Possible involvement of TWIST in enhanced peritoneal metastasis of epithelial ovarian carcinoma

Loss of E-cadherin triggers peritoneal dissemination, leading to an adverse prognosis for most patients with epithelial ovarian carcinoma (EOC). Because TWIST mainly regulates the epithelial-to-mesenchymal transition and is one of the E-cadherin repressors, we investigated the possibility that TWIST expression affects peritoneal metastasis of EOC using siRNA technique. In the present study, we showed a correlation between TWIST expression and EOC cellular morphology. Furthermore, we demonstrated that the suppression of TWIST expression in EOC cells (HEY) alters the cellular morphology from a fibroblastic and motile phenotype to an epithelial phenotype, and inhibits the adhesion of these cells to mesothelial monolayers. To investigate the mechanism by which down-regulation of TWIST leads to inhibition of adhesion to mesothelial cells (MCs), expression of adhesion molecules (CD29, CD44 and CD54) were observed. Moreover, matrix metalloproteinase 2 and membrane type 1 matrix metalloproteinase, important markers associated with invasive and metastatic potential, were remarkably reduced. This findings suggests that reduced expression of TWIST suppresses the multistep process of peritoneal dissemination (detachment from the primary lesion, adhesion to MCs and invasion of MCs) and may be a potential therapeutic target for the treatment of this carcinoma.     

Transforming growth factor beta2 autocrinally mediates neuronal cell death induced by amyloid-beta

Amyloid beta (Abeta), the major component of the senile plaques of Alzheimer's disease, is implicated in neuronal cell death. We have found that Abeta42, a neurotoxic form of Abeta peptide, induces both neuronal and glial expression of TGFbeta2. We have further demonstrated that the addition into culture media of neutralizing antibody to TGFbeta2 or a large amount of the recombinant soluble amyloid precursor protein alpha, the extracellular domain of amyloid precursor protein (APP) generated by alpha secretase, suppresses death in primary cortical neurons (PCNs) induced by Abeta42 in vitro. Combined with the finding in our recent study indicating that TGFbeta2 is a neuronal cell death-inducing ligand for APP, it is suggested that TGFbeta2 is an autocrinal mediator for Abeta42-induced death in PCNs.     

Association study of <Emphasis Type="Italic">interleukin 2</Emphasis> (<Emphasis Type="Italic">IL2</Emphasis>) and <Emphasis Type="Italic">IL4</Emphasis> with schizophrenia in a Japanese population

Interleukin 2 (IL-2) and IL-4 are pleiotropic cytokines regulating Th1/Th2 balance and have a regulatory activity in brain function. Thus these cytokines have been implicated in the pathophysiology of schizophrenia. The latest studies provided controversial results regarding the genetic associations of these cytokines. The functional polymorphisms, IL2-330T/G and IL4-590C/T, were associated with schizophrenia in a German population, although contradictory findings were also reported in a Korean population. To ascertain whether IL2 and IL4 contribute to vulnerability to schizophrenia, we conducted a moderate-scale case-control (536 patients and 510 controls) association study for seven polymorphisms in Japanese subjects. There were no significant associations of these genes with schizophrenia using either single marker or haplotype analyses. The present study suggests that IL2 and IL4 do not contribute to vulnerability to schizophrenia in the Japanese population.     

Leigh syndrome with spinal cord involvement due to a hemizygous NDUFA1 mutation

Leigh syndrome, which is a common phenotype of pediatric mitochondrial disease, is a progressive neurodegenerative disease. The typical neuroimaging findings of Leigh syndrome include bilateral symmetric lesions in the basal ganglia and/or the brainstem. However, there are a few reports on spinal cord involvement in patients with Leigh syndrome. In the present case, magnetic resonance imaging (MRI) obtained during infancy revealed symmetric lesions in the substantia nigra of a patient with Leigh syndrome with an NDUFA1 mutation; lesions of the bilateral putamen and brainstem were subsequently observed. Additionally, our patient presented large and extended spinal cord lesions. Therefore, this case is suggesting that we should consider the occurrence of spinal cord lesions as an atypical finding in Leigh syndrome.     

Recovery of dynamic balance after general anesthesia with sevoflurane in short-duration oral surgery

Purpose  Recovery of dynamic balance, involving adjustment of the center of gravity, is essential for safe discharge on foot after ambulatory anesthesia. The purpose of this study was to assess the recovery of dynamic balance after general anesthesia with sevoflurane, using two computerized dynamic posturographies. Methods  Nine hospitalized patients undergoing oral surgery of less than 2 h duration under general anesthesia (air-oxygensevoflurane) were studied. A dynamic balance test, assessing the ability of postural control against unpredictable perturbation stimuli (Stability System; Biodex Medical), a walking analysis test using sheets with foot pressure sensors (Walk Way-MG1000; Anima), and two simple psychomotor function tests were performed before anesthesia (baseline), and 150 and 210 min after the emergence from anesthesia. Results  Only the double-stance phase in the walking analysis test showed a significant difference between baseline and results at 150 min. None of the other variables showed any differences among results at baseline and at 150 and 210 min. Conclusion  The recovery times for dynamic balance and psychomotor function seem to be within 150 min after emergence from general anesthesia with sevoflurane in patients undergoing oral surgery of less than 2-h duration.     

Reliability of a coordinate system based on anatomical landmarks of the maxillofacial skeleton: an evaluation method for three-dimensional images obtained by cone-beam computed tomography

Objectives  We propose a method for evaluating the reliability of a coordinate system based on maxillofacial skeletal landmarks and use it to assess two coordinate systems. Methods  Scatter plots and 95% confidence ellipses of an objective landmark were defined as an index for demonstrating the stability of the coordinate system. A head phantom was positioned horizontally in reference to the Frankfurt horizontal and occlusal planes and subsequently scanned once in each position using cone-beam computed tomography. On the three-dimensional images created with a volume-rendering procedure, six dentists twice set two different coordinate systems: coordinate system 1 was defined by the nasion, sella, and basion, and coordinate system 2 was based on the left orbitale, bilateral porions, and basion. The menton was assigned as an objective landmark. Results  The scatter plot and 95% ellipse of the menton indicated the high-level reliability of coordinate system 2. The patterns with the two coordinate systems were similar between data obtained in different head positions. Conclusions  The method presented here may be effective for evaluating the reliability (reproducibility) of coordinate systems based on skeletal landmarks.     

Author index

CBA spleen cells have been stimulated in vitro with A/Jap influenza virus-infected CBA spleen cells to generate a ‘primary’ cytotoxic lymphocyte (CL) response. The culture conditions were devised to allow the segregation of individual clones of CL and cytotoxicity measured by the lysis of infected or non-infected L-929 cells. The specificity was assessed by splitting clones and measuring the ability of the clones to discriminate between pairs of targets. Influenza A/FMI and A/Jap strains were used. Subsets of clones were detected which could lyze either A/Jap-infected or A/FMI-infected target cells. In addition CL clones were found which lyzed uninfected L-929 cells and a fourth category were clones which could not discriminate between A/FMI- and A/Jap-infected targets.