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Query: UMLS:C0085110 (SCID)
 11,041 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients who received bone marrow transplantation (= BMT) for the treatment of severe combined immunodeficiency (= SCID), and who were reported in the medical literature from 1968 to 1977, were collected and analysed. Eighteen of these 80 children are still alive, 10 months to 9 years after transplantation. It is thus the first successful form of therapy for this otherwise invariably fatal disease. Fifteen of the 18 survivors received bone marrow cells from HLA and MLC compatible donors; the remaining 3 survivors received grafts from MLC-compatible but HLA-incompatible donors. Bone marrow transplantation is the treatment of choice for SCID when recipient and donor are HLA- and MLC-identical. All patients who received MLC-incompatible grafts died, and bone marrow transplantation for SCID from MLC-incompatible donors should be abandoned. Milt-to-severe graft-versus-host disease (= GVHD) occurred in spite of HLA- and/or MLC-compatibility, with some correlation to the number of cells transplanted. This should preferably be kept below 50 million cells per kilo body weight. Infection was the chief cause of death in all groups. Strict reverse isolation, bowel decontamination and routine pre- and post-transplant Pneumocystis carinii prophylactic treatment are recommended. The clinical picture and laboratory findings of these 80 children before BMT did not differ from non-transplanted SCID patients. Three of the 18 survivors are adenosinedeaminase deficient.
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PMID:Bone marrow transplantation for severe combined immunodeficiency disease. Reported from 1968 to 1977. 3 63

T cells are important in systemic anticryptococcal defenses, but a role in controlling an initial pulmonary infection has not been demonstrated. A murine model with intratracheal inoculation was developed to study the acquisition and expression of pulmonary T cell-mediated immunity against Cryptococcus neoformans. Infections with four strains of C. neoformans (305, 68A, 613D, and 52D) in two strains of mice (BALB/c and C57BL/6) were examined. Unencapsulated strain 305 and slowly growing strain 68A were readily controlled apparently by nonimmune pulmonary defenses, and no extrapulmonary dissemination was detected. Strain 613D grew progressively in the lungs and disseminated to the brain and spleen. Strain 52D initially grew rapidly in the lungs and disseminated to the spleen, but a clearance mechanism developed in the lungs after day 7 postinfection and in the spleen after day 28. SCID and athymic nude mice were unable to clear a strain 52D pulmonary infection, and a lethal disseminated infection occurred. Pulmonary clearance could be adoptively transferred into SCID mice infected with strain 52D by use of immune T cells from the spleen and lungs and hilar lymph nodes of infected immunocompetent donors. Furthermore, pulmonary clearance was almost 100-fold better in SCID mice that received immune T cells from the lungs and hilar lymph nodes than in those that received immune T cells from the spleen, even though equivalent levels of delayed-type hypersensitivity were transferred by both cell populations. These adoptive transfer studies suggested that the lung and hilar lymph node T cells from immune animals either are enriched in such a way as to mediate protective immunity or home to the lungs better than do splenic T cells.
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PMID:T cell-mediated immunity in the lung: a Cryptococcus neoformans pulmonary infection model using SCID and athymic nude mice. 182 90

The SCID-hu mouse is a small animal in which human hematolymphoid organs can be engrafted and maintained in vivo. In this study, parameters are described for reproducible infection of SCID-hu mice after i.v. inoculation. Infection was found to be dependent upon the time after inoculation, the virus isolate, the titer of virus, and the human target organ implanted into the mouse. Ten to 14 days after the i.v. administration of HIV isolates derived freshly from patients (e.g., JR-CSF, JR-FL, SM), 100% of engrafted human lymph nodes in SCID-hu mice were infected; greater than 95% of these animals were also viremic. Implants of human thymus or connective tissue, as well as the endogenous murine hematolymphoid organs, were not infected. As demonstrated by a combination of in situ hybridization and immunohistochemistry, both T-lymphoid and myelomonocytic lineage cells were infected in this system. HIV isolates that have been adapted to growth in vitro (e.g., HTLV-IIIb) were not infectious. When either 3'-azido-3'-deoxythymidine (AZT) or 2',3'-dideoxyinosine (ddIno) was administered to SCID-hu mice before HIV infection, the animals were protected in dose ranges similar to those used in man. This animal model may now be used as an efficient intermediate step between the lab and the clinic to study the infectious process in vivo and to best select efficacious antiviral compounds against HIV.
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PMID:Human immunodeficiency virus infection of human lymph nodes in the SCID-hu mouse. 190 43

Infection of C57BL/6J mice with Mycoplasma pulmonis (MP) enhanced NK cell function 3-7 days later, as detected by in vitro and in vivo assays. Moreover, spleen and lung cells of acutely infected C57BL/6J mice inhibited MP growth in vitro. The effectors were eliminated by treatment with anti-NK antibody in vivo and anti-asialo GM1 serum or anti-3A4 antibody plus complement in vitro. Clearance of viable and radiolabeled MP from the lungs was also enhanced in acutely infected mice. Acutely infected mice with severe combined immunodeficiency (SCID) eliminated viable MP faster than did uninfected mice. Antibodies to interferon-gamma (IFN-gamma) impaired clearance of MP from the lungs of SCID mice and decreased their survival times. Activated NK cells can function in resistance to early stages of infection with MP. NK cells directly inhibit MP with secrete IFN-gamma, which may activate macrophages or inhibit the growth of MP or both.
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PMID:Resistance to Mycoplasma pulmonis mediated by activated natural killer cells. 214 May 83

Suckling BALB-c mice, subjected to nutritional deprivation in artificially expanded litters (18 to 20 pups), were compared to normally nourished pups (7-9 per litter) in a series of experiments designed to provide data on morphologic and functional alterations of the small intestine during malnutrition and infection. The effects of protein calorie malnutrition (PCM) on the viral replication pattern and severity of clinical disease were examined in suckling mice infected with murine rotavirus (MRV). The infection in nutritionally deprived animals was characterized by a significant decrease in the minimal infectious dose and in the incubation period for the onset of diarrhea as well as increased severity of disease when compared to well nourished controls. Rotavirus-specific antibody, administered orally prior to virus inoculation, significantly reduced MRV replication in both groups but most strikingly in malnourished animals. Additional studies of the uptake of a macromolecule [ovalbumin (OVA)] following oral administration to experimental and control groups showed more rapid and complete absorption in the malnourished animals. Infection further enhanced the uptake of OVA, suggesting that both PCM and rotavirus infection alter the permeability of the small intestine. An unexpected observation of rotavirus-associated hepatitis in CB-17scid mice was also made in nearly 40% of malnourished mice inoculated with 10(6) PFU of Rhesus rotavirus (RRV). Mice with PCM exhibited a susceptibility to hepatitis between SCID mice (80%) and immunologically normal mice (18%). While these data are not sufficient to confirm a nutritionally-mediated immunoincompetence, they do suggest that either loss of immune competence and/or increased gut permeability in malnourished animals may allow a more severe homologous rotavirus infection as well as extraintestinal spread of heterologous rotavirus.
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PMID:Effect of nutritional deprivation on mucosal viral infections. 254 24

Deficiency of the enzyme adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4; ADA) leads to severe combined immunodeficiency, a disorder that potentially could be corrected by gene transfer into hematopoietic cells. We have constructed retroviruses containing human ADA cDNA and a dominant selectable marker, a mutated dihydrofolate reductase gene (DHFR*) encoding methotrexate resistance. Human ADA cDNA was inserted alone (DHFR*-ADA) or with a simian virus 40 (SV40) promoter (DHFR*-SVADA). Although NIH 3T3 cells infected with either construct produced human ADA activity, substantially greater levels were attained with DHFR*-SVADA. Infection of murine lymphoid cells in culture with DHFR*-SVADA led to expression of human enzyme at a level well above the mouse endogenous level. ADA activity was also increased after infection of a human ADA-deficient B-cell line. Lethally irradiated mice that were reconstituted with syngeneic marrow infected with the DHFR*-SVADA virus contained unrearranged, integrated proviral DNA in total spleen DNA or in spleen hematopoietic stem cell (CFU-S)-derived colonies. Nevertheless, no human ADA was detectable. RNA analysis showed relatively low and variable expression from the retroviral long terminal repeat, and no detectable expression from the internal SV40 promoter. These data suggest that intrinsic biologic differences exist between cultured cells and CFU-S in vivo.
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PMID:Retrovirus-mediated transfer of human adenosine deaminase gene sequences into cells in culture and into murine hematopoietic cells in vivo. 345 18

An analysis of a prospective study of viral infections in 12 patients with severe combined immunodeficiency is presented. Infections of viral etiology were common, with pulmonary and gastrointestinal infections being most frequent. Fourteen of 25 infections (56%) were nonsocomially acquired and 10 of 25 (40%) were community-acquired. The period of symptomatology and the duration of viral excretion were usually prolonged beyond those associated with disease in the general pediatric population. Pulmonary infections were associated with considerable morbidity and mortality. Gastrointestinal infections disrupted gastrointestinal function and possibly played a role in enteric Gram-negative bacillary sepsis. The inability of these patients to eradicate these viruses in the absence of immunologic reconstitution resulted in significant morbidity, often with a fatal outcome.
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PMID:Significance of viral infections in severe combined immunodeficiency disease. 686 84

Severe combined immunodeficiency (scid) mice have been useful in identifying specific host defense systems responsible for containing and eradicating Cryptosporidium parvum infection. Adult scid mice were given C. parvum oocysts and treated weekly with monoclonal antimurine interferon-gamma (anti-IFN-gamma). Anti-IFN-gamma-treated mice had more cryptosporidia seen in the intestines and had more severe morphologic changes associated with disease than control mice. To assess the mechanism of this effect, infected adult BALB/c and scid mice were treated with the nitric oxide synthase inhibitor, aminoguanidine. Infection in aminoguanidine-treated mice was not significantly different from that in control mice. Next, the effects of pharmacologic doses of IFN-gamma (10,000 IU) on the course of cryptosporidiosis in newborn scid mice were evaluated. IFN-gamma did not reverse the initial susceptibility of neonatal scid mice to cryptosporidiosis and continued treatment with IFN-gamma (10,000 IU weekly) did not alter survival. We conclude that IFN-gamma does not exert its anticryptosporidial effect by stimulation of nitric oxide production. Deficient IFN-gamma production by neonatal lymphocytes does not appear to be responsible for the increased severity of infection observed in neonatal animals. Also, IFN-gamma may not be useful in treating immunocompromised patients with cryptosporidiosis.
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PMID:Inability of interferon-gamma and aminoguanidine to alter Cryptosporidium parvum infection in mice with severe combined immunodeficiency. 751 9

Neurobehavioral and pathological data indicate that the central nervous system (CNS) becomes infected with HIV-1 soon after the virus enters the body. However, neuropathogenesis of HIV-1 infection is difficult to investigate because the brain parenchyma is not accessible to sampling during the course of AIDS. The second compartment of the CNS, cerebrospinal fluid (CSF), is accessible to sampling but how changes in the CSF relate to the changes in the parenchyma is poorly understood. Thus, knowledge of the neuropathogenesis of HIV-1 infection predominantly stems from either postmortem or in vitro studies. This raises the need for animal models of HIV infection of the CNS. Such models have been developed and are briefly reviewed here. The models faithfully recapitulate some aspects of the HIV/CNS disease. Appropriate neuropathological changes and neurobehavioral dysfunction (e.g., cognitive and motor deficits) occur in SIV-infected macaques. Central sensory electrophysiological changes and sleep disturbances occur in FIV-infected cats. Infection of the brain and behavioral changes comparable to some of the changes seen in humans occur in mice infected with a mixture of murine leukemia viruses. Genetically immunodeficient mice (e.g., SCID) accept HIV-infected human organs and or cell grafts. Evidence summarized here indicates that these HuSCID animals undergo neuropathological changes similar to those observed in brains of individuals who died with AIDS. Thus, presently available animal models provide an opportunity to investigate HIV/CNS disease, and to develop and test therapeutic interventions to prevent or cure the disease.
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PMID:Animal models recapitulate aspects of HIV/CNS disease. 757 36

Human immunodeficiency virus (HIV) can form pseudotypes with other enveloped viruses, including herpes simplex virus, when the two viruses coinfect the same cell. Pseudotypes between HIV and Epstein-Barr virus (EBV) have not been described. We observed unusually high levels of HIV-1 replication in SCID mice transplanted with human peripheral blood mononuclear cells (hu-PBL-SCID mice) when the mice developed EBV-associated human B cell lymphoproliferative disease. If this enhancement of HIV-1 replication were due to pseudotype formation rather than direct infection of B lymphoblastic cells by HIV-1, the pseudotypes could pose a novel biohazard to laboratory workers. To assess whether HIV-1 and EBV can form such pseudotypes, we established and characterized CD4-positive B lymphoblastoid cell lines (LCL) that contained cells infected with both EBV and HIV-1. A high-titered virus pool from these LCL could induce HIV infection in the Burkitt's lymphoma (BL) line BJA-B, but not in the BL line Ramos. Infection of BJA-B was blocked by neutralizing antibody to HIV gp120 but not by neutralizing anti-EBV gp350. These experiments provide no evidence for pseudotype formation, suggesting a low risk for EBV:HIV pseudotypes in natural infection of humans or in human cells transplanted to SCID mice.
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PMID:Lack of pseudotype formation between human immunodeficiency virus type 1 and Epstein-Barr virus in productively coinfected B lymphoblastoid cell lines. 777 96


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