Hepatitis C Virus-Related Lymphomagenesis in a Mouse Model

B cell non-Hodgkin lymphoma is a typical extrahepatic manifestation frequently associated with hepatitis C virus (HCV) infection. The mechanism by which HCV infection leads to lymphoproliferative disorder remains unclear. Our group established HCV transgenic mice that expressed the full HCV genome in B cells (RzCD19Cre mice). We observed a 25.0% incidence of diffuse large B cell non-Hodgkin lymphomas (22.2% in male and 29.6% in female mice) within 600 days of birth. Interestingly, RzCD19Cre mice with substantially elevated serum-soluble interleukin-2 receptor α-subunit (sIL-2Rα) levels (>1000 pg/mL) developed B cell lymphomas. Another mouse model of lymphoproliferative disorder was established by persistent expression of HCV structural proteins through disruption of interferon regulatory factor-1 (irf-1_/_/CN2 mice). Irf-1_/_/CN2 mice showed extremely high incidences of lymphomas and lymphoproliferative disorders. Moreover, these mice showed increased levels of interleukin (IL)-2, IL-10, and Bcl-2 as well as increased Bcl-2 expression, which promoted oncogenic transformation of lymphocytes

A Potassium Diboryllithate: Synthesis, Bonding Properties, and the Deprotonation of Benzene

A potassium diboryllithate (B2LiK) was synthesized and structurally characterized. DFT calculations, including NPA and AIM analyses of B2LiK, revealed ionic interactions between the two bridging boryl anions and Li+ and K+. Upon standing in benzene, B2LiK deprotonated the solvent to form a hydroborane and a phenylborane. On the basis of DFT calculations, a detailed reaction mechanism, involving deprotonation and hydride/phenyl exchange processes, is proposed. An NBO analysis of the transition state for the deprotonation of benzene suggests that the deprotonation should be induced by the coordination of benzene to the K+.A â LiK â of work: A potassium diboryllithate, B2LiK, was synthesized and structurally characterized. The bonding situation in this compound was examined by NMR, XRD, NPA, and AIM analyses. B2LiK is able to deprotonate benzene with concomitant formation of phenylborane as the major product. A detailed reaction mechanism based on DFT calculations suggests that the deprotonation of benzene should be initiated by a transition state involving the coordination of benzene to K+.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137264/1/anie201605005_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137264/2/anie201605005-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137264/3/anie201605005.pd

Factors related to employment in childhood cancer survivors in Japan: A preliminary study

PurposePrevious research has revealed vocational and academic difficulties in childhood cancer survivors, and explored impact of survivors' medical history and physical function on vocational and academic status. However, we often encounter survivors with similar diagnoses and late effects but different academic or employment statuses. This raises the question of what affects academic attainment and employment other than treatment or late effects. This study aimed to explore factors associated with childhood cancer survivors' employment status and academic achievement.MethodsComprehensive health check-up and questionnaire survey were conducted for 69 survivors who were over the age of 18 and participated in St. Luke's Lifetime cohort study. We obtained survivors' biological function using comprehensive health check-up, neurocognitive states, quality of life, transition readiness, and family function. We conducted univariate analysis (Mann–Whitney U tests or chi-square tests) to compare the differences between the regular workers/students and non-regular workers/unemployed groups. The variables with p-values <0.1 were used as independent variables multivariate logistic regression to explore predictors of employment status and academic attainment.ResultsResult of the univariate analysis, intelligence quotient, SF-8 PCS, transition readiness, family function were used for multivariate logistic regression as independent variables. The stepwise likelihood method was conducted; intelligence quotient (odds ratio [OR] = 1.100; 95% confidence interval [CI] 1.015–1.193; p = 0.021), transition readiness (OR = 0.612; 95% CI 0.396–0.974; p = 0.038), and family function (OR = 2.337; 95% CI 1.175–4.645; p = 0.015) were found to be associated with survivors' regular workers/students in the final regression model.ConclusionLong-term follow-up of pediatric cancer survivors requires the provision of total care, which supports physical, psychological, and social functions to improve health, readiness for transition to self-management, and family functioning

Host range and receptor utilization of canine distemper virus analyzed by recombinant viruses: Involvement of heparin-like molecule in CDV infection

AbstractWe constructed recombinant viruses expressing enhanced green fluorescent protein (EGFP) or firefly luciferase from cDNA clones of the canine distemper virus (CDV) (a Japanese field isolate, Yanaka strain). Using these viruses, we examined susceptibilities of different cell lines to CDV infection. The results revealed that the recombinant CDVs can infect a broad range of cell lines. Infectivity inhibition assay using a monoclonal antibody specific to the human SLAM molecule indicated that the infection of B95a cells with these recombinant CDVs is mainly mediated by SLAM but the infection of 293 cell lines with CDV is not, implying the presence of one or more alternative receptors for CDV in non-lymphoid tissue. Infection of 293 cells with the recombinant CDV was inhibited by soluble heparin, and the recombinant virus bound to immobilized heparin. Both F and H proteins of CDV could bind to immobilized heparin. These results suggest that heparin-like molecules are involved in CDV infection

High Serum Advanced Glycation End Products Are Associated with Decreased Insulin Secretion in Patients with Type 2 Diabetes: A Brief Report

Advanced glycation end products (AGEs) are important in the pathophysiology of type 2 diabetes mellitus (T2DM). They directly cause insulin secretory defects in animal and cell culture models and may promote insulin resistance in nondiabetic subjects. We have developed a highly sensitive liquid chromatography-tandem mass spectrometry method for measuring AGEs in human serum. Here, we use this method to investigate the relationship between AGEs and insulin secretion and resistance in patients with T2DM. Methods. Our study involved 15 participants with T2DM not on medication and 20 nondiabetic healthy participants. We measured the AGE carboxyethyllysine (CEL), carboxymethyllysine (CML), and methyl-glyoxal-hydro-imidazolone (MG-H1). Plasma glucose and insulin were measured in these participants during a meal tolerance test, and the glucose disposal rate was measured during a euglycemic-hyperinsulinemic clamp. Results. CML and CEL levels were significantly higher in T2DM than non-DM participants. CML showed a significant negative correlation with insulin secretion, HOMA-%B, and a significant positive correlation with the insulin sensitivity index in T2DM participants. There was no correlation between any of the AGEs measured and glucose disposal rate. Conclusions. These results suggest that AGE might play a role in the development or prediction of insulin secretory defects in type 2 diabetes

Relationship between second language speaking and writing skills and modality preference of university EFL students

This study compared the performance of second language learners between the written and spoken modalities in terms of three lexical aspects (fluency, lexical complexity, and grammatical complexity) for the same picture description task. It also examined their modality preference and whether it corresponded with their actual performance. The participants were 26 Japanese university EFL students. They described a six-panel cartoon orally and in writing, answered a questionnaire about their modality preference and educational experiences, and had a follow-up interview. Analysis of their spoken and written descriptions using four linguistic measures (text length, MTLD textual lexical diversity, content word frequency, and average sentence length) revealed that they used a wider variety of vocabulary and shorter sentences in writing than in speaking. About 70% of them preferred the written modality, but half of the students performed equally well in both modalities in terms of the four measures. Further analysis suggested that the variety of words available to learners in each modality may have affected their modality preference and that a study-abroad experience might have affected it as well

Recovery from Unrecognized Sleep Loss Accumulated in Daily Life Improved Mood Regulation via Prefrontal Suppression of Amygdala Activity

Many modern people suffer from sleep debt that has accumulated in everyday life but is not subjectively noticed [potential sleep debt (PSD)]. Our hypothesis for this study was that resolution of PSD through sleep extension optimizes mood regulation by altering the functional connectivity between the amygdala and prefrontal cortex. Fifteen healthy male participants underwent an experiment consisting of a baseline (BL) evaluation followed by two successive interventions, namely, a 9-day sleep extension followed by one night of total sleep deprivation (TSD). Tests performed before and after the interventions included a questionnaire on negative mood and neuroimaging with arterial spin labeling MRI for evaluating regional cerebral blood flow (rCBF) and functional connectivity. Negative mood and amygdala rCBF were significantly reduced after sleep extension compared with BL. The amygdala had a significant negative functional connectivity with the medial prefrontal cortex (FCamg–MPFC), and this negative connectivity was greater after sleep extension than at BL. After TSD, these indices reverted to the same level as at BL. An additional path analysis with structural equation modeling showed that the FCamg–MPFC significantly explained the amygdala rCBF and that the amygdala rCBF significantly explained the negative mood. These findings suggest that the use of our sleep extension protocol normalized amygdala activity via negative amygdala–MPFC functional connectivity. The resolution of unnoticed PSD may improve mood by enhancing frontal suppression of hyperactivity in the amygdala caused by PSD accumulating in everyday life

Pyridoxal in the Cerebrospinal Fluid May Be a Better Indicator of Vitamin B6–dependent Epilepsy Than Pyridoxal 5′-Phosphate

Background We aimed to demonstrate the biochemical characteristics of vitamin B6–dependent epilepsy, with a particular focus on pyridoxal 5′-phosphate and pyridoxal in the cerebrospinal fluid. Methods Using our laboratory database, we identified patients with vitamin B6–dependent epilepsy and extracted their data on the concentrations of pyridoxal 5′-phosphate, pyridoxal, pipecolic acid, α-aminoadipic semialdehyde, and monoamine neurotransmitters. We compared the biochemical characteristics of these patients with those of other epilepsy patients with low pyridoxal 5′-phosphate concentrations. Results We identified seven patients with pyridoxine-dependent epilepsy caused by an ALDH7A1 gene abnormality, two patients with pyridoxal 5′-phosphate homeostasis protein deficiency, and 28 patients with other epilepsies with low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. Cerebrospinal fluid pyridoxal and pyridoxal 5′-phosphate concentrations were low in patients with vitamin B6–dependent epilepsy but cerebrospinal fluid pyridoxal concentrations were not reduced in most patients with other epilepsies with low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. Increase in 3-O-methyldopa and 5-hydroxytryptophan was demonstrated in some patients with vitamin B6–dependent epilepsy, suggestive of pyridoxal 5′-phosphate deficiency in the brain. Conclusions Low cerebrospinal fluid pyridoxal concentrations may be a better indicator of pyridoxal 5′-phosphate deficiency in the brain in vitamin B6–dependent epilepsy than low cerebrospinal fluid pyridoxal 5′-phosphate concentrations. This finding is especially helpful in individuals with suspected pyridoxal 5′-phosphate homeostasis protein deficiency, which does not have known biomarkers