Analysis of the global gene expression profiles in genomic instability-induced cervical cancer cells

Preserving intact genetic material and delivering it to the next generation are the most significant tasks of living organisms. The integrity of DNA sequences is under constant threat from endogenous and exogenous factors. The accumulation of damaged or incompletely-repaired DNA can cause serious problems in cells, including cell death or cancer development. Various DNA damage detection systems and repair mechanisms have evolved at the cellular level. Although the mechanisms of these responses have been extensively studied, the global RNA expression profiles associated with genomic instability are not well-known. To detect global gene expression changes under different DNA damage and hypoxic conditions, we performed RNA-seq after treating human cervical cancer cells with ionizing radiation (IR), hydroxyurea, mitomycin C (MMC), or 1% O2 (hypoxia). Results showed that the expression of 184–1037 genes was altered by each stimulus. We found that the expression of 51 genes changed under IR, MMC, and hypoxia. These findings revealed damage-specific genes that varied differently according to each stimulus and common genes that are universally altered in genetic instability.

A Case Report of Recurrent Bacterial Meningitis with a Skull Base Abnormality

Recurrent bacterial meningitis is the reappearance of two or more episodes of meningitis caused by a different or same organism after an intervening period of full convalescence. Predisposing factors for recurrent bacterial meningitis include immunodeficiency and developmental and traumatic anatomical defects. Therefore, careful evaluation of children with recurrent meningitis is essential. We report the case of a patient with a skull base abnormality who had suffered from four events of bacterial meningitis between 8 and 17 years of age. He experienced another event of bacterial meningitis at the age of 21, without undergoing correction for the anatomical defect. Streptococcus agalactiae was identified in the patient's blood and cerebrospinal fluid culture. Afterwards, he underwent surgical treatment for a meningioma; this meningioma was strongly suspected as the cause of the recurrence.

Neonatal Screening Tests for Inherited Metabolic Disorders using Tandem Mass Spectrometry: Experience of a Clinical Laboratory in Korea

BACKGROUND: The purpose of this study is to investigate the positive rates of screening tests for inherited metabolic disorders, set cutoff values, and report the actual status of internal quality controls in LabGenomics Clinical Laboratories by using LC-MS/MS system. METHODS: We use Agilent 1260 Infinity HPLC System (Agilent Technologies, USA) for liquid chromatography, and API 2000 (AB Sciex, Canada) for MS/MS system. We set up screening tests for 55 diseases, which include metabolic disorders of 25 amino acids, 16 organic acids, and 14 fatty acids. RESULTS: We determined the analyte cutoff values as 99.9 or 0.1 percentiles in 15,000 newborn samples. The total number of samples tested from January 2012 to September 2014 was 119,948; of these, 6,681 were repeated. Of the repeated samples, 713 were presumed to be positive in the screening tests. Repeat screening with newly obtained dried blood spot specimens was recommended for these 713 samples and 600 specimens were obtained. Thus, the recall rate was 0.5% (600/119,948) for all samples and 84.2% (600/713) for the samples presumed to be positive in the screening tests. About 70 samples, that is, 0.06% of the total samples and 11.7% of the "reobtained" samples, again tested positive; we recommended confirmatory tests for these samples. CONCLUSIONS: We have presented data on the status of neonatal screening tests for inherited metabolic disorders using LC-MS/MS, including positive rates and recall rates of screening tests, set up cutoff values and reported the actual status of internal quality controls in a clinical laboratory in Korea.

Partial Retraction: Difference of Anxiety of Parents: before & after the VCUG

No abstract available.

Acute Tubulointerstitial Nephritis with Renal Failure Complicated by Typhoid Fever

Typhoid fever is a systemic infectious disease which affects many organs. In children, few cases have been reported of acute nephritic syndrome in typhoid fever. We report an immunocompetent 9-year old girl with typhoid fever complicated by acute tubulointerstitial nephritis who presented with prolonged fever and acute renal failure.

Nutcracker Syndrome in Siblings

Nutcracker syndrome refers to the compression of the left renal vein between the abdominal aorta and superior mesenteric artery which can lead to renal vein hypertension. Patients can present with hematuria, proteinuria, dysuria or abdominal pain. In diagnosing the nutcracker syndrome, measurement of the peak velocity ratio of aorto-mesenteric border versus renal hilum by Doppler sonography is useful. Currently, there are few reports about the genetic correlation in this syndrome. We report two cases of the nutcracker syndrome found in male siblings with hematuria.

Difference of Anxiety of Parents: before & after the VCUG

PURPOSE: The voiding cystourethrogram (VCUG) is the investigation of choice in detecting the vesicoureteral reflux in urinary tract infections in children. As it is a potentially distressing and invasive test, most of the parents are so concerned about the child's stress. In this study, we compared the difference of the state of anxiety of parents before and after the VCUG. METHODS: We divided 68 parents whose children underwent VCUG into 2 groups; who have given an explanation about VCUG in detail using pictures (group 1) Vs. who have given an oral explanation only (group 2). All the parents submitted the same questionnaire 2 times before and after the VCUG, which consisted of State-Trait-Anxiety-Inventory X-I (STAI-X-I) and visual analog scale (VAS) on the perception of worry, anxiety, confusion and pain. RESULTS: Before VCUG, the perception of pain was higher in group 1 (P < 0.05). After VCUG, the anxiety and confusion were significantly higher in group 2 than group 1 (P < 0.05). In group 1, STAI-X-I scores, the perception of worry and anxiety were significantly decreased after the VCUG (P < 0.05). In group 2, the confusion and pain were increased after VCUG (P < 0.05). CONCLUSION: It showed that doctor's explanation on the procedure in advance may raise the perception of pain and the possibility of refusal by parents. But the STAI-X-I, worry, anxiety after VCUG were significantly decreased in group 1, while the confusion and pain were increased in group 2. Therefore we suggest that prior and sufficient explanation about invasive procedure like VCUG can be helpful in ameliorating the anxiety of the parents.

Clinical Significance of Hydronephrosis in Febrile Urinary Tract Infection

PURPOSE: Hydronephrosis is found about 30% of children with urinary tract infection (UTI). It can be caused by various conditions, although most childhood hydronephrosis is congenital. This study was performed to investigate the relationship between febrile UTI and hydronephrosis. METHODS: We retrospectively reviewed the medical charts of 183 patients diagnosed as UTI between January 2007 and May 2009 at Korea University Guro Hospital. Inclusion criteria were as followings; 1) fever more than 37.5degrees C measured in the axilla , 2) positive urine culture, 3) no history of urinary tract anomaly on antenatal sonography and urinary tract infection. We classified the enrolled children into two groups of patients with hydronephrosis (HN) and those without hydronephrosis (NHN). RESULTS: The 80 patients were HN and 103 patients NHN. Hydronephrosis was found in 58 patients with left kidney, 8 right and 14 both kidneys. Most of hydronephrosis were of low grade. Compared with NHN group, initial renal cortical defects on DMSA scan significantly increased in HN group (HN 37.5%, NHN 16.5%, P < 0.05). The incidence of VUR was not different between the two groups (HN 22%, NHN 12.1%). White blood cell counts and C-reactive protein were not different between the two groups. Follow-up DMSA scan (about 6 months later after UTI) showed no difference of renal scarring in both two groups. CONCLUSION: Our data suggests that hydronephrosis in febrile UTI patients is clinically useful for detecting renal cortical defects, but is not associated with follow-up renal scar.

Stimulatory heterotrimeric G protein augments gamma ray-induced apoptosis by up-regulation of Bak expression via CREB and AP-1 in H1299 human lung cancer cells

Stimulatory heterotrimeric GTP-binding proteins (Gs protein) stimulate cAMP generation in response to various signals, and modulate various cellular phenomena such as proliferation and apoptosis. This study aimed to investigate the effect of Gs proteins on gamma ray-induced apoptosis of lung cancer cells and its molecular mechanism, as an attempt to develop a new strategy to improve the therapeutic efficacy of gamma radiation. Expression of constitutively active mutant of the alpha subunit of Gs (GalphasQL) augmented gamma ray-induced apoptosis via mitochondrial dependent pathway when assessed by clonogenic assay, FACS analysis of PI stained cells, and western blot analysis of the cytoplasmic translocation of cytochrome C and the cleavage of caspase-3 and ploy(ADP-ribose) polymerase (PARP) in H1299 human lung cancer cells. GalphasQL up-regulated the Bak expression at the levels of protein and mRNA. Treatment with inhibitors of PKA (H89), SP600125 (JNK inhibitor), and a CRE-decoy blocked GalphasQL-stimulated Bak reporter luciferase activity. Expression of GalphasQL increased basal and gamma ray-induced luciferase activity of cAMP response element binding protein (CREB) and AP-1, and the binding of CREB and AP-1 to Bak promoter. Furthermore, prostaglandin E2, a Galphas activating signal, was found to augment gamma ray-induced apoptosis, which was abolished by treatment with a prostanoid receptor antagonist. These results indicate that Galphas augments gamma ray-induced apoptosis by up-regulation of Bak expression via CREB and AP-1 in H1299 lung cancer cells, suggesting that the efficacy of radiotherapy of lung cancer may be improved by modulating Gs signaling pathway.

Inhibition of gamma ray-induced apoptosis by stimulatory heterotrimeric GTP binding protein involves Bcl-xL down-regulation in SH-SY5Y human neuroblastoma cells

Heterotrimeric GTP-binding proteins (G proteins) transduce extracellular signals into intracellular signals by activating effector molecules including adenylate cyclases that catalyze cAMP formation, and thus regulate various cellular responses such as metabolism, proliferation, and apoptosis. cAMP signaling pathways have been reported to protect cells from ionizing radiation-induced apoptosis, but however, the protective mechanism is not clear. Therefore, this study aimed to investigate the signaling molecules and the mechanism mediating the anti-apoptotic action of cAMP signaling system in radiation-induced apoptosis. Stable expression of a constitutively active mutant of G alpha s (G alpha sQL) protected gamma ray-induced apoptosis which was assessed by analysis of the cleavages of PARP, caspase-9, and caspase-3 and cytochrome C release in SH-SY5Y human neuroblastoma cells. G alpha sQL repressed the gamma ray-induced down-regulation of Bcl-xL protein, but transfection of Bcl-xL siRNA increased the gamma ray-induced apoptosis and abolished the anti-apoptotic effect of G alpha sQL. G alpha sQL decreased the degradation rate of Bcl-xL protein, and it also restrained the decrease in Bcl-xL mRNA by increasing the stability following ionizing irradiation. Furthermore, prostaglandin E2 that activates G alpha s was found to protect gamma ray-induced apoptosis, and the protective effect was abolished by treatment with prostanoid receptor antagonist specific to EP2/4R subtype. Moreover, specific agonists for adenosine A1 receptor that inhibits cAMP signaling pathway augmented gamma ray-induced apoptosis. From this study, it is concluded that Galphas-cAMP signaling system can protect SH-SY5Y cells from gamma ray-induced apoptosis partly by restraining down-regulation of Bcl-xL expression, suggesting that radiation-induced apoptosis can be modulated by GPCR ligands to improve the efficiency of radiation therapy.

Anatomical Characterization of Vanilloid Receptor 1 (VR1)-positive Primary Afferents in Lower Lumbar Cord in the Rat / 대한해부학회지

Primary afferents sensitive to capsaicin and noxious heat express vanilloid receptor 1(VR1) in both their peripheral and central fibers and terminals. We used multiple immunofluorescence and confocal microscopy to characterize their pattern of termination in rat spinal cord, colocalization of neurochemical markers of primary afferents and other presynaptic receptors. VR1-positive unmyelinated fibers mainly terminate in lamina I, where they co-stain for CGRP, and to a limited extent for SP, and in lamina II, especially its medial half, where they co-stain for IB4. VR1 positive thin myelinated fibers terminate in lamina I and co-stain for the neurochemical tracer CTB, injected in the sciatic nerve. As revealed by simultaneous staining for the synaptic marker synaptophysin, VR1-positive terminals are abundant in lamina I and sparse in lamina II. In L6-S1 spinal cord, VR1-positive fibers and terminals were abundant in Lissauer's tract, lamina I-V, medial collateral path to lamina X, and lateral collateral path to sacral parasympathetic nucleus. Most of VR1 positive fibers in Lissuer's tract and LCP are colocalized with SP. In conclusion, it is suggested that VR1 positive fibers in spinal cord are both peptidergic and non-peptidergic, IB4 positive fibers, mediating both somatic and visceral sensations, and that peptidergic VR1 positive fibers are mainly related with visceral sense.