Samter's triad (ST) is a well-known disease characterized by the triad of bronchial asthma, nasal polyps, and aspirin intolerance. Over the past few years, a rapid development in the knowledge of the pathogenesis and clinical characteristics of ST has happened. The aim of this paper is to review the recent investigations on the pathophysiological mechanisms and genetic background, diagnosis, and different therapeutic options of ST to advance our understanding of the mechanism and the therapeutic control of ST. As concern for ST increase, more application of aspirin desensitization will be required to manage this disease successfully. There is also a need for continued research efforts in pathophysiology, treatment, and possible prevention.
Aspirin ; Asthma ; Diagnosis ; Genetic Background ; Nasal Polyps ; Sinusitis

BACKGROUND: Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV). METHODS: We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development. RESULTS: We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron. CONCLUSION Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Child ; Humans ; Neurodevelopmental Disorders/epidemiology* ; Genetic Testing ; Phenotype ; Brain/pathology* ; Genetic Background ; SOX Transcription Factors/genetics*

The purpose of this study was to characterize the genetic contribution to endothelial adaptation to exercise training. Vasoreactivity was assessed in aortas from four inbred mouse strains (129S1, B6, NON, and SJL) after 4 weeks of moderate intensity continuous exercise training (MOD), high intensity interval training (HIT) or in sedentary controls (SED). Intrinsic variations in endothelium-dependent vasorelaxation (EDR) to acetylcholine (ACh) as well as vasocontractile responses were observed across SED groups. For responses to exercise training, there was a significant interaction between mouse strain and training intensity on EDR. Exercise training had no effect on EDR in aortas from 129S1 and B6 mice. In NON, EDR was improved in aortas from MOD and HIT compared with respective SED, accompanied by diminished responses to PE in those groups. Interestingly, EDR was impaired in aorta from SJL HIT compared with SED. The transcriptional activation of endothelial genes was also influenced by the interaction between mouse strain and training intensity. The number of genes altered by HIT was greater than MOD, and there was little overlap between genes altered by HIT and MOD. HIT was associated with gene pathways for inflammatory responses. NON MOD genes showed enrichment for vessel growth pathways. These findings indicate that exercise training has non-uniform effects on endothelial function and transcriptional activation of endothelial genes depending on the interaction between genetic background and training intensity.
Acetylcholine ; Animals ; Aorta ; Endothelium ; Gene Expression Profiling ; Genetic Background ; Mice ; Mice, Inbred Strains ; Transcriptional Activation ; Vasodilation

Family history of pancreatic cancer (PC) is a risk factor for PC development, and the risk level correlates with the number of affected families. A case of PC with ≥1 PC cases in the first-degree relative is broadly defined as familial pancreatic cancer (FPC) and accounts for 5% to 10% of total PC cases. FPC possesses several epidemiological, genetic and clinicopathological aspects that are distinct from those of conventional PCs. In Western countries, FPC registries have been established since the 1990s, and high-risk individuals are screened to detect early PCs. For the pharmacotherapy of FPC, especially in cases with germline pathogenic BRCA mutations, regimens using platinum and poly (ADP-ribose) polymerase inhibitor have recently been studied for their effectiveness. To date, the concept of FPC has prevailed in Western countries, and it has begun to infiltrate into Eastern countries. As the genetic background and environmental conditions vary in association with ethnicity and living area, we need to establish our own FPC registries and accumulate data in Asian countries.
Asian Continental Ancestry Group ; Drug Therapy ; Genetic Background ; Humans ; Pancreatic Neoplasms ; Platinum ; Registries ; Risk Factors

BACKGROUND/AIMS: Cancer is known to be a disease by many factors. However, specific results of reprogramming by pluripotency-related transcription factors remain to be scarcely reported. Here, we verified potential effects of pluripotent-related genes in hepatocellular carcinoma cancer cells. METHODS: To better understand reprogramming of cancer cells in different genetic backgrounds, we used four liver cancer cell lines representing different states of p53 (HepG2, Hep3B, Huh7 and PLC). Retroviral-mediated introduction of reprogramming related genes (KLF4, Oct4, Sox2, and Myc) was used to induce the expression of proteins related to a pluripotent status in liver cancer cells. RESULTS: Hep3B cells (null p53) exhibited a higher efficiency of reprogramming in comparison to the other liver cancer cell lines. The reprogrammed Hep3B cells acquired similar characteristics to pluripotent stem cells. However, loss of stemness in Hep3B-iPCs was detected during continual passage. CONCLUSIONS: We demonstrated that reprogramming was achieved in tumor cells through retroviral induction of genes associated with reprogramming. Interestingly, the reprogrammed pluripotent cancer cells (iPCs) were very different from original cancer cells in terms of colony shape and expressed markers. The induction of pluripotency of liver cancer cells correlated with the status of p53, suggesting that different expression level of p53 in cancer cells may affect their reprogramming.
Carcinoma, Hepatocellular ; Cell Line ; Genetic Background ; Induced Pluripotent Stem Cells* ; Liver Neoplasms* ; Pluripotent Stem Cells ; Transcription Factors ; Zidovudine

Although genetic background is known to contribute to colon carcinogenesis, the exact etiology of the disease remains elusive. The organ’s extensive interaction with microbes necessitated research on the role of microbiota on development of colon cancer. In this review, we summarized the defense mechanism of colon from foreign organism, and germ-free animal models that have been employed to elucidate microbial effect. We also comprehensively discussed the metabolic property of microbiota such as butyrate production, facilitation of heme toxicity, bile acid transformation, and nitrate reduction that has been shown to contribute to the development of the tumor. Finally, up-to-date subjects such as the effect of age and gender on microbiota are briefly discussed.
Bile ; Bile Acids and Salts ; Butyrates ; Butyric Acid ; Carcinogenesis ; Colon ; Colonic Neoplasms ; Genetic Background ; Heme ; Microbiota ; Models, Animal

The timing of pubertal onset is occurring at younger ages. This phenomenon is associated with many environmental factors such as sufficient nutrition, stress, many kinds of endocrine-disrupting chemicals, and genetic background. The loss of transcriptional repression induces kisspeptin release, resulting in pulsatile gonadotropin-releasing hormone secretion, which trigger pubertal onset. According to many reports, gonadotropin-releasing hormone agonists therapy for patients with rapidly progressive central precocious puberty is effective for improving final adult height. However, those results were obtained from the treatment of relatively young patients at earlier stages of puberty. A large cohort study investigating the environmental causes of precocious puberty as well as genetic factors is needed.
Adolescent ; Adult ; Cohort Studies ; Endocrine Disruptors ; Genetic Background ; Gonadotropin-Releasing Hormone ; Humans ; Puberty ; Puberty, Precocious ; Repression, Psychology

Inflammatory bowel diseases (IBD) are chronic conditions of the gastrointestinal tract-the main site of host-microbial interaction in the body. Development of IBD is not due to a single event but rather is a multifactorial process where a patient's genetic background, behavioral habits, and environmental exposures contribute to disease pathogenesis. IBD patients exhibit alterations to gut bacterial populations “dysbiosis” due to the inflammatory microenvironment, however whether this alteration of the gut microbiota precedes inflammation has not been confirmed. Emerging evidence has highlighted the important role of gut microbes in developing measured immune responses and modulating other host responses such as metabolism. Much of the work on the gut microbiota has been correlative and there is an increasing need to understand the intimate relationship between host and microbe. In this review, we highlight how commensal and pathogenic bacteria interact with host intestinal epithelial cells and explore how altered microenvironments impact these connections.
Bacteria ; Diplomacy ; Environmental Exposure ; Epithelial Cells ; Gastrointestinal Microbiome ; Genetic Background ; Humans ; Inflammation ; Inflammatory Bowel Diseases ; Intestinal Mucosa ; Metabolism ; Microbiota

Breast cancer is the school most common cancer in Korea women. The incidence of breast cancer is around 25 per 100,000 women, and more than 5,500 women are diagnosed as breast cancer annually. Epidemics show that the incidence and mortality of breast cancer are increasing due to rapid changes of women's life style and westernized food and so on. The risk factors for breast cancer include hormone-related factors (early menarche, late menopause, no or late birth, hormone replacement therapy) and genetic background. It is hard to change risk factors for breast cancer but early detection strategies are best for decreasing the mortality rate from breast cancer. Breast self examination, clinical breast examination, and mammography can be used for screening of breast cancer. Breast self examination is not sensitive enough to detect a small cancer but monthly exam makes women be awakening about breast cancer and feel changes of her breast. Meta-analysis shows annual mammography reduces breast cancer mortality around 35% in the ages over 50. Some randomized clinical trials also showed mortality reduction by mammography in the ages of 40s. Surprisingly, breast cancer is rapidly increasing in late thirties with a peak incidence in forties among Korean women. Whether the early peak makes mammography less accurate is controversial. However, data from qualified screening centers showed mammography has same sensitivity with that in westerns. Korean Breast Cancer Society and National Cancer Center organized the 1st Consensus meeting for the national guidelines for breast cancer screening on July 24, 2001. We recommend that women should have monthly self examination beginning at age 30, should receive biannual clinical breast exam from healthcare providers from age 35, and should receive clinical breast exam and mammography at 1~2-year intervals after age 40.
Breast Neoplasms* ; Breast Self-Examination ; Breast* ; Consensus ; Female ; Genetic Background ; Health Personnel ; Humans ; Incidence ; Korea ; Life Style ; Mammography ; Mass Screening* ; Menarche ; Menopause ; Mortality ; Parturition ; Risk Factors ; Self-Examination

Juvenile idiopathic arthritis (JIA) is a broad spectrum of disease defined by the presence of arthritis of unknown etiology, lasting more than six weeks duration, and occurring in children less than 16 years of age. JIA encompasses several disease categories, each with distinct clinical manifestations, laboratory findings, genetic backgrounds, and pathogenesis. JIA is classified into seven subtypes by the International League of Associations for Rheumatology: systemic, oligoarticular, polyarticular with and without rheumatoid factor, enthesitis-related arthritis, psoriatic arthritis, and undifferentiated arthritis. Diagnosis of the precise subtype is an important requirement for management and research. JIA is a common chronic rheumatic disease in children and is an important cause of acute and chronic disability. Arthritis or arthritis-like symptoms may be present in many other conditions. Therefore, it is important to consider differential diagnoses for JIA that include infections, other connective tissue diseases, and malignancies. Leukemia and septic arthritis are the most important diseases that can be mistaken for JIA. The aim of this review is to provide a summary of the subtypes and differential diagnoses of JIA.
Arthritis ; Arthritis, Infectious ; Arthritis, Juvenile* ; Arthritis, Psoriatic ; Child ; Connective Tissue Diseases ; Diagnosis ; Diagnosis, Differential* ; Genetic Background ; Humans ; Leukemia ; Rheumatic Diseases ; Rheumatoid Factor ; Rheumatology