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

Pneumocystis carinii is an important agent of pneumonia in immunocompromised individuals, especially in acquired immunodeficiency syndrome AIDS patients P. carinii attaches specifically to type 1 pneumocytes. Although this phenomenon must play a marked role in pneumocystosis pathophysiology, no therapeutic molecules able to inhibit specifically the parasite attachment were found. A killer toxin, secreted by the yeast Pichia anomala, induced a significant decrease in P. carinii in vitro attachment and inhibited the parasite infectivity in SCID mice. Killer toxins cannot be used as systemic antibiotics. However, it was possible to produce antiidiotypic antibodies against a monoclonal antibody specific of the toxin active site. These antilds were shown to mimic the in vitro killer effect for the toxin and were called 'antibiobodies'. The susceptibility of P. carinii to the antimicrobial activity of the killer toxin made it possible to hypothesize that the killer phenomenon could constitute a new way for the treatment and prophylaxis of P. carinii infections.
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PMID:The yeast killer phenomenon: a hypothetical way to control Pneumocystis carinii pneumonia. 781 73

A model for the in vivo evaluation of antipneumocystis drugs has been developed in SCID mice infected intratracheally with cryopreserved mouse-derived Pneumocystis carinii. The development of a highly reproducible fatal P. carinii pneumonia occurred within 10 weeks (mean survival time +/- SEM = 72.2 +/- 1.2 days). Continuous administration of dexamethasone (2 mg/liter in the drinking water) exacerbated the rate of onset of severe P. carinii pneumonia (mean survival time +/- SEM = 63 +/- 1.3 days) in SCID mice. The number of cysts per g of lung homogenate (homogenate counts) were maximal with an inoculum of 20,000 cysts at 6 weeks post infection. Homogenate counts correlated with infection scores (graded assessments of immunofluorescent cysts on lung impression smears) suggesting that infection scoring accurately and rapidly reflects the severity of P. carinii pneumonia in SCID mice. These studies led to the development of a drug screening protocol in which Pneumocystis-free female SCID mice (20-25 g) were started on dexamethasone 7 days prior to IT inoculation with a single dose of 20,000 cysts. Drugs were evaluated either for: a) prophylaxis (continuously from day 1 post infection) or b) treatment (from day 21 post infection) until day 42 post infection, when all mice were killed and infection scores determined. Co-trimoxazole (at 250 mg sulfamethoxazole + 50 mg trimethoprim/kg/day) given in the drinking water was found to be highly effective in both the prophylaxis and treatment of mouse P. carinii pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Artificial infections of Pneumocystis carinii in the SCID mouse and their use in the in vivo evaluation of antipneumocystis drugs. 786 80

The ability of monoclonal antibodies (MAbs) to passively cure an influenza virus pneumonia in the absence of endogenous T- and B-cell responses was investigated by treating C.B-17 mice, homozygous for the severe combined immunodeficiency (SCID) mutation, with individual monoclonal antiviral antibodies 1 day after pulmonary infection with influenza virus PR8 [A/PR/8/34 (H1N1)]. Less than 10% of untreated SCID mice survived the infection. By contrast, 100% of infected SCID mice that had been treated with a single intraperitoneal inoculation of at least 175 micrograms of a pool of virus-neutralizing (VN+) antihemagglutinin (anti-HA) MAbs survived, even if antibody treatment was delayed up to 7 days after infection. The use of individual MAbs showed that recovery could be achieved by VN+ anti-HA MAbs of the immunoglobulin G1 (IgG1), IgG2a, IgG2b, and IgG3 isotypes but not by VN+ anti-HA MAbs of the IgA and IgM isotypes, even if the latter were used in a chronic treatment protocol to compensate for their shorter half-lives in vivo. Both IgA and IgM, although ineffective therapeutically, protected against infection when given prophylactically, i.e., before exposure to virus. An Fc gamma-specific effector mechanism was not an absolute requirement for antibody-mediated recovery, as F(ab')2 preparations of IgGs could cure the disease, although with lesser efficacy, than intact IgG. An anti-M2 MAb of the IgG1 isotype, which was VN- but bound well to infected cells and inhibited virus growth in vitro, failed to cure. These observations are consistent with the idea that MAbs of the IgG isotype cure the disease by neutralizing all progeny virus until all productively infected host cells have died. VN+ MAbs of the IgA and IgM isotypes may be ineffective therapeutically because they do not have sufficient access to all tissue sites in which virus is produced during influenza virus pneumonia.
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PMID:Virus-neutralizing antibodies of immunoglobulin G (IgG) but not of IgM or IgA isotypes can cure influenza virus pneumonia in SCID mice. 788 53

Severe combined immunodeficiency (SCID) mice resolve naturally acquired Pneumocystis carinii pneumonia after reconstitution with immunocompetent spleen cells and can therefore be used as a model to study latent P. carinii infection. Neither P. carinii nor amplified P. carinii DNA was detected in the lungs of SCID mice killed 21 days after spleen cell reconstitution. Furthermore, SCID mice that recovered from P. carinii infection failed to reactivate the infection after they were either depleted of CD4+ cells for up to 84 days or depleted of CD4+ cells and treated with corticosteroid for 35 days. These results indicate that an immune response to P. carinii can completely clear the organism from the host. This supports the hypothesis that P. carinii pneumonia that develops in immunocompromised patients may be a new infection resulting from exposure to an exogenous source of P. carinii and not necessarily from reactivation of latent infection.
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PMID:Latency is not an inevitable outcome of infection with Pneumocystis carinii. 790 Nov 69

Host defense against murine Chlamydia trachomatis (mouse pneumonitis agent [MoPn]) in a murine model was investigated. Gamma interferon (IFN-gamma) was produced in the lungs by both MoPn-susceptible nude athymic (nu/nu) and MoPn-resistant heterozygous (nu/+) mice. In vivo depletion of IFN-gamma in nu/nu mice led to exacerbation of infection. Fluorescence-activated cell sorter analysis disclosed induction of GL3 antibody-positive cells (putatively gamma/delta+ T cells) in nu/nu mouse lung during infection with MoPn. Treatment of nu/nu mice in vivo with antibody to NK cells (anti-asialo GM1 antibody) or to gamma/delta cells (UC7-13D5) did not significantly decrease IFN-gamma production in the lung. However, treatment of severe combined immunodeficiency mice (which lack gamma/delta cells) with antibody to NK cells significantly reduced lung IFN-gamma levels.
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PMID:Gamma interferon levels during Chlamydia trachomatis pneumonia in mice. 833 89

The production of interleukin-6 (IL-6) and its possible relationship to host resistance and inflammatory response to Pneumocystis carinii infection were examined in mice with severe combined immunodeficiency (SCID mice). IL-6 activity was detected in the serum and lungs of P. carinii-infected mice but not in mice free of P. carinii. Moreover, the IL-6 levels in P. carinii-infected mice increased markedly after spleen cell reconstitution but then decreased to an undetectable level after the clearance of P. carinii. However, neutralization of IL-6 activity in spleen cell-reconstituted SCID mice by treatment with anti-IL-6 immunoglobulin G (IgG) resulted in no significant effect on the clearance of P. carinii (P > 0.05). Both the serum and lungs of treated mice contained an excess amount of anti-IL-6 IgG and lacked detectable IL-6. These results suggest that failure to inhibit the P. carinii clearance by anti-IL-6 treatment was not due to insufficient administration of antibody or incomplete neutralization of IL-6 activity. However, compared with mice receiving rat control IgG, mice treated with anti-IL-6 IgG had significantly higher numbers of neutrophils and lymphocytes (particularly CD8+ cells) in the lung lavage fluids (P < 0.05 for both) at day 19 after reconstitution. In addition, the levels of both total IgG (P < 0.001) and P. carinii-specific antibodies (P < 0.05) in the serum of mice treated with anti-IL-6 were significantly higher than those in control mice. These results indicate that although P. carinii infection causes both local and systemic production of IL-6 in SCID mice, IL-6 does not appear to play a crucial role in the clearance of P. carinii. However, it appears that during resolution of P. carinii pneumonia, IL-6 plays a role in the regulation of pulmonary inflammation and antibody responses.
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PMID:Interleukin-6 production in a murine model of Pneumocystis carinii pneumonia: relation to resistance and inflammatory response. 841 70

Mice homozygous for the mutant allele scid (severe combined immunodeficiency) have been described as excellent models for Pneumocystis carinii (Pc) pneumonia (PCP), a major health problem in patients with acquired immune deficiency syndrome (AIDS) and other immunodeficiency states. Other microorganisms have been shown to infect AIDS patients simultaneously with Pc, but whether one opportunist is able to directly influence the pathogenicity of another has not been determined previously. We have deliberately coinfected scid mice (with extent Pc infection) with a variety of primarily pneumotropic viruses and bacteria and have identified pneumonia virus of mice as causing a dramatic increase in the density of Pc organisms and the morbidity due to PCP in immunodeficient scid mice. This finding has clinical significance in the management of PCP, in that the identification and treatment of coinfecting pneumotropic pathogens may be as important as treatment targeted at Pc. A search for other synergistic (or antagonistic) microorganisms and determination of their mechanism(s) of action in altering the progression of PCP is indicated.
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PMID:Lethal exacerbation of Pneumocystis carinii pneumonia in severe combined immunodeficiency mice after infection by pneumonia virus of mice. 845 14

In a series of five experiments, we attempted to transmit Pneumocystis carinii from ferrets to SCID mice by intratracheal inoculation. Using highly specific and sensitive assay techniques, we could not document infection of SCID mice by P. carinii isolated from ferrets. In contrast, under identical inoculation conditions, P. carinii was easily transmissible from one SCID mouse to another. These results indicate that P. carinii organisms, at least those isolated from ferrets, have a restricted host range. The finding of restricted transmission of P. carinii is consistent with the increasing evidence for host species-specific antigenic variation among isolates of P. carinii. If restricted host range is a consistent biological feature of animal-derived P. carinii, it would suggest that P. carinii pneumonitis in humans may not be a zoonosis as previously speculated.
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PMID:Pneumocystis carinii is not universally transmissible between mammalian species. 851 91

Radiation-induced pneumonitis and fibrosis in the lung after treatment to the thoracic cavity for malignant disease currently limit the maximum tolerated dose to that region. It has been suggested that heterogeneity in susceptibility to radiation-induced fibrosis exists in the population, implying that the lung tolerance dose is defined by a sensitive subset of the patient population. Studies of radiotherapy patients have indicated that the survival at 2 Gy (SF2) of cultured skin fibroblasts correlates with the incidence and severity of postirradiation damage in a number of tissues, suggesting that this assay may be a useful predictor of late tissue effects. The goal of the studies presented here was to determine if the radiosensitivity of fibroblasts in vitro isolated from mouse lungs was correlated with the severity of radiation-induced fibrosis in the lungs of two inbred strains of mice previously shown to differ markedly in their susceptibility to radiation-induced lung fibrosis: the C3Hf/Kam strain, classified as fibrosis-resistant, and the C57BL/6J strain, classified as fibrosis-prone. Quantitative measurements of lung fibrosis after irradiation were compared to SF2 values for fibroblasts of skin and lung cultured from each strain. Lung fibrosis was quantified, using computerized image analysis, as the percentage of fibrosis on Masson's Trichrome-stained lung sections from both strains after single doses of radiation to the thorax. For the measurements of SF2, fibroblasts plated at the second passage and grown to confluence were given single doses of radiation ranging from 0 to 6 Gy. Survival curves were constructed and SF2 values obtained from a linear-quadratic fit to the data. The radiosensitivity of fibroblasts from the lung and skin of SCID mice was determined and served as a positive control. The percentage of radiation-induced lung fibrosis was significantly different between the two strains, 5.1% and 0.2% in the C57 strain and C3H strain, respectively. Follow-up of long-term survivors (two mice) from the C3H strain did not change this conclusion. However, the lung fibroblast SF2 for the C57BL/6J strain (fibrosis-prone), 0.50 +/- 0.03, was not statistically different from the C3Hf/Kam strain (fibrosis-resistant), 0.55 +/- 0.07. These data indicate that in vitro radiosensitivity of lung fibroblasts as assayed by survival at 2 Gy does not correlate with the development of lung fibrosis in this mouse model. The SF2 for lung fibroblasts from SCID mice was 0.10. Similar SF2 values were obtained for both the C3Hf/Kam mouse lung and skin fibroblasts, 0.55 and 0.56, respectively, and C57BL/6J mouse lung and skin fibroblasts, 0.50 and 0.52, respectively, indicating that the radiosensitivity of fibroblasts isolated from lung and skin within a strain is the same.
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PMID:Fibroblast radiosensitivity in vitro and lung fibrosis in vivo: comparison between a fibrosis-prone and fibrosis-resistant mouse strain. 867 99

This article reviews Pneumocystis carinii and presents four cases in the miniature dachshund. The cases presented with hyperpnoea, tachypnoea and exercise intolerance. There were also clinical signs suggestive of immune incompetence in all the dogs. P carinii pneumonia was diagnosed in all four cases on transtracheal aspirate cytology. Immunological studies showed low globulin levels on serum electrophoresis, decreased lymphoblast transformation response (in the two cases that were tested) and a deficiency of immunoglobulins A, G and M. Light and electron microscopy as well as anti-canine immunoglobulin G immunoperoxidase staining studies were performed on one case which had died because of the disease. From these four cases, it appears that P carinii pneumonia in the miniature dachshund may be the result of an immunodeficiency. It does not, however, appear to be a classic primary severe combined immunodeficiency syndrome as the dogs appeared to respond to treatment, did not show growth failure and did not manifest overwhelming commensurate bacterial infections.
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PMID:Pneumocystis carinii in the miniature dachshund: case report and literature review. 896 82


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