Sex Change and the Popular Press : Historical Notes on Transsexuality in the United States, 1930-1955, Meyerowitz, Joanne

本稿はデューク大学出版の季刊誌『レズビアン&ゲイ・スタディーズ』(GLQ)のトランスジェンダー特集号(1998年)で発表された、歴史学者ジョアン・マイエロウィッツの論文の翻訳である。[Meyerowitz, Joanne, Sex Change and the Popular Press: Historical Notes on Transsexuality in the United States, 1930-1955, GLQ: A Journal of Lesbian and Gay Studies, 4:2 (1998), pp.159-187.] マイエロウィッツはこの論文のなかで、従来のトランスセクシュアリティに関する歴史認識の見直しを主張する。そして、20世紀初めにヨーロッパで興った性別変更の医療化の過程、さらに、1930-50年代のアメリカで公表された性別変更の報道などの分析を通じて、当時のトランスジェンダーの人びとが、「読むこと」を通じて、自己のアイデンティティを構築し、再形成していった過程を明らかにしている。なお、マイエロウィッツは現在インディアナ大学の歴史学教授で、The Journal of American Historyの編集者でもある。主な編著書: How Sex Changed: A History of Transsexuality in the United States (Harvard UP, 2002); History and September 11th: Critical Perspectives on the Past (Temple UP, 2003)ほか

Metabolic Alterations in Pancreatic Cancer Progression

Pancreatic cancer is the third leading cause of cancer-related deaths in the USA. Pancreatic tumors are characterized by enhanced glycolytic metabolism promoted by a hypoxic tumor microenvironment and a resultant acidic milieu. The metabolic reprogramming allows cancer cells to survive hostile microenvironments. Through the analysis of the principal metabolic pathways, we identified the specific metabolites that are altered during pancreatic cancer progression in the spontaneous progression (KPC) mouse model. Genetically engineered mice exhibited metabolic alterations during PanINs formation, even before the tumor development. To account for other cells in the tumor microenvironment and to focus on metabolic adaptations concerning tumorigenic cells only, we compared the metabolic profile of KPC and orthotopic tumors with those obtained from KPC-tumor derived cell lines. We observed significant upregulation of glycolysis and the pentose phosphate pathway metabolites even at the early stages of pathogenesis. Other biosynthetic pathways also demonstrated a few common perturbations. While some of the metabolic changes in tumor cells are not detectable in orthotopic and spontaneous tumors, a significant number of tumor cell-intrinsic metabolic alterations are readily detectable in the animal models. Overall, we identified that metabolic alterations in precancerous lesions are maintained during cancer development and are largely mirrored by cancer cells in culture conditions

IL-33, IL-37, and Vitamin D Interaction Mediate Immunomodulation of Inflammation in Degenerating Cartilage

Chronic joint inflammation due to increased secretion of pro-inflammatory cytokines, the accumulation of inflammatory immune cells (mainly macrophages), and vitamin D deficiency leads to cartilage degeneration and the development of osteoarthritis (OA). This study investigated the effect of vitamin D status on the expression of mediators of inflammation including interleukin (IL)-33, IL-37, IL-6, tumor necrosis factor (TNF)-α, toll-like receptors (TLRs), damage-associated molecular patterns (DAMPs), and matrix metalloproteinases (MMPs) in degenerating the cartilage of hyperlipidemic microswine. Additionally, in vitro studies with normal human chondrocytes were conducted to investigate the effect of calcitriol on the expression of IL-33, IL-37, IL-6, TNF-α, TLRs, DAMPs, and MMPs. We also studied the effects of calcitriol on macrophage polarization using THP-1 cells. The results of this study revealed that vitamin D deficiency is associated with an increased expression of IL-33, IL-37, IL-6, TNF-α, TLRs, DAMPs, and MMPs, while vitamin D supplementation is associated with a decreased expression of the former. Additionally, vitamin D deficiency is associated with increased M1, while vitamin D-supplemented microswine cartilage showed increased M2 macrophages. It was also revealed that calcitriol favors M2 macrophage polarization. Taken together, the results of this study suggest that modulating expression of IL-33, IL-6, TNF-α, TLRs, DAMPs, and MMPs with vitamin D supplementation may serve as a novel therapeutic to attenuate inflammation and cartilage degeneration in osteoarthritis

COVID-19 and Kidney: The Importance of Follow-Up and Long-Term Screening

Renal involvement and kidney injury are common in COVID-19 patients, and the symptoms are more severe if the patient already has renal impairment. Renal involvement in COVID-19 is multifactorial, and the renal tubule is mainly affected, along with podocyte injury during SARS-CoV-2 infection. Inflammation, complement activation, hypercoagulation, and crosstalk between the kidney and lungs, brain, and heart are contributory factors. Kidney injury during the acute phase, termed acute kidney injury (AKI), may proceed to chronic kidney disease if the patient is discharged with renal impairment. Both AKI and chronic kidney disease (CKD) increase mortality in COVID-19 patients. Further, COVID-19 infection in patients suffering from CKD is more severe and increases the mortality rate. Thus, it is important to address both categories of patients, either developing AKI or CKD after COVID-19 or previously having CKD, with proper management and treatment. This review discusses the pathophysiology involved in AKI and CKD in COVID-19 infection, followed by management and treatment of AKI and CKD. This is followed by a discussion of the importance of screening and treatment of CKD patients infected with COVID-19 and future perspectives to improve treatment in such patients

Targets (Metabolic Mediators) of Therapeutic Importance in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC), an extremely aggressive invasive cancer, is the fourth most common cause of cancer-related death in the United States. The higher mortality in PDAC is often attributed to the inability to detect it until it has reached advanced stages. The major challenge in tackling PDAC is due to its elusive pathology, minimal effectiveness, and resistance to existing therapeutics. The aggressiveness of PDAC is due to the capacity of tumor cells to alter their metabolism, utilize the diverse available fuel sources to adapt and grow in a hypoxic and harsh environment. Therapeutic resistance is due to the presence of thick stroma with poor angiogenesis, thus making drug delivery to tumor cells difficult. Investigating the metabolic mediators and enzymes involved in metabolic reprogramming may lead to the identification of novel therapeutic targets. The metabolic mediators of glucose, glutamine, lipids, nucleotides, amino acids and mitochondrial metabolism have emerged as novel therapeutic targets. Additionally, the role of autophagy, macropinocytosis, lysosomal transport, recycling, amino acid transport, lipid transport, and the role of reactive oxygen species has also been discussed. The role of various pro-inflammatory cytokines and immune cells in the pathogenesis of PDAC and the metabolites involved in the signaling pathways as therapeutic targets have been previously discussed. This review focuses on the therapeutic potential of metabolic mediators in PDAC along with stemness due to metabolic alterations and their therapeutic importance

The Role of DAMPs and PAMPs in Inflammation-mediated Vulnerability of Atherosclerotic Plaques

Atherosclerosis is a chronic inflammatory disease resulting in the formation of the atherosclerotic plaque. Plaque formation starts with the inflammation in fatty streak and progress through atheroma, atheromatous plaque, and fibroatheroma leading to development of stable plaque. Hypercholesterolemia, dyslipidemia, hyperglycemia are the risk factors for atherosclerosis. Inflammation, infection with viruses and bacteria, and dysregulation in the endothelial and vascular smooth muscle cells leads to advanced plaque formation. Death of the cells in the intima due to inflammation results in secretion of damage-associated molecular patterns (DAMPs) such as high mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE), alarmins (S100A8, S100A9, S100A12, and oxidized low-density lipoproteins), and infection with pathogens leads to secretion of pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides, lipoteichoic acids, and peptidoglycans. DAMPs and PAMPs further activate the inflammatory surface receptors such as TREM-1 and TLRs and downstream signaling kinases and transcription factors leading to increased secretion of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and interferon (IFN)-γ and matrix metalloproteinases (MMPs). These mediators and cytokines along with MMPs render the plaque vulnerable for rupture leading to ischemic events. In this review, we have discussed the role of DAMPs and PAMPs in association with inflammation-mediated plaque vulnerability.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Regulation of TREM1-Mediated Inflammation in Hepatocellular Carcinoma Cells

Hepatocellular carcinoma (HCC), accounting for more than 90% of cases of primary liver cancer, is the third most common cause of cancer-related death worldwide. Chronic inflammation precedes the development of cirrhosis and HCC. TREM (triggering receptor expressed on myeloid cell)-1 is an inflammatory marker and amplifier of inflammation that signals through PI3K and ERK1/2 to activate transcription factors, resulting in increased secretion of pro-inflammatory cytokines, causing chronic inflammation and predisposing the liver to carcinogenesis. Thus, targeting TREM-1 in HCC might be a potential therapeutic target. A low level of vitamin D has been associated with chronic inflammation and poor prognosis in HCC. Thus, we evaluated the effect of vitamin D on TREM-1 expression in the HCC cell line. Additionally, the effects of high mobility group box-1, lipopolysaccharide, and transcription factor PU.1 on the expression of TREM-1 in normal liver cells and HCC cells have been investigated in the presence and absence of vitamin D. The results showed increased expression of TREM-1 in HCC cells and with IL-6, TNF-α, LPS, and rHMGB-1 and decreased expression with calcitriol. Calcitriol also attenuated the effect of IL-6, TNF-α, LPS, and rHMGB-1 on TREM-1. Calcitriol treatment attenuated the proliferation, migration, and invasion of HCC cells. These results (in vitro) provide molecular and biochemical evidence that calcitriol significantly attenuates the expression of mediators of inflammation, and thus might be used therapeutically together with conventional treatment to delay the progression of HCC. Additionally, the negative regulation of TREM-1 by PU.1 suggests PU.1 as a potential therapeutic target

Role of Risk Stratification and Genetics in Sudden Cardiac Death

Sudden cardiac death (SCD) is a major public health issue due to its increasing incidence in the general population and the difficulty in identifying high-risk individuals. Nearly 300,000-350,000 patients in the United States and 4- to 5 million patients in the world die from SCD. Coronary artery disease and advanced heart failure are the main etiology for SCD. Ischemia of any cause precipitates lethal arrhythmias, and ventricular tachycardia and ventricular fibrillation are the most common lethal arrhythmias precipitating SCD. Pulse-less electrical activity, brady-arrhythmia and electromechanical dissociation also result in SCD. Most sudden cardiac deaths occur out-of-the-hospital setting, so it is difficult to estimate the public burden, which results in overestimating the incidence of SCD. The insufficiency and limited predictive value of various indicators and criteria for SCD result in the increasing incidences. As a result, there is a need to develop better risk stratification criteria and find modifiable variables to decrease the incidence. Primary and secondary prevention and treatment of SCD need further research. This critical review is focused on the etiology, risk factors, prognostic factors and importance of risk stratification of SCD.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Transcriptional and Epigenetic Factors Associated with Early Thrombosis of Femoral Artery Involved in Arteriovenous Fistula

Arteriovenous fistulas (AVFs), created for hemodialysis in end-stage renal disease patients, mature through the outward remodeling of the outflow vein. However, early thrombosis and chronic inflammation are detrimental to the process of AVF maturation and precipitate AVF maturation failure. For the successful remodeling of the outflow vein, blood flow through the fistula is essential, but early arterial thrombosis attenuates this blood flow, and the vessels become thrombosed and stenosed, leading to AVF failure. The altered expression of various proteins involved in maintaining vessel patency or thrombosis is regulated by genes of which the expression is regulated by transcription factors and microRNAs. In this study, using thrombosed and stenosed arteries following AVF creation, we delineated transcription factors and microRNAs associated with differentially expressed genes in bulk RNA sequencing data using upstream and causal network analysis. We observed changes in many transcription factors and microRNAs that are involved in angiogenesis; vascular smooth muscle cell proliferation, migration, and phenotypic changes; endothelial cell function; hypoxia; oxidative stress; vessel remodeling; immune responses; and inflammation. These factors and microRNAs play a critical role in the underlying molecular mechanisms in AVF maturation. We also observed epigenetic factors involved in gene regulation associated with these molecular mechanisms. The results of this study indicate the importance of investigating the transcriptional and epigenetic regulation of AVF maturation and maturation failure and targeting factors precipitating early thrombosis and stenosis