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1.
Plant Cell Environ ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780063

ABSTRACT

Plasmodesmata (PDs) are intercellular organelles carrying multiple membranous nanochannels that allow the trafficking of cellular signalling molecules. The channel regulation of PDs occurs dynamically and is required in various developmental and physiological processes. It is well known that callose is a critical component in regulating PD permeability or symplasmic connectivity, but the understanding of the signalling pathways and mechanisms of its regulation is limited. Here, we used the reverse genetic approach to investigate the role of C-type lectin receptor-like kinase 1 (CLRLK1) in the aspect of PD callose-modulated symplasmic continuity. Here, we found that loss-of-function mutations in CLRLK1 resulted in excessive PD callose deposits and reduced symplasmic continuity, resulting in an accelerated gravitropic response. The protein interactome study also found that CLRLK1 interacted with actin depolymerizing factor 3 (ADF3) in vitro and in plants. Moreover, mutations in ADF3 result in elevated PD callose deposits and faster gravitropic response. Our results indicate that CLRLK1 and ADF3 negatively regulate PD callose accumulation, contributing to fine-tuning symplasmic opening apertures. Overall, our studies identified two key components involved in the deposits of PD callose and provided new insights into how symplasmic connectivity is maintained by the control of PD callose homoeostasis.

2.
Molecules ; 25(24)2020 Dec 18.
Article in English | MEDLINE | ID: mdl-33352899

ABSTRACT

We have isolated a filamentous fungus that actively secretes a pigmented exudate when growing on agar plates. The fungus was identified as being a strain of Epicoccum nigrum. The fungal exudate presented strong antifungal activity against both yeasts and filamentous fungi, and inhibited the germination of fungal spores. The chemical characterization of the exudate showed that the pigmented molecule presenting antifungal activity is the disalt of epipyrone A-a water-soluble polyene metabolite with a molecular mass of 612.29 and maximal UV-Vis absorbance at 428 nm. This antifungal compound showed excellent stability to different temperatures and neutral to alkaline pH.


Subject(s)
Antifungal Agents/pharmacology , Ascomycota/chemistry , Yeasts/drug effects , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Ascomycota/metabolism , Fungi/drug effects , Fungi/metabolism , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Spectrophotometry, Ultraviolet , Spores, Fungal/drug effects , Spores, Fungal/metabolism , Yeasts/metabolism
3.
J Clin Gastroenterol ; 52(5): 431-436, 2018.
Article in English | MEDLINE | ID: mdl-28277374

ABSTRACT

GOALS: This study sought to clarify sex differences in KRAS mutations and clinical predictors of KRAS 13 codon mutations. BACKGROUND: Sex differences in KRAS mutations and predictors for KRAS codon 13 mutations in colorectal cancer (CRC) are unclear. STUDY: Between October 2007 and May 2016, 328 patients underwent surgery for CRCs that were analyzed for KRAS mutations at a referral university hospital. Sex differences in the rates and distributions of KRAS mutations, and factors predictive of overall KRAS and KRAS codon 13 mutations were analyzed. RESULTS: KRAS mutations were significantly more common in women than men patients (46.0% vs. 34.4%, P<0.033). However, no sex differences were detected for KRAS mutations by codon subtypes (P=0.592). The Gly13Asp (GGC>GAC) point mutation was identified only within codon 13 in both sexes. For right-sided CRC, KRAS mutations were twice as frequent in men as in women (univariate analysis; P=0.016, multivariate analysis; P=0.019). High-plasma cholesterol level was an independent predictive factor of KRAS codon 13 mutations by univariate (odds ratio, 1.013; 95% confidence interval, 1.003-1.023) and multivariate analysis (odds ratio, 1.011; 95% confidence interval, 1.001-1.021). CONCLUSIONS: Sex differences may affect the presentation of KRAS mutations, as they were more frequently detected in women and in right-sided CRC in men. KRAS codon 13 mutations were significantly associated with high-plasma cholesterol. Further studies are needed on the clinical implications of this finding.


Subject(s)
Cholesterol/blood , Colorectal Neoplasms/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Aged , Aged, 80 and over , Codon/genetics , Colorectal Neoplasms/pathology , Female , Hospitals, University , Humans , Male , Middle Aged , Multivariate Analysis , Mutation , Point Mutation , Retrospective Studies , Sex Factors
4.
Anaerobe ; 25: 11-7, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24239979

ABSTRACT

The utilisation of various prebiotic oligosaccharides by probiotic strains of Bifidobacterium lactis, Lactobacillus rhamnosus and Lactobacillus acidophilus was investigated in order to determine the synbiotic potential of various prebiotic/probiotic combinations. Analysis by HPLC and high-performance anion-exchange chromatography of the cell-free medium taken during growth of the three probiotic bacteria showed differences in the consumption of the various oligosaccharides. Analysis of galactooligosaccharides showed that both L. rhamnosus and B. lactis consumed mostly mono- and di-saccharide, while L. acidophilus consumed oligosaccharides up to trisaccharide. Both B. lactis and L. acidophilus utilised fructooligosaccharides and inulin, but showed different patterns of oligosaccharide consumption. Only L. rhamnosus grew on ß-glucan oligosaccharides and preferentially consumed the trisaccharide. The results indicate the synbiotic potential of the various probiotic/prebiotic combinations, particularly L. acidophilus/galactooligosaccharides, L. acidophilus/fructooligosaccharides or inulin and L. rhamnosus/ß-glucan oligosaccharides.


Subject(s)
Bifidobacterium/metabolism , Lacticaseibacillus rhamnosus/metabolism , Lactobacillus acidophilus/metabolism , Oligosaccharides/metabolism , Prebiotics , Bifidobacterium/growth & development , Fermentation , Lactobacillus acidophilus/growth & development , Lacticaseibacillus rhamnosus/growth & development
5.
Reprod Biol Endocrinol ; 11: 8, 2013 Feb 12.
Article in English | MEDLINE | ID: mdl-23402365

ABSTRACT

BACKGROUND: The members of the microtubule-associated protein 1 light chain (MAP1LC) family, especially those of the LC3 family (MAP1LC3A, B, C), are known to induce autophagy upon localization onto the autophagosomal membrane. In this regard, LC3 can be utilized as a marker for the formation of autophagosomes during the process of autophagy. The aims of this study are to clone porcine MAP1LC3A, and analyze the pattern of its expression in the ovarian tissues of normal and miniature pig ovary in an attempt to understand the distinct mode of apoptosis between two strains. METHODS: Rapid amplification of cDNA ends (RACE) were used to obtain the 5' and 3' ends of the porcine MAP1LC3A full length cDNA. Reverse-transcriptase-PCR (RT-PCR), real-time PCR, and western blot analysis were performed to examine the expression of porcine MAP1LC3A. The localization of MAP1LC3A in the ovary was determined by In situ Hybridization and Immunohistochemical staining. RESULTS: We cloned the full-length cDNA of porcine MAP1LC3A and identified an open reading frame of 980 bp encoding 121 amino acids. Based on its homology to known mammalian proteins (98%) this novel cDNA was designated as porcine MAP1LC3A and registered to the GenBank (Accession No. GU272221). We compared the expression of MAP1LC3A in the Graafian follicles of normal and miniature pigs by in situ hybridization at day 15 of the estrus cycle. While normal pigs showed a stronger expression of MAP1LC3A mRNA than miniature pigs in the theca cell area, the expression was lower in the granulosa cells. Immunofluorescence analysis of the MAP1LC3A fusion reporter protein showed the subcellular localization of porcine MAP1LC3A and ATG5 as a punctate pattern in the cytoplasm of porcine granulosa cells under stress conditions. In addition, the expressions of MAP1LC3A and ATG5 were higher in normal pigs than in miniature pigs both in the presence and absence of rapamycin. CONCLUSIONS: The newly cloned porcine MAP1LC3A provides a novel autophagosomal marker in both normal and miniature pig. We demonstrated that the expression of MAP1LC3A in graafian follicle is distinct in normal and miniature pig, which may explain the unique folliculogenesis of miniature pigs.


Subject(s)
Autophagy , Gene Expression Regulation , Granulosa Cells/metabolism , Microtubule-Associated Proteins/metabolism , Protein Subunits/metabolism , Amino Acid Sequence , Animals , Animals, Inbred Strains , Base Sequence , Biomarkers/chemistry , Biomarkers/metabolism , Cells, Cultured , Female , Granulosa Cells/cytology , Microtubule-Associated Proteins/chemistry , Microtubule-Associated Proteins/genetics , Molecular Sequence Data , Ovarian Follicle/cytology , Ovarian Follicle/metabolism , Protein Subunits/chemistry , Protein Subunits/genetics , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , Sequence Alignment , Sequence Homology, Amino Acid , Species Specificity , Sus scrofa , Swine , Swine, Miniature , Theca Cells/cytology , Theca Cells/metabolism
6.
Adv Ther ; 40(3): 1047-1061, 2023 03.
Article in English | MEDLINE | ID: mdl-36624354

ABSTRACT

INTRODUCTION: SB2 is a biosimilar of infliximab (IFX), which is approved for rheumatoid arthritis (RA), ankylosing spondylitis (AS), adult and pediatric Crohn's disease (CD), adult and pediatric ulcerative colitis (UC), psoriatic arthritis (PsA), and plaque psoriasis (PsO). The drug approval process in Korea includes post-marketing surveillance (PMS) studies to re-examine the safety and effectiveness of approved new medications. METHODS: This was a prospective, multi-center, open-label, observational, phase 4 PMS study of IFX-naïve patients or patients switched from reference IFX or another IFX-biosimilar to SB2 in all approved indications. The primary endpoint was to evaluate the safety of SB2 reported as adverse events (AEs) and adverse drug reactions (ADRs). The secondary endpoint was to evaluate the effectiveness measured as investigators' overall effectiveness assessment, categorized as improved, stable, or worsened. Furthermore, disease-specific activity scores were collected for each indication [28-joint Modified Disease Activity Score (DAS28) for RA, Korean Bath Ankylosing Spondylitis Disease Activity Index (KBASDAI), Crohn's Disease Activity Index (CDAI), and Full Mayo Score for UC]. RESULTS: In the safety and effectiveness analysis, 180 and 128 patients were included, respectively. Most patients (83.9%) were IFX-naïve patients and 16.1% were switched patients. RA (48.9%) and AS (31.1%) were the most frequent indications. Overall, 23 (12.8%) patients reported AEs and 14 (7.8%) patients reported ADRs. Serious adverse events (SAEs) were reported by 3 (1.7%) patients. As per investigators' overall effectiveness assessments, SB2 was effective in 94.6% (105/111) of IFX-naïve patients and 82.4% (14/17) of switched patients. In IFX-naïve patients, disease activity scores decreased significantly from baseline to week 30 (week 24 for AS); mean (SD) changes of disease scores for each indication were DAS28 - 1.9 (0.79) for RA, KBASDAI - 3.8 (1.68) for AS, CDAI - 200.4 (112.47) for CD, and Full Mayo Score - 6.6 (2.92) for UC. The persistence rate of SB2 treatments was 88.3% with median treatment duration of 30.1 weeks. CONCLUSION: This PMS study of the IFX-biosimilar SB2 in Korea confirmed the safety and effectiveness of SB2 in major indications.


Subject(s)
Arthritis, Psoriatic , Arthritis, Rheumatoid , Biosimilar Pharmaceuticals , Spondylitis, Ankylosing , Child , Humans , Adult , Infliximab/adverse effects , Spondylitis, Ankylosing/drug therapy , Biosimilar Pharmaceuticals/adverse effects , Prospective Studies , Arthritis, Psoriatic/drug therapy , Arthritis, Rheumatoid/drug therapy , Treatment Outcome , Republic of Korea , Product Surveillance, Postmarketing
7.
JOP ; 13(3): 312-3, 2012 May 10.
Article in English | MEDLINE | ID: mdl-22572140

ABSTRACT

CONTEXT: Hemosuccus pancreaticus is a rare cause of intermittent upper gastrointestinal bleeding, commonly caused by aneurysmal rupture. Prompt diagnosis and treatment is required. The standard treatment involves embolization via interventional radiology or a surgical approach. CASE REPORT: We report a novel endoscopic approach to hemosuccus pancreaticus with a successful tamponade via pancreatic biliary stents and resolution clips. CONCLUSION: This is the only report of endoscopy as a therapeutic modality in a case of hemosuccus pancreaticus.


Subject(s)
Ampulla of Vater/surgery , Balloon Occlusion/methods , Common Bile Duct Diseases/surgery , Endoscopy, Digestive System/methods , Hemorrhage/surgery , Stents , Female , Humans , Middle Aged , Surgical Instruments , Treatment Outcome
8.
Dig Endosc ; 24(3): 185-7, 2012 May.
Article in English | MEDLINE | ID: mdl-22507094

ABSTRACT

Pancreatic pseudocysts are frequent complications of pancreatitis episodes. The current therapeutic modalities for drainage of pancreatic pseudocysts include surgical, percutaneous, and endoscopic drainage modalities. Endosonography-assisted endoscopic drainage of these pseudocysts with the placement of multiple plastic or fully covered self-expanding biliary metal stents is becoming more commonly carried out. The present case report discusses the unique and successful drainage of a pancreatic pseudocyst with the placement of a partially covered self-expanding metal stent.


Subject(s)
Endosonography , Gastrostomy/methods , Pancreatic Pseudocyst/surgery , Stents , Drainage/instrumentation , Female , Fluoroscopy , Humans , Middle Aged , Pancreatic Pseudocyst/diagnostic imaging , Radiography, Interventional , Tomography, X-Ray Computed , Ultrasonography, Interventional
9.
Dig Dis Sci ; 56(3): 786-91, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20632097

ABSTRACT

BACKGROUND: Risk stratification of patients with acute upper GI bleeding (UGIB) in the emergency room (ER) enables appropriate triage to urgent endoscopy and therapeutic intervention. AIM: The aim of this study was to evaluate the ability of Live View Video Capsule Endoscopy (VCE) with Pillcam Eso(®) to accurately identify high and low risk patients with UGIB. METHODS: Twenty-four patients with a history of UGIB within 48 h of admission to the ER were randomized to VCE versus standard clinical assessment. VCE was read real-time at the bedside and later reviewed after download. Positive VCE findings included coffee grounds, blood clot, red blood, or a bleeding lesion. VCE positive patients underwent EGD within 6 h. Control patients and VCE negative patients underwent EGD within 24 h. RESULTS: Seven of 12 patients were VCE positive. All seven had confirmatory stigmata at EGD. Of the five VCE negative patients, four had no stigmata at EGD and one was not endoscoped due to comorbidities. The actual lesion was visualized at VCE in four of 12 patients during live view and in an additional two patients after download (6/12). Time to endoscopy in the VCE positive group was significantly shorter than control patients (2.5 vs. 8.9 h, P = 0.029). There was no mortality. Blood transfusion requirement and length of stay were not significantly different in the two groups. CONCLUSIONS: Live view VCE accurately identifies high and low risk ER patients with UGIB. Use of VCE to risk stratify these patients significantly reduced time to emergent EGD and therapeutic intervention.


Subject(s)
Capsule Endoscopy/methods , Emergency Medical Services/methods , Endoscopy, Digestive System/instrumentation , Endoscopy, Digestive System/methods , Gastrointestinal Hemorrhage/diagnosis , Acute Disease , Aged , Female , Humans , Male , Middle Aged , Pilot Projects , Risk , Triage , Upper Gastrointestinal Tract
10.
Exp Parasitol ; 127(1): 322-5, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20723543

ABSTRACT

Aloes have been widely used for a broad range of pharmacological activities, including parasitic problems. Avian coccidiosis is the most costly and wide-spread parasitic disease in the poultry industry, and has been mainly controlled by the use of chemotherapeutic agents. Due to the emergence of drug-resistant strains, alternative control strategies are needed. In this study, the protective effects of Aloe vera-based diets were assessed in broiler chickens following oral infection with Eimeria maxima. Chickens were fed a regular diet supplemented with ground Aloe vera throughout the duration of the experiment beginning 2 days prior to infection with 1 × 10(4) sporulated oocysts of E. maxima. No significant differences were found in body weight gain or loss between the Aloe vera-supplemented and unsupplemented groups with or without E. maxima infections. Fecal oocyst shedding decreased significantly (p < 0.05) in all of the treatment groups that were supplemented with Aloe vera as compared to the unsupplemented group. Furthermore, the Aloe vera-supplemented group showed significantly fewer intestinal lesions (p < 0.05) than the unsupplemented group following infection. The findings of this study suggest that Aloe vera could be used an alternative treatment for controlling avian coccidiosis.


Subject(s)
Aloe , Chickens/parasitology , Coccidiosis/veterinary , Eimeria , Poultry Diseases/diet therapy , Animal Feed , Animals , Antibodies, Protozoan/blood , Coccidiosis/diet therapy , Coccidiosis/prevention & control , Diet/veterinary , Dietary Supplements , Eimeria/immunology , Enzyme-Linked Immunosorbent Assay/veterinary , Feces/parasitology , Intestines/pathology , Male , Parasite Egg Count/veterinary , Poultry Diseases/prevention & control , Powders , Random Allocation , Weight Gain
11.
Ecotoxicol Environ Saf ; 74(5): 1280-7, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21397328

ABSTRACT

The aims of this study were to determine the sorption coefficient (LogK(DOC)) of 17ß-estradiol (E2), according to the size and composition of dissolved organic matter (DOM) isolated from wastewater effluent using a fluorescence quenching (FQ) method, and to measure the estrogenic changes due to the extent of E2 sorption onto effluent DOM (EfOM) by using an E-screen bioassay. The highest logK(DOC) of E2 for a DOM size fraction less than 0.2 µm was observed by 4.87 ± 1.87 Lkg(-1)(DOC), and its estrogenicity was the lowest among all the size fractions at 1.2 ng-EEQL⁻¹. However, E2 estrogenicity for a DOM size fraction less than 5 kDa was as high as that for the positive control due to the absence of fulvic acid- and protein-like DOM to bind with E2. The estrogenic activity for the hydrophobic fraction bound with E2 was significantly reduced to 1.6 ng-EEQL⁻¹, while that for the hydrophilic fraction having no binding with E2 was 2.6 ng-EEQL⁻¹, which was similar to that of the positive control (i.e., 2.8 ng-EEQL⁻¹). The results support a conclusion that the change in estrogenicity was due to the strong sorption affinity of E2 onto DOM.


Subject(s)
Estradiol/toxicity , Estrogens/toxicity , Tannins/chemistry , Water Pollutants, Chemical/toxicity , Adsorption , Benzopyrans/chemistry , Estradiol/chemistry , Estrogens/chemistry , Waste Disposal, Fluid , Water Pollutants, Chemical/chemistry
12.
J Environ Monit ; 13(1): 101-9, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21046056

ABSTRACT

Broad scale monitoring of estrogenic compounds was performed at 19 sampling points throughout the Yeongsan and Seomjin river basins and 5 wastewater treatment plants (WWTPs) adjacent to the Gwangju area, Korea, from December 2005 to August 2007. The concentrations of estrogenic compounds, including estrone (E1), 17ß-estradiol (E2), 17α-ethynylestradiol (EE2), bisphenol-A, nonylphenol (NP) and 4-octylphenol (OP), in the samples was measured with gas chromatography/mass spectrometry (GC-MS). In addition, the estrogenic activities throughout the river were investigated using the E-screen assay. Of the six estrogenic chemicals, NP (114.6-336.1 ng L(-1)) and EE2 (0.23-1.90 ng L(-1)) were detected at the highest and lowest levels, respectively in both the river waters and the WWTP effluents. Bisphenol-A showed the largest concentration range, from 7.5 to 335 ng L(-1). The concentrations of E1, E2 and octylphenol ranges were 3.6-69.1, 1.2-10.7, and 2.2-16.9 ng L(-1), respectively. According to the calculated estradiol equivalent concentration (EEQ); however, no estrogenic contribution was observed due to the phenolic compounds in the river waters and effluents. E1 and E2 dominated in both the river water and effluent samples, with contributions to the calculated EEQ of over 79 and 77%, respectively. Conversely, EE2 was rarely detected in the river waters (21%) and effluents (0%). The largest contribution of EE2 to the calculated EEQ was 21% in the river water at S-7. The levels of E1, E2, and EE2 were remarkably decreased in the effluents, indicating that the 5 WWTPs did not contribute to the estrogenic effect of the receiving streams. Overall, the WWTPs did not contributed to the estrogenic activity of the receiving waters, but the livestock industry or wildlife may play an important role in the estrogenic contribution to river water.


Subject(s)
Estrogens/analysis , Fresh Water/analysis , Water Pollutants, Chemical/analysis , Water Purification/standards , Environmental Monitoring , Estrogens, Non-Steroidal/analysis , Republic of Korea
13.
Am J Health Behav ; 44(1): 54-66, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31783932

ABSTRACT

Objectives: We reviewed the current status of healthy eating behaviors in South Korea and analyzed the influencing factors. Methods: A single-equation robust estimator and a seemingly unrelated regression were completed for the effects of access to food retailers, single households, and patients living in the household on healthy eating. Data were retrieved from a consumer survey of 3043 household members preparing food. Results: Better access to retailers is positively related to healthy eating status. Single households are least likely to practice healthy eating and the presence of a patient in the household is negatively related to healthy eating status. Conclusions: The 3 factors have significant effects on South Koreans' healthy eating status.


Subject(s)
Commerce , Diet, Healthy , Food Supply , Patients , Adult , Aged , Commerce/statistics & numerical data , Feeding Behavior , Female , High-Intensity Interval Training , Humans , Male , Middle Aged , Qualitative Research , Regression Analysis , Republic of Korea , Surveys and Questionnaires , Young Adult
14.
Clin Exp Allergy ; 39(12): 1852-6, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19735272

ABSTRACT

BACKGROUND: The danger hypothesis provides a new perspective of the mechanisms underlying drug allergy. In this study, we evaluated associations between variations in the genes involved in danger signal pathways and antibiotic-induced cutaneous allergic reactions (AICARs). METHODS: Two hundred cases with urticaria, angio-oedema, maculopapular rash, and erythema multiforme caused by antibiotics were extracted from the database of the Adverse Drug Reaction Research Group in Korea. All cases were confirmed by an allergy specialist. Causative antibiotics included penicillin, cephalosporin, quinolone, and others (approximately 40 different types). Ten single nucleotide polymorphisms (SNPs) in seven genes (-318C>T, +49A>G, and +6230G>A in CTLA4, IVS+17T>C in CD28, -3479T>G and I170V in CD86, -1C>T in CD40, -3458A>G in CD40LG, -308G>A in TNF, and -31T>C in IL1B) were scored for cases and for healthy subjects without a history of AICARs. RESULTS: Our analysis failed to reveal differences in the distribution of the 10 SNPs between cases and controls. However, we could find a gene-gene interaction between -1C>T in CD40 and -3458A>G in CD40L using multifactor dimensionality reduction analysis. Subjects with minor alleles of both SNPs showed a significant risk for developing AICARs [P=0.017, odds ratio (OR) (95% confidence interval)=2.93 (1.20-7.97)]. CONCLUSION: Our findings suggest that a genetic interaction between CD40 and CD40L favours the development of AICARs.


Subject(s)
Anti-Bacterial Agents/immunology , CD40 Antigens/genetics , CD40 Ligand/genetics , Drug Eruptions/genetics , Drug Eruptions/immunology , Adolescent , Adult , Alleles , Anti-Bacterial Agents/adverse effects , Antigens, CD/genetics , B7-2 Antigen/genetics , CD28 Antigens/genetics , CTLA-4 Antigen , Female , Genetic Association Studies , Genotype , Humans , Interleukin-1beta/genetics , Korea , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , Polymorphism, Single Nucleotide/immunology , Tumor Necrosis Factor-alpha/genetics , Young Adult
15.
Int J Cancer ; 121(12): 2661-7, 2007 Dec 15.
Article in English | MEDLINE | ID: mdl-17721994

ABSTRACT

The CHEK2-1100delC mutation is recurrent in the population and is a moderate risk factor for breast cancer. To identify additional CHEK2 mutations potentially contributing to breast cancer susceptibility, we sequenced 248 cases with early-onset disease; functionally characterized new variants and conducted a population-based case-control analysis to evaluate their contribution to breast cancer risk. We identified 1 additional null mutation and 5 missense variants in the germline of cancer patients. In vitro, the CHEK2-H143Y variant resulted in gross protein destabilization, while others had variable suppression of in vitro kinase activity using BRCA1 as a substrate. The germline CHEK2-1100delC mutation was present among 8/1,646 (0.5%) sporadic, 2/400 (0.5%) early-onset and 3/302 (1%) familial breast cancer cases, but undetectable amongst 2,105 multiethnic controls, including 633 from the US. CHEK2-positive breast cancer families also carried a deleterious BRCA1 mutation. 1100delC appears to be the only recurrent CHEK2 mutation associated with a potentially significant contribution to breast cancer risk in the general population. Another recurrent mutation with attenuated in vitro function, CHEK2-P85L, is not associated with increased breast cancer susceptibility, but exhibits a striking difference in frequency across populations with different ancestral histories. These observations illustrate the importance of genotyping ethnically diverse groups when assessing the impact of low-penetrance susceptibility alleles on population risk. Our findings highlight the notion that clinical testing for rare missense mutations within CHEK2 may have limited value in predicting breast cancer risk, but that testing for the 1100delC variant may be valuable in phenotypically- and geographically-selected populations.


Subject(s)
Breast Neoplasms/ethnology , Breast Neoplasms/genetics , Mutation , Prostatic Neoplasms/ethnology , Prostatic Neoplasms/genetics , Protein Serine-Threonine Kinases/genetics , Adult , Black or African American/genetics , Age of Onset , Aged , Asian People/genetics , Case-Control Studies , Checkpoint Kinase 2 , DNA Mutational Analysis , DNA, Complementary/analysis , Female , Gene Frequency , Genetic Predisposition to Disease , Germ-Line Mutation , Hawaii/ethnology , Hispanic or Latino/genetics , Histidine , Humans , Isoleucine , Leucine , Male , Middle Aged , Mutation, Missense , Predictive Value of Tests , Proline , Risk Assessment , Risk Factors , Threonine , Tyrosine , United States/epidemiology , White People/genetics
17.
J Sports Med Phys Fitness ; 56(12): 1574-1582, 2016 Dec.
Article in English | MEDLINE | ID: mdl-26783700

ABSTRACT

BACKGROUND: To examine the impact of a single bout of exercise on cardiac function and the blood level of brain natriuretic peptide (BNP) in healthy subjects. METHODS: Thirty untrained, healthy young (aged between 20 and 29 years) volunteers (15 men and 15 women) were prospectively recruited. The plasma N-terminal pro-B-type BNP (NT-proBNP) level was checked, cardiac function was assessed using echocardiography in baseline conditions, and the values were compared with those obtained after treadmill exercise according to the Bruce protocol. RESULTS: Left ventricular (LV) ejection fraction decreased after exercise in men, but not in women. Parameters of LV diastolic function were likely to change unfavorably in both sexes after exercise. NT-proBNP levels were significantly elevated by exercise in both sexes (from 22.1±18.3 to 24.7±20.2 pg/mL, P=0.006 in men; from 41.1±21.5 to 46.5±24.9 pg/mL, P<0.001 in women). Changes in NT-proBNP levels were significantly associated with those in E wave velocity, E wave deceleration time, E/e' and E/propagation velocity (Vp) in men (P<0.05 for each) even after controlling for the effects of blood pressure and heart rate. In women, there were no significant associations between changes in parameters of LV diastolic function and those in NT-proBNP levels. CONCLUSIONS: LV systolic and diastolic functions may deteriorate, and proBNP levels could be elevated even by a single bout of treadmill exercise in untrained young subjects. Dynamic change in LV diastolic function is a major stimulus to NT-proBNP release following exercise in men but not in women.


Subject(s)
Exercise/physiology , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Ventricular Function, Left/physiology , Adult , Biomarkers/blood , Echocardiography , Female , Healthy Volunteers , Humans , Male , Prospective Studies , Republic of Korea , Systole , Young Adult
18.
World J Gastroenterol ; 21(37): 10683-7, 2015 Oct 07.
Article in English | MEDLINE | ID: mdl-26457029

ABSTRACT

AIM: To evaluate a new imaging device for colonoscopy that adds two side viewing CMOS lenses, the Third Eye Panoramic cap. METHODS: In this prospective observational feasibility study, 33 patients, 18 male and 15 female, underwent routine screening, surveillance or diagnostic colonoscopy with the new Third Eye Panoramic cap clipped on to the distal tip of a high definition Fuji EC530-LS Slim Colonoscope. All procedures were performed at the New York Presbyterian-Queens Endoscopy unit by two experienced endoscopists (Rubin M and Kim SH). Main outcome measurements included evaluation of the image quality of the Third Eye Panoramic cap, adenoma detection rate, cecal intubation rate, withdrawal time and total procedure time. RESULTS: The Third Eye Panoramic cap enabled enhanced views without affecting the quality of the colonoscope's image or its handling characteristics through the colon. Ileal intubation was accomplished in most cases, but was more challenging. The side view lenses detected polyps and diverticula hidden behind folds and in flexures not seen on the standard view. The side view lenses were easily cleaned utilizing an Endogator Irrigation Pump (Medivators, Minneapolis, MN, United States) by angling the scope tip against the mucosa while washing. The cecum was reached in all 33 patients. Mean cecal intubation time was 8.19 ± 2.17 min, mean withdrawal time was 10.15 ± 5.56 min and mean total procedure time was 20.31 ± 5.14 min. The overall adenoma detection rate was 44%. CONCLUSION: The Third Eye Panoramic cap enables wide view colonoscopy with enhanced visualization utilizing standard forward view colonoscopes.


Subject(s)
Colonoscopes , Colonoscopy/methods , Adenoma/diagnosis , Adenoma/pathology , Aged , Cecum/pathology , Colon/pathology , Colonic Neoplasms/diagnosis , Colonic Neoplasms/pathology , Colonic Polyps/pathology , Endoscopes , Endoscopy/methods , Equipment Design , Feasibility Studies , Female , Humans , Male , Middle Aged , Prospective Studies
19.
Therap Adv Gastroenterol ; 7(1): 14-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24381644

ABSTRACT

BACKGROUND: The incidence, recurrence, and all-cause mortality rate for Clostridium difficile-associated diarrhea (CDAD) has increased markedly over the past 10 years despite treatment. Low vitamin D levels are known to impair immune responses to infection and are associated with increased mortality. We compared the role of patient comorbidity measured by the Charlson Comorbidity Index (CCI) with vitamin D levels to ascertain whether vitamin D levels were an independent variable affecting the outcome of CDAD or a marker of overall comorbidity. METHODS: A prospective cohort study studied 62 patients hospitalized between 2008 and 2009 with manifestations of CDAD and a positive C. difficile toxin assay. All patients received standard antibiotics (metronidazole and/or vancomycin). Their status at 30-day follow up was classified as resolved or recurred/expired. Patients' CCI was calculated using their medical history. Logistic regression analysis of variables including 25-hydroxyvitamin D, CCI, age, gender, white blood cell count (WBC), albumin and residence type were performed. RESULTS: There were 62 patients (43.6% men, 56.4% women) with CDAD; mean age was 75 ± 17 years. At 30-day follow up, 28 (45.2%) expired, 10 (16.1%) had persistent or recurrent diarrhea and 24 (38.7%) resolved. Nonresolution was seen in 38 (61.3%). There was no significant association between 30-day resolution status and CCI, gender, WBC, albumin level or residence type. Two variables were found to be independent predictors of resolution of CDAD: normal vitamin D levels (p = 0.028) and age <70 years (p = 0.024). Subjects with low vitamin D were 4.75 times more likely to fail to resolve CDAD than subjects with normal Vitamin D. CONCLUSION: In this study, vitamin D level and age are independent predictors of CDAD resolution in hospitalized patients. Low vitamin D levels and age >70 years old are associated with increased likelihood of recurrence. Low vitamin D levels are not a marker of comorbidity or advanced age.

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Therap Adv Gastroenterol ; 6(3): 193-8, 2013 May.
Article in English | MEDLINE | ID: mdl-23634183

ABSTRACT

BACKGROUND: Upper gastrointestinal bleeding (UGIB) accounts for 400,000 hospital admissions in the US each year. Despite advances, mortality rates remain high and are estimated to be 5-10%. Early therapeutic endoscopy is widely recommended as a means of reducing morbidity and mortality. The Rockall and Blatchford scores are clinical scoring systems devised to assist in risk stratifying patients with UGIB. In a prior study we found that rapid live bedside video capsule endoscopy (VCE) utilizing Pillcam ESO(®) correctly identified patients with high-risk stigmata of bleeding seen on upper endoscopy. In this study, we compare the accuracy of the Rockall and Blatchford scores with Pillcam ESO(®) in predicting high-risk endoscopic stigmata. METHODS: Pre-endoscopy Blatchford and Rockall scores were calculated for 25 patients (14 males, 11 females) presenting to the emergency room with acute UGIB. The average patient was 66 years of age. A total of 24 out of 25 patients underwent upper endoscopy within 24 hours. One patient did not undergo endoscopy due to clinical instability. The timing of endoscopy was based on clinical parameters in 12 patients, and on live view VCE with Pillcam ESO(®) in the other 13 patients. Positive VCE was defined as red blood, clot or coffee grounds. Mean Rockall and Blatchford scores for all 24 patients were compared to determine potential differences between high- and low-risk patients. Rockall and Blatchford scores were also compared with VCE findings. RESULTS: Of 24 patients, 13 had high-risk stigmata on upper endoscopy. The mean Rockall and Blatchford scores were 3 and 13, respectively. In the 11 patients without stigmata, the mean Rockall and Blatchford scores were 2 and 11, respectively. There was no statistically significant difference between the Blatchford scores of the two groups (95% confidence interval [CI] -5.1 to 1.3; p = 0.22). There was no statistically significant difference between the Rockall scores of the two groups (95% CI -2.3 to 0.3; p = 0.11). In the subgroup of 12 patients who underwent VCE prior to endoscopy, 8/12 had positive findings, which were all confirmed at endoscopy. All 4 patients with negative VCE had no high-risk stigmata at endoscopy. CONCLUSION: In emergency room patients with acute UGIB, neither the Rockall nor the Blatchford scores were able to differentiate high- and low-risk patients identified at endoscopy. Live view VCE, however, was accurate in predicting high-risk endoscopic stigmata, and may be better suited as a risk stratification tool. Additional studies with a larger cohort will be required to validate these findings.

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