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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Animal models for Pneumocystis carinii, for the most part, have been limited to immunosuppressed rats and ferrets, while a dependable mouse model has been more difficult to develop. A P. carinii mouse model has now been established with several strains of mice, including C3Heb/FeJ, C3HeN, BALB/c, DBA/2N, and BALB/c nu/nu (athymic). In lieu of using invasive methods for initiating P. carinii infections, mice harboring P. carinii transmitted the disease to mice without latent infection via short-term cohabitation. After the exposure period, the seed mice were sacrificed to confirm the presence of acute P. carinii pneumonia. Acute infections in recipient mice developed at approximately 7 to 8 weeks, while control unseeded littermates remained uninfected. All recipient mice and their littermates were maintained in isolation hoods to eliminate the possibility of exposure to other sources of P. carinii. This approach allows investigators to consistently transmit P. carinii to mice and to select the strain of mouse desired for use in a particular study. The results presented here suggest that more attention should be given to the potential for patient-to-patient transmission of P. carinii in immunocompromised patients such as those with AIDS.
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PMID:Mouse model for Pneumocystis carinii pneumonia that uses natural transmission to initiate infection. 154 65

Delineation of major T helper cell recognition sites of human immunodeficiency virus (HIV-1) proteins represents one important step in the design of an efficient acquired immune deficiency syndrome (AIDS) vaccine. Towards this end, we have explored the immunogenicity of HIV-1BRU proteins in the mouse model. Preliminary experiments revealed that inbred mice primed with whole inactivated HIV-1 developed strong CD4+ T cell proliferative responses to a variety of recombinant viral proteins including reverse transcriptase (RT). To characterize further the mouse T cell responses to this protein, several Ad- or Ed-restricted T hybridoma cells (THC) were established from BALB/c or DBA/2 mice. These THC were tested for their capacity to recognize a series of 15-mer synthetic overlapping peptides spanning three segments of HIV-1 RT that had been preselected on the basis of either alpha-helicity, amphipaticity, and/or for containing rare amino acid sequence patterns. Peptides corresponding to a C-terminal region (residues 528-560) of RT were recognized by several of the THC established from RT-primed mice. Furthermore, a non-alpha-helical peptide from this region (A3, 528-543) was capable of priming mice with different H-2 haplotypes for both peptide A3 and native RT CD4+ T cell recognition. In addition to the recently identified RT determinant 203-219 capable of triggering both mouse and human CD8+ CTL, the present results identify a good candidate for an immunodominant RT epitope capable of eliciting RT-specific T helper cell responses.
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PMID:Identification of a major human immunodeficiency virus-1 reverse transcriptase epitope recognized by mouse CD4+ T lymphocytes. 171 May 63

Studies were performed in a murine model to determine if there is genetic control of the development of toxoplasmic encephalitis. Ten weeks after infection with the ME49 strain of Toxoplasma gondii, mice with the H-2b haplotype (C57BL/6, C57BL/10) and H-2k haplotype (C3H/He, CBA/J) developed remarkable inflammatory changes in their brains, whereas mice with the H-2a haplotype (A/J) and H-2d haplotype (BALB/c, DBA/2) did not. In the area of acute focal inflammation in mice with the H-2b and H-2k haplotypes, tachyzoites and toxoplasma antigens were demonstrated by immunoperoxidase staining, suggesting that the focal inflammation was induced by toxoplasma organisms. B10 congenic mice were used for further analysis of this genetic regulation. Presence of the encephalitis in B10 and B10.BR but not in B10.A and B10.D2 mice at 10 weeks after infection indicated regulation of the inflammation by a gene(s) within the H-2 complex. The encephalitis developed in B10.A (2R) and B10.A (4R) mice but not in B10.A (3R) and B10.A (18R) during infection. These results clearly indicated that the development of toxoplasmic encephalitis was controlled by a gene(s) in the H-2D region. The Qa and Tla genes did not appear to be critical in determining susceptibility to the encephalitis. There was no correlation between serum toxoplasma antibody titres and occurrence of the encephalitis. Injection of a monoclonal antibody to interferon-gamma (IFN-gamma) remarkably augmented the inflammatory changes in the brains of the infected B10 mice. In contrast, the treatment did not induce any inflammatory response in the brains of the infected BALB/c mice. A similar genetic regulation may be operative in determining development of toxoplasmic encephalitis in AIDS and other immunocompromised patients.
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PMID:A gene(s) within the H-2D region determines the development of toxoplasmic encephalitis in mice. 178 31

Cryptosporidium, a protozoan parasite of man and animals, is an important etiological agent of diarrhea throughout the world, particularly in children and immunocompromised individuals such as AIDS patients. Unfortunately, because of the lack of both in vivo laboratory models and reliable in vitro parasite culture systems, virtually nothing is known about the immunological events occurring during disease. In order to identify reliable animal models for infection, we studied C. parvum infections in 19 different strains of mice representing 12 H-2 haplotypes: A/J, AKR/J, B10.D2/J, B10.M/J, C3H/HeJ, C57BL/65, C57BL/6J-bgJ, CBA/NJ, DBA/1J, DBA/2J, HRS/J, HTG/J, NZB/B1NJ, NZW/J, P/J, RIII/J, SJL/J, SWR/J, and WB/ReJ, and in one gerbil: Meriones unguiculatus. Fecal samples and histological sections of the intestine taken on day 7 post-Cryptosporidium inoculation indicated that only the beige mouse (C57BL/6J-bgJ) harbored significant numbers of parasites compared to the other strains. The numbers of parasites harbored in these NK cell-deficient beige mice were, however, considerably lower than those seen in neonatal mice. Adult inbred mouse strains susceptible to Cryptosporidium infections are discussed.
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PMID:Cryptosporidium infections in inbred strains of mice. 181 24

Current therapy of cryptococcosis is unsatisfactory, particularly in patients with AIDS. Experimental cryptococcosis models in DBA/2 mice were used to determine whether the murine monoclonal anticryptococcal antibody (designated E1) might potentiate the chemotherapeutic effect of amphotericin B (AmB). According to the inoculum size, these mice died spontaneously from acute pneumonia (high inoculum) or from brain swelling (lower inoculum). AmB and E1 together significantly improved the survival of mice in both models compared with AmB alone. The mechanisms by which E1 might potentiate AmB activity were investigated in vitro. When cryptococci were preincubated with AmB or another polyene antibiotic, nystatin, there was an augmented binding of E1. AmB enhanced phagocytosis by unstimulated peritoneal macrophages in the presence of E1 or normal rabbit immunoglobulins. Normal and immune IgG deserve further study to determine under what circumstances the chemotherapeutic effect of AmB can be enhanced.
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PMID:Improved amphotericin B activity by a monoclonal anti-Cryptococcus neoformans antibody: study during murine cryptococcosis and mechanisms of action. 201 59

Specific pathogen-free C57Bl/6 X DBA/2 (B6D2) F1 hybrid mice were challenged aerogenically with M. avium, M. intracellulare and M. scrofulaceum and the resulting lung and spleen infections were followed over a period of several months. Growth of the mouse virulent M. avium 724 and M. intracellulare D673 was more extensive in the susceptible (Balb/c or C57Bl/6) mice than it was in the resistant A/J and B6D2 strains. Oral challenge of normal C57Bl/6 mice with virulent M. avium-complex serotypes resulted in substantial infection of the gut-associated lymphoid tissues, the lungs and spleen. No infection developed when the mice were infected orally with the avirulent MAC serotypes. T-cell depleted Balb/c (nude or Thxb) mice infected with virulent M. avium developed markedly enhanced lung and spleen infections compared to those seen in the immunocompetent controls. T-cell depletion did not potentiate the systemic growth of the avirulent MAC strains. The significance of these growth patterns (especially in the T-cell depleted mouse) is discussed in relation to the development of life-threatening M. avium-complex infections in patients with Acquired Immune Deficiency Syndrome.
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PMID:Mycobacterium avium-complex infections in normal and immunodeficient mice. 295 62

The murine AIDS (MAIDS) virus has a unique sequence in the gag p12 region, which could be responsible for MAIDS development. RNA preparations from the spleens of normal uninfected C57BL/6 mice contain a transcript hybridizing with this sequence. Levels of the transcript in the kidney of C57BL/6 mice were higher than in the spleen, liver or thymus. Although BALB/c, NFS, DBA/2 and SL murine strains also contained genomic sequences hybridizing with the MAIDS virus-specific probe, no transcript hybridizing with the probe was detected in these strains of mice. The cDNAs carrying the transcript expressed in C57BL/6 mice were molecularly cloned. The complete nucleotide sequence of the clone indicates that the transcript is one of the endogenous murine leukaemia virus-related sequences containing large deletions from the R and U5 regions of the 5' long terminal repeat (LTR) to gag p15, from the C-terminal region of pol p40 (integrase) to the N-terminal region of env p15E, and many short deletions in the 3' LTR U3 region. The nucleotide sequence in the gag p12 region of the transcript was closely similar to that of the MAIDS virus, but the amino acid sequence was less similar because of frameshifting, even when translated. As the MAIDS virus was isolated from C57BL/6 mice with radiation-induced leukaemia, this transcript may be the progenitor of the MAIDS virus. To determine whether the gag p12 region of the transcript contains a functional sequence, a recombinant virus was generated by replacing the gag p12 region of a replication-competent BM5eco virus with that of the endogenous transcript. The recombinant virus was replication-competent, and the p12 region of the transcript retained the functional sequence present in the BM5eco virus.
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PMID:Molecular cloning and characterization of a murine AIDS virus-related endogenous transcript expressed in C57BL/6 mice. 751 20

Systemic lupus erythematosus (SLE) and infection with the human immunodeficiency virus type 1 (HIV) are diseases that are characterized by immune dysregulation and autoantibody production. In this article we identify and characterize IgG antibodies from mice with SLE and SLE patients that bind HIV gp120 and HIV envelope-derived peptides. SLE can be induced in susceptible mouse strains by immunization with a human monoclonal anti-DNA antibody that bears a common idiotype designated 16/6 Id. We tested sera from various strains of mice in which experimental SLE was induced by this method, as well as from 93 patients with SLE and 31 controls (17 healthy controls, 14 patients with other autoimmune diseases) for the presence of antibodies reactive to gp120 by an ELISA. Antibodies reactive with gp120 were produced by BALB/c, C3H.SW, AKR, and DBA/2 mice, all of which were 16/6 Id immunized and had experimental SLE. C57BL/6 mice, which are resistant to induction of SLE by this method, did not produce antibodies reactive with gp120 despite 16/6 immunization. Forty-three percent of SLE patients made antibodies that bound to gp120 at titers greater than 1:40, whereas 12% of healthy control sera (p < or = 0.02) and 14% of patients with other autoimmune diseases contained such antibodies (p < or = 0.05). We delineated the specificity of this antibody activity by testing for reactivity to six HIV envelope peptides. In both mice and SLE patients, sera reactive with gp120 recognized the same three envelope peptides. Removal of the anti-DNA antibodies from the sera by DNA-agarose affinity purification did not change anti-gp120 specificity.
AIDS Res Hum Retroviruses 1994 Sep
PMID:Binding of glycoprotein 120 and peptides from the HIV-1 envelope by autoantibodies in mice with experimentally induced systemic lupus erythematosus and in patients with the disease. 782 94

The transplantation of polymer encapsulated myoblasts genetically engineered to secrete erythropoietin (Epo) may obviate the need for repeated parenteral administration of recombinant Epo as a treatment for chronic renal failure, cancer or AIDS-associated anemia. To explore this possibility, the human and mouse Epo cDNAs under the control of the housekeeping mouse PGK-1 promoter were transfected into mouse C2C12 myoblasts, which can be terminally differentiated upon exposure to low serum-containing media. Pools releasing 150 IU human Epo per 10(6) cells per day and 390 IU mouse Epo per 10(6) cells per day were selected. Polyether-sulfone (PES) capsules loaded with approximately 200,000 transfected myoblasts from these pools were implanted on the dorsal flank of DBA/2J, C3H and C57BL/6 mice. With human Epo secreting capsules, only a transient increase in the hematocrit occurred in DBA/2J mice, whereas no significant response was detected in C3H or C57BL/6 mice. On the contrary, all mice implanted with capsules releasing mouse Epo increased their hematocrit over 85% as early as 7 days after implantation and sustained these levels for at least 80 days. All retrieved implants released Epo and contained well preserved myoblasts. Moreover most capsules were surrounded by a neovascularization. Mice transplanted with nonencapsulated C2C12 cells releasing mouse Epo showed only a transitory elevation of their hematocrit reflecting the poor engraftment of injected myoblasts. These results indicate that polymer encapsulation of genetically engineered myoblasts is a promising approach for the long-term delivery of bioactive molecules, allowing the resolution of the shortcomings of free myoblast transfer.
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PMID:Continuous delivery of human and mouse erythropoietin in mice by genetically engineered polymer encapsulated myoblasts. 1032 23

We have characterized a novel animal model of the common inflammatory skin disease seborrheic dermatitis (SD) that involves the expression of the self-specific 2C transgenic T cell receptor on the DBA/2 genetic background. Opportunistic fungal pathogens are present in the primary histological lesions and severe disease can be mitigated by the administration of fluconazole, demonstrating a role for infection in disease pathogenesis. Spontaneous disease convalescence occurs at 70-90 d of age and is preceded by an expansion of CD4+ T cells that partially restores the T cell lymphopenia that occurs in these animals. The adoptive transfer of syngeneic CD4+ T cells into pre-diseased DBA/2 2C mice completely abrogates the development of cutaneous disease. The pattern of disease inheritance in DBA/2 backcrosses suggests that one, or a closely linked group of genes, may control disease penetrance. Bone marrow reconstitution experiments demonstrated that the DBA/2 susceptibility factor(s) governing disease penetrance is likely non-hematopoietic since bone marrow from disease-resistant 2C mice can adoptively transfer the full disease phenotype to non-transgenic DBA/2 animals. This model implicates fungal organisms and CD4+ T cell lymphopenia in the development of a SD-like condition and, as such, may mimic the development of SD in acquired immunodeficiency syndrome.
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PMID:A novel T cell receptor transgenic animal model of seborrheic dermatitis-like skin disease. 1565 69


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