A Case of Systemic Lupus Erythematosus Presenting with an Acute Abdomen: Successful Treatment with Steroid

Abdominal pain continues to pose diagnostic challenges for emergency clinicians. A 56-year-old Japanese woman was referred to our hospital due to severe abdominal pain which presented as occasional epigastric pain five months before and intermittent abdominal pain. She had a past history of ileus twice, for both of which laparotomy was performed without an alimentary tract resection. The wall thickening with marked three-wall structure from terminal ileum to sigmoid colon was seen and bladder wall was irregularly thick and enhanced irregularly. Among the differential diagnosis of the acute abdomen, autoimmune diseases were suspected, especially lupus erythematosus and Henoch-Schönlein purpura. On the second day of admission, abdominal pain worsened. The results of examinations of antinuclear antibody, anti-double-stranded DNA antibody, ANCA, and the complements were not obtained at that time; however, we started 1-g steroid pulse treatment for three days with success. With the results obtained later, the patient was given a diagnosis of probable systemic lupus erythematosus (SLE). The present case shows that SLE can present with acute abdomen and should be included in the wide range of the differential diagnosis of acute abdomen

Metastatic breast cancer presenting as severe anemia, platelet reduction and abnormal cells in peripheral blood

　Worldwide, breast cancer accounts for 22.9% of all cancers excluding non-melanoma skin cancers in women. More than 80% of breast cancer cases are discovered when a woman discovers a lump that feels different from the rest of the breast tissue. We report the case of a 60-year-old woman who had been treated for one year at a psychiatric hospital for suspected schizophrenia, and was referred to our hospital on March 23, 2011 for consultation regarding complete blood count abnormalities: hemoglobin, 4.8g/㎗ ; Plt, 1.9×104/μl ; WBC, 12,700/μl with 18.5% abnormal cells. Computed tomography revealed an enhanced, irregular mass in her right breast as well as right axillary lymph node swelling, suggestive of breast cancer. BM biopsy confirmed the presence of abnormal, keratin-positive cells, suggesting metastasis to the bone. CA15-3 was 300U/㎖ (normal range ＜25). The patient died on April 11, 2011, post-admission day 20. We found a rare case of terminal breast cancer that presented with peripheral blood abnormality. Breast cancer in patients who do not notice breast abnormality can present with peripheral blood abnormality

Ethanol-induced Stress Leads to Apoptosls Via Endoplasmic Reticulum Stress in SK-Hepl Cells

Alcoholic liver disease causes oxidative stress and induces apoptosis during alcohol metabolism. Ethanol causes endoplasmic reticulum (ER) stress in hepatocytes, stimulating the unfolded protein response (UPR) pathway and/or Ca2+-dependent calpain and caspase-4 activities. However, it is poorly understood whether ethanol-induced oxidative stress directly leads to apoptosis promoted by ER stress-associated pathways. This study investigated this question in human liver adenocarcinoma (SK-Hep1) cells, which were treated with 200 mM ethanol for 5 hours in the presence or absence of the antioxidant N-acetyl-cysteine (NAC). We found that treatment with ethanol significantly increased ROS production and cellular apoptosis in the SK-Hep1 cells, and that this response was significantly suppressed by pretreatment with NAC. Furthermore, pretreatment with NAC significantly reduced the observed increases in the mRNA expressions of Bip, Chop, and sXbp-1, and the activity of caspase-3 in ethanol-induced apoptotic cells. However, pretreatment with NAC did not attenuate the transient rise in cytosolic Ca2+ nor the activities of caspase-4 and calpain induced by ethanol. Together, these results revealed that ethanol-induced stress promotes apoptosis not only through mitochondria-mediated pathways, but also via ER stress. The findings further suggested that ethanol-induced oxidative stress and non-oxidative stress both stimulate the pathway regulating ER stress-mediated apoptosis

Metastatic breast cancer presenting as severe anemia, platelet reduction and abnormal cells in peripheral blood

　Worldwide, breast cancer accounts for 22.9% of all cancers excluding non-melanoma skin cancers in women. More than 80% of breast cancer cases are discovered when a woman discovers a lump that feels different from the rest of the breast tissue. We report the case of a 60-year-old woman who had been treated for one year at a psychiatric hospital for suspected schizophrenia, and was referred to our hospital on March 23, 2011 for consultation regarding complete blood count abnormalities: hemoglobin, 4.8g/㎗ ; Plt, 1.9×104/μl ; WBC, 12,700/μl with 18.5% abnormal cells. Computed tomography revealed an enhanced, irregular mass in her right breast as well as right axillary lymph node swelling, suggestive of breast cancer. BM biopsy confirmed the presence of abnormal, keratin-positive cells, suggesting metastasis to the bone. CA15-3 was 300U/㎖ (normal range ＜25). The patient died on April 11, 2011, post-admission day 20. We found a rare case of terminal breast cancer that presented with peripheral blood abnormality. Breast cancer in patients who do not notice breast abnormality can present with peripheral blood abnormality

Population health and regional variations of disease burden in Japan, 1990–2015:a systematic subnational analysis for the Global Burden of Disease Study 2015

BackgroundJapan has entered the era of super-ageing and advanced health transition, which is increasingly putting pressure on the sustainability of its health system. The level and pace of this health transition might vary across regions within Japan and concern is growing about increasing regional variations in disease burden. The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides a comprehensive, comparable framework. We used data from GBD 2015 with the aim to quantify the burden of disease and injuries, and to attribute risk factors in Japan at a subnational, prefecture-level.MethodsWe used data from GBD 2015 for 315 causes and 79 risk factors of death, disease, and injury incidence and prevalence to measure the burden of diseases and injuries in Japan and in the 47 Japanese prefectures from 1990 to 2015. We extracted data from GBD 2015 to assess mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), life expectancy, and healthy life expectancy (HALE) in Japan and its 47 prefectures. We split extracted data by prefecture and applied GBD methods to generate estimates of burden, and attributable burden due to known risk factors. We examined the prefecture-level relationships of common health system inputs (eg, health expenditure and workforces) to the GBD outputs in 2015 to address underlying determinants of regional health variations.FindingsLife expectancy at birth in Japan increased by 4·2 years from 79·0 years (95% uncertainty interval [UI] 79·0 to 79·0) to 83·2 years (83·1 to 83·2) between 1990 and 2015. However, the gaps between prefectures with the lowest and highest life expectancies and HALE have widened, from 2·5 to 3·1 years and from 2·3 to 2·7 years, respectively, from 1990 to 2015. Although overall age-standardised death rates decreased by 29·0% (28·7 to 29·3) from 1990 to 2015, the rates of mortality decline in this period substantially varied across the prefectures, ranging from -32·4% (-34·8 to -30·0) to -22·0% (-20·4 to -20·1). During the same time period, the rate of age-standardised DALYs was reduced overall by 19·8% (17·9 to 22·0). The reduction in rates of age-standardised YLDs was very small by 3·5% (2·6 to 4·3). The pace of reduction in mortality and DALYs in many leading causes has largely levelled off since 2005. Known risk factors accounted for 34·5% (32·4 to 36·9) of DALYs; the two leading behavioural risk factors were unhealthy diets and tobacco smoking in 2015. The common health system inputs were not associated with age-standardised death and DALY rates in 2015.InterpretationJapan has been successful overall in reducing mortality and disability from most major diseases. However, progress has slowed down and health variations between prefectures is growing. In view of the limited association between the prefecture-level health system inputs and health outcomes, the potential sources of regional variations, including subnational health system performance, urgently need assessment.FundingBill & Melinda Gates Foundation, Japan Ministry of Education, Science, Sports and Culture, Japan Ministry of Health, Labour and Welfare, AXA CR Fixed Income Fund and AXA Research Fund

FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters

乳がんの再発を起こす原因細胞を解明. 京都大学プレスリリース. 2023-11-16.The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain–containing ion transport regulator 3 (FXYD3), a component of the Na⁺/K⁺ pump. Accordingly, FXYD3⁺ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3⁺ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3⁺ CSCs were sensitive to senolytic Na⁺/K⁺ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3⁺ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na⁺/K⁺ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis

Lexical Stratification and Ranking Invariance in Constraint-based Grammars*

this paper, we discuss a model of lexical stratification which fully adheres to the assumption of invariant ranking. The model, originally proposed by Fukazawa (1997), solves the conflict between language-internal variability and ranking invariance by projecting multiple sets of Input-Output faithfulness constraints. Each set of faithfulness constraints is associated with a sub-lexicon (or stratum) in the language, and all the stratum-specific constraints are ranked with other types of constraints. Such a system can account for stratum-specific phonological phenomena in a single constraint ranking. The main goal of the paper is to demonstrate the conceptual and empirical advantage of this approach, using lexical stratification in Japanese as a domain of investigation. Further, we will address two issues that arise regarding the claim that multiple projections of faithfulness constraints derive the effects of lexical stratification: i) the question of how multiple faithfulness constraints can be instantiated, and ii) implications for the fundamental organization of the lexicon with strata. This paper is organized as follows. Section 2 illustrates the superiority of the Correspondence Theoretic approach to lexical stratification to the re-ranking system. We present an analysis of hybrid words in Japanese and show that simultaneous reference to multiple sets of Input-Output faithfulnes constraints is necessary to account for the data. Section 3 provides an answer to the question: how are those multiple sets of IO constraints established? We will indicate that contradicting phonological data touch off multiplication of faithfulness constraints and ranking of constraints in the process of acquisition. Section 4 discusses the relationship between split faithfulness constraint..