Electric foot-shock stress drives TNF-alpha production in the liver of IL-6-deficient mice

Objectives: Accumulating evidence has shown that interleukin-6 (IL-6) has pleiotropic effects on a variety of biological functions, including its antiapoptotic potential during liver injury. Our previous work demonstrated that restraint stress-induced elevation of plasma IL-6 negatively regulates plasma tumor necrosis factor-alpha (TNF-alpha). Herein, we further clarified the mechanism underlying the above finding and investigated the effect of IL-6 on liver apoptosis triggered by stress. Methods: Male C57BL/6J and IL-6-deficient C57BL/SV129 mice were exposed to 1 h of electric foot-shock stress. Thereafter, the serum, liver and spleen TNF-alpha levels were measured at several time points. Serum alanine aminotransferase (ALT), liver caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling ( TUNEL) activities were analyzed to evaluate the severity of liver injury and apoptosis. Results: The liver, but not the spleen, of the IL-6-deficient mice exhibited a significant increase in TNF-alpha level after stress in parallel with serum TNF-alpha elevation, whereas no such TNF-alpha responses were found in the wild animals. No significant differences in stress-induced elevation of serum ALT levels, liver caspase-3 activities and the number of TUNEL-positive hepatocytes were found between the wild and IL-6-deficient mice. Conclusions: Taken together, these results indicate that IL-6 may play a critical role in suppressing TNF-alpha production in the liver, thereby decreasing the blood TNF-alpha level. In contrast, IL-6 secretion was shown to have no protective effect on stress-triggered liver injury. Copyright (C) 2004 S. Karger AG, Basel

LLRF upgrade status at the KEK Photon Factory 2.5 GeV ring

In 2023, we are replacing the LLRF system for the KEK-PF 2.5 GeV ring. The new system is composed of digital boards such as eRTM, AMC, and {\mu}RTM, based on the MTCA.4 standard. In our system, we adopted the non-IQ direct sampling method for RF detection. We set the sampling frequency at 8/13 (307.75 MHz) of the RF frequency, where the denominator (13) is the divisor of the harmonic number (312) of the storage ring. This allows us to detect the transient variation of the cavity voltage that is synchronized with the beam revolution. We also plan to compensate for the voltage variation by implementing a feedforward technique. These functions will be useful in a double RF system for KEK future synchrotron light source. Production and installation of the new system were complete and the new system is under commissioning. In this presentation, we introduce our new system and report the upgrade status.Comment: Talk presented at LLRF Workshop 2023 (LLRF2023, arXiv: 2310.03199

Thiazolidinediones enhance vascular endothelial growth factor expression and induce cell growth inhibition in non-small-cell lung cancer cells

<p>Abstract</p> <p>Background</p> <p>It is known that thiazolidinediones are involved in regulating the expression of various genes, including the vascular endothelial growth factor (VEGF) gene via peroxisome proliferator-activated receptor γ (PPARγ); VEGF is a prognostic biomarker for non-small-cell lung cancer (NSCLC).</p> <p>Methods</p> <p>In this study, we investigated the effects of troglitazone and ciglitazone on the mRNA expression of VEGF and its receptors in human NSCLC cell lines, RERF-LC-AI, SK-MES-1, PC-14, and A549. These mRNA expressions were evaluated by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. We also studied the effect of Je-11, a VEGF inhibitor, on the growth of these cells.</p> <p>Results</p> <p>In NSCLC cells, thiazolidinediones increased the mRNA expression of VEGF and neuropilin-1, but not that of other receptors such as fms-like tyrosine kinase and kinase insert domain receptor-1. Furthermore, the PPARγ antagonist GW9662 completely reversed this thiazolidinedione-induced increase in VEGF expression. Furthermore, the addition of VEGF inhibitors into the culture medium resulted in the reversal of thiazolidinedione-induced growth inhibition.</p> <p>Conclusions</p> <p>Our results indicated that thiazolidinediones enhance VEGF and neuropilin-1 expression and induce the inhibition of cell growth. We propose the existence of a pathway for arresting cell growth that involves the interaction of thiazolidinedione-induced VEGF and neuropilin-1 in NSCLC.</p

HIV Types, Groups, Subtypes and Recombinant Forms: Errors in Replication, Selection Pressure and Quasispecies

HIV-1 is a chimpanzee virus which was transmitted to humans by several zoonotic events resulting in infection with HIV-1 groups M P, and in parallel transmission events from sooty mangabey monkey viruses leading to infections with HIV-2 groups A H. Both viruses have circulated in the human population for about 80 years. In the infected patient, HIV mutates, and by elimination of some of the viruses by the action of the immune system individual quasispecies are formed. Along with the selection of the fittest viruses, mutation and recombination after superinfection with HIV from different groups or subtypes have resulted in the diversity of their patterns of geographic distribution. Despite the high variability observed, some essential parts of the HIV genome are highly conserved. Viral diversity is further facilitated in some parts of the HIV genome by drug selection pressure and may also be enhanced by different genetic factors, including HLA in patients from different regions of the world. Viral and human genetic factors influence pathogenesis. Viral genetic factors are proteins such as Tat, Vif and Rev. Human genetic factors associated with a better clinical outcome are proteins such as APOBEC, langerin, tetherin and chemokine receptor 5 (CCR5) and HLA B27, B57, DRB1{*}1303, KIR and PARD3B. Copyright (C) 2012 S. Karger AG, Base

Association of paraoxonase 1 gene polymorphism with Intima-Media Thickness (IMT) of the carotid arteries in japanese type 2 diabetic patients

Purpose: We investigated the association between paraoxonase 1 (PON1)-192 genotypes and intimamedia thickness (IMT) of carotid arteries in diabetic patients. Methods: One hundred and fifty-five Japanese type 2 diabetic patients aged from 40 to 79 years were enrolled in this study. Genotypes of the patients were determined using the PCR-RFLP method. The IMT of carotid arteries of the subjects was measured by ultrasound imaging. Results: The PON1 genotypes frequencies were as follows: 18QQ (0.116), 70QR (0.452) and 67RR (0.432). IMT values of the RR group were significantly greater (1.08±0.41 mm, n=67) than those of the Q group, which consisted of patients carrying one or two Q alleles (0.95±0.27 mm, n=88, P=0.023). There were no significant difference in the clinical characteristics between the two groups. Conclusion: The results indicate that the PON1-192RR genotype is associated with intima media thickening of the carotid arteries in diabetic patients

Performance of in-hospital mortality prediction models for acute hospitalization: Hospital Standardized Mortality Ratio in Japan

<p>Abstract</p> <p>Objective</p> <p>In-hospital mortality is an important performance measure for quality improvement, although it requires proper risk adjustment. We set out to develop in-hospital mortality prediction models for acute hospitalization using a nation-wide electronic administrative record system in Japan.</p> <p>Methods</p> <p>Administrative records of 224,207 patients (patients discharged from 82 hospitals in Japan between July 1, 2002 and October 31, 2002) were randomly split into preliminary (179,156 records) and test (45,051 records) groups. Study variables included Major Diagnostic Category, age, gender, ambulance use, admission status, length of hospital stay, comorbidity, and in-hospital mortality. ICD-10 codes were converted to calculate comorbidity scores based on Quan's methodology. Multivariate logistic regression analysis was then performed using in-hospital mortality as a dependent variable. C-indexes were calculated across risk groups in order to evaluate model performances.</p> <p>Results</p> <p>In-hospital mortality rates were 2.68% and 2.76% for the preliminary and test datasets, respectively. C-index values were 0.869 for the model that excluded length of stay and 0.841 for the model that included length of stay.</p> <p>Conclusion</p> <p>Risk models developed in this study included a set of variables easily accessible from administrative data, and still successfully exhibited a high degree of prediction accuracy. These models can be used to estimate in-hospital mortality rates of various diagnoses and procedures.</p

Charge transfer to ground-state ions produces free electrons

Inner-shell ionization of an isolated atom typically leads to Auger decay. In an environment, for example, a liquid or a van der Waals bonded system, this process will be modified, and becomes part of a complex cascade of relaxation steps. Understanding these steps is important, as they determine the production of slow electrons and singly charged radicals, the most abundant products in radiation chemistry. In this communication, we present experimental evidence for a so-far unobserved, but potentially very important step in such relaxation cascades: Multiply charged ionic states after Auger decay may partially be neutralized by electron transfer, simultaneously evoking the creation of a low-energy free electron (electron transfer-mediated decay). This process is effective even after Auger decay into the dicationic ground state. In our experiment, we observe the decay of Ne2+ produced after Ne 1s photoionization in Ne-Kr mixed clusters