the tick bite, infection of distant organs, and induction of a chronic inflammatory process. Recent studies indicate that the spirochetes may utilize host-derived enzyme systems to increase their virulence/pathogenicity. It was found that lipOspA serves as a surface receptor for the host-derived proteolytic enzyme plasmin(ogen), the central component of the so-called plasminogen activator system. Moreover, it was found that spirochetes are able to activate endothelial cells and blood-derived leukocytes, such as monocytes/macrophages, B cells and T cells, to express functions and/or secrete molecules, which are known to promote inflammatory responses. Part of these activities were exerted by the isolated lipOspA. The studies indicate an important role of lipOspA, both for the induction of a protective immune response by the host, as well as for the pathogenic processes elicited during B. burgdorferi infection.
Infection
PMID:The outer surface protein A (OspA) of Borrelia burgdorferi: a vaccine candidate and bioactive mediator. 874 Jan 21

Infection of rodents with murine coronavirus JHM results in a subacute or chronic demyelinating disease which serves as a model for the human disease multiple sclerosis. Previous studies with JHMV have established a role for the immune system in both viral clearance and demyelination. To further clarify the role of the immune system in JHMV pathogenesis, several strains of congenitally immunodeficient mice were studied. Infection of immunocompetent C57BL/6 mice with JHMV resulted in severe paralysis and demyelination and complete clearance of infectious virus from the brain (C+D+ phenotype). In contrast, infected SCID mice showed little or no paralysis or demyelination and were unable to clear infectious virus (C-D- phenotype). Athymic nude mice and a proportion of mice lacking MHC Class I or II expression exhibited robust demyelination but did not completely clear infectious virus from the brain (C-D+ phenotype). These results are consistent with an immune-mediated mechanism for JHMV-induced demyelination, but indicate that the immune mechanisms which participate in demyelination and viral clearance are distinct. It may thus be possible to experimentally alter immunopathological responses without impairing antimicrobial immunity.
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PMID:Dissociation of demyelination and viral clearance in congenitally immunodeficient mice infected with murine coronavirus JHM. 879 1

A Borrelia garinii isolate (NE11H) was obtained from the hemolymph of infed Ixodes ricinus. NE11H expressed four major proteins of 33 kDa, 32 kDa, 23 kDa and 22 kDa. During in vitro culture, NE11H successively lost the expression of the 22 kDa and 23 kDa proteins and the NE11H variant (NE11Hp15) was not recognized by an immune serum specific for the OspC protein (anti-OspC IS). However, when reintroduced into tick midguts, NE11Hp15 spirochetes present in the midgut again reacted with anti-OspC IS. A clone derived from the wild type line, cNE11H, lacked the 22 kDa but not the 23 kDa protein. The 23 kDa protein of cNE11H was recognized by anti-OspC IS. In addition, the two descendant lines (NE11Hp15 and cNE11H) lost their capacity to induce clinical arthritis in SCID mice. When cNE11H was reintroduced into ticks and reisolated from various tick organs, most reisolates presented the same reaction with anti-OspC IS as cNE11H. Interestingly, two reisolates obtained from the tick midgut reexpressed large amounts of the 22 kDa protein which was recognized by anti-OspC IS and these two reisolates induced clinical arthritis in SCID mice. The results confirm that proteins of 22/23 kDa are differentially expressed during in vitro subcultures and in ticks, and show that proteins which are not detectable after in vitro culture may be reexpressed after reexposure of B. burgdorferi to its former environment in the tick. The data suggest that the pathogenicity of B. burgdorferi for mice might be influenced by environmental factors via differential expression of 22/23 kDa proteins.
Infection
PMID:Tick factors and in vitro cultivation influence the protein profile, antigenicity and pathogenicity of a cloned Borrelia garinii isolate from Ixodes ricinus hemolymph. 881 66


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