Background and Aims: Lymphangioleiomyomatosis (LAM) is a rare destructive lung disease characterized by multiple thin-walled pulmonary cysts.The currently proposed diagnostic algorithm emphasizes the characteristic cystic appearance on high-resolution computed tomography (HRCT) so atypical HRCT appearances present challenges to establishing the proper LAM diagnosis.The objective of this study is to accrue atypical chest HRCT appearances, determine frequencies in both tuberous sclerosis complex (TSC)-associated LAM (TSC-LAM) and sporadic LAM (S-LAM) patients.Methods: We retrospectively evaluated radiologic findings of chest HRCT (with a section thickness of 2 mm) from 311 females, including 272 patients with S-LAM (mean age 39.2 years) and 39 patients with TSC-LAM (mean age 38.3 years) who were seen at our hospital between April 2009 and December 2016.Results: We found 2 types of radiologic findings likely to make HRCT cyst appearance atypical: characteristics of the cyst itself and atypical findings in addition to cysts.We found that approximately 80% of LAM patients, whether TSC-associated or sporadic, showed typical HRCT appearance with mild to severe cystic destruction.The remaining 20% displayed unusual profiles in cyst appearance as well as additional findings aside from cyst: the former includes large cyst, thickened walls, and irregularly shaped whereas the latter includes ground glass attenuation and diffuse noncalcified nodules.
An innovative pre-competitive virtual screening collaboration was engaged to validate and subsequently explore an imidazo[1,2-a]pyridine screening hit for visceral leishmaniasis. Parasitology and early ADME data is presented.
Key Clinical Message Organizing pneumonia (OP) and pulmonary alveolar proteinosis (PAP) are rare complications in patients with hematologic disorders. We herein report a case of PAP that developed during steroid treatment for OP in a patient with atypical chronic myeloid leukemia. Physicians should pay close attention to these complications in patients with hematologic malignancies.
The semiautomated kinetic procedure for determining cytoplasmic aspartate aminotransferase (c-AST) and mitochondrial aspartate aminotransferase (m-AST) activities was studied by the use of the immunoprecipitation method with anti-c-AST antibody in serum samples. The measured activity for m-AST remained constant after the addition of c-AST up to 1,000 IU/l throughout the 60-min incubation period. The measurements of m-AST activity were reproducible, selective and complete as determined by a purified m-AST. The precision of this method was as good as that of the manual method (CV 2.04%). The present method and the manual method gave approximately equal results for m-AST (r = 0.987). The effects of activations on m- and c-AST activity were compared by the addition of pyridoxal 5'-phosphate to sera of various diseases. A higher activation ratio by pyridoxal 5'-phosphate was observed on both aspartate aminotransferase activities in the serum of patients with ischemic heart diseases than in the serum of patients with liver diseases.
A case of toxic shock-like syndrome due to Streptococcus pyogenes is reported. A 76-year-old female was admitted with complaints of fever and chills. She had been suffering from cellulitis on her right dorsum pedis for 7 months. Laboratory data on admission showed elevated values of WBC, CRP, and dysfunction of the liver and kidney. She was diagnosed as sepsis due to the cellulitis, and was treated with PIPC and FMOX. However, several hours after admission, her blood pressure decreased and oliguria appeared. Bacteriological examinations from the blood and the cellulitis revealed group A β-hemolytic Streptococcus which gave streptococcal pyrogenic exotoxin (T-28, SPE-B+C). She died 23 hours after her admission in spite of changing antibiotics to a high-dose of PC-G therapy. This is one of the rare cases of toxic shock-like syndrome due to Streptococcus pyogenes from the cellulitis of the dorsum pedis.
Idiopathic pulmonary fibrosis (IPF) is a progressive aging-related lung disease associated with increased lung cancer risk. Although previous studies have shown that IPF worsens the survival of patients with lung cancer, whether IPF independently affects cancer malignancy and prognosis remains inconclusive. Extracellular vesicles (EVs) have recently emerged as active carriers of molecular biomarkers and mediators of intercellular communication in lung homeostasis and pathogenesis. EV cargo-mediated fibroblast-tumor cell communication might participate in the development and progression of lung cancer by modulating various signaling pathways. In this study, we examined the impact of lung fibroblast (LF)-derived EVs on non-small cell lung cancer (NSCLC) malignancy in the IPF microenvironment. Here, we showed that LFs derived from patients with IPF have phenotypes of myofibroblast differentiation and cellular senescence. Furthermore, we found that IPF LF-derived EVs have markedly altered microRNA compositions and exert proproliferative functions on NSCLC cells. Mechanistically, the phenotype was attributed mainly to the enrichment of miR-19a in IPF LF-derived EVs. As a downstream signaling pathway, mir-19a in IPF LF-derived EVs regulates ZMYND11-mediated c-Myc activation in NSCLC, potentially contributing to the poor prognosis of patients with NSCLC with IPF. Our discoveries provide novel mechanistic insights for understanding lung cancer progression in the IPF microenvironment. Accordingly, blocking the secretion of IPF LF-derived EV miR-19a and their signaling pathways is a potential therapeutic strategy for managing IPF and lung cancer progression.
A 60-year-old man was admitted to our hospital because of a persistent fever with enlargement of multiple lymph nodes in the mediastinum and around the pancreatic head. He was diagnosed with tuberculosis and human immunodeficiency virus infection. We started antiretroviral therapy three weeks after the initiation of anti-tuberculous therapy. Two weeks later, jaundice appeared with dilatation of the biliary tract due to further enlargement of the lymph nodes, which seemed to be immune reconstitution inflammatory syndrome (IRIS). The administration of corticosteroids resolved the obstructive jaundice without surgical treatment or endoscopic drainage. Obstructive jaundice caused by IRIS should first be treated with corticosteroids before invasive treatment.
Abstract Phenotypic alterations in the lung epithelium have been widely implicated in Chronic obstructive pulmonary disease (COPD) pathogenesis, but the precise mechanisms orchestrating this persistent inflammatory process remain unknown due to the complexity of lung parenchymal and mesenchymal architecture. To identify cell type-specific mechanisms and cell-cell interactions among the multiple lung resident cell types and inflammatory cells that contribute to COPD progression, we profiled 52,764 cells from lungs of COPD patients, non-COPD smokers, and never smokers using single-cell RNA sequencing technology. We predicted pseudotime of cell differentiation and cell-to-cell interaction networks in COPD. While epithelial components in never-smokers were relatively uniform, smoker groups represent extensive heterogeneity in epithelial cells, particularly in alveolar type 2 (AT2) clusters. Among AT2 cells, which are generally regarded as alveolar progenitors, we identified a unique subset that significantly increased in COPD patients, and specifically expressed a series of chemokines and PD-L1. A trajectory analysis revealed that the inflammatory AT2 cell subpopulation followed a unique differentiation path, and a prediction model of cell-to-cell interactions inferred significantly increased intercellular networks of inflammatory AT2 cells. Our results identify previously unidentified cell subsets and provide an insight into the biological and clinical characteristics of COPD pathogenesis.
