Lung cancer is a disease with a high mortality rate for the U.S. Black population. There had been considerable research done on different population demographics, necessary to achieve the Healthy People 2020 overarching goals to eliminate health disparities, gain health equity and maintain quality health. Yet, the African-born Black (AFBB) population has been understudied for nonsmall cell lung cancer (NSCLC). This study sought to determine whether within race differences in stage at diagnosis and treatment of NSCLC exists between AFBB and American-born Blacks (AMBB) populations in the United States. The study data is secondary data collected as part of the National Cancer Institute's Surveillance Epidemiologic and End Result (SEER) Program from 2004-2011. Athough no significant difference was found between AFBB (n = 119) and AMBB (n = 238) relative to NSCLC stage at diagnosis, differences in treatments were found. The proportion of AFBB patients with early stage (I and II) NSCLC who underwent surgery differed significantly from that of AMBB (p < 0.05); AFBB patients were more likely to receive surgical therapy. The proportion of AFBB patients with stages I-IV of the disease who received radiation treatment also differed significantly from that of AMBB patients (p < 0.05); the latter were more likely to receive radiation therapy. Results from logistic regression analysis indicate that AFBB patients were more likely to receive surgical treatment while AMBB patients were more likely to receive radiation treatment. This study outcome can inform other NSCLC research to provide better insights to the cause of the treatment differences within the race from differing birth places, and efficient planning, evaluation of control programs and management of the disease.

Indiana University-Purdue University Indianapolis (IUPUI) / Sensing, integrating, and relaying signals from the environment through proteins, metabolites, and lipids to the lung are critical for proper development. Moonlighting proteins, such as AIMP1, are a unique subset that serves at least two independent physiological functions. Encoded by gene AIMP1, AIMP1 has two known functions: (1) C-terminus EMAP II domain of full-length AIMP1 can be secreted out of the cell to chemoattract myeloid cells; (2) intracellular full-length protein interacts with tRNA synthetases in protein translation. However, despite the linkage of protein expression levels of with several lung pathologies such as bronchopulmonary dysplasia (BPD), effectively targeting the protein encoded by AIMP1 has been a challenge due to poorly understood mechanisms. This thesis explores physiological, signaling, and immunological moonlighting mechanisms of first, the extracellular EMAP II then the intracellular AIMP1. Experiments utilize both in vitro and in vivo models, including a murine model of BPD and Cre-mediated exon-deletion knockout. Experimental results provide evidence that in the BPD model, EMAP II levels are elevated and sustained – first in bronchial epithelial cells then in macrophages. Mice exposed to sustained and elevated EMAP II protein levels resemble the BPD phenotype while neutralization partially rescued the phenotype, implying EMAP II as a potential therapeutic target against BPD. Results from studies exploring EMAP II’s signaling mechanism identify transient stimulation of JAK-STAT3 phosphorylation, commonly found in inflammation-resolving macrophages. In contrast, it induces unique transcriptional changes that are reversible both by JAK-STAT inhibitor and siRNA-mediated knockdown of Stat3. Studies using AIMP1 knockout mouse reveal a novel function for the intracellular AIMP1. AIMP1 knockout mice exhibited neonatal lethality with a respiratory distress phenotype, decreased type I alveolar cell expression, and disorganized bronchial epithelium, suggesting a role in lung maturation. In vitro experiments suggest that a portion of AIMP1 residing in the cell’s membrane interacts with various phosphatidylinositols and contributes toward F-actin deposition and assembly. Data from these experimental studies provide insight into how the various functions of the promiscuous AIMP1 gene affect lung development. These studies exemplify not only characterize novel moonlighting mechanisms of AIMP1, but also highlight the importance of characterizing moonlighting proteins to promote therapeutic preventions. / 2020-02-21

Indiana University-Purdue University Indianapolis (IUPUI) / With urbanization, indoor exposure to microbial communities has changed significantly. While indoor bacterial exposure has decreased, indoor fungal exposure has increased. Along with increases in fungal species diversity, indoor air in urbanized countries is characterized by 1,000+ fold differences in mold spore density between buildings. Americans are estimated to spend ~87% of their lives in this new indoor environment, where airborne spore concentrations are unregulated. While the effects of mold exposure on certain respiratory diseases are well established, little is known about how inhaled mold affects extra-respiratory disease. Mold exposure is associated with central nervous system (CNS) symptoms in humans, but very little is known about how mold affects the CNS. Here, I show that subchronic inhalation of a common indoor mold, Aspergillus versicolor, causes neuroinflammatory gene transcription in five out of five brain regions tested, at both 1 and 2 days post inhalation. How peripheral inflammation from mold inhalation causes neuroinflammation is unknown. The mechanisms by which mold is inhaled and cleared implicate the lung, systemic circulation, and gastrointestinal tract as potential areas of immune response. After mold spores are inhaled and deposited in the lung, they are killed by antifungal immunity, cleared from the lung by the mucociliary escalator, swallowed, and excreted through the gastrointestinal tract. Molds produce many mycotoxins which enter enterohepatic recirculation with known toxic effects, including intestinal epithelial disruption. Mycotoxin concentrations in food are regulated in countries comprising ~85% of the world’s population. Inhaled molds produce these same mycotoxins, yet pulmonary exposure is unregulated. The multi-system effects of fungal exposure are poorly understood, and are part of a growing nascent field. Here, I discuss the current state of the indoor fungal environment, known health effects of mold exposure, how fungi activate the immune system, the CNS effects of a common indoor mold, how neuroinflammation from mold exposure might be occurring, future work needed for the systematic analysis of the CNS effects of mold, what is needed to determine the extent to which fungal exposure influences disease, and what might be done to mitigate those effects. / 2022-08-17

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19550号 / 医博第4057号 / 新制||医||1012(附属図書館) / 32586 / 京都大学大学院医学研究科医学専攻 / (主査)教授 坂井 義治, 教授 三嶋 理晃, 教授 開 祐司 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20082号 / 医博第4175号 / 新制||医||1018(附属図書館) / 33198 / 京都大学大学院医学研究科医学専攻 / (主査)教授 小池 薫, 教授 湊谷 謙司, 教授 山下 潤 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21627号 / 医博第4433号 / 新制||医||1033(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 平井 豊博, 教授 松原 和夫, 教授 羽賀 博典 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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A 65‐year‐old man presented with progessive dysphagia, which proved to be the first clinical manifestation of a periperal lung carcinoma (secondary to a submucosal metatasis in the esophagus). The lung tumor, hidden by the diaphragm on chest x‐ray, was not suspected until a thoracotomy was done. Although dysphagia is known to be the first manifestation of bron‐chogenic carcinomas, such presentation in a case of a peripheral lung carcinoma has not been well described. This case is reported with a review of the literature for cases with dysphagia secondary to a metastatic tumor in the esophagus.

No description available.

Common presenting symptoms of Lung cancer are cough, hemoptysis, chest pain, dyspnea, pleurisy. Dysphagia is a very uncommon presenting feature of Lung cancer. Incidence of Dysphagia in Lung cancer is unclear from Literature. Causes of Dysphagia in case of Lung cancer are Anatomically classified as Oropharyngeal and Esophageal. Causes of oropharyngeal dysphagia are oral candidiasis, oropharyngeal Metastasis of Lung cancer. Causes of esophageal dysphagia are Cervical or Mediastinal Lymphadenopathy, Motor dysfunction because of Brain stem Metastasis, Lambert eaton syndrome, Esophageal candidiasis, Radiation esophagitis. Here by we present an Unusual presentation of an aggressive disease, poorly differentiated SCLC presenting as Mid esophageal dysphagia secondary to extrinsic esophageal compression. 65 year old female with past medical history of Diabetes, Hypertension presented with complaints of worsening sub sternal chest pain radiating to back since last 2 days and progressive dysphagia. Pt underwent Left heart catheterization revealing non obstructive coronary artery disease. Modified Barium swallow showed stasis of contrast in mid esophagus, Endoscopy showed extrinsic compression of the proximal esophagus, normal mucosa. Computerized tomography of chest was done for further evaluation, revealing extensive left cervical, mediastinal, left hilar lymphadenopathy causing extrinsic compression of the esophagus and encasement of the left hilar structures. Further evaluation through Bronchoscopic biopsy of her left upper lobe mass reveals poorly differentiated small cell carcinoma. Staging was performed revealing limited stage disease. Started on concurrent chemotherapy with cisplatin, etoposide and radiation. As SCLC is highly responsive to chemotherapy and radiotherapy sensitive patient got symptomatic relief by the end of first cycle. SCLC is an aggressive lung cancer. As it is a micro metastatic disease in nature at presentation, it’s management is entirely different from Non SCLC. SCLC being an aggressive disease can cause dysphagia in 1-2% during the disease course. SCLC presenting as dysphagia is almost never reported in the literature. Our patient presented with severe dysphagia, described it as “a tennis ball sitting in her food pipe”. Fortunately she presented to the Emergency room with dysphagia and associated chest pain, we were able to make early diagnosis of SCLC, initiate treatment. Delay in the diagnosis lead to rapid progression of disease and poor prognosis. Through our case we wanted to convey that it is very important to obtain meticulous history, keeping broad differentials, which can help improve prognosis. Because not always the presenting features are from the organ of involvement it could be from the contiguous spread or compression.