Assessing head and trunk symmetry during sleep using tri-axial accelerometers

Using two types of small, lightweight tri-axial accelerometers, we obtained evidence for the effectiveness of an approach for assessing head–trunk symmetrical or asymmetrical positions during sleep. First, we assessed the accuracy of our monitoring system in five healthy young adults (age range, 22–24 years). The participants wore acceleration monitors on the sternum and forehead; then spent 5?min in six different positions. Once accuracy was confirmed, we assessed head–trunk symmetry during night-time sleep in 10 healthy children (age range, 3–13 years) and 10 young adults (age range, 21–26 years) in their home environments. All participants wore the monitors during one night’s sleep in their homes. After computing head–trunk positions using the orientation data obtained by the accelerometers, head and trunk symmetry were evaluated. The head and trunk positions were correctly detected: the positional data from the trunk had 99% agreement, and the data from the head had 96% agreement. Both the young adults and children were observed to spend time with the head–trunk in asymmetric positions; however, the subjects changed position frequently so the asymmetrical postures were mobile. We concluded that the proposed monitoring system is a reliable and valid approach for assessing head–trunk symmetry during sleep at home.

• Implications for Rehabilitation

• We propose a head and trunk symmetry monitoring system using accelerometers.

• The proposed system could accurately identify head and trunk position.

• Asymmetrical positioning was seen in healthy participants but it was not immobile.

     

Amebic colitis in asymptomatic subjects with positive fecal occult blood test results: clinical features different from symptomatic cases

Amebiasis is a common parasitic infectious disease in developing countries. In developed countries, it is occasionally encountered in travelers to the tropics and in homosexual males. During the past eight years, we detected four cases of amebic colitis among 5,193 subjects who underwent colonoscopy because of positive fecal occult blood test results in a mass screening. All four cases did not have any abdominal symptoms. Ulcerative lesions were observed only in the cecum and ascending colon; another portion of the colon and rectum appeared normal. We may encounter amebic colitis during colonoscopic examination even in subjects who are asymptomatic.     

Predictors for typical asthma onset from cough variant asthma.

Cough variant asthma is recognized to be a precursor of asthma or preasthmatic state because nearly 30% patients with cough variant asthma develop typical asthma within several years. However, predictors for risk of typical asthma onset from cough variant asthma are unknown. Forty-one patients with cough variant asthma (median age 50 years, 13 men and 28 women), who had undertaken spirometry, bronchial reversibility test, methacholine provocation test, measurements of peripheral blood eosinophil count, serum total IgE, and specific IgE to common allergens, and induced sputum eosinophil count at presentation, were followed up with special emphasis on typical asthma onset during 1 year or more (median 4 years, range 1-12.4). Long-term inhaled corticosteroids (ICS) were taken in 27 patients. Univariate and multivariate logistic analyses were performed to determine the predictors for typical asthma onset. Asthma onset was recognized in 7 patients. Bronchial hyperresponsiveness, peripheral blood eosinophil count, and no use of ICS were significant predictors for the typical asthma onset by univariate analysis. However, only bronchial hyperresponsiveness was the significant predictor when multivariate analysis was used (adjusted OR 0.028, 95% CI 0.001-0.783, p = 0.0355). Bronchial hyperresponsiveness may be the most important predictor for risk of typical asthma onset from cough variant asthma.     

Essential role of Sox9 in the pathway that controls formation of cardiac valves and septa

Epithelial-mesenchymal transformation is a critical developmental process reiterated in multiple organs throughout embryogenesis. Formation of endocardial cushions, primordia of valves and septa, is a classic example of epithelial-mesenchymal transformation. Several gene mutations are known to affect cardiac valve formation. Sox9 is activated when endocardial endothelial cells undergo mesenchymal transformation and migrate into an extracellular matrix, called cardiac jelly, to form endocardial cushions. In Sox9-null mutants, endocardial cushions are markedly hypoplastic. In these mutants, Nfatc1 is ectopically expressed and no longer restricted to endothelial cells. Further, Sox9-deficient endocardial mesenchymal cells fail to express ErbB3, which is required for endocardial cushion cell differentiation and proliferation. Our results reveal a succession of molecular steps in the pathway of endocardial cushion development. We propose that loss of Sox9 inhibits epithelial-mesenchymal transformation after delamination and initial migration, but before definitive mesenchymal transformation.     

Characterization of alphaT3-1 cells stably transfected with luteininzing hormone beta-subunit complementary deoxyribonucleic acid

Luteinizing hormone (LH) consists of alpha- and beta-subunits, and synthesis and secretion of LH are regulated by gonadotropin-releasing hormone (GnRH). In order to examine the molecular mechanisms by which GnRH regulates LH secretion, we transfected alphaT3-1 cells with rat LHbeta-subunit cDNA under the control of a constitutive promoter and established a stable cell line of LH2 cells which secreted LH in response to GnRH. Pulsatile and continuous GnRH pretreatments increased gene expression of the alpha-subunit and synthesis of LH, and enhanced the LH secretion by brief treatments with GnRH and 56 mM KCl. The LH secretions were partially blocked by elimination of extracellular Ca2+. GnRH-induced LH secretion was completely inhibited by calphostin C (a protein kinase C inhibitor) and 1 microM wortmannin. In contrast to the GnRH induction, high K+-induced LH secretion was inhibited by KN93, a Ca2+/calmodulin-dependent protein kinase II inhibitor, as well as by 1 microM wortmannin. We also confirmed that activation of cAMP-pathway induced LH secretion, but activation of mitogen-activated protein (MAP) kinase pathway was not involved in LH secretion. These results suggest that GnRH directly regulates LH secretion as well as LHbeta-subunit synthesis, and that LH2 cells are a useful model for the study of LH secretion induced by several secretagogues.     

Helicobacter pylori induces antiapoptosis through buclear factor-kappaB activation

Although Helicobacter pylori is classified as a definite carcinogen, the mechanism underlying gastric carcinogenesis is not yet clear. We previously have shown that H. pylori activates an antiapoptotic gene, the cellular inhibitor of apoptosis protein 2 (c-IAP2), the underlying mechanism of which was investigated in the present study. cDNA array and real-time PCR analyses indicated that H. pylori showed a stimulatory effect on the expression of c-IAP2. Isogenic mutant strains with impaired cag pathogenicity island (cagPAI) expression showed weaker induction. Analyses that used the in situ terminal deoxynucleotide transferase-mediated dUTP nick end-labeling method indicated suppression of antiapoptosis by the antisense c-IAP2 oligonucleotide. Reporter assays with deletion and mutation constructs for the c-IAP2 promoter showed that nuclear factor-kappaB (NF-kappaB) binding sites are indispensable for transactivation. Super-repressor IkappaBalpha or NF-kappaB inhibitor reduced c-IAP2 transactivation by H. pylori, and exogenous expression of c-IAP2 inhibited apoptosis seen with H. pylori. In conclusion, H. pylori induces antiapoptosis through c-IAP2 transactivation following cagPAI-dependent NF-kappaB activation. The interaction of these stimuli may play a role in gastric carcinogenesis.     

Zinc transporter SLC39A10/ZIP10 facilitates antiapoptotic signaling during early B-cell development

The immune system is influenced by the vital zinc (Zn) status, and Zn deficiency triggers lymphopenia; however, the mechanisms underlying Zn-mediated lymphocyte maintenance remain elusive. Here we investigated ZIP10, a Zn transporter expressed in the early B-cell developmental process. Genetic ablation of Zip10 in early B-cell stages resulted in significant reductions in B-cell populations, and the inducible deletion of Zip10 in pro-B cells increased the caspase activity in parallel with a decrease in intracellular Zn levels. Similarly, the depletion of intracellular Zn by a chemical chelator resulted in spontaneous caspase activation leading to cell death. Collectively, these findings indicated that ZIP10-mediated Zn homeostasis is essential for early B-cell survival. Moreover, we found that ZIP10 expression was regulated by JAK-STAT pathways, and its expression was correlated with STAT activation in human B-cell lymphoma, indicating that the JAK-STAT-ZIP10-Zn signaling axis influences the B-cell homeostasis. Our results establish a role of ZIP10 in cell survival during early B-cell development, and underscore the importance of Zn homeostasis in immune system maintenance.Zinc (Zn) has wide-ranging effects on immunity. Zn deficiency has uncovered the importance of Zn homeostasis in immune cell maintenance and function (1). Dramatic effects of Zn on immunity have been observed in several immune and allergy-related cells, including lymphocytes such as B cells (2–6). B cells develop in the bone marrow (BM); the initial commitment to pro-B cells is followed by their differentiation into pre-B cells, and subsequently into immature B cells, which express the B-cell receptor on their surface (7). The immature B cells reach the spleen as transitional B cells, further differentiating into follicular or marginal zone mature B cells (7). Although the perturbation of Zn homeostasis causes splenic atrophy associated with lymphocyte reduction, and compromises cellular and humoral immune responses (6), the mechanisms underlying how Zn controls immune cell function, and in particular, the impact on early B-cell development, have been largely unknown.Zn homeostasis is tightly controlled by Zn transporter family members, Zrt- and Irt-like proteins (ZIPs, Zn importers) and zinc transporters (ZnTs, Zn exporters) (8), and recent studies revealed that alterations in Zn homeostasis mediated by specific Zn transporters play indispensable roles in a variety of cellular events (9). The intestinal Zn transporter ZIP4 is important for the initial absorption of dietary Zn, and patients with mutations in the SLC39A4/ZIP4 gene suffer from the inherited disorder acrodermatitis enteropathica (10, 11). ZIP13 controls the formation of bone, teeth, and connective tissues by modulating BMP/TGF-β signaling (12), and its loss-of-function mutation causes spondylocheiro dysplastic Ehlers-Danlos syndrome in humans (12, 13). ZIP14 controls systemic growth by regulating G protein-coupled receptor (GPCR) signaling (14), and ZIP8 is involved in osteoarthritis (15) and negatively manipulates NF-κB activation (16). In addition, ZnT5 regulates cytokine production by controlling the activation of protein kinase C upon antigen exposure in mast cells (17). Thus, Zn homeostasis mediated by Zn transporters is linked to a wide variety of biological and regulatory functions, and the disruption of a Zn transporter-Zn axis can lead to various symptoms in the absence of redundant machinery (18).Here we demonstrate a definitive role of ZIP10 in early B-cell development. We found that a loss of ZIP10 during an early B-cell stage specifically abrogated cell survival, resulting in the absence of mature B cells, which led to splenoatrophy and reduced Ig levels. The inducible deletion of Zip10 in pro-B cells increased the caspase activity because of the reduced intracellular Zn level, leading to cell death. This phenomenon was mimicked by the intracellular chelation of Zn. These findings indicated that Zn homeostasis via ZIP10 plays an indispensable role in early B-cell survival. We also demonstrated that the ZIP10 expression levels were regulated by STAT3/STAT5 activation, and that ZIP10 was highly expressed in human B-cell lymphoma samples in which both STAT proteins were activated, indicating that the JAK-STAT-ZIP10-Zn signaling axis is important for B-cell maintenance. Our results establish a functional link between ZIP10 and the survival of early stages of B cells, revealing a molecular mechanism underlying the requirement of Zn for maintenance of the immune system.     

The use of infliximab in the prevention of postsurgical recurrence in polysurgery Crohn's disease patients: a pilot open-labeled prospective study

Purpose

Crohn's disease (CD) commonly recurs after surgery, and a number of patients need repeated surgery, especially smokers and those with repeated surgeries or penetrating disease. Whether infliximab prevents postsurgical recurrence in high-risk CD remains unknown. In the present pilot open-labeled study, we investigated the safety and efficacy of scheduled infliximab, which was started early after surgery, in maintaining remission of CD patients who have undergone multiple surgeries due to penetrating disease.

Methods

Eleven patients (nine male, two female; age range, 26–48?years) who had undergone repeated surgeries (median, 4; range, 2–5) for penetrating disease were enrolled. Two to 4?weeks after surgery, the patients were started on intravenous infliximab (5?mg/kg) at an 8-week interval. The primary end points were the proportion of patients in clinical remission at the end of the study, the rate of endoscopic/radiologic remission at 24?months, and the rate of adverse effects.

Results

One patient dropped out due to non-compliance, and ten patients were eligible for analysis. Clinical remission was maintained in six of ten patients (60.0%) at the end of the study. At 24?months, four out of ten patients were in endoscopic or radiological remission (40.0%). Two patients experienced adverse effects (18.2%), one of whom elected to withdraw from the study.

Conclusion

The findings of no major safety concern and possible clinical benefit in our study suggest that further investigation of infliximab as a treatment for prevention of postsurgical recurrence in high-risk CD is warranted.