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Cigarette smoking, alcohol consumption, and Lugol-voiding lesions (LVLs) are the major causative risk factors of esophageal squamous cell carcinoma (ESCC); however, reports on ESCC cases unrelated to these risk factors are very limited. Here, we investigated the clinicopathological features and etiology of such cases. We retrospectively analyzed 704 consecutive superficial ESCC tumors of 512 patients who were treated with endoscopic submucosal dissection. The enrolled patients were divided into two groups—the very low-risk (VLR)-group and risk (R)-group—based on the presence of the abovementioned risks. Clinical, endoscopic, and pathological characteristics and genetic findings were assessed in both groups. The VLR-group consisted of 21 (4.1%) patients, who were characteristically female. Patients in the VLR-group presented gastroesophageal reflux disease (GERD), hiatal hernia, and non-open-type atrophic gastritis, and were negative for Helicobacter pylori. We found unique endoscopic features—frequently observed in the posterior wall of the middle thoracic esophagus—with a linear shape that closely resembled the erosion-like form of GERD. Additionally, histopathological examination showed that these tumors presented atypical nuclei limited to the basal and parabasal layer, sequential to the surrounding changes that presented pathological chronic inflammation of esophagitis. Evaluation of somatic mutations in cancer-related genes using next-generation sequencing revealed that the positive carcinogenic potential (TP53 mutation) of the tumors was relatively frequent in the VLR-group. Our study suggests that ESCC without major causative factors is related to GERD, with no remarkable oncogenic difference.

Schizophrenia (SCZ) is known to be a heritable disorder; however, its multifactorial nature has significantly hampered attempts to establish its pathogenesis. Therefore, in this study, we performed genome-wide copy-number variation (CNV) analysis of 2940 patients with SCZ and 2402 control subjects and identified a statistically significant association between SCZ and exonic CNVs in the ARHGAP10 gene. ARHGAP10 encodes a member of the RhoGAP superfamily of proteins that is involved in small GTPase signaling. This signaling pathway is one of the SCZ-associated pathways and may contribute to neural development and function. However, the ARHGAP10 gene is often confused with ARHGAP21, thus, the significance of ARHGAP10 in the molecular pathology of SCZ, including the expression profile of the ARHGAP10 protein, remains poorly understood. To address this issue, we focused on one patient identified to have both an exonic deletion and a missense variant (p.S490P) in ARHGAP10. The missense variant was found to be located in the RhoGAP domain and was determined to be relevant to the association between ARHGAP10 and the active form of RhoA. We evaluated ARHGAP10 protein expression in the brains of reporter mice and generated a mouse model to mimic the patient case. The model exhibited abnormal emotional behaviors, along with reduced spine density in the medial prefrontal cortex (mPFC). In addition, primary cultured neurons prepared from the mouse model brain exhibited immature neurites in vitro. Furthermore, we established induced pluripotent stem cells (iPSCs) from this patient, and differentiated them into tyrosine hydroxylase (TH)-positive neurons in order to analyze their morphological phenotypes. TH-positive neurons differentiated from the patient-derived iPSCs exhibited severe defects in both neurite length and branch number; these defects were restored by the addition of the Rho-kinase inhibitor, Y-27632. Collectively, our findings suggest that rare ARHGAP10 variants may be genetically and biologically associated with SCZ and indicate that Rho signaling represents a promising drug discovery target for SCZ treatment.

Although magnifying endoscopy with narrow-band imaging (ME-NBI) can help identify the horizontal margin (HM) of early gastric cancer (EGC), little is known about the factors that can clarify the HM by using ME-NBI. We aimed to characterize the pathological features of lesions in which the HM was identified using ME-NBI. The HMs of 639 differentiated-type EGCs treated with endoscopic submucosal dissection or surgery were analyzed using conventional endoscopy and ME-NBI. The number and width of the intervening parts (IP) and the number, width, and depth of the subepithelial capillaries (SEC) in cancerous and noncancerous areas were measured. In 13 lesions (2.0%), more than 90% of the HM was not recognized with conventional endoscopy, but 11 of these lesions were detectable with ME-NBI (NBI group). The HMs of the other 626 lesions were mostly recognized using conventional endoscopy (WLI/CE group). In the NBI group, the IP width, standard deviation (SD), and number of IPs did not significantly differ between the cancerous and noncancerous areas. However, the SEC number was significantly larger and the depth was shallower in cancerous areas. In the WLI/CE group, the IP width and SD were significantly larger, but the IP number was significantly smaller in cancerous areas. The SEC depth was significantly shallower in cancerous areas. Differences of IP width, SD, and IP number may be factors for identifying HMs with conventional endoscopy. Because NBI can better visualize vessel structures, the increased SEC number and shallow SECs may clarify the HM.

In this paper we present results that demonstrate the utility of a continuously frequency-tunable 0.4 THz-gyrotron in a dynamic nuclear polarization (DNP)-enhanced solid-state NMR (SSNMR) spectroscopy at one of the highest magnetic fields, B0 = 14.1 T (600 MHz for 1H Larmor frequency). Our gyrotron called FU CW VI generates sub-mm wave at a frequency near 0.4 THz with an output power of 4–25 W and a tunability over a range of more than 1 GHz by sweeping the magnetic field at the gyrotron cavity. We observed overall down shifting of the central frequency by up to ~1 GHz at high radiation duty factors and beam current, presumably due to the cavity thermal expansion by a heating, but the tunable range was not significantly changed. The frequency tunability facilitated the optimization of the DNP resonance condition without time-consuming field-sweep of the high-resolution NMR magnet, and enabled us to observe substantial enhancement of the SSNMR signal (eDNP = 12 at 90 K).

A high frequency gyrotron with a 15 T superconducting magnet named Gyrotron FU CW VI has achieved continuous frequency tuning through the relatively wide range of 1.5 GHz near 400 GHz. The operation is at the fundamental cyclotron resonance of the TE06 cavity mode with many higher order axial modes. The output power measured at the end of the circular waveguide system ranges from 10 to 50 watts at the low acceleration voltage of 12 kV for beam electrons. The beam current is also low. It is around 250 mA. This gyrotron is designed as a demountable radiation source for the 600 MHz DNP-NMR spectroscopy. The design and operation results of the gyrotron FU CW VI are presented.

Kidney stone formation is a complex process, and numerous genes participate in this cascade. The binding and internalization of calcium oxalate monohydrate (COM) crystals, the most common crystal in renal stones by renal epithelial cells may be a critical step leading to kidney stone formation. Exposure to COM crystals alters the expression of various genes, but previous studies on gene expression have generally been limited. To obtain more detailed insight into gene expression, we examined gene expression profiles in renal epithelial cells exposed to COM crystals using cDNA macroarray. NRK-52E cells were exposed to COM crystals for 60 and 120 min. Poly (A)(+) RNA was isolated and converted into (32)P-labeled first-strand cDNA, then the cDNA probe was hybridized to the membrane. Hybridization images were scanned and the signal intensities were quantified. Expression of mRNA of 1,176 genes was analyzed with global sum normalization methods. Exposure to COM crystals altered the expression of some of the genes reported previously. Furthermore, novel genes were also identified. Over 20 genes were found to be regulated at least twofold. We performed a large-scale analysis of gene expression in renal epithelial cells exposed to COM crystals, and identified the genes differentially regulated. cDNA macroarray is a useful tool for evaluating gene expression in urolithiasis research.

Experimental hyperoxaluria and calcium oxalate (CaOx) crystals are associated with renal epithelial injury and cell death. A recent study has demonstrated an oxalate-induced increase in cellular apoptosis in vitro, and speculates that this phenomenon may contribute to stone formation. We investigated the incidence of apoptotic cells and the expression of apoptosis related genes in the kidneys of stone-forming rats. Male Wistar rats were administrated ethylene glycol in drinking water and force fed with 1alpha-OH-D3. Apoptosis was detected as a ladder of fragmented DNA in agarose gels of electrophoresed genomic DNA. Apoptotic cells were localized by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. The expression of apoptosis-related genes was analyzed by both reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. While no labeling was detected in the controls or on the first day of administration by the TUNEL method, labeling began to be detected in the renal tubular epithelium of the outer medulla at day 3, and the number of labeled cells increased progressively during the observation period. A ladder of DNA fragments was demonstrated in the kidneys of rats after 2 weeks. Immunohistochemical studies revealed the expression of Fas ligand (Fas L), Bax and interleukin-1 beta converting enzyme (ICE) in the renal tubular epithelium of the descending limb of loop of Henle and the distal convoluted tubules. mRNA of the ICE, c-myc, p53 and Fas L genes was also upregulated in the kidneys of the stone-forming rats.

Recently carbon-11 acetate (AC) positron emission tomography (PET) has been reported to be of clinical value for the diagnosis of cancer that is negative on fluorine-18 fluorodeoxyglucoce (FDG) PET. We investigated the uptake of AC in lung cancer to determine whether this tracer is of potential value for tumour detection and characterisation, and to compare AC PET imaging with FDG PET and technetium-99m sestamibi (MIBI) single-photon emission tomography (SPET). Twenty-three patients with 25 lung cancers underwent AC and FDG PET. Twenty of 23 patients were also investigated with MIBI SPET. Dynamic images were acquired for 26 min after the injection of 555 MBq of AC. Standardised uptake values (SUVs) and/or tumour to non-tumour activity ratios (T/N) for each tumour were investigated at 10–20 min after AC administration, 40–60 min after administration of 185 MBq FDG and 15–45 min after administration of 555 MBq MIBI. Twenty lung cancers were resected surgically, and the degree of tracer uptake in the primary lesion was correlated with histopathological features (cell dedifferentiation and aggressiveness) and prognosis. Rapid uptake of AC followed by extremely slow clearance was observed. For the purpose of tumour identification, AC PET was inferior to FDG PET in 8 of 25 (32%) lung cancers, and the T/N of AC was lower than that of FDG. However, AC PET was superior to FDG PET in the identification of a slow-growing tumour (bronchiolo-alveolar carcinoma). There was a positive correlation between AC uptake (T/N) and MIBI uptake (T/N) (r=0.799, P

18F-fluorodeoxyglucose (FDG) PET imaging provides physiologic and metabolic information that characterizes lesions that are indeterminate by CT. FDG PET imaging is sensitive to the detection of lung cancer in patients who have indeterminate lesions on CT, whereas low grade malignancy such as bronchioloalveolar carcinoma and carcinoid may be negative on FDG PET. The specificity of PET imaging is less than its sensitivity because some inflammatory processes, such as active granulomatous infections, avidly accumulate FDG. This possibility should be kept in mind in the analysis of PET studies of glucose metabolism aimed at differentiating malignant from benign solitary pulmonary nodules. FDG uptake is considered to be a good marker of cell differentiation, proliferative potential, aggressiveness, and the grade of malignancy in patients with lung cancer. FDG PET accurately stages the distribution of lung cancer. Several studies have documented the increased accuracy of PET compared with CT in the evaluation of the hilar and mediastinal lymphnode status in patients with lung cancer. Whole-body PET studies detect metastatic disease that is unsuspected by conventional imaging. Management changes have been reported in up to 41% of patients on the basis of the results of whole-body studies. Whole-body FDG PET is also useful for the detection of recurrence. Several studies have indicated that the degree of FDG uptake in primary lung cancer can be used as an independent prognostic factor. Thus, whole-body FDG PET is clinically very useful in the management of lung cancer.