Human protective monoclonal antibodies against the HA stem of group 2 HAs derived from an H3N2 virus-infected human

Objectives

Broadly reactive human monoclonal antibodies against the HA stem of influenza A virus are being developed as therapeutic agents as well as to understand the epitopes that are essential for a universal influenza virus vaccine.

Flow cytometry-based diagnosis of primary immunodeficiency diseases

Primary immunodeficiencies (PIDs) are a heterogeneous group of inherited diseases of the immune system. The definite diagnosis of PID is ascertained by genetic analysis; however, this takes time and is costly. Flow cytometry provides a rapid and highly sensitive tool for diagnosis of PIDs.Flow cytometry can evaluate specific cell populations and subpopulations, cell surface, intracellular and intranuclear proteins, biologic effects associated with specific immune defects, and certain functional immune characteristics, each being useful for the diagnosis and evaluation of PIDs. Flow cytometry effectively identifies major forms of PIDs, including severe combined immunodeficiency, X-linked agammaglobulinemia, hyper IgM syndromes, Wiskott-Aldrich syndrome, X-linked lymphoproliferative syndrome, familial hemophagocytic lymphohistiocytosis, autoimmune lymphoproliferative syndrome, IPEX syndrome, CTLA 4 haploinsufficiency and LRBA deficiency, IRAK4 and MyD88 deficiencies, Mendelian susceptibility to mycobacterial disease, chronic mucocuneous candidiasis, and chronic granulomatous disease. While genetic analysis is the definitive approach to establish specific diagnoses of PIDs, flow cytometry provides a tool to effectively evaluate patients with PIDs at relatively low cost.     

Outpatient treatment of moderately severe active ulcerative colitis with pulsed steroid therapy and conventional steroid therapy

Pulsed steroid therapy may induce rapid remission in patients with moderately severe ulcerative colitis in outpatient clinics. A total of 19 patients with moderately severe active ulcerative colitis who refused hospitalization were treated between October 1999 and September 2001 in the outpatient clinic. Patients were treated with either conventional oral steroid therapy or intravenous pulsed steroid therapy followed by conventional oral steroid therapy. Eight patients received conventional steroid therapy and 11 patients received pulsed steroid therapy followed by conventional steroid therapy. The efficacies of the two types of steroid therapy were equal, but patients with active colitis responded more quickly to pulsed steroid therapy than to conventional steroid therapy. No serious adverse effects were observed. Moderately severe colitis can be safely treated with either conventional or pulsed steroid therapy in the outpatient clinic, but pulsed steroid therapy may induce clinical remission more quickly than conventional steroid therapy.     

Does Helicobacter pylori Exacerbate Gastric Mucosal Injury in Users of Nonsteroidal Anti-Inflammatory Drugs? A Multicenter,Retrospective, Case-Control Study

Background/Aims

The interaction between nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori remains controversial. We retrospectively investigated whether H. pylori infection exacerbates severe gastric mucosal injury among chronic NSAID users.

Methods

From January 2010 to December 2013, a total of 245 long-term NSAID (including low-dose aspirin) users who had undergone an esophagogastroduodenoscopy and had been evaluated for H. pylori infection were enrolled at Okayama University Hospital and Tsuyama Chuo Hospital. The degree of gastric mucosal injury was assessed according to the modified Lanza score (MLS). Severe gastric mucosal injury was defined as an MLS ≥4. Univariate and multivariate logistic regression analyses were performed.

Results

In the univariate analysis, age ≥75 years (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.3 to 4.2), H. pylori-positivity (OR, 2.0; 95% CI, 1.2 to 3.5), and the concomitant use of proton pump inhibitors (PPIs) (OR, 0.48; 95% CI, 0.26 to 0.86) were significantly associated with severe gastric mucosal injury. The multivariate analysis was adjusted by age and sex and demonstrated that H. pylori-positivity (OR, 1.8; 95% CI, 1.0 to 3.3) and the concomitant use of PPIs (OR, 0.53; 95% CI, 0.28 to 0.99) significantly contributed to severe gastric mucosal injury.

Conclusions

H. pylori infection exacerbates severe gastric mucosal injury among chronic NSAID users.     

Failing to deactivate: the association between brain activity during a working memory task and creativity

Working memory (WM) is an essential component for human higher order cognitive activities. Creativity has been essential to the development of human civilization. Previous studies from different fields have suggested creativity and capacity of WM have opposing characteristics possibly in terms of diffuse attention. However, despite a number of functional imaging studies on creativity, how creativity relates to brain activity during WM has never been investigated. In this functional magnetic resonance imaging (fMRI) study, we investigated this issue using an n-back WM paradigm and a psychometric measure of creativity (a divergent thinking test). A multiple regression analysis revealed that individual creativity was significantly and positively correlated with brain activity in the precuneus during the 2-back task (WM task), but not during the non-WM 0-back task. As the precuneus shows deactivation during cognitive tasks, our findings show that reduced task induced deactivation (TID) in the precuneus is associated with higher creativity measured by divergent thinking. The precuneus is included in the default mode network, which is deactivated during cognitive tasks. The magnitude of TID in the default mode network is considered to reflect the reallocation of cognitive resources from networks irrelevant to the performance of the task. Thus, our findings may indicate that individual creativity, as measured by the divergent thinking test, is related to the inefficient reallocation of attention, congruent with the idea that diffuse attention is associated with individual creativity.     

Both global gray matter volume and regional gray matter volume negatively correlate with lifetime alcohol intake in non-alcohol-dependent Japanese men: a volumetric analysis and a voxel-based morphometry

BACKGROUND: Non-alcohol-dependent heavy drinkers, as well as alcohol-dependent individuals, show brain atrophy. The purpose of this study was to evaluate whether there are correlations between global and regional gray matter volumes and the lifetime alcohol intake using volumetric analysis and voxel-based morphometry (VBM) among Japanese non-alcohol-dependent male individuals. METHODS: High-resolution three-dimensional magnetic resonance images were acquired from 405 Japanese non-alcohol-dependent male individuals. The collected images were normalized, segmented for volumetric analysis, and additionally smoothed for VBM. For volumetric analysis, the partial correlation coefficient was estimated between the gray matter ratio, which represents the percentage of gray matter volume in the intracranial volume, and the lifetime alcohol intake adjusted for the age of each subject. Multiple regression analysis was performed among regional gray matter volume, lifetime alcohol intake, and age using VBM. RESULTS: Volumetric analysis revealed that gray matter ratio showed a negative correlation with the lifetime alcohol intake adjusted for age (p=0.059, partial correlation coefficient=-0.091). The VBM revealed that the gray matter volumes of the bilateral middle frontal gyri showed a significant negative correlation with the lifetime alcohol intake adjusted for age and systolic blood pressure (left side, p=0.006, Z=4.77; right side, p=0.023, Z=4.45, and p=0.046, Z=4.27). CONCLUSIONS: Our study suggests that non-alcohol-dependent Japanese male individuals show that both global gray matter volume and regional gray matter volume have negative correlations with the lifetime alcohol intake. Our study may contribute to clarifying the mechanism underlying the brain structural changes because of alcohol influence in healthy non-alcohol-dependent individuals.     

Bepridil inhibits sub-acute phase of atrial electrical remodeling in canine rapid atrial stimulation model.

Background The effect of bepridil, a multichannel blocker, on atrial electrical remodeling was evaluated in a canine rapid atrial stimulation model. Methods and Results In 10 beagle dogs, the right atrial appendage (RAA) was paced at 400 beats/min for 2 weeks. The atrial electrophysiological parameters, including effective refractory period (AERP), were evaluated at three atrial sites: RAA, the right atrium close to the inferior vena cava (IVC) and the left atrium (LA), during the time course of rapid pacing. Five of the dogs were given bepridil (10 mg . kg (-1) . day(-1) po). In the control group, AERP was significantly shortened at all atrial sites and the AERP shortening (DeltaAERP) was larger for the RAA and LA than at the IVC site (p<0.05). In the bepridil group, DeltaAERP was smaller than that of the controls at all atrial sites, and the AERP started to return slowly to the pre-pacing level in the second week, regardless of the continuation of rapid pacing. Conclusions In a canine rapid atrial stimulation model, bepridil suppressed AERP shortening. Bepridil might have a reverse electrical remodeling effect, at least for AERP shortening, because it showed slow recovery of AERP in the subacute phase of rapid atrial pacing. (Circ J 2006; 70: 206 - 213).     

The human prefrontal and parietal association cortices are involved in NO-GO performances: an event-related fMRI study

One of the important roles of the prefrontal cortex is inhibition of movement. We applied an event-related functional magnetic resonance imaging (fMRI) technique to observe changes in fMRI signals of the entire brain during a GO/NO-GO task to identify the functional fields activated in relation to the NO-GO decision. Eleven normal subjects participated in the study, which consisted of a random series of 30 GO and 30 NO-GO trials. The subjects were instructed to press a mouse button immediately after the GO signal was presented. However, they were instructed not to move when the NO-GO signal was presented. We detected significant changes in MR signals in relation to the preparation phases, GO responses, and NO-GO responses. The activation fields related to the NO-GO responses were located in the bilateral middle frontal cortices, left dorsal premotor area, left posterior intraparietal cortices, and right occipitotemporal area. The fields of activation in relation to the GO responses were found in the left primary sensorimotor, right cerebellar anterior lobule, bilateral thalamus, and the area from the anterior cingulate to the supplementary motor area (SMA). Brain activations related to the preparation phases were identified in the left dorsal premotor, left lateral occipital, right ventral premotor, right fusiform, and the area from the anterior cingulate to the SMA. The results indicate that brain networks consisting of the bilateral prefrontal, intraparietal, and occipitotemporal cortices may play an important role in executing a NO-GO response.     

Neural correlates of processing situational relationships between a part and the whole: An fMRI study

Daily situations involve many objects and behaviors. To comprehend the meaning of situations, the relationships between objects, behaviors, and the situational context are important. To reveal the cortical networks involved in processing these relationships we used functional magnetic resonance imaging to compare brain activation during processing of behavior–situation and object–situation relationships. Each session examined two aspects of situational relationship processing: monitoring of the situational relationship and responses to irrelevant relationships. Monitoring was analyzed by comparing cortical activation during a situational relevance judgment task with that during a physical appropriateness judgment task. Responses were analyzed by comparing neural responses to situationally irrelevant and situationally relevant components. The left medial frontal cortex, fusiform gyrus, inferior frontal gyrus, calcarine sulcus, right anterior middle temporal gyrus, orbitoinsular junction, and occipito-temporo-parietal junction were commonly activated while monitoring relationships of both types. The right anterior middle temporal gyrus and orbitoinsular junction were considered to have roles in implicit monitoring because they were more deactivated during physical judgment tasks than during the resting state; this deactivation seemed to reflect unconscious situational monitoring in the resting state. Other regions seemed to be linked to explicit conscious monitoring. Responses to irrelevance were linked to separate and category-specific cortical activation in the left medial frontal cortex and frontal pole for behavioral irrelevance and in the left orbitofrontal cortex for irrelevant objects. We demonstrated that the hierarchical structure of processing situational relationships consisted of implicit monitoring, explicit monitoring, and category-specific responses to irrelevance.