A novel de novo mutation in the serine-threonine kinase STK11 gene in a Korean patient with Peutz-Jeghers syndrome

BACKGROUND: Peutz-Jeghers syndrome (PJS) is an unusual autosomal dominant disorder characterized by mucocutaneous pigmentation and multiple gastrointestinal hamartomatous polyps. Patients with PJS are at an increased risk of developing multi-organ cancer, most frequently those involving the gastrointestinal tract. Germline mutation of the STK11 gene, which encodes a serine-threonine kinase, is responsible for PJS. METHODS: Using DNA samples obtained from the patient and his family members, we sequenced nine exons and flanking intron regions of the STK11 gene using polymerase chain reaction (PCR) and direct sequencing. RESULTS: Sequencing of the STK11 gene in the proband of the family revealed a novel 1-base pair deletion of guanine (G) in exon 6 (c.826delG; Gly276AlafsX11). This mutation resulted in a premature termination at codon 286, predicting a partial loss of the kinase domain and complete loss of the C-terminal domain. We did not observe this mutation in both parents of the PJS patient. Therefore, it is considered a novel de novo mutation. CONCLUSION: The results presented herein enlarge the spectrum of mutations of the STK11 gene by identifying a novel de novo mutation in a PJS patient and further support the hypothesis that STK11 mutations are disease-causing mutations for PJS with or without a positive family history

Predictive Scale for Amyloid PET Positivity Based on Clinical and MRI Variables in Patients with Amnestic Mild Cognitive Impairment

The presence of amyloid-β (Aβ) deposition is considered important in patients with amnestic mild cognitive impairment (aMCI), since they can progress to Alzheimer's disease dementia. Amyloid positron emission tomography (PET) has been used for detecting Aβ deposition, but its high cost is a significant barrier for clinical usage. Therefore, we aimed to develop a new predictive scale for amyloid PET positivity using easily accessible tools. Overall, 161 aMCI patients were recruited from six memory clinics and underwent neuropsychological tests, brain magnetic resonance imaging (MRI), apolipoprotein E (APOE) genotype testing, and amyloid PET. Among the potential predictors, verbal and visual memory tests, medial temporal lobe atrophy, APOE genotype, and age showed significant differences between the Aβ-positive and Aβ-negative groups and were combined to make a model for predicting amyloid PET positivity with the area under the curve (AUC) of 0.856. Based on the best model, we developed the new predictive scale comprising integers, which had an optimal cutoff score ≥ 3. The new predictive scale was validated in another cohort of 98 participants and showed a good performance with AUC of 0.835. This new predictive scale with accessible variables may be useful for predicting Aβ positivity in aMCI patients in clinical practice

Relationship between binge drinking experience and suicide attempts in Korean adolescents: based on the 2013 Korean Youth Risk Behavior Web-based Survey

OBJECTIVES Suicide and drinking problems in adolescents are increasing every year, and it is known that suicide is related to drinking. This study aims to identify the relationship between binge drinking experience (BDE) and suicide attempts in Korean adolescents. METHODS The Ninth Korean Youth Risk Behavior Web-based Survey (KYRBS), conducted in 2013, was used for analysis. Multiple logistic regression analysis was used to identify the relationship between BDE and suicide attempts, and the relationship between BDE and suicide attempts in middle and high school students was stratified by age. RESULTS BDE and suicide attempts were highly related. The odds ratio (OR) of attempted suicide in BDE was 1.63 times (95% confidence interval [CI], 1.28 to 2.09) higher then non-drinking in males. And the OR of attempted suicide in females was 1.21 times (95% CI, 1.07 to 1.37) higher then non-drinking in non-BDE, 1.79 times (95% CI, 1.47 to 2.19) higher in BDE. BDE was associated with suicide attempts in males aged 12 or 13 years (OR, 3.97; 95% CI, 1.57 to 10.03) and in females aged 15 years (OR, 2.66; 95% CI, 1.79 to 3.96). CONCLUSIONS BDE is an important factor related to suicide attempts in adolescents. In order to reduce suicide attempts, it is necessary to educate the youth about the regulation of BDE and drinking prevention

Anti-stress effects of ginseng via down-regulation of tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH) gene expression in immobilization-stressed rats and PC12 cells

Catecholamines are among the first molecules that displayed a kind of response to prolonged or repeated stress. It is well established that long-term stress leads to the induction of catecholamine biosynthetic enzymes such as tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH) in adrenal medulla. The aim of the present study was to evaluate the effects of ginseng on TH and DBH mRNA expression. Repeated (2 h daily, 14 days) immobilization stress resulted in a significant increase of TH and DBH mRNA levels in rat adrenal medulla. However, ginseng treatment reversed the stress-induced increase of TH and DBH mRNA expression in the immobilization-stressed rats. Nicotine as a ligand of the nicotinic acetylcholine receptor (nAChR) in adrenal medulla stimulates catecholamine secretion and activates TH and DBH gene expression. Nicotine treatment increased mRNA levels of TH and DBH by 3.3- and 3.1-fold in PC12 cells. The ginseng total saponin exhibited a significant reversal in the nicotine-induced increase of TH and DBH mRNA expression, decreasing the mRNA levels of TH and DBH by 57.2% and 48.9%, respectively in PC12 cells. In conclusion, immobilization stress induced catecholamine biosynthetic enzymes gene expression, while ginseng appeared to restore homeostasis via suppression of TH and DBH gene expression. In part, the regulatory activity in the TH and DBH gene expression of ginseng may account for the anti-stress action produced by ginseng

Impacts of coexisting bronchial asthma on severe exacerbations in mild-to-moderate COPD : results from a national database

Acknowledgments The authors would like to thank Kyungjoo Kim for the confident statistical analyses in this work. This study was supported by a grant (2014P3300300) from the Korea Centers for Disease Control and Prevention. The abstract of this paper was presented at the Asian Pacific Society of Respirology 20th Congress as an oral presentation with interim findings. The poster’s abstract was published in “Poster Abstracts” in Respirology.Peer reviewedPublisher PD

Neural Dynamics of Olfactory Perception: Low- and High-Frequency Modulations of Local Field Potential Spectra in Mice Revealed by an Oddball Stimulus

Recent brain connectome studies have evidenced distinct and overlapping brain regions involved in processing olfactory perception. However, neural correlates of hypo- or anosmia in olfactory disorder patients are poorly known. Furthermore, the bottom-up and top-down processing of olfactory perception have not been well-documented, resulting in difficulty in locating the disease foci of olfactory disorder patients. The primary aim of this study is to characterize the bottom-up process of the neural dynamics across peripheral and central brain regions in anesthetized mice. We particularly focused on the neural oscillations of local field potential (LFP) in olfactory epithelium (OE), olfactory blub (OB), prefrontal cortex (PFC), and hippocampus (HC) during an olfactory oddball paradigm in urethane anesthetized mice. Odorant presentations evoked neural oscillations across slow and fast frequency bands including delta (1–4 Hz), theta (6–10 Hz), beta (15–30 Hz), low gamma (30–50 Hz), and high gamma (70–100 Hz) in both peripheral and central nervous systems, and the increases were more prominent in the infrequently presented odorant. During 5 s odorant exposures, the oscillatory responses in power were persistent in OE, OB, and PFC, whereas neural oscillations of HC increased only for short time at stimulus onset. These oscillatory responses in power were insignificant in both peripheral and central regions of the ZnSO4-treated anosmia model. These results suggest that olfactory stimulation induce LFP oscillations both in the peripheral and central nervous systems and suggest the possibility of linkage of LFP oscillations in the brain to the oscillations in the peripheral olfactory system

Changes in Sensitization Rate to Weed Allergens in Children with Increased Weeds Pollen Counts in Seoul Metropolitan Area

The prevalence of allergic diseases in children has increased for several decades. We evaluated the correlation between pollen count of weeds and their sensitization rate in Seoul, 1997-2009. Airborne particles carrying allergens were collected daily from 3 stations around Seoul. Skin prick tests to pollen were performed on children with allergic diseases. Ragweed pollen gradually increased between 1999 and 2005, decreased after 2005 and plateaued until 2009 (peak counts, 67 in 2003, 145 in 2005 and 83 grains/m3/day in 2007). Japanese hop pollen increased between 2002 and 2009 (peak counts, 212 in 2006 and 492 grains/m3/day in 2009). Sensitization rates to weed pollen, especially ragweed and Japanese hop in children with allergic diseases, increased annually (ragweed, 2.2% in 2000 and 2.8% in 2002; Japanese hop, 1.4% in 2000 and 1.9% in 2002). The age for sensitization to pollen gradually became younger since 2000 (4 to 6 yr of age, 3.5% in 1997 and 6.2% in 2009; 7 to 9 yr of age, 4.2% in 1997 and 6.4% in 2009). In conclusion, sensitization rates for weed pollens increase in Korean children given increasing pollen counts of ragweed and Japanese hop

APOE Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of APOE ε4 on Alzheimer's Disease Risk in a Multiracial Sample

Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer's disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10-94; GT: OR = 15.87, p = 2.62 × 10-9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10-108; GT: OR = 12.63, p = 3.44 × 10-64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes