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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congenitally immunodeficient and immunosuppressed normal mice with naturally acquired Pneumocystis carinii infection were compared as models for testing anti-P. carinii drugs. Among the immunodeficient mice, mice with severe combined immunodeficiency disease (scid), which lack B and T cells, had higher levels of P. carinii pneumonia than did microMT mice, which lack K cells. Normal mice administered dexamethasone in the drinking water had more extensive pneumocystosis than mice administered parenteral methylprednisolone or hybridoma cells making a monoclonal antibody to CD4 cells. The standard anti-P. carinii drugs trimethoprim (TMP)-sulfamethoxazole (SMX), pentamidine, and atovaquone, which work well in rats and humans, worked well in the mice. Clindamycin and primaquine were effective in the scid and microMT mice but not in the immunosuppressed normal mice. High doses of epiroprim, an analog of TMP, appeared to enhance the activities of low doses of SMX and dapsone, while high doses of TMP did not; however, further studies are needed before definitive conclusions about the actions of these drugs can be drawn. Taken together, the data obtained in this study support the growing body of literature suggesting that the mouse is a valid alternative to the rat as a model for testing anti-P. carinii drugs. Additional differences involving the activities of individual drugs in these models will probably emerge as more experience is gained.
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PMID:Immunodeficient and immunosuppressed mice as models to test anti-Pneumocystis carinii drugs. 902 Nov 75

Mice (C57BL/6), treated with progesterone and infected intravaginally with the mouse pneumonitis strain of Chlamydia trachomatis (MoPn), acquired genital tract disease that ascended from the endocervix to the uterine horns, oviducts, and ovaries in a temporal fashion before the occurrence of spontaneous microbiological resolution by about 28 days after infection. Surprisingly, dissemination of MoPn in small numbers to draining lymph nodes, the peritoneal cavity, spleen, liver, kidneys, and lungs occurred in normal mice during the early stages of disease (7 to 14 days) in a portion of infected animals but resolved from these tissues, by microbiological criteria, prior to resolution of genital tract involvement. In contrast, gamma interferon knockout (IFN-gamma KO) mice exhibited dissemination of infection to a greater extent and for longer periods in a variety of tissues, and a portion of infected IFN-gamma KO mice failed to microbiologically resolve their genital tract disease. By comparison, C57BL/6 SCID mice uniformly failed to resolve their genital tract disease and exhibited high levels of dissemination to all tissues tested for extended (50-day) periods of times. Interestingly, although IFN-gamma KO mice failed to completely clear organisms from their genital tracts, they exhibited an attenuated infection indistinguishable from that of heterozygous littermates when challenged 112 days after primary infection. These data support a role for IFN-gamma in containing dissemination of MoPn from the genital tract to extragenital sites and in the microbiological resolution of infection. Data also indicate that IFN-gamma is not required for modulating reinfections, which normally follow a shorter and less dramatic course.
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PMID:Dissemination of Chlamydia trachomatis chronic genital tract infection in gamma interferon gene knockout mice. 916 44

A new species of Mycoplasma, M. volis, was isolated from the respiratory tract of clinically normal field-trapped prairie voles (Microtus ochrogaster) that were to be housed in close proximity to other rodents. To determine the pathogenic potential of the new mycoplasmal isolate, three groups of rodents (Sprague Dawley rats, BALB/c mice, and severe combined immunodeficient [SCID] mice) were intranasally inoculated with 2 x 10(8) color-changing units (CCU) of M. volis and were observed for 4 to 6 weeks. Experimental animals did not manifest clinical signs of disease; however, one experimental SCID mouse was euthanized 5 days after inoculation because of a severe circling disorder. Lung lesions in experimental SD rats ranged from mild to severe bronchial-associated lymphoid tissue (BALT) hyperplasia. Lung lesions in BALB/c and SCID mice ranged from no lesions to mild pneumonia. We were able to isolate M. volis from some control mice, none of which had lung lesions. All mice were seronegative for Sendai virus, mouse hepatitis virus, and M. pulmonis. All immunocompetent experimental animals (BALB/c mice and Sprague Dawley rats) were seropositive for M. volis. All immunocompetent control animals and SCID mice were seronegative for M. volis. Our data suggest that M. volis is capable of causing microscopic lesions and seroconversion in rats and mice, and therefore these rodents should not be housed in close proximity to voles.
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PMID:Pathogenicity of Mycoplasma volis in mice and rats. 951 88

Respiratory syncytial virus and parainfluenza virus infection carry a poor prognosis in severe combined immunodeficiency (SCID), particularly if the viral load is high. Patients with high viral load develop severe pneumonitis at engraftment which may possibly be modulated by immunotherapy, including high dose nebulised corticosteroids. Further work is required to develop effective treatment for this severe condition.
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PMID:Parainfluenza virus and respiratory syncytial virus infection in infants undergoing bone marrow transplantation for severe combined immunodeficiency. 978 36

As in vitro culture systems allowing to isolate Pneumocystis samples from patients or other mammal hosts are still not available, animal models have critical importance in Pneumocystis research. The parasite was reported in numerous mammals but P. carinii pneumonia (PCP) experimental models were essentially developed by using rats, mice, rabbits and ferrets. The rat treated with corticosteroids for 9-12 weeks is a useful PCP model. Like laboratory rats, conventional mice develop PCP after prolonged corticosteroid administration. The ferret (Mustela putorius furo) also develop PCP under corticosteroid regime. Whilst bronchoalveolar lavage (BAL) is really difficult to perform on live laboratory rodents, serial BAL sampling can be performed on live ferrets. Rabbits currently develop spontaneous PCP at weaning without corticosteroid administration. For this reason this model has been used for studying the host immune response as well as Pneumocystis-surfactant interactions. Pigs and horses also develop spontaneous PCP. Treated with corticosteroids, piglets develop extensive PCP and could be used as a non-rodent model. Pneumocystis was detected in many non-human primates. Primates could represent a source of parasites taxonomically related to P. carinii sp. f. hominis. Moreover, primates might be used as experimental hosts to human Pneumocystis. A marked variability of parasite levels among corticosteroid-treated animals and the fact that the origin of the parasite strain remains unknown, are important drawbacks of the corticosteroid-treated models. For these reasons, inoculated animal models of PCP were developed. The intratracheal inoculation of lung homogenates containing viable parasites in corticosteroid-treated non-latently infected rats resulted in extensive, reproducible Pneumocystis infections. Extensive PCP can be obtained within 5-7 weeks, whilst 9-12 weeks are needed in the classical model. The severe combined immunodeficiency (SCID) mouse inoculated by nasal route and the athymic nude rats intratracheally inoculated were used to test the infectivity of Pneumocystis samples coming from cultures or from different hosts. They were also used to test the anti-Pneumocystis activity of antimicrobial molecules.
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PMID:Animal models of pneumocystosis. 979 75

Severe combined immunodeficiency (SCID) is a rare pediatric medical emergency in Taiwan. The early diagnosis of infants with SCID is very important because it can save the life of these critical infants. The essential clues important for early diagnosis of SCID patients include positive family history of early infant death, paucity of tonsil and lymphoid tissue, cutaneous fungal infection and lymphopenia. Severe combined immunodeficiency is a heterogeneous group of inherited disorders characterized by the failure of both cellular and humoral immunity. It can be categorized into SCID with B-lymphocytes predominant (T-B+SCID) and SCID with paucity of B-lymphocytes (T-B-SCID), according to the number of B-lymphocytes in the patient's peripheral circulation. We report two male infants with T-B+SCID who had been suffering from severe pulmonary distress with persistent O2 desaturation when they were transferred to our pediatric intensive care unit. Tracing back these infant's family histories, it was discovered that both of them had an elder brother who had died to overwhelming infection within the first year of life, and Pneumocystis carinii pneumonitis (PCP) was confirmed in the elder brother of case 2. After hospitalization, the immune condition of these two infants were evaluated which showed a decrease in T-cell and NK cell number, an increase in B-cell number, and decreased serum levels of all the Igs except IgM, which was elevated in case 1. These were the diagnostic immunological findings for T-B+SCID, which included X-linked SCID and Jak-3-deficient SCID. During hospitalization, severe mucocutaneous candidiasis and PCP were noted and confirmed in case 1 and PCP was highly suspected in case 2. Bone marrow transplantation, the only curable treatment for T-B+SCID at present, could not be performed in these two patients because of their grave clinical condition. Both of them expired due to their progressively downhill pulmonary conditions.
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PMID:Severe combined immunodeficiency with B-lymphocytes (T-B+SCID): report of two cases. 992 17

The efficacy of cidofovir for treatment of cowpox virus infection in BALB/c mice was investigated in an effort to evaluate new therapies for virulent orthopoxvirus infections of the respiratory tract in a small animal model. Exposure to 2(-5)x10(6) pfu of cowpox virus by aerosol or intranasally (inl) was lethal in 3- to 7-week-old animals. One inoculation of 100 mg/kg cidofovir on day 0, 2, or 4, with respect to aerosol infection, resulted in 90%-100% survival. Treatment on day 0 reduced peak pulmonary virus titers 10- to 100-fold, reduced the severity of viral pneumonitis, and prevented pulmonary hemorrhage. The same dose on day -6 to 2 protected 80%-100% of inl infected mice, whereas 1 inoculation on day -16 to -8 or day 3 to 6 was partially protective. Cidofovir delayed but did not prevent the death of inl infected mice with severe combined immunodeficiency. Treatment at the time of tail scarification with vaccinia virus did not block vaccination efficacy.
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PMID:Cidofovir protects mice against lethal aerosol or intranasal cowpox virus challenge. 1060 45

Pneumocystis carinii is a ubiquitous fungus and opportunistic resident of the bronchoalveolar lumen of men and a variety of other mammalian species. This microorganism replicates under immunosuppressive conditions, ultimately resulting in lethal pneumonia (PcP) if left untreated. In the past decade, considerable progress has been made concerning the understanding of the underlying pathogenic mechanisms of this infection, mostly with the help of animal models such as SCID (severe combined immunodeficiency) or gene-knock-out mice. Partially conflicting data derived from animal studies lead to the assumption that there is no single relevant model for PcP. The T cell-mediated branch of the immune system is recognised as the major component in the host's ability to resist or overcome an infection with P. carinii. Natural, nonspecific immune mechanisms involving mononuclear phagocytes and elaborating a variety of cytokines and other immunomediators play an important role in initiating the immunoresponse as well as in its effector phase, but it is the CD4+ T lymphocytes which are essential for coordinating the complete eradication of this pathogen. The biological function and immunological effects of antigens expressed on the surface of or secreted by P. carinii organisms is not yet fully known. Hopefully, characterisation of these molecules, clarification of their immunological properties and the evaluation of the interactions between humoral and cellular as well as specific and nonspecific parts of the immune system will lead to new insights into the pathogenesis of P. carinii pneumonia.
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PMID:[Pathogenesis of pneumocystis carinii pneumonia]. 1061 69

Seven miniature dachshunds, all under the age of 1 year, were presented with polypnea, tachypnea, and exercise intolerance as a result of Pneumocystis carinii pneumonia, which was diagnosed on transtracheal aspirate cytology. In all of the dogs, historical and clinical signs were suggestive of immune incompetence. Immunological studies undertaken were leukogram parameters, serum immunoglobulin fraction quantification, lymphocyte transformation assay. CD3 and CD79a lymphocyte markers on lymphoid tissue, and anti-canine immunoglobulin G immunoperoxidase staining. The immunological studies showed hypogammaglobulinemia, deficiency of serum immunoglobulins A, G, and M, decreased lymphocyte transformation response to phytohemagglutinin and pokeweed mitogens and absence of B lymphocytes with presence of T lymphocytes in the lymphoid tissue stained with CD3 and CD79a lymphocyte markers. The preceding findings suggest that P. carinii pneumonia occurring in the miniature dachshund is a result of both a T- and B-cell deficiency. This presentation is not the classic primary severe combined immunodeficiency syndrome but rather combined variable immunodeficiency, which has been well documented in humans but never in the dog.
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PMID:Common variable immunodeficiency in miniature dachshunds affected with Pneumonocystis carinii pneumonia. 1069 Jul 74

RSV is one of the major causes of pneumonia and bronchiolitis in infants and young children and is associated with high mortality. RSV neutralizing human antibody (hu-Ab) is known to mediate resistance to viral infection as well as to be an effective treatment for severe lower respiratory tract RSV infection. We have previously demonstrated that human primary and secondary immune responses can be established in severe combined immunodeficient mice engrafted with human peripheral blood lymphocytes (hu-PBL-SCID). By combining this animal model with the single-chain Fv antibody (scFv) phage display library technique, we were able to investigate further its clinical potential by generating a panel of human scFvs that exhibit both high F glycoprotein (RSV-F) binding affinities ( approximately 108 M(-1)) and strong neutralizing activities against RSV infection in vitro. Sequencing analysis of the randomly isolated anti-RSV-F scFv clones revealed that they were derived from different VH families with mutations in the complementarity-determining region 1 (CDR1). The results suggest that: (i) RSV-F-specific human immune responses and affinity maturation can be induced in hu-PBL-SCID mice; and (ii) this approach can be applied to generate large numbers of human scFvs with therapeutic potential. Despite the fact that hu-PBL-SCID mouse and human scFv phage display library have individually been established, our approach contributes a simple and significant step toward the generalization of antigen-specific human monoclonal antibody (hu-MoAb) production and their clinical applications.
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PMID:Efficient generation of respiratory syncytial virus (RSV)-neutralizing human MoAbs via human peripheral blood lymphocyte (hu-PBL)-SCID mice and scFv phage display libraries. 1101 23


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