cAMP signaling inhibits radiation-induced ATM phosphorylation leading to the augmentation of apoptosis in human lung cancer cells

Background: The ataxia–telangiectasia mutated (ATM) protein kinase plays a central role in coordinating the cellular response to radiation-induced DNA damage. cAMP signaling regulates various cellular responses including metabolism and gene expression. This study aimed to investigate the mechanism through which cAMP signaling regulates ATM activation and cellular responses to ionizing radiation in lung cancer cells. Methods: Lung cancer cells were transfected with constitutively active stimulatory G protein (GαsQL), and irradiated with γ-rays. The phosphorylation of ATM and protein phosphatase 2A was analyzed by western blotting, and apoptosis was assessed by western blotting, flow cytometry, and TUNNEL staining. The promoter activity of NF-κB was determined by dual luciferase reporter assay. BALB/c mice were treated with forskolin to assess the effect in the lung tissue. Results: Transient expression of GαsQL significantly inhibited radiation-induced ATM phosphorylation in H1299 human lung cancer cells. Treatment with okadaic acid or knock down of PP2A B56δ subunit abolished the inhibitory effect of Gαs on radiation-induced ATM phosphorylation. Expression of GαsQL increased phosphorylation of the B56δ and PP2A activity, and inhibition of PKA blocked Gαs-induced PP2A activation. GαsQL enhanced radiation-induced cleavage of caspase-3 and PARP and increased the number of early apoptotic cells. The radiation-induced apoptosis was increased by inhibition of NF-κB using PDTC or inhibition of ATM using KU55933 or siRNA against ATM. Pretreatment of BALB/c mice with forskolin stimulated phosphorylation of PP2A B56δ, inhibited the activation of ATM and NF-κB, and augmented radiation-induced apoptosis in the lung tissue. GαsQL expression decreased the nuclear levels of the p50 and p65 subunits and NF-κB-dependent activity after γ-ray irradiation in H1299 cells. Pretreatment with prostaglandin E2 or isoproterenol increased B56δ phosphorylation, decreased radiation-induced ATM phosphorylation and increased apoptosis. Conclusions: cAMP signaling inhibits radiation-induced ATM activation by PKA-dependent activation of PP2A, and this signaling mechanism augments radiation-induced apoptosis by reducing ATM-dependent activation of NF-κB in lung cancer cells.This study was supported by a National Research Foundation (NRF) grant funded by the Korea government (MEST) (No. 2007–2001258), by Basic Science Research Program through the NRF funded by the Ministry of Education, Science and Technology (2012R1A1A2044374), and a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (0720540).Peer Reviewe

Linguistic Validation of the Intermittent Self-catheterization Questionnaire for Patients With Neurogenic Bladder Who Perform Intermittent Catheterization for Voiding Dysfunction

Purpose In recent years, the importance of patient satisfaction and quality of life—referred to as patient-related outcomes— has been emphasized, in addition to the evaluation of symptoms and severity through questionnaires. However, the questionnaires that can be applied to Korean patients with neurogenic bladder are limited. Therefore, the current study linguistically validated the Intermittent Self-Catheterization Questionnaire (ISC-Q) as an instrument to evaluate the quality of life of Korean patients with neurogenic bladder who regularly perform clean intermittent catheterization (CIC). Methods The validation process included permission for translation, forward translations, reconciliation, backward translation, cognitive debriefing, and proofreading. Two bilingual translators independently translated the original version of the ISC-Q into Korean and then combined the initial translations. A third bilingual translator performed a backward translation of the reconciled version into English. Five Korean-speaking patients with neurogenic bladder carried out the cognitive debriefing. Results During the forward translation process, the 24 questions of the ISC-Q were translated into 2 Korean versions. The terms used in each version were adjusted from the original version to use more conceptually equivalent expressions in Korean. During the backward translation process, several changes were involving substitutions of meaning. In the cognitive debriefing process, 5 patients were asked to complete the questionnaire. All patients agreed that the questionnaire explained their situation well. Conclusions This study presents a successful linguistic validation of the Korean version of the ISC-Q, which could be a useful tool for evaluating treatment satisfaction in patients with neurogenic bladder performing CIC regularly

Predictors of Successful Trial without Catheter for Postoperative Urinary Retention Following Non-Urological Surgery

Purpose To investigate the success rate of trial without catheter (TWOC) for postoperative urinary retention (POUR) after non-urological surgery and to determine predictors of successful TWOC. Methods A total of 104 patients who underwent non-urological surgery and were referred to the department of urology for POUR were included in this retrospective study. All eligible patients underwent indwelling catheterization as an initial treatment and then TWOC was performed 3 to 7 days later. POUR was defined as micturition difficulty with greater than 400 mL of postvoid residual (PVR) urine volume measured by catheterization after non-urological surgery. Successful TWOC was defined as voiding with less than 100 mL of PVR urine volume. Predictive factors were identified by multivariate regression analysis. All definitions corresponded to recommendations of the International Continence Society. Results The mean age of the patients was 65.2 (range, 23 to 92) years. There were 45 male and 59 female patients. Intraoperative indwelling catheterization was performed in 69 (66.3%) patients. Mean duration of indwelling catheterization for POUR was 5.0 (range, 3.0 to 7.0) days and 83 (79.8%) patients received medication with an alpha-blocker. A successful TWOC was observed in 70 (67.4%) patients. The mean age of the patients with failure of TWOC was significantly higher than that of the patients with successful TWOC. The percentages of female patients, spinal surgery, and prone position during surgery in patients with unsuccessful TWOC were higher than in those with successful TWOC. In the multivariate logistic regression analysis, age and location of surgery (spine vs. non-spine) were the independent predictors of successful TWOC for POUR. Conclusions Our data suggest that older age and spinal surgery may be important risk factors for failure of TWOC for POUR after non-urological surgery. Thus, adequate prevention measures may be necessary for POUR after non-urological surgery, especially in patients with these risk factors

XANES and EXAFS study of a platinum phthalocyanine

Extended X-ray absorption fine structure (EXAFS) and X-ray absorption near-edge structure (XANES) studies on [octa(2-ethylhexyloxy)phthalocyaninato]platinum [PtL] as a film at room temperature suggest that the structure consists of non-planar, concave discotic molecules packed perpendicular to the stacking axis.Peer reviewedChemistr

Quantitative agreement of Dzyaloshinskii-Moriya interactions for domain-wall motion and spin-wave propagation

The magnetic exchange interaction is the one of the key factors governing the basic characteristics of magnetic systems. Unlike the symmetric nature of the Heisenberg exchange interaction, the interfacial Dzyaloshinskii-Moriya interaction (DMI) generates an antisymmetric exchange interaction which offers challenging opportunities in spintronics with intriguing antisymmetric phenomena. The role of the DMI, however, is still being debated, largely because distinct strengths of DMI have been measured for different magnetic objects, particularly chiral magnetic domain walls (DWs) and non-reciprocal spin waves (SWs). In this paper, we show that, after careful data analysis, both the DWs and SWs experience the same strength of DMI. This was confirmed by spin-torque efficiency measurement for the DWs, and Brillouin light scattering measurement for the SWs. This observation, therefore, indicates the unique role of the DMI on the magnetic DW and SW dynamics and also guarantees the compatibility of several DMI-measurement schemes recently proposed.Comment: 24 pages, 5 figure

Glutaric Aciduria Type 1 in Korea: Report of Two Novel Mutations

Glutaric aciduria type I (GA I) is an autosomal recessive disorder caused by a deficiency of glutaryl-CoA dehydrogenase. Although over 400 patients confirmed as GA I have been reported, reports from the Asian population had contributed to the minor proportion. We recently diagnosed two cases of GA I confirmed with mutational analysis. Here, we present their rather atypical clinical presentations with genetic characteristics for the first time in Korea. Profound developmental delay from birth, association of hearing loss, and neurological improvement after surgical intervention, were considered to be different clinical features from most reported cases. One patient was a compound heterozygote for p.Ser139Leu and p.Asp220Tyr, and the other for p.Ser139Leu and Glu160X. The mutations of the two alleles (p.Asp220Tyr and p.Glu160X) were novel and reports of p.Ser139Leu were rare both in Western and other Asian populations. These might suggest different genetic spectrum of Korean GA I patients

Regulation of Pituitary Adenylate Cyclase-activating Polypeptide Gene Transcription by TTF-1, a Homeodomain-containing Transcription Factor

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an important hypophysiotrophic factor as well as a regulator for immune, reproductive, and neural tissues. We recently found that TTF-1, a homeodomain-containing transcription factor essential for the development of the fetal diencephalon, is postnatally expressed in the hypothalamic area and plays a transcription regulatory role for certain neurohormones. Based on the similarity of synthesis sites between PACAP and TTF-1 and, moreover, on the presence of conserved core TTF-1 binding motifs in the 5′-flanking region of the PACAP gene, we sought to uncover a regulatory role of TTF-1 in PACAP gene transcription. The TTF-1 homeodomain binds to six of the seven putative binding domains observed in the 5′-flanking region of the PACAP gene. In the C6 glioma cell-line, TTF-1 activates the PACAP promoter in a dose-dependent manner. This transactivation of PACAP by TTF-1 was totally removed when the core TTF-1 binding motif at −369 was deleted. RNase protection assays showed that TTF-1 and PACAP mRNAs have daily fluctuations in the rat hypothalamus. They both were at low levels during the day and high levels during the night. Intracerebroventricular administration of an antisense TTF-1 oligodeoxynucleotide significantly decreased the PACAP mRNA level as well as TTF-1 protein content in the rat hypothalamus, suggesting that TTF-1 also regulates PACAP transcription in vivo. Moreover, the TTF-1 promoter was inhibited by molecular oscillators of CLOCK and BMAL-1. Taken together, these data suggest that TTF-1 plays an important regulatory role in the gene transcription for PACAP, which may be important for the generation of a daily rhythm of hypothalamic PACAP gene expression

Magnetic Resonance Imaging Compatibility of the Polymer-based Cochlear Implant

ObjectivesIn this study, we compared the magnetic resonance (MR) image artifacts caused by a conventional metal-based cochlear implant and a newly developed liquid crystal polymer (LCP)-based device.MethodsThe metal-based cochlear implant system (Nurobiosys Co.) was attached to side of the head of a subject and the LCP-based device was attached to opposite side. In both devices, alignment magnets were removed for safety. Magnetic resonance imaging (MRI) was performed on a widely used 3.0 T and an ultra-high 7.0 T MRI machine. 3.0 and 7.0 T MR images were acquired using T1- and T2*-weighted gradient echo sequences, respectively.ResultsIn the 3.0 T images, the metal-based device on the left side generated the significant amount of artifacts. The MR images in the proximity of the metal package were obscured by the artifacts in both axial and sagittal views. On the other hand, the MR images near the LCP-based device were relatively free from the artifacts and clearly showed the brain structures. 7.0 T MR images showed the more severe distortion in the both sides but the metal-based cochlear implant system caused a much larger obscure area than the LCP-based system.ConclusionThe novel LCP-based cochlear implant provides a good MRI compatibility beyond present-day cochlear implants. Thus, MR images can be obtained from the subjects even with the implanted LCP-based neural prosthetic systems providing useful diagnostic information. Furthermore, it will be also useful for functional MRI studies of the auditory perception mechanism after cochlear implantations as well as for positron emission tomography-MRI hybrid imaging

A Case of Swallow Syncope Associated With Cold Beverage Ingestion

Swallow syncope (also known as deglutition syncope) is a relatively rare type of syncope that is treatable if diagnosed correctly. We report a case of a 39-year-old man with recurrent swallow syncope. The patient did not have structural heart disease. He developed a complete atrioventricular block upon drinking a cold beverage (Chilsung cider) while undergoing a repeated head-up tilt test. The patient was advised to avoid cold beverages and has been symptom free for 5 months