Pathologic stage I non–small cell lung cancer with high levels of preoperative serum carcinoembryonic antigen: Clinicopathologic characteristics and prognosis

ObjectiveSurgery alone remains the standard therapy for patients with stage I non–small cell lung cancer. Although the preoperative serum level of carcinoembryonic antigen has been shown to be an independent prognostic factor, it has not yet been included in the staging system and does not alter the treatment strategy, especially in the selection of patients for adjuvant chemotherapy.MethodsFrom 1986 to 2003, preoperative and postoperative serum carcinoembryonic antigen levels were measured in 455 patients with completely resected pathologic stage I non–small cell lung cancer. We compared the clinicopathologic characteristics and outcomes among patients who had preoperative serum carcinoembryonic antigen levels within the normal range (N group, n = 323), patients who had high carcinoembryonic antigen levels before surgery but normal levels after surgery (HN group, n = 112), and patients who had high carcinoembryonic antigen levels before and after surgery (HH group, n = 20).ResultsThe significant characteristics of the HN group included the male sex, greater age, smoking, squamous cell histology, T2 status, lymphatic invasion, vascular invasion, and pleural invasion. Adenocarcinomas in patients of the HN group were more likely to be moderately to poorly differentiated. The 5-year survivals in the HN and HH groups were significantly lower (56.2% and 43.1%, respectively) than those in the N group (85.9%). Multivariate analysis revealed that greater age, non-adenocarcinoma histology, pleural invasion, and the carcinoembryonic antigen in the HN and HH groups were independent prognostic factors.ConclusionPatients with resected pathologic stage I non–small cell lung cancer and high preoperative serum carcinoembryonic antigen levels are a subgroup with a distinctly poor prognosis who display smoking-related clinicopathologic characteristics

How Are Statistical Parameters of the Velocity Vector of Body Sway Distributed in Normal Human Subjects?

The velocity vector when the human body sways has been qualitatively evaluated in clinical sessions. We quantitatively measured the velocity vector for 1 min in 89 normal subjects standing in a stable posture, and examined distributions of quantities of the velocity vector. The velocity vector was measured with a stabilometer, which visualizes the vector as magnitudes radially projected from the center to the periphery into 36 directions by 10°. The 3 quantities we calculated from the 36 scalars of the vector per subject were the coefficient of correlation (CV), skewness and kurtosis, which were analyzed statistically. Values of skewness were normally distributed. Values of CV and kurtosis were log-normally distributed when adjusted with log transformation. Then, we calculated standardized values of the normal distributions, from which the lower and upper cutoff values in the 95% and 99% areas were available. The 3 quantities showed statistically significant correlations with one another, although the levels were low. Thus, in the present study, use of the 3 parameters enabled us to quantitatively evaluate the whole image of velocity vector, which would simplify the procedures of examination and shorten the time required for differential diagnosis

The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome.

X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X's gene content, gene expression, and evolution

Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network

Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism

Epidemiology of uveitis (2013–2015) and changes in the patterns of uveitis (2004–2015) in the central Tokyo area: a retrospective study

Abstract Background The distribution of uveitis varies with genetic, ethnic, geographic, environmental, and lifestyle factors. Epidemiological information about the patterns of uveitis is useful when an ophthalmologist considers the diagnosis of uveitis. Therefore, it is important to identify the causes of uveitis over the years in different regions. The purposes of this study were to characterize the uveitis patients who first arrived at the University of Tokyo Hospital in 2013–2015, and to analyze the changes in the patterns of uveitis from 2004 to 2012 to 2013–2015. Methods We retrospectively identified 750 newly arrived patients with uveitis who visited the Uveitis Clinic in the University of Tokyo Hospital between January 2013 and December 2015, using clinical records. We extracted data on patient age, sex, diagnosis, anatomic location of inflammation, laboratory test results of blood and urine, and chest X-ray and fluorescein fundus angiography findings for each patient. In addition, we compared these data with those from 2004 to 2012 to analyze the changes in the patterns of uveitis. Results A definite diagnosis was established in 445 patients (59.3%). The most common diagnoses were herpetic iridocyclitis (7.5%), sarcoidosis (6.1%), Behçet’s disease (4.4%), Vogt–Koyanagi–Harada disease (4.1%), and intraocular lymphoma (4.1%). The most frequent unclassified type of uveitis was suspected sarcoidosis (22.3%). Analysis of the changes in the patterns of uveitis in the central Tokyo area from 2004 to 2012 to 2013–2015 revealed notable increasing trends of herpetic iridocyclitis and intraocular lymphoma, and increasing trends of bacterial endophthalmitis, fungal endophthalmitis, and juvenile chronic iridocyclitis. In contrast, the frequency of sarcoidosis, Behçet’s disease, and Vogt–Koyanagi–Harada disease decreased. Conclusions The patterns of uveitis changed considerably from 2004 to 2012 to 2013–2015. Continuous investigations about the epidemiology of uveitis are needed to diagnose uveitis more accurately

Lymphocyte proliferation induced by high-affinity peptides for HLA-B*51:01 in Behçet's uveitis.

Several proteins have been proposed as candidate auto-antigens in the pathogenesis of Behçet's disease (BD). In this study, we aimed to confirm the cellular responses to candidate peptide autoantigens with high affinity for the HLA-B*51:01 molecule using computerized binding predictions and molecular dynamics simulations. We identified two new candidate peptides (HSP65PD, derived from heat shock protein-65, and B51PD, derived from HLA-B*51:01) with high-affinity to the HLA-B*51:01 binding pocket using the Immune Epitope Database for Major Histocompatibility Complex-I Binding Prediction and molecular dynamics simulations. The peptide-induced proliferation of lymphocytes from patients with BD, sarcoidosis, Vogt-Koyanagi-Harada disease (VKH) with panuveitis, systemic scleroderma (SSc) without uveitis, and healthy controls (HC) was investigated using the bromodeoxyuridine assay. The proliferative response of leukocytes to HSP65PD was significantly higher in BD (SI 1.92 ± 0.65) than that in sarcoidosis (SI 1.38 ± 0.46), VKH (SI 1.40 ± 0.33), SSc (SI 1.32 ± 0.31), and HC (SI 1.27 ± 0.28) (P = 0.0004, P = 0.0007, P < 0.0001, P < 0.0001, respectively, Mann-Whitney's U-test). The proliferative response of leukocytes to B51PD was also higher in BD than that in sarcoidosis, VKH, SSc without uveitis, and HC, whereas no significant differences were observed among the five groups in response to a control peptide derived from topoisomerase 1. A significantly higher response to HPS65PD and B51PD was observed in the HLA-B*51:01-positive patients with BD than in the HLA-B*51:01-negative patients. In conclusion, two peptides that had high affinity to HLA-B*51:01 in computerized binding prediction showed significantly higher response in HLA-B*51:01-positive patients with BD, indicating the usefulness of computerized simulations for identifying autoreactive peptides to HLAs