Pneumocystis pneumonia. Animal model: pneumocystis cartinii pneumonia in the immunosuppressed rat.
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BACKGROUND: Pneumocystis pneumonia (PCP) remains a major cause of morbidity and mortality in immunocompromised individuals. Although baicalin (Ba), a natural bioactive flavonoid, has demonstrated protective and therapeutic effects against PCP, its molecular mechanisms remain undefined. We employed dual RNA sequencing (dual RNA-seq) to characterize host and pathogen transcriptional responses to Ba treatment in an immunosuppressed rat model of PCP. METHODS: Comparative transcriptomic analyses identified differentially expressed genes in both the host and Pneumocystis, followed by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses. Candidate targets were further investigated using network pharmacology, protein-protein interaction analysis, molecular docking, and molecular dynamics simulations. Key findings were validated by immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative PCR. RESULTS: Ba markedly remodeled host and pathogen transcriptomes. Host transcriptomic analyses showed that Ba attenuated inflammatory and oxidative stress responses by modulating immune-related pathways, including Toll-like receptor, NF-κB, cytokine-cytokine receptor interaction, chemokine signaling, Th17 cell differentiation, and antigen processing and presentation. Experimental validation demonstrated that Ba reduced pulmonary expression of indoleamine 2,3-dioxygenase 1 (IDO1), Toll-like receptor 2 (TLR2), and TLR4 while increasing nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant enzyme heme oxygenase-1 (HO-1). Pathogen transcriptomic analysis identified Pneumocystis Rtt109 (PcRtt109), a fungal histone acetyltransferase, as a potential pathogen-specific target that was significantly downregulated after Ba treatment. Molecular docking and molecular dynamics simulations supported stable interactions between Ba and IDO1, Nrf2, TLR2, TLR4, and PcRtt109, with the strongest predicted binding observed for PcRtt109. CONCLUSION: Dual RNA-seq revealed that Ba exerts anti-PCP activity through coordinated modulation of host and pathogen molecular networks. Its therapeutic effects are associated with suppression of inflammatory signaling, enhancement of antioxidant defenses, and inhibition of a fungal virulence-associated target. These findings provide mechanistic insights into host-pathogen interactions during PCP and support Ba as a potential therapeutic candidate for PCP.
A fatal pneumocystis pneumonia after renal transplantation is described. The diagnosis, which was suspected on clinical and radiological grounds, was confirmed at autopsy. The radiological features and differential diagnosis and the clinical and pathological findings are described. Needle biopsy is recommended for a definitive diagnosis. Specific treatment at the earliest possible moment.
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This is a case report of pneumocytosis of an eight month old Dachschund from the Cape Province. Clinically it was an afebrile disease with signs limited primarily to the lower respiratory tract. The report consists of a short history, the histopathologic findings, evidence of the electron microscopic confirmation of the diagnosis and a brief discussion. It is believed to represent the first case of canine pneumocystosis in the Republic of South Africa.
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Pneumocystis carinii pneumonitis is a diffuse bilateral alveolopathy encountered in the immunocompromised host with cancer, a congenital immune deficiency disorder, an organ transplant, severe protein-energy malnutrition or recipients of immunosuppressive therapy for other conditions. The onset is abrupt with fever and tachypnea. No rales are heard and the roentgenogram reveals a diffuse alveolar disease. Once the pneumonitis is evident, the infection is usually fatal if no treatment is given. The diagnosis is best established by the demonstration of the causative organism in specimens obtained by open lung biopsy, or other invasive methods, and stained with Gomori's methenamine silver nitrate, toluidine blue O or polychrome stains. Of the two drugs available for treatment, trimethoprim-sulfamethoxazole is preferred over pentamidine isethionate because of relative difference in adverse effects. With either drug the recovery rate is about 75%. The infection can be prevented in high risk patients by the administration of trimethoprim-sulfamethoxazole prophylactically.
Between Jan 1 and Oct 31, 1975, a cluster of ten cases of pneumocystis pneumonia occurred in children with acute lymphocytic leukemia (ALL) at the James Whitcomb Riley Hospital for Children in Indianapolis. The risk of infection appeared to be related to the intensity of chemotherapy. Furthermore, illness developed in nine of the ten patients between 30 and 100 days after initiation of therapy, suggesting a period of heightened susceptibility to infection. An indirect immunofluorescent test was used to detect antipneumocystis antibodies in serum samples collected from patients with pneumocystis pneumonia and their contacts. Members of the Riley Hospital staff who had close contact with infected children had a higher prevalence of elevated antibody titers (7/12) than other staff members (2/22; P = .004) or parents of infected patients (0/8; P = .01). This suggests that transmission of pneumocystis may occur within the hospital environment.
BACKGROUND: X-linked hyper-immunoglobulin M (XHIGM) syndrome is a rare primary immunodeficiency caused by mutations in the CD40 ligand gene (CD40LG), characterized by defective T-cell-dependent B-cell class-switch recombination. Patients typically present with recurrent infections in early childhood, but diagnosis is often delayed due to heterogeneous clinical manifestations and the fact that serum IgM levels may remain within the normal range in a significant proportion of patients. Here we report a case of XHIGM in an infant whose diagnostic journey began with recurrent lymphadenitis and culminated in life-threatening Pneumocystis jirovecii pneumonia (PJP). CASE PRESENTATION: A 6-month-old male infant was admitted with severe respiratory distress and hypoxemia. He had recurrent axillary lymphadenitis at 1 and 2 months of age and significant failure to thrive. Chest CT showed bilateral consolidative and interstitial opacities. Immunological evaluation revealed markedly decreased IgA, normal IgM and IgG, and profound T-cell lymphopenia. Sputum metagenomic sequencing identified Pneumocystis jirovecii. Whole-genome sequencing identified a hemizygous likely pathogenic CD40LG mutation (NM_000074.3:c.520C>T, p.Q174*); his mother was a carrier. He was treated with mechanical ventilation, trimethoprim-sulfamethoxazole (TMP-SMX), micafungin, corticosteroids, and intravenous immunoglobulin (IVIG), and was discharged after 36 days. CONCLUSIONS: In infants with recurrent or opportunistic infections, persistently low IgA and declining T-cell counts-even when initial screening appears normal-should raise suspicion for underlying immunodeficiency and prompt genetic evaluation. Early aggressive management and evaluation for hematopoietic stem cell transplantation are essential to improve outcomes.Serial immunological evaluation is essential in infants with recurrent or opportunistic infections, as persistently low IgA and declining T-cell counts-even when initial screening appears normal-should prompt genetic evaluation for underlying immunodeficiency. Early aggressive management and evaluation for hematopoietic stem cell transplantation are essential to improve outcomes.
In the diagnosis of Pneumocystis carinii infection in man, rather exacting methods of staining must be used for the organism to be visualized in lung tissue. Techniques for sample collection, which range from open lung biopsy to endobronchial brush methods or collection of sputum, are discussed. Recent advances in the serologic diagnosis and in the culture of the organism are also covered.
Unlike most pneumonias, the diagnosis of Pneumocystis carinii pneumonia is based solely on identifying organisms by stain, usually with methenamine-silver. Because of technical problems involved with adequate staining, control samples usually are done concurrent with tissue specimens to be examined. Lung containing fungi often is used as a control. We recently observed false-negative biopsy specimens in a case of P carinii pneumonia where the Pneumocystis organism failed to stain with methenamine-silver on several occasions, although fungal controls were positive. This report emphasizes the importance of using P carinii as a control whenever attempting to diagnose P carinii pneumonia.
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