Pulmonary histoplasmosis producing a spindle cell "pseudotumor".

Pulmonary spindle cell proliferations have been reported in association with a limited group of infectious agents. These lesions are rare and identified most often in the setting of immunosuppression. Because their appearance can simulate a spindle cell neoplasm, they are diagnostically treacherous, sometimes delaying antimicrobial therapy or resulting in unnecessary surgery. We report a case of a spindle pseudotumor of the lung resulting from Histoplasma capsulatum infection, a previously unreported cause of a spindle cell lesion in the lung. The patient was a 67-year-old woman in whom positron emission tomography-positive nodules developed in the left lung and left mediastinum. The patient had undergone renal transplantation and was receiving immunosuppressive therapy with mycophenolate, tacrolimus, and low-dose prednisone. Infection with H capsulatum was confirmed by culture of pleural effusion fluid, DNA probe analysis of the pleural fluid culture isolate, urinary Histoplasma antigen detection, and Grocott methenamine silver stains of tissue sections. To our knowledge, this is the first case of a spindle cell "pseudotumor" of the lung resulting from histoplasmosis. It highlights the importance of performing special stains for organisms when evaluating pulmonary spindle cell lesions in an immunocompromised host.

The enhancement of pericentromeric cohesin association by conserved kinetochore components promotes high-fidelity chromosome segregation and is sensitive to microtubule-based tension.

Sister chromatid cohesion, conferred by the evolutionarily conserved cohesin complex, is essential for proper chromosome segregation. Cohesin binds to discrete sites along chromosome arms, and is especially enriched surrounding centromeres, but past studies have not clearly defined the roles of arm and pericentromeric cohesion in chromosome segregation. To address this issue, we developed a technique that specifically reduced pericentromeric cohesin association on a single chromosome without affecting arm cohesin binding. Under these conditions, we observed more extensive stretching of centromeric chromatin and elevated frequencies of chromosome loss, suggesting that pericentromeric cohesin enrichment is essential for high-fidelity chromosome transmission. The magnitude of pericentromeric cohesin association was negatively correlated with tension between sister kinetochores, with the highest levels of association in cells lacking kinetochore-microtubule attachments. Pericentromeric cohesin recruitment required evolutionarily conserved components of the inner and central kinetochore. Together, these observations suggest that pericentromeric cohesin levels reflect the balance of opposing forces: the kinetochore-mediated enhancement of cohesin binding and the disruption of binding by mechanical tension at kinetochores. The involvement of conserved kinetochore components suggests that this pathway for pericentromeric cohesin enrichment may have been retained in higher eukaryotes to promote chromosome biorientation and accurate sister chromatid segregation.

The ferritin-like Dps protein is required for Salmonella enterica serovar Typhimurium oxidative stress resistance and virulence.

Resistance to phagocyte-derived reactive oxygen species is essential for Salmonella enterica serovar Typhimurium pathogenesis. Salmonella can enhance its resistance to oxidants through the induction of specific genetic pathways controlled by SoxRS, OxyR, sigma(S), sigma(E), SlyA, and RecA. These regulons can be found in a wide variety of pathogenic and environmental bacteria, suggesting that evolutionarily conserved mechanisms defend against oxidative stress both endogenously generated by aerobic respiration and exogenously produced by host phagocytic cells. Dps, a ferritin-like protein found in many eubacterial and archaebacterial species, appears to protect cells from oxidative stress by sequestering iron and limiting Fenton-catalyzed oxyradical formation. In Escherichia coli and some other bacterial species, Dps has been shown to accumulate during stationary phase in a sigma(S)-dependent fashion, bind nonspecifically to DNA, and form a crystalline structure that compacts and protects chromatin from oxidative damage. In the present study, we provide evidence that Dps protects Salmonella from iron-dependent killing by hydrogen peroxide, promotes Salmonella survival in murine macrophages, and enhances Salmonella virulence. Reduced numbers of dps mutant bacteria in the livers and spleens of infected mice are consistent with a role of Dps in protecting Salmonella from oxidative stress encountered during infection.