Treatment of spontaneously hypertensive rats during pregnancy and lactation with the antioxidant tempol lowers blood pressure and reduces oxidative stress.

Genetic and environmental factors interact in a complex manner in the pathogenesis of essential hypertension in humans. Oxidative stress is considered one of the more important environmental factors. We used the spontaneously hypertensive rat (SHR) model to test whether continuous feeding with the antioxidant tempol reduces maternal oxidative stress during pregnancy and potentially contributes to the prevention of cardiovascular disease onset. Pregnant female rats were divided into control and tempol-treated groups. Tempol was continuously administered in the drinking water. The administration period lasted approximately 40 days from the confirmation of a vaginal plug until birth of the pups and their subsequent weaning. The blood pressure (BP) of each adult female was measured three times during pregnancy and post parturition. Milk was collected three times in the immediate postpartum period from nursing mother rats. Markers of oxidative stress were measured: 8-hydroxyl-2'-deoxyguanosine (8-OHdG) levels in milk during the experimental period, 8-OHdG levels and corticosterone levels in urine of adult and neonatal rats. The urinary level of 8-OHdG in the tempol-treated group was significantly lower than in the control group. Corticosterone levels were significantly lower in urine of neonatal rats from the tempol-treated group compared to the control group. 8-OHdG and corticosterone levels in milk of the tempol-treated group were significantly greater than in the control group. This study demonstrates that continuous administration of tempol to pregnant SHRs reduced maternal oxidative stress and contributed to reduced oxidative stress in neonatal rats.

Apolipoprotein E-depletion accelerates arterial fat deposition in the spontaneously hypertensive rat.

Hypertension and atherosclerosis are often found in one patient causing serious cardiovascular events. An animal model simultaneously expressing hypertension and atherosclerosis would be useful to study such a complex risk status. We therefore attempted to introduce a null mutation of the apolipoprotein E (ApoE) gene into the spontaneously hypertensive rat (SHR) using CRISPR/Cas9 to establish a genetic model for atherosclerosis with hypertension. We successfully established SHRApoE(-/-) having a 13-bps deletion in the 5'-end of ApoE gene. Deletion of ApoE protein was confirmed by Western blotting. Blood pressure of SHRApoE(-/-) was comparable to that of SHR. Feeding the rats with high fat high cholesterol diet (HFD) caused a significant increase in LDL cholesterol as well as in triglyceride in SHRApoE(-/-). After 8 weeks of HFD loading, superficial fat deposition was observed both in the aorta and the mesenteric arteries of SHRApoE(-/-) instead of mature atheromatous lesions found in humans. In addition, a null mutation of peroxiredoxin 2 (Prdx2) was introduced into SHRApoE(-/-) to examine the effect of increased oxidative stress on the development of atherosclerosis. SHR with the double depletion of ApoE and Prdx2 did not show mature atheroma either. Further, salt loading did not promote development of atheroma although it accelerated the development of fat deposition. These results indicated that when compared with ApoE-knockout mice, SHRApoE(-/-) was more resistant to atherosclerosis even though they have severe hypertension.

Changes in prevalence of Helicobacter pylori in Japan from 2008 to 2018: a repeated cross-sectional study.

OBJECTIVES: To understand the recent prevalence and time trends of Helicobacter pylori infection rates in the Japanese population. DESIGN: Repeated cross-sectional study. PARTICIPANTS: A total of 22 120 workers (age: 35-65 years) from one Japanese company, who underwent serum H. pylori antibody tests in a health check-up between 2008 and 2018. MEASURES: H. pylori infection rates among participants aged 35 years from 2008 to 2018, and participants aged 35, 40, 45, and 50-65 years in 2018, based on the results of serum antibody tests, were analysed. In the 2018 analysis, in addition to the antibody test results, all participants who had undergone eradication treatment for H. pylori were considered as infected. Trends were examined using joinpoint analysis. RESULTS: H. pylori was detected in 1100 of 7586 male and 190 of 1739 female participants aged 35 years. Annual infection rates among those aged 35 years showed linear downward trends as follows: men, 17.5% in 2008 to 10.1% in 2018 (slope: -0.66); women, 12.3% in 2008 to 9.2% in 2018 (slope: -0.51) without joinpoints. In the 2018 analysis, 2432 of 9580 men and 431 of 1854 women were H. pylori positive. Infection rates tended to increase with older age (men: 11.0% (35 years) to 47.7% (65 years); women: 10.0% (35 years) to 40.0% (65 years)), and showed joinpoints in both sexes (men: 54 years; women: 45 years). Although both the first and second trends were upward, the second trend for both men and women was steeper than the first trend (p<0.05). CONCLUSIONS: Our study demonstrated that in the previous 11 years, infection rates of H. pylori in 35-year-old male and female Japanese workers have constantly decreased, and furthermore, analysis of various age groups showed joinpoints around 50 years, suggesting a consistent declining trend in H. pylori infection rates in Japan.

COL1A1 expression induced by overexpression of both a 15­amino acid peptide from the fibrinogen domain of tenascin­X and integrin α11 in LX­2 cells.

Extracellular matrix tenascin­X (TNX) is the largest member of the tenascin family. Our previous study demonstrated that TNX was involved in hepatic dysfunction, including fibrosis, in mice that were administered a high­fat and high­cholesterol diet with high levels of phosphorus and calcium. The present study investigated whether overexpression of both the fibrinogen domain of TNX (TNX­FG) and integrin α11, one of the TNX cell surface receptors, induces in vitro fibrosis in LX­2 human hepatic stellate cells. Overexpression of both a 15­amino acid peptide (hTNX­FGFFFF) derived from the TNX­FG domain and integrin α11 induced the expression of type I collagen α1 chain (COL1A1). Treatment with verteporfin [YAP (Yes­associated protein) inhibitor] attenuated the elevated COL1A1 expression elicited by overexpression of both hTNX­FGFFFF and integrin α11. In addition, small interfering RNA­mediated knockdown of YAP1 resulted in a decrease in COL1A1 expression induced by overexpression of both hTNX­FGFFFF and integrin α11. These results indicated that overexpression of both hTNX­FGFFFF and integrin α11 induced COL1A1 expression via the YAP signaling pathway.

Effects of hydrogen-rich water and ascorbic acid treatment on spontaneously hypertensive rats.

Hydrogen-rich water (HW) has been suggested to possess antioxidant properties of value in treatments of lifestyle diseases and for prevention of latent pathologies. To date, the potential benefits of HW against the deleterious effects of excessive salt intake and hypertension have not been investigated. Here, we first examined the effects of HW or HW supplemented with 0.1% ascorbic acid (HWA) on spontaneously hypertensive rats (SHR) that had been fed a normal diet. In comparison to control rats given distilled water (DW), we found that HW did not significantly influence systolic blood pressure (SBP) or diastolic blood pressure (DBP) in SHR; however, the increase in SBP and DBP were inhibited in the HWA group. Next, four groups of SHR were given DW, 0.1% ascorbic acid-added DW (DWA), HW, or HWA in combination with a 4% NaCl-added diet. SHR fed the 4% NaCl-added diet showed increased hypertension; HWA treatment resulted in a significant reduction in blood pressure. The HWA group tended to have lower plasma angiotensin II levels than the DW group. In addition, urinary volumes and urinary sodium levels were significantly lower in the HWA group than the DW group. Urinary isoprostane, an oxidative stress marker, was also significantly lower in the HWA group, suggesting that the inhibitory effect of HWA on blood pressure elevation was caused by a reduction in oxidative stress. These findings suggest a synergistic interaction between HW and ascorbic acid, and also suggest that HWA ingestion has potential for prevention of hypertension.

Comparison of survival rates in four inbred mouse strains under different housing conditions: effects of environmental enrichment.

Housing conditions can affect the well-being of laboratory animals and thereby affect the outcomes of experiments. The appropriate environment is essential for the expression of natural behavior in animals. Here, we compared survival rates in four inbred mouse strains maintained under three different environmental conditions. Three mouse strains (C57BL/6J, C3H/HeN, and DBA/2J) housed under environmental enrichment (EE) conditions showed improved survival; however, EE did not alter the survival rate of the fourth strain, BALB/c. None of the strains showed significant differences in body weights or plasma corticosterone levels in the three environmental conditions. For BALB/c mice, the rates of debility were higher in the EE group. Interestingly, for C57BL/6J and C3H/HeN mice, the incidence of animals with alopecia was significantly lower in the EE groups than in the control group. It is possible that the enriched environment provided greater opportunities for sheltering in a secure location in which to avoid interactions with other mice. The cloth mat flooring used for the EE group was bitten and chewed by the mice. Our findings suggest that depending on the mouse strains different responses to EE are caused with regard to health and survival rates. The results of this study provide basic data for further studies on EE.

Adsorption of phosphate onto lanthanum-doped coal fly ash-Blast furnace cement composite.

We develop a high-performance adsorbent for phosphate removal from water or wastewater by impregnating lanthanum (La) on a coal fly ash-blast furnace cement composite (La-FACC). The optimized impregnation percentage of La and calcination conditions of the La-FACC were 1% and 800 â„ƒ for 2 h, respectively. The adsorption kinetics of phosphate onto the La-FACC was well fit by the intra-particle diffusion model, indicating that film and intra-particle diffusion were the rate-controlling step in the adsorption process of phosphate onto the La-FACC. The pseudo second-order kinetic model could also describe the adsorption kinetics of phosphate. Hence, adsorption of phosphate onto the La-FACC occurred mainly via chemisorption. The Langmuir isotherm was appropriate for describing the phosphate adsorption behavior onto the La-FACC. The monolayer maximum adsorption capacity was 24.9 mg-P g-1. The La-FACC showed high adsorption capacity and selectivity for phosphate with a wide range of pH, and with high concentrations of coexisting ions attributed to both formation of inner sphere complexes and electrostatic interaction. Magnesium ion slightly inhibited the adsorption of phosphate. Hence, the La-FACC developed in this study is a promising adsorbent for water treatment with a wide pH range and high ion strength.

Current status of first- and second-line Helicobacter pylori eradication therapy in the metropolitan area: a multicenter study with a large number of patients.

BACKGROUND: The environment surrounding Helicobacter pylori eradication treatment is dramatically changing. Recently, vonoprazan, a first-in-class potassium-competitive acid blocker (P-CAB), was introduced onto the market in 2015. The aging of Japan's demographic structure is becoming pronounced. In this study, we examined the trend of the eradication rate of H. pylori in the metropolitan area and examined factors concerning successful eradication. METHODS: We collected data from 20 hospitals in the Tokyo metropolitan area on patients who received first-line eradication therapy with a proton-pump inhibitor (PPI)/P-CAB, amoxicillin, and clarithromycin for 1 week and second-line eradication therapy with a PPI/P-CAB, amoxicillin, and metronidazole for 1 week from 2013 to 2018. The annual eradication rate and associated factors for successful eradication were analyzed. RESULTS: We collected data of 4097 and 3572 patients in the first- and second-line eradication therapies, respectively. The eradication rate decreased from 2013 to 2014 and increased again from 2015 to 2018 with the first-line therapy [the eradication rates in 2013, 2014, 2015, 2016, 2017 and 2018 were 71.8%, 63.7%, 78.5%, 84.6%, 89.7 and 90.1%, respectively, in the per protocol (PP)]. The second-line eradication rates were 90.0%, 82.6%, 88.8%, 87.5%, 91.8% and 90.1% in 2013, 2014, 2015, 2016, 2017 and 2018, respectively, in PP. Vonoprazan was an independent factor for successful eradication in not only first-line, but also second-line eradication. Age over 75 years was an independent factor for eradication failure in both first- and second-line eradication therapies. CONCLUSION: The eradication rate improved from 2015 to 2018 with the first-line therapy because of the introduction of vonoprazan in the market. The eradication rates with first- and second-line regimens in elderly patients were lower than those in younger patients.

TNX deficiency results in bone loss due to an increase in multinucleated osteoclasts.

Tenascin-X (TNX), a glycoprotein of the extracellular matrix (ECM), is expressed in various tissues and plays an important role in ECM architecture. The TNXB gene encoding TNX is known as the gene responsible for classic-like Ehlers-Danlos syndrome (clEDS). To date, the role of TNX in dermal, muscular and obstetric features has been reported, but its role in bone homeostasis remains to be clarified. In this study, we found significant bone loss and upregulation of osteoclast marker gene expression in TNX-deficient mice. Further, TNX deficiency in the bone marrow promoted multinucleation of osteoclasts and resulted in increased bone resorption activity. These results indicate that multinucleated osteoclasts are the cause of bone loss in a TNX-deficient environment. Our findings provide new insight into the mechanism of osteoclast differentiation mediated by TNX and the pathology of clEDS.

Screening for 15 pathogenic viruses in human cell lines registered at the JCRB Cell Bank: characterization of in vitro human cells by viral infection.

Human cell lines have been used in a variety of research fields as an in vitro model. These cells are all derived from human tissue samples, thus there is a possibility of virus infection. Virus tests are routinely performed in clinical practice, but are limited in cell lines. In this study, we investigated 15 kinds of viruses in 844 human cell lines registered at the Japanese Collection of Research Bioresources (JCRB) Cell Bank. Our real-time PCR analysis revealed that six viruses, EBV, HTLV-1, HBV, B19V, HHV-6 and HHV-7, were detected in 43 cell lines. Of them, 20 cell lines were transformed by intentional infection in vitro with EBV or HTLV-1. Viruses in the other 23 cell lines and one EBV transformed cell line are derived from an in vivo infection, including five de novo identifications of EBV, B19V or HHV-7 carriers. Among them, 17 cell lines were established from patients diagnosed with virus-associated diseases. However, the other seven cell lines originated from in vivo cells unrelated to disease or cellular tropism. Our approach to screen for a set of 15 viruses in each cell line has worked efficiently to identify these rare cases. Virus tests in cell lines contribute not only to safety assessments but also to investigation of in vivo viral infection which can be a characteristic feature of cell lines.

Antihypertensive Effect of γ-Aminobutyric Acid-Enriched Brown Rice on Spontaneously Hypertensive Rats.

'Haiibuki' is a giant embryo rice cultivar that contains abundant γ-aminobutyric acid (GABA) compared with conventional rice cultivars. Here, we performed a functional evaluation of 'GABA-enriched brown rice' (GEBR) prepared by modifying the 'Haiibuki' cultivar to contain more GABA. Study 1: Spontaneously hypertensive rats were divided into three groups [control (cornstarch), normal brown rice, and GEBR] and fed an orally administered diet for 4 wk. A significant blood pressure elevation-inhibitory effect was observed in the GEBR group as compared with the other groups. Study 2: Rats were divided into two groups and fed ad libitum for 12 wk. The two groups were control (commercial feed with 5% cornstarch) and GEBR (commercial feed with 5% GEBR). Body weight, blood pressure, food consumption, and water intake were measured during the study period, and blood chemistry was analyzed after the study. Plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) and urinary isoprostane were measured 12 and 10 wk after the start of the study, respectively. A significant blood pressure elevation-inhibitory effect was observed in the GEBR group. The 8-OHdG and isoprostane levels were significantly lower in the GEBR group than in the control group, demonstrating an oxidative stress-reducing effect. Therefore, GEBR exhibited a blood pressure elevation-inhibitory effect under the conditions of this study. The antioxidative action may occur secondarily to the antihypertensive action of GABA, suggesting that the long-term ad libitum ingestion of GEBR prevents hypertension. A reduction in oxidative stress could reduce the chances of complications in cardiovascular diseases.

Suppression of hepatic dysfunction in tenascin­X­deficient mice fed a high­fat diet.

Extracellular matrix glycoprotein tenascin­X (TNX) is the largest member of the tenascin family. In the present study, the contribution of TNX to liver dysfunction was investigated by administration of high­fat and high­cholesterol diet with high levels of phosphorus and calcium (HFCD) to wild­type (WT) and TNX­knockout (KO) mice. After 16 weeks of HFCD administration, the ratio of liver weight to body weight was approximately 22% higher in the HFCD­fed WT mice compared with the HFCD­fed TNX­KO mice, indicating hepatomegaly in HFCD­fed WT mice. Histological analyses with hematoxylin and eosin staining at 21 weeks revealed that hepatocyte hypertrophy in HFCD­fed TNX­KO mice was suppressed to 85% of that in HFCD­fed WT mice. By contrast, there was a 1.2­fold increase in lipid deposition in hepatocytes from HFCD­fed TNX­KO mice compared with HFCD­fed WT mice at 18 weeks, as demonstrated by Oil Red O staining. In addition, TNX­KO mice at 21 weeks and 27 weeks post­HFCD administration exhibited significant suppression of inflammatory cell infiltrate to 51 and 24% of that in WT mice, respectively. Immunofluorescence analysis for type I collagen and Elastica van Gieson staining demonstrated a clear hepatic fibrosis progression in HFCD­fed WT mice at 27 weeks, whereas hepatic fibrosis was undetected in HFCD­fed TNX­KO mice. The present findings indicated that TNX deficiency suppressed hepatic dysfunction induced by HFCD administration.

A potential contribution of tenascin-X to blood vessel formation in peripheral nerves.

Tenascin-X (TNX), an extracellular matrix protein, is abundantly expressed in peripheral nerves. However, the physiological role of TNX in peripheral nerves remains unknown. In this study, we found that actin levels in sciatic nerves of TNX-deficient mice were markedly decreased. Since actin was highly expressed in endothelial cells in wild-type sciatic nerves, we assessed morphological alterations of blood vessels in TNX-null sciatic nerves. The density of blood vessels was significantly decreased and the size of blood vessels was larger than those in wild-type sciatic nerves. Immunofluorescence showed that TNX was expressed by Schwann cells and fibroblasts in sciatic nerves. The results suggest that TNX secreted from Schwann cells and/or fibroblasts is involved in blood vessel formation in peripheral nerves.

Prevalence of Helicobacter pylori infection with healthy subjects in Japan.

BACKGROUND AND AIM: Only few large-scale epidemiological studies have examined the prevalence of Helicobacter pylori (H. pylori) infection in Japan. The aim of the present study was to estimate the prevalence and incidence of H. pylori infection in Japan in terms of gender, age and region. METHODS: Serum anti-H. pylori antibody testing was included in workers' annual health checks conducted by T-company's health insurance association in 2008. The testing was continued for the next 5 years in 35-year-old subjects. RESULTS: The total number of subjects was 21 144 (18 398 males and 2746 females). Stratified for age, there were 5016 subjects (male:female=4219:797) in their 30s, 8748 (7770:978) in their 40s, 5589 (4807:782) in their 50s, and 1769 (1584:185) in their 60s. The H. pylori seropositive rate (male:female) was 27.5% (27.5:27.7) overall, 18.0% (18.3:16.1) in subjects in their 30s, 22.9% (22.7:24.7) in those in their 40s, 37.4% (37.2:38.2) in those in their 50s, and 46.1% (45.7:49.2) in those in their 60s. The prevalence of H. pylori seropositivity increased as age increased; however, no significant differences were seen between genders or among regions (χ2 test). The numbers of 35-year-old subjects from 2008 to 2012 were 1072, 1107, 941, 1065, and 940, respectively. The corresponding H. pylori seropositive rates were 17.4, 17.4, 14.3, 13.3, and 14.0%, respectively. CONCLUSION: The Japanese H. pylori infection rate had already declined to 27.5% in 2008, with subjects in the 35-70 age range. The prevalence of H. pylori infection is also decreasing gradually from 2008 to 2012.

Changes in the first line Helicobacter pylori eradication rates using the triple therapy-a multicenter study in the Tokyo metropolitan area (Tokyo Helicobacter pylori study group).

BACKGROUND AND AIM: Helicobacter pylori (H. pylori) infection is a strong risk factor for the development of gastric cancer. In 2013, the Japanese government approved H. pylori eradication therapy in patients with chronic gastritis as well as peptic ulcer. However, the continuing decline in eradication rates for first-line H. pylori eradication therapies is an urgent problem. In this study, we investigated changes in the first-line eradication rate from 2001 to 2010. METHODS: Eradication rates for 7-day triple therapy [proton pump inhibitor (rabeprazole 20 mg, lansoprazole 60 mg, or omeprazole 40 mg)+amoxicillin 1500 mg + clarithromycin (CAM) 400 or 800 mg, daily] were collated from 14 hospitals in the Tokyo metropolitan area. The urea breath test was used for the evaluation of eradication. The cut-off value was less than 2.5%. RESULTS: The yearly eradication rates (intention to treat/per protocol) were 78.5/79.5% (2001, n=242), 71.2%/72.9% (2002, n=208), 67.8%/70.5% (2003, n=183), 75.6%/84.6% (2004, n=131), 56.4%/70.5% (2005, n=114), 70.5%/75.8% (2006, n=271), 67.4%/82.0% (2007, n=135), 64.0%/76.3% (2008, n=261), 60.5%/74.3% (2009, n=329), and 66.5%/78.8% (2010, n=370), respectively. Examination of eradication rates according to CAM dosage revealed an eradication rate of 65.6% (383/584) for CAM 400 mg daily, and 68.5% (1124/1642) for CAM 800 mg daily, with no significant difference seen between dosages. CONCLUSION: In recent years, eradication rates for first-line triple therapy have obviously decreased, but no noticeable decrease has occurred after 2001.

Trends of second-line eradication therapy for Helicobacter pylori in Japan: a multicenter study in the Tokyo metropolitan area.

BACKGROUND: In Japan, the eradication rate of first-line therapy for Helicobacter pylori (H. pylori) with a proton pump inhibitor (PPI), amoxicillin (AMPC) and clarithromycin (CAM) has been decreasing because of a high prevalence of CAM resistance. A possible decrease of the eradication rate for second-line therapy with a PPI, AMPC and metronidazole (MNZ) is of concern. The aim of this study is to assess the trends in second-line eradication therapy for H. pylori in Japan. MATERIALS AND METHODS: We accumulated data retrospectively on patients administered second-line eradication therapy for Helicobacter pylori with a PPI, AMPC, and MNZ for 1 week after failure of first-line eradication therapy with a PPI, AMPC and CAM at 15 facilities in the Tokyo metropolitan area in Japan from 2007 to 2011. Trends for second-line eradication rates in modified intention-to-treat (ITT) analyses were investigated. Second-line eradication rates were categorized by three PPIs (rabeprazole (RPZ), lansoprazole (LPZ) or omeprazole (OMZ)) and evaluated. RESULTS: We accumulated data on 1373 patients. The overall second-line eradication rate was 92.4%. Second-line eradication rates in 2007, 2008, 2009, 2010 and 2011 were 97.7, 90.6, 94.5, 91.8 and 91.8%, respectively, with no significant trends revealed. Second-line eradication rates categorized by three PPIs for the entire 5-year period were 91.6, 93.4 and 92.4% (RPZ, LPZ and OPZ, respectively) with no significant differences among the three PPIs. CONCLUSIONS: From 2007 to 2011, there were no significant trends in the second-line eradication rates and the rates remained consistently high. From the viewpoint of high prevalence of CAM resistance in Japan, triple therapy with PPI, AMPC and MNZ may be a better strategy for first-line therapy compared to triple therapy with PPI, AMPC and CAM.

Color preferences of laboratory mice for bedding materials: evaluation using radiotelemetry.

Preferences for different housing conditions in mice were evaluated by radiotelemetry. Male C57BL/6J and ICR mice were used. Preference for bedding materials in mice was compared among three materials, wood shavings (WS), paper (CF) and cloth (AG), using the length of stay in cages as a parameter. The results indicated that mice stayed longer in a cage with AG than in cages with other bedding materials. The present study confirmed our previous results and thereby indicated that radiotelemetry is a useful method to evaluate impacts of housing conditions on animal welfare. In the second part of this study, we used radiotelemetry to evaluate color preference of the mice for cloth bedding material. In C57BL/6J mice, staying time in black cloth was significantly longer than that in white cloth. In ICR mice, staying time in white cloth was significantly longer than that in black cloth. The mice preferred the environment with the same color as their fur, which may be important for animal welfare.

Narrow-band imaging on screening of esophageal lesions using an ultrathin transnasal endoscopy.

BACKGROUND AND AIM: Ultrathin transnasal endoscopy, used extensively in Japan, is considered to have inferior image quality and suction performance, and questionable diagnostic performance. So the aim of the present study was to compare the diagnostic performance of white light (WL) examination and non-magnified narrow-band imaging (NBI) examination in screening for esophageal disorders with ultrathin transnasal endoscopy. METHODS: A prospective case study of 105 consecutive patients screened for upper gastrointestinal disorders at a single clinic in Tokyo Medical University Hospital. All subjects were diagnosed using WL, NBI and Lugol-staining examinations. Areas ≥ 5 mm clearly not a Lugol-staining lesion were defined as esophageal disorders and the rates of detection of the two examination methods (WL vs NBI) were compared. RESULTS: For WL examination, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy (concordance rate) for esophageal disorders were 19.6%, 98.1%, 90.9%, 55.4%, and 59.2%, respectively, versus 60.8% 96.2%, 93.9%, 71.4%, and 78.6% for NBI. CONCLUSION: A useful level of diagnostic performance for esophageal disorders can be achieved with non-magnified narrow-band NBI ultrathin transnasal endoscopy.

Behavioral alterations in mice lacking the gene for tenascin-x.

Tenascin-X (TNX) is the largest member in the tenascin family of large oligomeric glycoproteins of the extracellular matrix (ECM). TNX is expressed in the leptomeningeal trabecula and connective tissue of choroid plexus in the brain as well as in muscular tissues. Interestingly, single nucleotide polymorphism (SNP) analysis in human showed that TNX is significantly associated with schizophrenia. Previously we generated TNX-deficient (TNX-/-) mice by homologous recombination using embryonic stem (ES) cells. In the present study, we analyzed behaviors relevant to affect, learning and memory, and motor control in TNX-/- mice. TNX-/- mice showed increased anxiety in light-dark and open-field tests and superior memory retention in a passive avoidance test. Also, TNX-/- mice displayed higher sensorimotor coordination than did wild-type mice in a rotorod test. However, TNX-/- mice did not differ from wild-type mice in locomotor activity in a home-cage activity test using telemetric monitoring. These findings suggest that TNX has diverse roles including roles in behavioral functions such as anxiety, emotional learning and memory, and sensorimotor ability.