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Definitive chemoradiotherapy (CRT) is a less invasive therapy for esophageal squamous cell carcinoma (ESCC). Five-year survival rate of locally advanced ESCC patients by definitive CRT were 37%. We previously reported that tumor-specific cytotoxic T-lymphocyte (CTL) activation signatures were preferentially found in long-term survivors. However, it is unknown whether the CTL activation is actually driven by CRT. We compared gene expression profiles among pre- and post-treatment biopsy specimens of 30 ESCC patients and 121 pre-treatment ESCC biopsy specimens. In the complete response (CR) cases, 999 overexpressed genes including at least 234 tumor-specific CTL-activation associated genes such as IFNG, PRF1, and GZMB, were found in post-treatment biopsy specimens. Clustering analysis using expression profiles of these 234 genes allowed us to distinguish the immune-activated cases, designating them as I-type, from other cases. However, despite the better CR rate in the I-type, overall survival was not significantly better in both these 30 cases and another 121 cases. Further comparative study identified a series of epithelial to mesenchymal transition-related genes overexpressed in the early relapse cases. Importantly, the clinical outcome of CDH2-negative cases in the I-type was significantly better than that of the CDH2-positive cases in the I-type. Furthermore, NK cells, which were activated by neutrophils-producing S100A8/S100A9, and CTLs were suggested to cooperatively enhance the effect of CRT in the CDH2-negative I-type. These results suggested that CTL gene activation may provide a prognostic advantage in ESCCs with epithelial characteristics.

A 57-year-old man with rheumatoid arthritis developed severe anemia during treatment with adalimumab plus methotrexate. Cold agglutinin disease was diagnosed because haptoglobin was undetectable, cold agglutinin was positive (1 : 2048), and the direct Coombs test was positive (only to complement). Although the cold agglutinin titer was normalized (1 : 64) after treatment with prednisolone (0.7 mg/kg/day for two weeks), the patient’s hemoglobin did not increase above 8 g/dL. When cold agglutinins were reexamined using red blood cells suspended in bovine serum albumin, the titer was still positive at 1 : 1024. Furthermore, the cold agglutinin had a wide thermal amplitude, since the titer was 1 : 16 at 30°C and 1 : 1 at 37°C. This suggested that the cold agglutinin would show pathogenicity even at body temperature. After the dose of prednisolone was increased to 1 mg/kg/day, the patient’s hemoglobin rapidly returned to the normal range. The thermal amplitude test using red blood cells suspended in bovine serum albumin is more sensitive than the standard test for detecting pathogenic cold agglutinins.

Diffuse-type solid tumors are often composed of a high proportion of rarely proliferating (i.e., dormant) cancer cells, strongly indicating the involvement of cancer stem cells (CSCs) Although diffuse-type gastric cancer (GC) patients have a poor prognosis due to high-frequent development of peritoneal dissemination (PD), it is limited knowledge that the PD-associated CSCs and efficacy of CSC-targeting therapy in diffuse-type GC. In this study, we established highly metastatic GC cell lines by in vivo selection designed for the enrichment of PD-associated GC cells. By microarray analysis, we found C-X-C chemokine receptor type 4 (CXCR4) can be a novel marker for highly metastatic CSCs, since CXCR4-positive cells can grow anchorage-independently, initiate tumors in mice, be resistant to cytotoxic drug, and produce differentiated daughter cells. In clinical samples, these CXCR4-positive cells were found from not only late metastasis stage (accumulated ascites) but also earlier stage (peritoneal washings). Moreover, treatment with transforming growth factor-β enhanced the anti-cancer effect of docetaxel via induction of cell differentiation/asymmetric cell division of the CXCR4-positive gastric CSCs even in a dormant state. Therefore, differentiation inducers hold promise for obtaining the maximum therapeutic outcome from currently available anti-cancer drugs through re-cycling of CSCs.

We have carried out cDNA array analysis in order to characterize the gene expression profiles of reactive astrocytes from dopamine-depleted striatum. Astrocytes were cultured from the striatum of normal adult rats (adult astrocytes) or adult rats in which the substantia nigra had been lesioned 1 week earlier with 6-hydroxydopamine (reactive astrocytes), an animal model for Parkinson's disease. Three antibodies, 19D1, O1E4, and 13A11, known to label only reactive astrocytes in vivo, stained cultured reactive astrocytes but not adult astrocytes. Analysis with cDNA arrays showed that 38 genes were up-regulated and 75 genes down-regulated in reactive astrocytes compared to normal adult astrocytes. The expression of growth factor and transcription factor genes predominated among the up-regulated genes while those for signal transduction molecules, metabolic enzymes, and receptors for growth factors, hormones, and neurotransmitters predominated among the down-regulated genes. These results will allow the field to address the molecular profiles and functions of astrocytes activated in response to dopamine depletion and may be useful for developing new therapies for Parkinson's disease.

To develop a new fertilizing system with a reduced amount of phosphatic fertilizer in sweet corn production, we applied potassium phosphate to the plug seedlings before transplanting to the field, and examined its effects on growth, yield, photosynthetic activity and absorption of minerals. The amount of phosphatic and potash fertilizers necessary to grow sweet corn could be reduced by the pre-transplanting KP application (PTKPA) to the plug seedlings. We considered the mechanisms involved in the reduction of P and K application rate by PTKPA as follows; 1) PTKPA increased the P content of plant, which accelerated the root establishment. 2) The advanced root establishment not only reduced the duration of water stress, but also increased absorption of the essential nutrients such as N and Mg. 3) Higher content of N and Mg led to higher chlorophyll content and possibly protein content, which activated photosynthesis during the early growth stage. 4) Improved photosynthetic activities increased NAR during the early growth stage. 5) This increase in NAR accelerated leaf expansion, increasing LAI. 6) Larger LAI during the early growth stage led to larger LAI throughout the growing stage, resulting in a higher CGR and ear yield.

We examined whether very low-density lipoprotein receptors (VLDLR) on the oocyte membrane contributed to changes in VLDL uptake into the yolk by the ovarian follicle during the ovulation cycle of the laying hen. White and yellow (F5-F1) follicles were collected from laying hens at 14-16 h (when the yellow follicles actively uptake yolk) and 0-2 h (when the yolk uptake is less active) before ovulation and subjected to binding experiments with 125I-VLDL and assays for aromatase activity. The preparations from white follicles did not bind to 125I-VLDL, while yellow follicle preparations bound to the radioligand. The 125I-VLDL bindings of F3-F1 yellow follicles were higher at 14-16 h than 0-2 h before ovulation. Values of the dissociation constant (Kd) and the maximum binding capacity (Bmax) of VLDLR calculated from the 125I-VLDL bindings to the oocyte membranes showed profiles related to the changes in 125I-VLDL bindings; in F3 and F2 follicles Bmax values were higher at 14-16 h than 0-2 h before ovulation and Kd values were higher at 0-2 h than 14-16 h before ovulation. High aromatase activities of the F3-F1 yellow follicles of 14-16 h before ovulation decreased 0-2 h before ovulation, which was a change consistent with the change in 125I-VLDL bindings of the same follicles. These results suggest that the yolk VLDL uptake during the ovulation cycle is regulated by changes in VLDL binding underlined by changes in Bmax and Kd of VLDLR. Estrogen produced by the aromatase of the theca layer of the yellow follicles might facilitate VLDL binding by affecting VLDLR on the oocyte membrane of the same follicles in a paracrine manner.

An aromatase inhibitor, Fadrozole (CGS16949A), was administered into chick embryo on the 5th day of incubation to clarify the roles of endogenous estrogen in the regulation of circulating lipoprotein levels during the development. The plasma of 10-, 16- and 20-day embryos and neonatal chicks were separated by polyacrylamide gel electrophoresis. Amounts of plasma lipoproteins, high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) were then measured using a densitometer and expressed as a percentage in total lipoproteins. Changes in HDL percentages of the groups treated with the aromatase inhibitor (AI group) and propylene glycol (Vehicle group) showed similar patterns during the experimental period. This was also the case in the changes in LDL percentages. The 16-day embryos of the AI group, in which endogenous estrogen synthesis was inhibited, showed a distinctly high VLDL percentage, whereas plasma VLDL in the Vehicle group showed only a little developmental changes. The plasma concentration of triglyceride (a major component of VLDL), phospholipid and total cholesterol in the AI group showed a profile similar to that of VLDL, with the maximum level in the 16-day embryo. These results suggest that endogenous estrogen of the embryo plays an important role in the utilization and resulting clearance of plasma lipids from the circulation, in addition to its well-documented role in sex differentiation.

The noise and vibration caused by pressure pulsation are one of detrimental problems in hydraulic systems. A Helmholtz type hydraulic silencer, which is based on the resonant phenomena of a mass-spring-damper system for its attenuate principle, is known as one of the most practical silencers in the hydraulic systems. In the previous researches, the transmission loss characteristics of the Helmholtz type hydraulic silencer were modeled by a distributed parameter model. However, in the design case that the ratio of the length and diameter L/D of the cylindrical volume is smaller, the resonance frequency of the existing model begins to deviate from the experimental results and the disparity increases with decreasing the ratio of L/D. The purpose of this research is to clarify the influence of a neck and volume geometry on the attenuation characteristics. In particular, a mathematical model that considers the flow for the radial direction of the cylindrical volume is newly proposed for the design case that L/D is smaller. The transmission loss characteristics of the Helmholtz type hydraulic silencer are investigated theoretically for both the proposed model and existing models. In addition, the experimental examination of the influence of volume geometry on the attenuation characteristics is carried out in order to verify the theoretical investigations.

This paper presents a real-time simulation for coupled system with rigid body system and hydraulic system. The equations of motion for the rigid body are derived by transforming the rigid body motion to the linear element motion. The system equations can be presented as the ordinary differential equations of motion for the coupled system of the rigid body system and the hydraulic system without introducing the constraint conditions, describing the motions of the rigid body system using the linear element motion. Then, this modeling is useful for the real time simulation for the coupled system, as numerical stability is improved by carrying out coupled system simulation in one software package. Firstly, rigid body system driven by the linear element is formulated, coupled analysis theory with the hydraulic system is derived, and electric motor drive system is formulated. Finally, the actual digging simulations of a hydraulic excavator are implemented using the present technique. It is clarified that the real time simulation is successfully conducted.

The ultraviolet photoluminescence of ZnO/ZnGa2O4 composite layer grown by the thermal oxidation of ZnS with gallium was investigated by the time-resolved photoluminescence as a function of measuring temperature and excitation power. With increase of excitation power, the D0X emission is easily saturated than the DAP emission from ZnO/ZnGa2O4 composite layer, and which is dramatically enhanced as compared with that from pure ZnO layer grown without gallium. The radiative recombination process with ultra-long lifetime controlled the carrier recombination of ZnO/ZnGa2O4 composite layer.

A mutation that confers white plumage with black eyes was identified in the Minohiki breed of Japanese native chicken (Gallus gallus domesticus). The white plumage, with a few partially pigmented feathers, was not associated with the tyrosinase gene, and displayed an autosomal recessive mode of inheritance against the pigmented phenotype. All F1 offspring derived from crosses with mottled chickens (mo/mo), which show characteristic pigmented feathers with white tips, had plumage with a mottled-like pattern. This result indicates that the white plumage mutation is a novel allele at the mo locus; we propose the gene symbol mo(w) for this mutant allele. Furthermore, the F1 hybrid between the mo(w) /mo(w) chicken and the panda (s/s) mutant of Japanese quail (Coturnix japonica), whose causative gene is the endothelin receptor B2 (EDNRB2) gene, showed a mo(w)/mo(w) chicken-like plumage, suggesting the possibility that the mutations in parental species are alleles of the same gene, EDNRB2. Nucleotide sequencing of the entire coding region of EDNRB2 revealed a non-synonymous G1008T substitution, which causes Cys244Phe amino acid substitution in exon 5 (which is part of the extracellular loop between the putative fourth and fifth transmembrane domains of EDNRB2) in the mutant chicken. This Cys244Phe mutation was also present in individuals of four Japanese breeds with white plumage. We also identified a non-synonymous substitution leading to Arg332His substitution that was responsible for the mottled (mo/mo) plumage phenotype. These results suggest that the EDN3 (endothelin 3)-EDNRB2 signaling is essential for normal pigmentation in birds, and that the mutations of EDNRB2 may cause defective binding of the protein with endothelins, which interferes with melanocyte differentiation, proliferation, and migration.

Vast quantities of data on human behavior are being created by our everyday internet usage. Building upon a recent study by Preis, Moat, Stanley, and Bishop (2012), we used search engine query data to construct measures of the time-perspective of nations, and tested these measures against per-capita gross domestic product (GDP). The results indicate that nations with higher per-capita GDP are more focused on the future and less on the past, and that when these nations do focus on the past, it is more likely to be the distant past. These results demonstrate the viability of using nation-level data to build psychological constructs.

A obtenção de cultivares de citros com pequeno número de sementes é importante quando o objetivo é a produção de frutas para o consumo in natura. O objetivo deste trabalho foi o de avaliar, por três anos (1997, 1998 e 1999), o número médio de sementes e 15 outras características agronômicas, de 127 mutantes putativos de laranja-'Pêra', selecionados após irradiação de borbulhas com raios-gama e 8 plantas selecionadas do controle não irradiado. Os mutantes foram divididos em 16 grupos baseados nos tipos de mutações observados e em cada grupo, como controle comum, foram incluídas plantas de laranja-'Pêra' comercial. Observou-se que 46 mutantes putativos e uma planta do controle não irradiado (PSC) apresentaram redução significativa no número de sementes por fruto, nos três anos consecutivos, sendo que 15 mutantes apresentaram frutos com média entre uma e duas sementes e 9 mutantes, frutos com média inferior a uma semente. Dentre estes 9 mutantes, os de número 27, 28 e 58, que apresentaram também alterações significativas no diâmetro de copa ou na altura de planta, além do 59 e 101, que não apresentaram alterações nas outras 15 características avaliadas, possuem um maior potencial para serem lançados como novos mutantes de laranja-'Pêra' com pequeno número de sementes.

We report a rare appearance of cystitis glandularis forming a tumorous lesion with blueberry spots in the urinary bladder. A 49-year-old woman was admitted to our hospital with pollakisuria and recurrent gross hematuria. Urine examination showed no pyuria. Computed tomography (CT) scan showed an extravesical invasive mass and cystoscopy revealed a non-papillary tumor with blueberry spots in the bladder. Transurethral resection (TUR) was performed. Histopathological examination revealed cystitis glandularis with cystitis cystica in the part. Postoperative CT scan and cystoscopy showed reduction of the mass in the bladder without any treatments. She is currently well with no evidence of tumor growth three months after TUR.

Phosphatidylinositol-3,4,5-trisphosphate (PIP3) is highly regulated in a spatiotemporal manner and plays multiple roles in individual cells. However, the local dynamics and primary functions of PIP3 in developing neurons remain unclear because of a lack of techniques for manipulating PIP3 spatiotemporally. We addressed this issue by combining optogenetic control and observation of endogenous PIP3 signaling. Endogenous PIP3 was abundant in actin-rich structures such as growth cones and "waves", and PIP3-rich plasma membranes moved actively within growth cones. To study the role of PIP3 in developing neurons, we developed a PI3K photoswitch that can induce production of PIP3 at specific locations upon blue light exposure. We succeeded in producing PIP3 locally in mouse hippocampal neurons. Local PIP3 elevation at neurite tips did not induce neurite elongation, but it was sufficient to induce the formation of filopodia and lamellipodia. Interestingly, ectopic PIP3 elevation alone activated membranes to form actin-based structures whose behavior was similar to that of growth-cone-like "waves". We also found that endocytosis regulates effective PIP3 concentration at plasma membranes. These results revealed the local dynamics and primary functions of PIP3, providing fundamental information about PIP3 signaling in neurons.

The effects of orally administered dipeptidyl peptidase IV (DPP-IV) inhibitor on the glucose-lowering effect of glibenclamide are still unknown. We evaluated the effects of combination treatment with a long-lasting DPP-IV inhibitor, K579 ((S)-1-[4-methyl-1-(2-pyrimidinyl)-4-piperidylamino]acetyl-2-pyrrolidinecarbonitrile), and glibenclamide on the glycemic responses to glucose loading in rats. Treatment with K579 inhibited the plasma DPP-IV activity even 8 h after the administration. K579 significantly suppressed the blood glucose elevation in glibenclamide-pretreated rats without excessive hypoglycemia. These profiles of K579 indicate that it could be useful agent to correct the postprandial glucose excursion in type 2 diabetes patients by combination treatment with glibenclamide. Keywords:: dipeptidyl peptidase IV, glibenclamide, glucose tolerance

BACKGROUND: Surgical samples have long been used as important subjects for cancer research. In accordance with an increase of neoadjuvant therapy, biopsy samples have recently become imperative for cancer transcriptome. On the other hand, both biopsy and surgical samples are available for expression profiling for predicting clinical outcome by adjuvant therapy; however, it is still unclear whether surgical sample expression profiles are useful for prediction via biopsy samples, because little has been done about comparative gene expression profiling between the two kinds of samples. METHODOLOGY AND FINDINGS: A total of 166 samples (77 biopsy and 89 surgical) of normal and malignant lesions of the esophagus were analyzed by microarrays. Gene expression profiles were compared between biopsy and surgical samples. Artificially induced epithelial-mesenchymal transition (aiEMT) was found in the surgical samples, and also occurred in mouse esophageal epithelial cell layers under an ischemic condition. Identification of clinically significant subgroups was thought to be disrupted by the disorder of the expression profile through this aiEMT. CONCLUSION AND SIGNIFICANCE: This study will evoke the fundamental misinterpretation including underestimation of the prognostic evaluation power of markers by overestimation of EMT IN past cancer research, and will furnish some advice for the near future as follows: 1) Understanding how long the tissues were under an ischemic condition. 2) Prevalence of biopsy samples for in vivo expression profiling with low biases on basic and clinical research. 3) Checking cancer cell contents and normal- or necrotic-tissue contamination in biopsy samples for prevalence.

A new circadian variant was isolated by screening the intercross offspring of wild-caught mice (Mus musculus castaneus). This variant was characterized by an initial maintenance of damped oscillations and subsequent loss of rhythmicity after being transferred from light-dark (LD) cycles to constant darkness (DD). To map the genes responsible for the persistence of rhythmicity (circadian ratio) and the length of free-running period (tau), quantitative trait locus (QTL) analysis was performed using F(2) mice obtained from an F(1) cross between the circadian variant and C57BL/6J mice. As a result, a significant QTL with a main effect for circadian ratio (Arrhythmicity; Arrh-1) was mapped on Chromosome (Chr) 8. For tau, four significant QTLs, Short free-running period (Sfp-1) (Chr 1), Sfp-2 (Chr 6), Sfp-3 (Chr 8), Sfp-4 (Chr 11) were determined. An epistatic interaction was detected between Chr 3 (Arrh-2) and Chr 5 (Arrh-3). An in situ hybridization study of clock genes and mouse Period1::luciferase (mPer1::luc) real-time monitoring analysis in the suprachiasmatic nucleus (SCN) suggested that arrhythmicity in this variant might not be attributed to core circadian mechanisms in the SCN neurons. Our strategy using wild-derived variant mice may provide a novel opportunity to evaluate circadian and its related disorders in human that arise from the interaction between multiple variant genes.

Abstract Background The weight-loss effect of team medical care in which counseling is provided by clinical psychologists was investigated in an university hospital obesity (OB) clinic. Nutritional and exercise therapy were also studied. In our previous study, we conducted a randomized, controlled trial with obese patients and confirmed that subjects who received counseling lost significantly more weight than those in a non-counseling group. The purpose of this study was to identify the psychological characteristics assessed by ego states that promote behavior modification by obese patients. Methods 147 obese patients (116 females, 31 males; mean age: 45.9 ± 15.4 years) participated in a 6-month weight-loss program in our OB clinic. Their psychosocial characteristics were assessed using the Tokyo University Egogram (TEG) before and after intervention. The Wilcoxon signed rank test was used to compare weight and psychological factors before and after intervention. Multiple regression analysis was used to identify factors affecting weight loss. Results Overall, 101 subjects (68.7%) completed the program, and their data was analyzed. The subjects mean weight loss was 6.2 ± 7.3 kg (Z = 7.72, p < 0.01), and their mean BMI decreased by 2.4 ± 2.7 kg/m2 (Z = 7.65, p < 0.01). Significant differences were observed for the Adult (A) ego state (0.68 ± 3.56, Z = 1.95, p < 0.05) and the Free Child (FC) ego state (0.59 ± 2.74, Z = 2.46, p < 0.01). The pre-FC ego state had a significant effect on weight loss (β = 0.33, p < 0.01), and a tendency for changes in the A ego state scores to affect weight loss (β = - 0.20, p = 0.06) was observed. Conclusion This study of a 6-month weight-loss program that included counseling by clinical psychologists confirmed that the A ego state of obese patients, which is related to their self-monitoring skill, and the FC ego state of them, which is related to their autonomy, were increased. Furthermore, the negative aspects of the FC ego state related to optimistic and instinctive characteristics inhibited the behavior modification, while the A ego state represented objective self-monitoring skills that may have contributed to weight loss.

Objective: Although reports of endovascular treatment for intracranial arterial stenosis have been increasing recently, their efficacy remains to be elucidated. This study aimed to investigate the changes in cerebral hemodynamics of severe middle cerebral artery (MCA) stenosis patients by performing CT perfusion (CTP) after endovascular treatment., Methods: Subjects were those who underwent balloon angioplasty and stenting for symptomatic MCA M1 stenosis refractory to medical therapy at our hospital between 2008 and 2022. We included 36 patients (mean age 63.69 ± 15.24 years, 20 males) who underwent CTP before and within three weeks after treatment. The CTP parameters such as relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and relative mean transit time (rMTT) were calculated as ipsilateral values divided by contralateral value., Results: Endovascular treatment consisted of 26 balloon angioplasty and 10 stenting procedures performed at an average of 1 month from onset. CTP was performed at an average of 5.5 days postoperatively. The mean overall stenosis rate decreased from 79.0% to 30.3%. In the balloon angioplasty group, it decreased from 77.6% to 35.3%, and in the stent group, it decreased from 82.7% to 17.5%. After treatment, rCBF and rMTT measured by CTP improved significantly (both p  < 0.001), whereas there was no significant change in rCBV. The improvement rates of rCBF and rMTT were mild higher in the stent group, but not significantly so., Conclusion: Balloon angioplasty and stenting for symptomatic MCA improved cerebral hemodynamics, resulting in significantly increased rCBF and decreased rMTT., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.