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LGR5, known as a target of Wnt signaling, has been reported as an intestinal stem cell marker. Recent reports showed that LGR5 was associated with carcinogenesis and tumor invasion in colorectal cancer. CD44 is a ubiquitously expressed cell adhesion molecule and also a potential cell surface marker on colon cancer stem cells. Both LGR5 and CD44 have been also reported to be Wnt signal targets. The aim of this study was to investigate the association of these markers with clinical outcome in rectal cancer after preoperative chemoradiotherapy (CRT). A total of 52 rectal cancer specimens were obtained from patients who underwent preoperative CRT. We performed transcriptional and immunohistochemical analyses, and retrospectively studied the association of LGR5 and CD44 expression levels with clinical outcomes. For CD44, its expression in cancer stroma was also evaluated. The levels of cancer LGR5 and CD44 gene expression were significantly and positively correlated. LGR5 gene expression level in cancer and positivity of CD44 gene expression in cancer stroma were significantly correlated with disease recurrence. Elevated cancer LGR5 gene expression and positive CD44 gene expression in cancer stroma were significantly associated with poor recurrence-free and overall survival. Multivariate analysis indicated that positivity of stromal CD44 gene expression was an independent prognostic factor for the recurrence and overall survival of patients with rectal cancer after preoperative CRT. In conclusion, LGR5 and CD44 expression may be coordinately associated with tumor relapse in locally advanced rectal cancer after preoperative CRT.

In Japan, rice seed are immersed in pesticide solutions to prevent seedborne diseases that attack greenhouse seedlings. However, disposal of large quantities of waste pesticide solutions after treatment is costly. As an alternative treatment, bacteriophages (phages) that are highly specific to the target bacteria are considered as potential biocontrol agents. Here, we isolated three phage strains that lyse Burkholderia glumae and B. plantarii, the causative pathogens of seedling rot and seedling blight, respectively. Two phages could lyse both bacteria and clearly suppress these diseases. One of these phages (BGPP-Ar) suppressed these diseases more effectively than existing pesticides: the ratio of seedlings exhibiting disease to the total number of seedlings examined after treatment with BGPP-Ar 1.0 × 108 plaque-forming units (PFU)/ml was 0.0 for seedling rot and 2.0 for seedling blight; after treatment with ipconazole/copper (II) hydroxide, the ratios were 14.3 and 15.0, respectively. BGPP-Ar was highly effective in suppressing seedling rot of rice, even at the low concentration of 1.0 × 105 PFU/ml. The best phage treatment effect for sterilizing seed is achieved indoors to avoid phage inactivation by UV irradiation. Treatment effect was demonstrated on seed infected with pathogens. Therefore, we consider that phage treatment was effective in this study.

To determine prognostic factors in patients with colorectal liver metastases who were not surgical candidates and received liver radiofrequency (RF) ablation. RF ablation was done for 141 colorectal liver metastases in 84 patients. There were 63 (75.0 %, 63/84) males and 21 (25.0 %, 21/84) females, with a mean age of 64.6 ± 10.3. The mean maximum tumor diameter was 2.3 ± 1.4 cm (range 0.5–9.0 cm). Extrahepatic metastases were associated at the time of liver RF ablation in 23 patients (27.4 %, 23/84), and 12 (14.3 %, 12/84) had lung metastases considered controllable by planned lung RF ablation. Prognostic factors were evaluated by univariate and multivariate analyses. There was no procedure-related mortality. The 1-, 3-, and 5-year overall survival rates were 90.6 % (95 %CI, 83.9–97.2 %), 44.9 % (95 %CI, 31.8–57.9 %), and 20.8 % (95 %CI, 7.3–34.3 %), respectively, with a median survival of 34.9 months. The univariate analysis showed that tumor diameter larger than 3 cm, tumor multiplicity, uncontrollable extrahepatic disease, and previous chemotherapy history were significantly worse prognostic factors. The former three factors remained significant for worse prognosis in the multivariate Cox model. Extrahepatic disease was not a prognostic factor when it could be controlled. Tumor size and number, and uncontrollable extrahepatic metastases were significant prognostic factors.

Background E-cadherin expression has been associated with an outcome in patients with colorectal cancer, and serum levels of soluble E-cadherin (sE-cadherin) are significantly elevated in patients with malignant disease. However, the prognostic value of serum sE-cadherin level has not been demonstrated in colorectal cancer. Methods Serum samples were collected from 186 patients with colorectal cancer and 21 normal volunteers. Serum sE-cadherin levels were measured using an enzyme-linked immunosorbent assay kit. We investigated the relationship between serum sE-cadherin level and clinicopathologic findings. Results Mean serum sE-cadherin levels were significantly higher in CRC patients than in controls. Mean sE-cadherin levels were significantly correlated with hepatic metastasis, UICC classification, and poor prognosis. Elevated serum sE-cadherin level was an independent risk factor for predicting poor prognosis, and was an independent marker for predicting hepatic metastasis. Among patients with synchronous hepatic metastases, the prognosis was significantly worse in patients with elevated serum sE-cadherin levels than in those with lower levels. Conclusions Preoperative elevated sE-cadherin level is associated with poor prognosis in colorectal cancer. Measuring serum sE-cadherin may provide valuable information for predicting prognosis in patients with hepatic metastasis.

Tumor regression grading (TRG) reportedly has a prognostic value in rectal cancer patients who have undergone preoperative chemoradiotherapy (CRT). However, TRG is difficult to evaluate objectively. The aim of this study was to identify pathological features associated with clinical outcome, compared with conventional TRG, following preoperative CRT. A total of 67 patients with locally advanced rectal cancer underwent preoperative CRT and curative surgery. The association of two pathological features, solitary single glandular appearance (SSGA) and superficial viable cancer cells (SVCC), with clinicopathological variables was investigated, and the clinical significance of these features was compared to conventional TRG. Moreover, transcriptional analyses were performed on residual cancer cells associated with these pathological features. Of the 67 patients, 34.3 and 74.6 % had detectable SSGA and SVCC, respectively. Patients with tumor recurrence had a significantly higher frequency of SSGA (P

Actin filaments have a double-helix structure consisting of globular actin molecules. In many mechanical cellular activities, such as cell movement, division, and shape control, modulation of the extensional and torsional dynamics of the filament has been linked to regulatory actin-binding protein functions. Therefore, it is important to quantitatively evaluate extension–torsion coupling of filament to better understand the actin filament dynamics. In the present study, the extension–torsion coupling was investigated using molecular dynamics simulations. We constructed a model for the actin filament consisting of 14 actin subunits in an ionic solvent as a minimal functional unit, and analyzed longitudinal and twisting Brownian motions of the filament. We then derived the expected value of energy associated with extension and torsion at equilibrium, and evaluated the extension–torsion stiffness of the filament from the thermal fluctuations obtained from the MD simulations. The results demonstrated that as the analyzed sampling-window duration was increased, the extension–torsion coupling stiffness evaluated on a nanosecond scale tended to converge to a value of 7.6 × 10−11 N. The results obtained from this study will contribute to the understanding of biomechanical events, under mechanical tension and torque, involving extension–torsion coupling of filaments.

Afferent limb obstruction can be a persistent complication after restorative proctocolectomy with ileal pouch-anal anastomosis. We present a case of afferent limb obstruction complicated by a long efferent limb of the ileal pouch that we successfully treated with side-to-side anastomosis of the afferent and efferent limbs. The procedure involved using a transanal endoscopic stapling device assisted by transanal endoscopy with a thin intestinal video endoscope. This allowed reliable, safe visualization of the lesion from the tight pouch-anal anastomosis and facilitated repair with an endoscopic stapling device. Because the technique was performed without enterotomy, it reduced the risks of contamination and leakage from transabdominal small bowel anastomosis. Laparotomy view also prevented of injury to the pouch itself and entrapment of the mesentery of the afferent and efferent limbs of the pouch between the stapler anvils.

Laparoscopic surgery is becoming the preferred technique for most colorectal interventions. This study aimed to clarify the time trend of surgical treatment for familial adenomatous polyposis (FAP) and its relevance to clinical outcomes in Japan over a 13-year period. This was a multicenter retrospective cohort study comprising 23 specialist institutions for colorectal disease and a cohort of 282 FAP patients who underwent total colectomy or proctocolectomy during 2000–2012. Patient clinical backgrounds and surgical outcomes were compared between the first and second halves of the study period. The proportion of surgical types adopted over the entire study period was 46, 21, 30, and 3 % for ileoanal anastomosis (IAA), ileoanal canal anastomosis, ileorectal anastomosis, and permanent ileostomy, respectively. FAP patients undergoing laparoscopic surgery have increased since 2008 and reached 74 % in the past 3 years. In particular, the number of patients undergoing laparoscopic proctocolectomy with IAA increased approximately four-fold from the first to the second half of the study period. A laparoscopic approach was increasingly used in patients with coexisting colorectal malignancies. Despite this trend, surgical results of the laparoscopic approach between the two study periods showed similar morbidity, pouch operation and stoma closure completion rates. No postoperative mortality was observed in this series, and laparoscopic surgery was comparable to open surgery in terms of stoma closure rate, incidence of intra-abdominal/abdominal desmoid tumors, and postoperative survival rate in both study periods. Laparoscopic approach is increasingly being adopted for prophylactic FAP surgery in Japan and may provide clinically acceptable practical outcomes.

CD133 and CD44 have been considered as markers for colorectal cancer stem cells (CSCs). The association of CD133 and CD44 expression with radiation has not been fully examined in rectal cancer. Both CD133 (PROM) and CD44 mRNA levels were measured in post-chemoradiotherapy (CRT) specimens of 52 rectal cancer patients using real-time RT-PCR and compared to clinicopathological variables and clinical outcome. Their protein levels were examined in the radiation-treated HT29 human colon cancer cell line. Post-CRT CD133 in residual cancer cells was significantly higher than matched pre-CRT CD133 in biopsy specimens (n=30). By contrast, CD44 was significantly lower in post-CRT specimens (P

Most cancer cells exhibit increased glycolysis. The elevated glucose transporter 1 (GLUT1) expression has been reported to be associated with resistance to therapeutic agents and a poor prognosis. We wondered whether GLUT1 expression was associated with the clinical outcome in rectal cancer after preoperative chemoradiotherapy (CRT), and whether glycolysis inhibition could represent a novel anticancer treatment. We obtained total RNA from residual cancer cells using microdissection from a total of 52 rectal cancer specimens from patients who underwent preoperative CRT. We performed transcriptional analyzes, and studied the association of the GLUT1 gene expression levels with the clinical outcomes. In addition, we examined each proliferative response of three selected colorectal cancer cell lines to a glycolysis inhibitor, 3-bromopyruvic acid (3-BrPA), with regard to their expression of the GLUT1 gene. An elevated GLUT1 gene expression was associated with a high postoperative stage, the presence of lymph node metastasis, and distant recurrence. Moreover, elevated GLUT1 gene expression independently predicted both the recurrence-free and overall survival. In the in vitro studies, we observed that 3-BrPA significantly suppressed the proliferation of colon cancer cells with high GLUT1 gene expression, compared with those with low expression. An elevated GLUT1 expression may be a useful predictor of distant recurrence and poor prognosis in rectal cancer patients after preoperative CRT.

Although interlaminar fracture at a YBa2Cu3O7−δ (YBCO)/CeO2 interface was reported for YBCO coated conductors, this has not yet been investigated by a fracture mechanical approach. In the present study, we developed a mode I type fracture toughness test method for a YBCO coated conductor with an additional Cu layer using double cantilever beam (DCB) specimens. Fracture mechanism was investigated by microscopic observation by a scanning electron microscope (SEM), together with composition analysis by an energy dispersive X-ray spectroscope (EDS). A pre-crack introduced at the YBCO/CeO2 interface deviated from the interface, and propagated into the YBCO layer, and sometimes reached the Ag/YBCO interface. The fracture toughness, GR, for YBCO and the Ag/YBCO interface was evaluated to be 7–10 J/m2 and 80–120 J/m2, respectively. The complex stress intensity factor ratio, K2/K1, at YBCO/CeO2 interface was evaluated to be −0.19, and this ratio controlled the formation of microcracks in the YBCO layer. The main crack propagated into the YBCO layer accompanied with the formation of microcracks.

Background and Objectives Distant metastatic relapse occurs in approximately 20% of rectal cancer patients treated with 5-fluorouracil (5-FU)-based chemoradiotherapy (CRT) followed by surgery. This study aimed to investigate mRNA level of 5-FU metabolizing enzymes in post-treatment specimens and to evaluate their predictive value of distant recurrence after CRT. Methods Forty patients with rectal cancer underwent 5-FU-based CRT followed by surgery. After microdissection, total RNA of residual cancer was isolated from formalin-fixed paraffin-embedded (FFPE) specimens. Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyl transferase (OPRT) as 5-FU metabolizing enzyme were measured using real-time reverse transcription polymerase chain reaction. Results Patients (n = 6) who developed distant recurrence had a significantly higher TS (P = 0.01), DPD (P = 0.02), and TP (P = 0.01) levels, compared with those patients (n = 34) without recurrence. High TS, DPD, and positive lymph node metastasis (pN) were significantly poorer prognostic factors for DFS (TS: P

Hepatocellular adenoma (HCA) is a benign condition occurring most frequently in young women using oral contraceptives. We herein report the first case of a 28-year-old man with familial adenomatous polyposis (FAP) who experienced hepatocellular carcinoma (HCC) within HCA. A preoperative computed tomography scan of the abdomen disclosed a tumor measuring 5.8 cm in diameter in the left lobe of the liver. A total proctocolectomy with construction of a linear stapled J-pouch, a hand-sewn ileoanal anastomosis and a liver tumor resection were performed. The pathology of the resected specimen confirmed the diagnosis of HCA containing HCC. Five cases of HCA have been reported that developed in patients with FAP, but this is the first case of HCA containing HCC. Hepatocellular adenomas occur due to the inactivation of hepatic nuclear factor 1α, but the mechanism underlying the malignant transformation from HCA to HCC could not be identified in this case.

Epithelial-mesenchymal transition (EMT) promotes and facilitates migration and invasion of epithelial tumor cells. EMT is induced by factors such as hepatocyte growth factor (HGF). This study aimed to establish whether the HGF/c-Met pathway is associated with gastric cancer metastasis; especially peritoneal dissemination. HGF and c-Met expression and EMT-related molecules were evaluated using real-time PCR and immunohistochemistry. The role of the HGF/c-Met pathway in EMT and anoikis was determined, and kinase inhibitor SU11274 was tested for its ability to block HGF-induced biological effects. In HGF(-) /c-Met(+) gastric cancer cells, recombinant HGF promoted an EMT phenotype that was characterized by morphology, impaired E-cadherin and induction of vimentin. HGF promoted cell growth, invasiveness and migration and inhibition of anoikis. SU11274 blocked HGF-induced EMT and biological effects in vitro. In HGF(+) /c-Met(+) gastric cancer cells, HGF did not affect the biological outcome of EMT and anoikis, but SU11274 exerted the same inhibitory effects as in HGF(-) /c-Met(+) cells. In vivo, HGF(+) /c-Met(+) gastric cancer cells only established peritoneal dissemination and SU11274 inhibited tumor growth. Clinically, HGF expression was significantly correlated with c-Met expression in gastric cancer. Increased HGF and c-Met had a significant association with poor prognosis and predicted peritoneal dissemination. We demonstrated that the HGF/c-Met pathway induces EMT and inhibition of anoikis in gastric cancer cells. Co-expression of HGF and c-Met has the potential to promote peritoneal dissemination in gastric cancer. Blockade of the autocrine HGF/c-Met pathway could be clinically useful for the treatment of peritoneal dissemination in gastric cancer.

Stem cells are thought to contribute to tissue regeneration as well as carcinogenesis. Ulcerative colitis-associated colorectal cancer (UC-CRC) has shown distinct characteristics compared with those of sporadic CRC. The aim of this study was to evaluate the expression of stem cell markers CD133, OCT4 and NANOG in UC-CRC and the inflamed colonic epithelium of UC patients. Total RNAs of UC-CRC (n=6), inflamed colonic epithelium (n=24), sporadic CRC (n=37) and adjacent normal colonic epithelium (n=37) were isolated from formalin-fixed, paraffin-embedded specimens using microdissection techniques in order to purify colonic epithelial cells. Relative mRNA levels of CD133 (PROM), OCT4 (POU5F1) and NANOG were measured using real-time reverse transcription polymerase chain reaction. Three stem cell markers were also investigated immunohistochemically. PROM, POU5F1 and NANOG levels were found to be significantly lower in UC-CRC than in inflamed colonic epithelium of UC patients. By contrast, sporadic CRC showed a significantly higher expression of PROM, POU5F1 and NANOG compared with adjacent normal colonic epithelium. POU5F1 and NANOG levels were significantly lower in UC-CRC than in sporadic CRC. PROM and NANOG levels in inflamed colonic epithelium were significantly higher among younger UC patients (P

A major challenge of cancer biology is to visualize the dynamics of the metastatic process in secondary organs at high optical resolution in vivo real-time. Here, we presented intravital, dual-colored imaging of liver metastasis formation from a single cancer cell to metastatic colonies in the living liver of living mice using two photon laser scanning microscopy (TPLSM). Red fluorescent protein expressing murine (SL4) or human (HT29) colorectal cancer cell lines were inoculated to the spleen of green fluorescent protein expressing mice. Intravital TPLSM was performed by exteriorizing and fixing the liver lobe of living mice. This was repeated several times for the long-term imaging of the same mouse. Viable cancer cells in the living liver of living mice were visualized intravitally at a magnification of over 600×. Single cancer cells were arrested within hepatic sinusoids 2 h after injection. Platelet aggregation surrounding a cancer cell was observed, indicating a phenomenon of tumor-cell induced platelet aggregation. Cancer cells were extravasated from hepatic sinusoids to the space of Disse. Protrusions of Kupffer cells surrounding a cancer cell were observed, indicating that Kupffer cells appear to phagocytose cancer cells. SL4 cells formed liver metastatic colonies with extensive stromal reaction. Liver metastases by HT29 cells were observed as a cluster of micrometastatic nodules. High-resolution, dual-colored, real-time visualization of cancer metastasis using intravital TLPSM can help to understand spatiotemporal tumor-host interactions during metastatic processes in the living organs of living animals.

Actomyosin contractility is a major force-generating mechanism that drives rearrangement of actomyosin networks; it is fundamental to cellular functions such as cellular reshaping and movement. Thus, to clarify the mechanochemical foundation of the emergence of cellular functions, understanding the relationship between actomyosin contractility and rearrangement of actomyosin networks is crucial. For this purpose, in this study, we present a new particulate-based model for simulating the motions of actin, non-muscle myosin II, and α ‐ actinin . To confirm the model's validity, we successfully simulated sliding and bending motions of actomyosin filaments, which are observed as fundamental behaviors in dynamic rearrangement of actomyosin networks in migrating keratocytes. Next, we simulated the dynamic rearrangement of actomyosin networks. Our simulation results indicate that an increase in the density fraction of myosin induces a higher-order structural transition of actomyosin filaments from networks to bundles, in addition to increasing the force generated by actomyosin filaments in the network. We compare our simulation results with experimental results and confirm that actomyosin bundles bridging focal adhesions and the characteristics of myosin-dependent rearrangement of actomyosin networks agree qualitatively with those observed experimentally.

Recent advances in micro- and nano-technologies and high-end computing have enabled the development of new experimental and modeling approaches to study biomechanics at the micro- and nano-scales that were previously not possible. These new cutting-edge approaches are contributing toward our understanding in emerging areas such as mechanobiology and mechanochemistry. Another important potential contribution lies in translational medicine, since biomechanical studies at the cellular and molecular levels have direct relevance in areas such disease diagnosis, nano-medicine and drug delivery. Thus, the developed experimental and modeling approaches are critical in elucidating important mechanistic insights in both basic sciences and clinical treatment. While it is hard to cover all the recent advances in this mini-review, we focus on several important approaches. For experimental techniques, we review the assays involving shear flow, cellular imaging, microbead, microcontact printing, and micropillars at the micro-scale, and micropipette aspiration, optical tweezers, parallel flow chamber, and atomic force microscopy at the nano-scale. In modeling and simulations, we outline the theoretical modeling for actin dynamics in migrating cell and actin-based cell motility in cellular mechanics, as well as the receptor–ligand binding in cell adhesion and the application of free, steered, and flow molecular dynamics simulations in molecular biomechanics. Relevant scientific issues and applications are also discussed.

Actin filaments are the most abundant components of the cellular cytoskeleton, and play critical roles in various cellular functions such as migration, division and shape control. In these activities, mechanical tension causes structural changes in the double-helical structure of the actin filament, which is a key modulator of cytoskeletal reorganization. This study performed large-scale molecular dynamics (MD) and steered MD simulations to quantitatively analyze the effects of tensile force on the mechanical behavior of actin filaments. The results revealed that when a tensile force of 200pN was applied to a filament consisting of 14 actin subunits, the twist angle of the filament decreased by approximately 20°, corresponding to a rotation of approximately -2° per subunit, representing a critical structural change in actin filaments. Based on these structural changes, the variance in filament length and twist angle was found to decrease, leading to increases in extensional and torsional stiffness. Torsional stiffness increased significantly under the tensile condition, and the ratio of filament stiffness under tensile force to that under no external force increased significantly on longer temporal scales. The results obtained from this study contribute to the understanding of mechano-chemical interactions concerning actin dynamics, showing that increased tensile force in the filament prevents actin regulatory proteins from binding to the filament.

Aims The mechanism of distant recurrence in rectal cancer after preoperative chemoradiotherapy (CRT) has yet to be fully elucidated. Further improvements in survival rates cannot be achieved without decreasing distant recurrence after preoperative CRT. Recently, it was reported that hypoxic conditions were correlated with cancer stem cell generation. Therefore, we investigated the correlation between the expression of CD133 and hypoxia inducible factor-1α (HIF-1α), and their association with clinical outcome. Materials and methods Fifty-two patients with rectal cancer underwent preoperative CRT. Residual cancer cells after CRT were obtained from formalin-fixed paraffin-embedded specimens using micro-dissection. The expression levels of CD133 ( PROM1 ) and HIF-1α genes were measured using real-time reverse transcription polymerase chain reaction. The correlation between expression and irradiation was evaluated using colon cancer cell lines. Immunohistochemical staining of these proteins after CRT was also investigated. Results We observed a significant inverse correlation between the gene expression of CD133 ( PROM1 ) and HIF-1α genes in residual cancer cells after CRT. Elevated CD133 gene expression was associated with distant recurrence and poor recurrence-free survival. Elevated HIF-1α gene expression was associated with poor overall survival. In vitro , the change in gene expression levels after irradiation showed inverse patterns. Immunohistochemical analyses showed that residual cancer cells strongly expressed CD133 and lacked HIF-1α expression. Conclusion Our results suggest that CD133 and HIF-1α expression is associated with tumour re-growth and distant recurrence after CRT. These results may assist in clarifying the development of future cancer therapeutics in rectal cancer patients undergoing preoperative CRT.

Objective There is compelling evidence that tinnitus is associated with functional alterations in the central nervous system. Repetitive transcranial magnetic stimulation (rTMS) is a potent tool for modifying neural activity at the stimulated area and at a distance along the functional anatomical connections. Depending on the stimulation parameters, cortical networks can be functionally disturbed or modulated in their activities. Low-frequency rTMS has been shown to result in a decrease in cortical excitability. The technique can alleviate tinnitus by modulating the excitability of neurons in the auditory cortex. We aimed to investigate the effects of low-frequency rTMS in patients and determine the factors that predict a beneficial outcome with rTMS treatment. Methods Sixteen patients (male 10, female 6) with chronic tinnitus underwent low-frequency (1 Hz) rTMS (intensity: 110% motor threshold; number of stimuli: 1200) to the left auditory cortex. The treatment outcome was assessed with a visual analog scale (VAS) of loudness, annoyance and duration, loudness balance test, and tinnitus handicap inventory (THI). Therapeutic success was studied according to the patients’ clinical characteristics. Results A significant reduction in the VAS (loudness and annoyance) occurred immediately after rTMS, with a gradual return to pretreatment levels after 7 days. The tinnitus patients with sudden deafness were significant resistant to rTMS treatment compared with those diagnosed with age-related hearing loss. Conclusion These results support the potential of rTMS as a new therapeutic tool for the treatment of chronic tinnitus. Because this study was performed with a small sample size and showed high interindividual variability in treatment effects, further development of the technique is needed before it can be recommended for clinical applications.

Objective: To assess factors that contribute to Tinnitus Handicap Inventory (THI) scores in Japan. Design: Case series with chart review. Study sample: Two hundred and eighty-five tinnitus patients at tertiary referral center, who completed the Japanese version of the THI, the Self-rating Depression Scale (SDS), and the State Trait Anxiety Inventory (STAI). Results: In multiple regression analysis, the SDS score contributed the most to the THI score. The state section of the STAI score and pure tone average (PTA) at four high frequencies also contributed significantly, but to lesser degrees. The other following factors were not statistically significant: age, gender, time from the onset of tinnitus to the first clinical visit, PTA at three mid frequencies, and trait section of the STAI score. This model may account for approximately 45% of THI score variability. Conclusions: The THI scores may be influenced by depressive symptoms, state anxiety, and pure tone thresholds in Japan.SumarioObjetivo: E...

Pure tone auditory thresholds can change according to duration of interrupted tones in patients with mild to severe psychogenic hearing loss (PHL).To examine how the duration of stimulus tones affects the hearing thresholds of patients with PHL.Twelve patients with PHL (21 ears) were enrolled in this study. We initially measured their hearing thresholds using interrupted tones with a duration of 2 s and equal length of on-time and off-time, 225 ± 35 ms, respectively. After a 10 min interval, we measured their hearing thresholds using the same interrupted tones conditions lasting 5 s. The average threshold gains (2 s thresholds minus 5 s thresholds) were compared to those of 15 control subjects with normal hearing (25 ears), 15 patients with cochlear hearing loss (23 ears), and 4 patients with retrocochlear lesions (4 ears). Patients with profound PHL (4 patients, 6 ears) were analyzed separately.The average threshold gain of PHL patients (excluding profound PHL patients) at all frequencies was 18.3 dB, which was significantly larger than that of other groups: 0.3 dB (profound PHL patients), 3.8 dB (controls with normal hearing), 3.0 dB (patients with cochlear hearing loss), and 3.2 dB (patients with retrocochlear lesions).

Background Combining ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI) and fine-needle aspiration cytology (FNAC) usually results in the best preoperative diagnosis of cervical masses, including neoplasms. This may not be true, however, especially in occult papillary thyroid carcinoma (PTC) associated with single cystic cervical lymph node metastasis. We assessed the role of thyroglobulin measurement in FNA fluid (FNATg) in differentially diagnosing cystic cervical mass lesions, including PTC cystic lymph node metastasis. Methods We reviewed the records of 17 subjects with cervical cystic masses undergoing both FNATg measurement and surgery. FNA was done under ultrasonographic guidance. We also measured FNATg concentrations from extrathyroid lesions, consisting of cystic cervical lymph node metastases and benign cystic lesions. Results Pathological diagnosis involved 5 PTC lymph node metastases, 3 lateral cervical cysts, 7 thyroglossal duct cysts, and 2 squamous cell carcinoma (lung and oropharynx) lymph node metastases. FNATg of PTC lymph node metastasis was much higher than the reference range of blood serum thyroglobulin, although much lower for the lateral cervical cyst detection threshold. FNAC and FNATg measurement are thought to be mutually complementary in the differential diagnosis of PTC cystic lymph node metastasis. Conclusion High concentrations of FNATg in a cystic cervical mass is considered specific to PTC lymph node metastasis, indicating its usefulness in distinguish PTC cystic metastasis from other cystic lesions. Including FNATg measurement with FNAC may thus improve preoperative diagnosis accuracy without additionally stressing subjects with PTC cystic lymph node metastasis.

Purpose: The purpose of this study is to determine the presence of bacteriostatic effects of hyaluronan-based bioresorbable membrane (HA/CMC) on selected major bacterial strains in digestive organs. Methods: We firstly evaluated the growth inhibition effect of HA/CMC for E. coli and S. aureus by determining the optical density (OD)650 in the incubation medium. At second, to determine the viable counts of bacteria, total adenosine triphosphate (ATP) were measured with five groups; several concentrations of HA/CMC and control. Results: OD curve gradually elevated and reached to plateau at 4 hours in E. coli. and 6 hours in S. aureus. After reaching plateau, the growth inhibition of both strains was statistically significantly correlated to the concentrations of HA/CMC. The ATP productions had statistically significant differences at 6 hours after incubation and inhibited in dose-dependence of a well-dissolved HA/CMC. Conclusion: HA/CMC may have dose-dependently bacteriostatic effects on S. aureus and E. coli.

Recent studies have revealed the Glasgow prognostic score (GPS) to aid in the prediction of postoperative outcome in colorectal cancer patients. However, whether GPS predicts poor prognosis in curative colorectal cancer patients has yet to be ascertained. Furthermore, there is no information on the association between GPS and adjuvant chemotherapy in stage II or III colorectal cancer patients. A total of 219 patients with stage II and III colorectal cancer were included in this trial. The modified GPS (mGPS) defined in this study was calculated on the basis of admission data as follows: patients with an elevated level of both C-reactive protein (0.5 mg/dl) and hypoalbuminemia (Alb

Background: Interleukin-6 (IL-6) binds both the membrane and soluble forms of the IL-6 receptor (sIL-6R), which induces a complex with gp130, and proliferation of tumour cells. The aim of this study is to clarify the relationship between tumoral sIL-6R expression and disease progression in colorectal cancer patients. Methods: We measured tissue concentrations of sIL-6R in tumour and normal mucosa from 161 colorectal cancer patients undergoing surgery, and in supernatants from colon cancer cell lines. The expression of IL-6, IL-6R and gp130 was evaluated by immunohistochemical analysis. Results: Loss of tumour expression of sIL-6R as defined by sIL-6R Ca/N ratio

Membrane protrusion is a mechanochemical process of active membrane deformation driven by actin polymerization. Previously, Brownian ratchet (BR) was modeled on the basis of the underlying molecular mechanism. However, because the BR requires a priori load that cannot be determined without information of the cell shape, it cannot be effective in studies in which resultant shapes are to be solved. Other cellular-scale models describing the protrusion have also been suggested for modeling a whole cell; however, these models were not developed on the basis of coarse-grained physics representing the underlying molecular mechanism. Therefore, to express the membrane protrusion on the cellular scale, we propose a novel mathematical model, the coarse-grained BR (CBR), which is derived on the basis of nonequilibrium thermodynamics theory. The CBR can reproduce the BR within the limit of the quasistatic process of membrane protrusion and can estimate the protrusion velocity consistently with an effective elastic constant that represents the state of the energy of the membrane. Finally, to demonstrate the applicability of the CBR, we attempt to perform a cellular-scale simulation of migrating keratocyte in which the proposed CBR is used for the membrane protrusion model on the cellular scale. The results show that the experimentally observed shapes of the leading edge are well reproduced by the simulation. In addition, The trend of dependences of the protrusion velocity on the curvature of the leading edge, the temperature, and the substrate stiffness also agreed with the other experimental results. Thus, the CBR can be considered an appropriate cellular-scale model to express the membrane protrusion on the basis of its underlying molecular mechanism.

The human kallikrein-related peptidases (KLK) are considered important prognostic biomarkers in cancer. The aim of the current study is to demonstrate gene expression of KLK7 in colorectal cancer (CRC) and to correlate the relative KLK7 expression level with clinicopathological factors of CRC. KLK7 messenger RNA (mRNA) expression was examined in nine CRC cancer cell lines by real-time polymerase chain reaction. The expression levels of KLK7 mRNA in cancerous tissues (n = 136) and paired normal tissues (n = 136) of CRC patients were also examined. Six of the nine cell lines expressed the KLK7 gene. KLK7 mRNA expression levels in cancer tissues were significantly higher than those in normal tissues. Multivariate analysis revealed that the KLK7 mRNA expression level in cancer was an independent prognostic factor, especially in liver metastasis. We provide evidence suggesting that KLK7 mRNA expression is correlated with prognosis in CRC patients, especially in liver metastasis.

This is the report of rare cases to show the potential ototoxicity of Burow's solution in clinical use. We encountered two cases of acute sensorineural hearing loss occurring after the administration of 8% Burow's solution (pH 2.93) into the tympanic cavities. Prior to treatment, both cases presented with tympanic membrane perforations in the posterior and inferior portions and a small amount of serous discharge. Fortunately, hearing loss recovered almost completely except for high tones within a few weeks. These two case reports demonstrate that the ototoxicity of Burow's solution should be considered when it is used to treat otitis media accompanied by tympanic membrane perforation.

Local control of rectal cancer and patient survival have improved remarkably with advances in surgical techniques and adjuvant therapy. By applying advanced surgical principles, surgeons can now excise most rectal cancers completely, often preserving the anal sphincter and leaving the patient with relatively normal bowel and pelvic function. Historically, the earliest surgical approaches to rectal cancer were via the perineum. As surgical techniques and general anesthesia improved, other approaches such as a posterior approach were undertaken to improve access to the whole rectum. Consequently, abdominoperineal resection became the standard treatment until anterior resection was introduced for proximal rectal cancers. The most important surgical breakthrough in recent years has been the advent of total mesorectal excision (TME). The emphasis in rectal cancer surgery is on preservation of function, with dissection being done in appropriate anatomical planes. Thus, mobilization of the rectum has a long history, and is seen in modern procedures including TME and intersphincter resection. This article reviews the progression of the surgical management of rectal cancer with reference to historical perspectives. We discuss the major surgical considerations for mobilization of the rectum in several surgical procedures, from conventional operations to modern standardized TME.

To determine the long-term prognosis of low-frequency hearing loss and predictive factors for the 10-year outcome of low-frequency hearing loss.Case series with chart review.Tertiary referral center.From 1979 to 1998, 466 consecutive patients with low-frequency hearing loss received initial treatment at the Hearing and Tinnitus Clinic of Keio University Hospital. Of the 49 eligible patients, pure-tone threshold data obtained over a period of 10 years after onset of low-frequency hearing loss were available for analysis. To determine the progression of hearing loss, we analyzed audiometric pattern changes. We also examined how the following factors affected 10-year prognosis: sex, age, side of hearing loss, accompanying dizziness, pre-therapeutic hearing thresholds at low frequencies, initial therapy results, and fluctuation of hearing during the first year after onset.High- and pan-frequency hearing loss increased as time progressed. About half of the cases developed high- or pan-frequency hearing loss within 10 years of onset. Audiometric patterns measured at 10 years significantly correlated with those measured at one (r = 0.57), three (r = 0.73), and five years (r = 0.85). The 10-year prognosis significantly correlated with only two factors: initial therapy results (r = 0.49) and fluctuation of hearing during the first year (r = 0.43).About half of the cases in our study developed high- or pan-frequency hearing loss within 10 years of onset of low-frequency hearing loss. The initial therapy results and fluctuation of hearing during the first year may indicate the long-term prognosis of patients presenting with low-frequency hearing loss.

It is essential to investigate the mechanical behaviour of cytoskeletal actin filaments in order to understand their critical role as mechanical components in various cellular functional activities. These actin filaments consisting of monomeric molecules function in the thermal fluctuations. Hence, it is important to understand their mechanical behaviour on the microscopic scale by comparing the stiffness based on thermal fluctuations with the one experimentally measured on the macroscopic scale. In this study, we perform a large-scale molecular dynamics (MD) simulation for a half-turn structure of an actin filament. We analyse its longitudinal and twisting Brownian motions in equilibrium and evaluated its apparent extensional and torsional stiffness on the nanosecond scale. Upon increasing the sampling-window durations for analysis, the apparent stiffness gradually decreases and exhibits a trend to converge to a value that is close to the experimental value. This suggests that by extrapolating the data obtained in the MD analysis, we can estimate the experimentally determined stiffness on the microsecond to millisecond scales. For shorter temporal scales, the apparent stiffness is larger than experimental values, indicating that fast, local motions of the molecular structure are dominant. To quantify the local structural changes within the filament on the nanosecond scale and investigate the molecular mechanisms, such as the binding of the actin-regulatory proteins to the filaments, it is preferable to analyse the mechanical behaviour on the nanometre and nanosecond scales using MD simulation.

To investigate void formation during resin transfer molding (RTM) processes, we developed a numerical code of a multiphase fluid model that employs Navier-Stokes equation including the interfacial tension term and Cahn-Hilliard equation for capturing the resin-air interface. We performed preliminary numerical simulations of microscale resin-air flow around a regular-lattice array of four single filaments. From the analysis, we found that (1) Laplace pressure arisen from the finite curvature of the resin-air interface could drive a capillary-driven flow penetrating into the gap between the two filaments located in longitudinal direction; (2) there was another dual time scale even at the microscale on the determination of flow patters: one was caused by the main flow, and the other by capillary driven transverse flow; (3) voids could be formed when the time scale of the main flow was shorter than that of capillary flow; (4) two modes of void formations were revealed numerically: longitudinal gaps fully capped by the resin-air interface leading to the void formation under a high interfacial tension coefficient; and a small bubble left at the back-step of the filament under a relatively weak interfacial tension coefficient.

Conductive hearing impairiment induced by otosclerosis, a typical otological disease, can be dramatically improved by surgery. This review introduces an original surgical procedure using a ceramic apatite implant, and summarizes successful surgical results involving 160 otosclerotic ears.

We previously reported that a combination of serum hepatocyte growth factor (HGF) and carcinoembryonic antigen (CEA) was useful for selecting early-stage colorectal cancer patients with aggressive disease. The aim of the present study was to determine whether serum HGF could provide CEA-independent prognostic information on patients undergoing surgery with curative intent. Serum samples were collected from 184 patients with colorectal cancer and 30 controls. Reverse-transcription polymerase chain reaction was used to detect HGF expression in colorectal cancer cell lines. Serum and tissue levels of HGF were measured by enzyme-linked immunosorbent assay. The serum HGF levels in colorectal cancer patients were compared with those in healthy controls, and we retrospectively assessed the association between serum HGF levels and clinicopathological findings and survival. Expression of HGF was significantly higher in colorectal cancer tissues compared with non-tumor tissues. The serum HGF levels were closely correlated with the HGF levels in cancer tissue. The mean serum HGF level in patients was significantly higher than that in controls, and significantly higher in patients with large tumor, lymph-node involvement and distant metastasis. According to the receiver operating characteristic (ROC) analysis, elevated serum HGF levels can predict patients with larger tumor, lymph-node and distant metastasis. Elevated serum HGF level demonstrated a significant association with poor survival, and was only an independent risk factor for poor survival in Stage II or/and III. Elevated serum HGF level is significantly associated with colorectal cancer development, lymph or distant invasive phenotypes and survival, especially in Stage II or III patients.

PURPOSE: Vascular cell adhesion molecule 1 plays an important role in solid tumor enlargement and/or metastasis. This study evaluated the clinical significance of measuring serum levels of soluble vascular cell adhesion molecule 1 in colorectal cancer and aimed to clarify the biologic significance of its local expression. METHODS: Serum was collected from 161 patients with colorectal cancer and 26 healthy volunteers. Cancer tissue was collected from 128 patients. The level of soluble vascular cell adhesion molecule 1 in serum and cancer tissue was measured by enzyme-linked immunosorbent assay. RESULTS: The mean soluble vascular cell adhesion molecule 1 level in patients was significantly higher than that in control subjects. Elevated serum soluble vascular cell adhesion molecule 1 was significantly associated with clinicopathologic parameters such as tumor size, lymph node metastasis, distant metastasis, and poor prognosis. In Cox multivariate analysis, distant metastasis and elevated serum soluble vascular cell adhesion molecule 1 level were independent risk factors predicting poor prognosis. The prognosis for Stage 2 patients positive for soluble vascular cell adhesion molecule 1 was comparable to that for Stage 3 patients. In addition, the serum level of soluble vascular cell adhesion molecule 1 level was correlated negatively with the cancer tissue level. CONCLUSION: The preoperative level of soluble vascular cell adhesion molecule 1 level reflected disease progression and was a sensitive biomarker for colorectal cancer, especially Stage 2 disease.

Background and Objectives Vascular adhesion protein-1 (VAP-1) is an endothelial cell molecule that controls leukocyte tissue infiltration. Elevated serum soluble VAP-1 (sVAP-1) has been described in certain diseases with an inflammatory component. However, sVAP-1 expression or function has not been studied in colorectal cancer. The present study determined the relationships between preoperative serum sVAP-1 and clinicopathological features and prognosis in colorectal cancer. Methods One hundred patients with histologically proven colorectal cancer and 33 normal volunteers were included. Preoperative serum was collected, and sVAP-1 levels were assayed by enzyme-linked immunosorbent assay. Results Mean sVAP-1 level in patients was significantly higher than in controls, and decreased with disease progression. Mean sVAP-1 level was significantly correlated with venous invasion, lymph node metastasis, distant metastasis including hepatic metastasis, and advanced TNM classification. Furthermore, sVAP-1 was an independent marker for predicting lymph node or hepatic metastasis. Prognosis of patients with a lower sVAP-1 level was significantly worse than those with elevated sVAP-1. Conclusions Preoperative low sVAP-1 level is associated with poor prognosis in colorectal cancer. Measuring serum sVAP-1 may provide valuable information in predicting patients with lymph node or hepatic metastasis. J. Surg. Oncol. 2009;99:368–372. © 2009 Wiley-Liss, Inc.

We describe a case of multiple desmoid tumors (DT) that developed in an ileal J pouch, which were successfully treated by low-dose combination chemotherapy using vinblastine (VBL) and methotrexate (MTX). Serial changes in the serum D-dimer levels reflected the treatment response. DT involving both the abdominal wall and the ileal pouch developed after total proctocolectomy with ileoanal anastomosis for familial adenomatous polyposis in a 26-year-old female who was treated in an outpatient unit with low-dose VBL and MTX biweekly for 12 months. The treatment response was assessed at routine intervals by physical examination and abdominal computer tomography (CT) imaging. We assessed serial changes in plasma D-dimers, a potential marker for angiogenic activity, during the low-dose VBL and MTX treatment. DT were successfully treated with low-dose VBL and MTX chemotherapy without any significant side effects or pouch sacrifice. Abdominal CT imaging revealed a decrease in tumor size, and the plasma D-dimer levels decreased in association with tumor regression. This case report shows the efficacy of a low-dose combination chemotherapeutic regimen of VBL and MTX for the treatment of ileoanal pouch mesenteric DT in an outpatient setting. In addition, plasma D-dimers may be a marker for desmoid tumor treatment efficacy.

YBa2Cu3O7−δ, (YBCO) coated conductors with an additional Cu layer are expected to be applied as coils used in superconducting magnetic energy storage, SMES. In the operation of SMES, large cyclic hoop stress is applied to the coated conductor in the longitudinal direction. In the present study, we carried out fatigue tests in liquid nitrogen, LN2, and measured the critical current, Ic, after a specific number of fatigue cycles to clarify its fatigue fracture mechanism. All fatigue tests were carried out under a stress ratio (the ratio of the minimum to maximum load) of 0.5. The frequency of stress cycling was 30 Hz. Our results showed that the addition of a Cu layer increased the fatigue strength after 106 cycles, F N = 10 6 , by about 19%. Decrease of Ic was more than 30% of the initial critical current, Ic0, without loading at the point of final overall fracture when the maximum load in the stress cycles was close to that corresponding to irreversible strain. Furthermore, microscopic observation and the change in Ic showed that fatigue fracture mainly initiated from the Hastelloy C-276 substrate. Fatigue fracture also initiated from the Cu layer, but only when the maximum load was approximately F N = 10 6 .

Otosclerosis is an otological disease that typicaly causes conductive hearing loss. This disease is an important clinical entity since hearing impairment in these case can be dramatically improved by surgery. In this review paper, we review recent research into the pathophysiology of otosclerosis and summarize clinical features, audiometry and diagnostic imaging examinations in 160 ears with otosclerosis that we treated surgically in our department.