Clinical features of pulmonary cryptococcosis in non-HIV patients in Japan

OBJECTIVE: To clarify the clinical features of pulmonary cryptococcosis in Japanese non-HIV population.METHODS: Retrospective investigation of 151 pulmonary cryptococcosis cases between 1977 and 2012 was executed. The underlying disease (UDs), aggravating factors, radiological characteristics, and treatment were examined.RESULTS: Sixty-seven patients (44.4%) had no UDs. The common UDs were diabetes (32.1%) followed by hematologic disease (22.6%), and collagen disease (22.6%). Peripherally distributed pulmonary nodules/masses were most commonly seen. Lesions in the right middle lobe (p = 0.01) and air bronchogram (P = 0.05) were significantly more frequent, respectively, in patients with UDs than patients without them. Azoles were mainly selected for the patients without meningoencephalitis. Mean treatment duration for patients with and without UDs was 6.64 and 2.87 months, respectively. Patients whose pulmonary nodules improved after treatment continued to experience gradual reduction of cryptococcosis antigen titers, even if antigen titers were positive at the time of treatment cessation. The average time for antigen titers to become negative after treatment cessation was 13.1 and 10.7 months for patients with and without UDs, respectively. When groups were compared according to the presence of meningoencephalitis complications, deaths, and survivals, factors contributing to cryptococcosis prognosis included higher age, hypoproteinemia, hypoalbuminemia, steroid use, high C-reactive protein levels, and meningoencephalitis complications.CONCLUSIONS: It is crucial to consider the presence of UDs and meningoencephalitis for the choice of antifungals and treatment duration for cryptococcosis in non-HIV patients. Three- and six months-administration of azoles for pulmonary cryptococcosis with or without UDs, respectively is reasonable

TRPV2 channels mediate insulin secretion induced by cell swelling in mouse pancreatic β-cells

β-Cell swelling induces membrane depolarization, which has been suggested to be caused at least partly by the activation of cation channels. Here, we show the identification of the cation channels. In isolated mouse pancreatic β-cells, the exposure to 30% hypotonic solution elicited an increase in cytosolic Ca 2+ concentration ([Ca 2+ ] c ). The [Ca 2+ ] c elevation was partially inhibited by ruthenium red, a blocker of several Ca 2+ -permeable channels including transient receptor potential vanilloid receptors [transient receptor potential cation channel subfamily V (TRPV)], and by nicardipine, but not by the depletion of intracellular Ca 2+ stores with thapsigargin and caffeine. The hypotonic stimulation also increased insulin secretion from isolated mouse islets, which was significantly suppressed by ruthenium red. Expression of TRPV2 and TRPV4 was confirmed in mouse pancreatic islets and the MIN6 β-cell line by RT-PCR, Western blot, and immunohistochemical analyses. However, neither 4α-phorbol 12,13-didecanoate nor GSK1016790A, TRPV4 activators, showed any apparent effect on [Ca 2+ ] c in isolated mouse β-cells or in MIN6 cells. In contrast, probenecid, a TRPV2 activator, induced an increase in [Ca 2+ ] c in MIN6 cells, which was attenuated by ruthenium red. Moreover, the [Ca 2+ ] c elevation induced by 30% hypotonic stimulation was significantly reduced by knockdown of TRPV2 with siRNA and by tranilast, a TRPV2 inhibitor. The knockdown of TRPV2 also decreased insulin secretion induced by the hypotonic stimulation. In addition, glucose-stimulated insulin secretion was also significantly reduced in the TRPV2-knockdown MIN6 cells. These results suggest that osmotic cell swelling activates TRPV2 in mouse β-cells, thereby causing membrane depolarization and subsequent activation of voltage-dependent Ca 2+ channels and insulin secretion.info:eu-repo/semantics/publishe

Pulmonary Sarcoidosis Showing a Solitary Large Nodule with a "Pseudo-alveolar" Pattern

An abnormal shadow was detected on chest radiograph in a 28-year-old male on a routine medical check. The chest radiograph showed a solitary mass-like opacity in the right upper lung field. The patient attended our hospital for further examination on May 22, 2002. High-resolution computed tomography showed an aggregate of micronodular opacities consistent with the "pseudo-alveolar" pattern described in recent reports. The final diagnosis was pulmonary sarcoidosis as confirmed by the presence of epithelioid granulomas in specimens from transbronchial lung biopsy. Pulmonary sarcoidosis with a pseudo-alveolar pattern is unusual, particularly in the absence of bilateral hilar lymphadenopathy. Therefore, this case might be instructive for the diagnosis of pulmonary sarcoidosis