Quercetin-induced apoptosis ameliorates vascular smooth muscle cell senescence through AMP-activated protein kinase signaling pathway

Aging is one of the risk factors for the development of cardiovascular diseases. During the progression of cellular senescence, cells enter a state of irreversible growth arrest and display resistance to apoptosis. As a flavonoid, quercetin induces apoptosis in various cells. Accordingly, we investigated the relationship between quercetin-induced apoptosis and the inhibition of cellular senescence, and determined the mechanism of oxidative stress-induced vascular smooth muscle cell (VSMC) senescence. In cultured VSMCs, hydrogen peroxide (H₂O₂) dose-dependently induced senescence, which was associated with increased numbers of senescence-associated β-galactosidase-positive cells, decreased expression of SMP30, and activation of p53-p21 and p16 pathways. Along with senescence, expression of the anti-apoptotic protein Bcl-2 was observed to increase and the levels of proteins related to the apoptosis pathway were observed to decrease. Quercetin induced apoptosis through the activation of AMP-activated protein kinase. This action led to the alleviation of oxidative stress-induced VSMC senescence. Furthermore, the inhibition of AMPK activation with compound C and siRNA inhibited apoptosis and aggravated VSMC senescence by reversing p53-p21 and p16 pathways. These results suggest that senescent VSMCs are resistant to apoptosis and quercetin-induced apoptosis attenuated the oxidative stress-induced senescence through activation of AMPK. Therefore, induction of apoptosis by polyphenols such as quercetin may be worthy of attention for its anti-aging effects.

CD9 Expression in Tumor Cells Is Associated with Poor Prognosis in Patients with Invasive Lobular Carcinoma / 한국유방암학회지

PURPOSE: We investigated the prognostic significance of CD9 expression in tumor cells of patients with invasive lobular carcinoma (ILC). METHODS: CD9 expression was evaluated by immunohistochemistry in 113 ILC tissue samples. Correlation of CD9 expression with the patients' clinicopathological parameters and overall survival was assessed. RESULTS: CD9 expression was detected in 48 (42.5%) ILC patients. However, no significant relation could be determined between CD9 expression and the clinicopathological parameters of the patient including tumor size, lymph node metastasis, lymphovascular invasion, histologic grade, expression of hormone receptors, human epidermal growth factor receptor 2 status, and Ki-67 labeling index. Patients with CD9 expression had worse overall survival (p = 0.051) and disease-free survival (DFS, p = 0.014) compared to patients without CD9 expression. Multivariate analysis revealed that CD9 expression was an independent prognostic factor for DFS (p = 0.049). CONCLUSION: CD9 expression in tumor cells could be a significant prognostic marker in patients with ILC.

Can we rejuvenate? Implications of biological aging research / 영남의대학술지

The life history of man is summarized as a birth-aging-disease-death. Man eventually ages and dies. How long can humans live? What is aging? Why do we age? Is aging inevitable? Can we rejuvenate? Recent researches on biological aging suggest that humans might overcome aging and rejuvenate. In this paper, we review the biologic characteristics of aging and the latest results of biological aging research, implicating that aging can be controlled, further treated, and that humans can ultimately be rejuvenated.

Comparison and Evaluation of Diagnostic Assays for Clostridium difficile Infection

BACKGROUND: Clostridium difficile is a leading causative microorganism of pseudomembranous colitis (PMC) and antibiotic-associated diarrhea. In patients who have a history of antibiotic use and diarrhea, the presence of the C. difficile toxin should be confirmed to diagnose C. difficile infection (CDI). In this study, the results of three assays for CDI, which were performed on 1,363 clinical stool samples at a tertiary hospital, were analyzed to evaluate the performance and usefulness of these assays for diagnosis of CDI. METHODS: The results of the VIDAS C. difficile Toxin A&B Immunoassay (bioMérieux SA, France), Xpert C. difficile Real-Time PCR Assay (Cepheid, USA), and ChromID C. difficile Agar (bioMérieux SA, France) culture were analyzed retrospectively. Cases were defined as CDI according to the positive Xpert assay or the positive VIDAS assay and/or culture in the presence of PMC findings after radiological imaging or endoscopic procedures. RESULTS: A total of 1,027 samples (75.8%) tested negative in all three assays, 101 samples (7.4%) tested positive in all three assays, and overall agreement among them was 82.7%. In this study, 291 cases (21.3%) were diagnosed as CDI. Sensitivity and specificity of the VIDAS assay were 38.8% and 99.3%, and those of ChromID culture were 71.5% and 96.5%, respectively. The Xpert assay showed good sensitivity (98.6%, 287/291), whereas the VIDAS assay and ChromID culture showed low sensitivities. CONCLUSIONS: These results suggest that rapid molecular diagnostic assays, such as the Xpert assay, are promising candidates for an initial diagnostic test for CDI.

Can we rejuvenate? Implications of biological aging research / 영남의대학술지

The life history of man is summarized as a birth-aging-disease-death. Man eventually ages and dies. How long can humans live? What is aging? Why do we age? Is aging inevitable? Can we rejuvenate? Recent researches on biological aging suggest that humans might overcome aging and rejuvenate. In this paper, we review the biologic characteristics of aging and the latest results of biological aging research, implicating that aging can be controlled, further treated, and that humans can ultimately be rejuvenated.

Impaired Antioxidant Ability of HDL and More Oxidized LDL are associated with Male Patients with Atrial Fibrillation

OBJECTIVE: Atrial fibrillation (AF) is a common arrhythmia which is generally more prevalent in the elderly population. However, the new onset of AF is frequently found in young populations. In order to identify putative prognostic biomarkers for detection of young-onset AF, we purified and characterized lipoproteins in terms of oxidative and inflammatory properties. METHODS: Male patients with AF (46±7 years of age, n=19) were recruited. Their serum and individual lipoproteins were analyzed and compared with healthy controls (48±9 years of age, n=17). RESULTS: The patients with AF revealed hypertriglyceridemia, hyperuricemia with mild obesity, elevated levels of CRP, and a normal level of cholesterol. All lipoproteins from patients with AF demonstrated higher levels of TG and advanced glycated end products, and decreased particle size than controls. AF-LDL showed an increased extent of oxidation with increased atherogenic macrophage phagocytosis. AF-HDL showed impaired antioxidant ability and a lower level of apoA-I expression. CONCLUSION: These data suggest that lipoprotein properties are severely modified in young AF patients, which were correlated with increased oxidation and inflammation.

Acoustic Change Complex: Clinical Implications

The acoustic change complex (ACC) is a cortical auditory evoked potential elicited in response to a change in an ongoing sound. The characteristics and potential clinical implications of the ACC are reviewed in this article. The P1-N1-P2 recorded from the auditory cortex following presentation of an acoustic stimulus is believed to reflect the neural encoding of a sound signal, but this provides no information regarding sound discrimination. However, the neural processing underlying behavioral discrimination capacity can be measured by modifying the traditional methodology for recording the P1-N1-P2. When obtained in response to an acoustic change within an ongoing sound, the resulting waveform is referred to as the ACC. When elicited, the ACC indicates that the brain has detected changes within a sound and the patient has the neural capacity to discriminate the sounds. In fact, results of several studies have shown that the ACC amplitude increases with increasing magnitude of acoustic changes in intensity, spectrum, and gap duration. In addition, the ACC can be reliably recorded with good test-retest reliability not only from listeners with normal hearing but also from individuals with hearing loss, hearing aids, and cochlear implants. The ACC can be obtained even in the absence of attention, and requires relatively few stimulus presentations to record a response with a good signal-to-noise ratio. Most importantly, the ACC shows reasonable agreement with behavioral measures. Therefore, these findings suggest that the ACC might represent a promising tool for the objective clinical evaluation of auditory discrimination and/or speech perception capacity.

First Case of Pulmonary Mycobacterium parascrofulaceum Infection in a Patient With Bronchiectasis in Korea

No abstract available.

Acute Cellulitis Caused by Neisseria skkuensis / 대한임상미생물학회지

A 73-year-old man visited our hospital because of pain with swelling and redness on the right foot dorsum. He was diagnosed with liver cirrhosis and nodular hepatic cellular carcinoma. Lower extremity CT scan and MRI showed abscess formation in the right foot dorsum. Gram-negative cocci were recovered from the culture of drained pus at the site and identified as Neisseria skkuensis by 16S rRNA gene sequencing. Here, we report the first case of cellulitis due to N. skkuensis and provide a literature review.

Frequency and Clinicohematologic Characteristics of MPL W515 Mutations in Patients with Myeloproliferative Neoplasms

BACKGROUND: Recently, myeloproliferative leukemia (MPL) W515 mutations have been reported to be molecular markers for myeloproliferative neoplasms (MPNs). We studied the association between MPL W515 mutations and the clinico-hematological features of patients with MPNs. METHODS: Our study included 154 consecutive patients diagnosed with MPNs (31 had polycythemia vera [PV]; 106, essential thrombocythemia [ET]; and 17, primary myelofibrosis [PMF]). MPL W515 mutations were detected by real-time PCR and direct sequencing methods. RESULTS: The MPL W515L mutation was found in 4 patients and the MPL W515A mutation was detected in 1 patient. These 5 patients were diagnosed with JAK2 V617F-negative ET, and they accounted for 12.5% of patients with JAK2 V617F-negative ET. The patients with MPL W515-positive ET showed significantly lower hemoglobin levels and WBC counts than did patients with MPL W515-negative ET or JAK2 V617F-positive ET. CONCLUSIONS: MPL W515 mutation is a useful diagnostic marker for JAK2 V617F-negative MPNs and it is associated with specific hematologic characteristics such as lower hemoglobin levels and WBC counts.

Damage of Spiral Ganglion Cell Induced by Ouabain Application in Cat / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Auditory neuropathy is a hearing disorder characterized by the absence or the marked impairment of the auditory brainstem responses with the preservation of the cochlear microphonics (CMs) and otoacoustic emissions. This suggests that outer hair cell (OHC) function is normal but proximal auditory function to OHCs is impaired. It is assumed that the lesion is localized at the level of the inner hair cells (IHCs), auditory nerve fibers, or the synapse between them. This study was aimed to observe the change of hearing threshold and pathology of spiral ganglion cell induced by ouabain application, and present basic data to explain the auditory neuropathy. MATERIALS AND METHOD: Twenty ears of twenty normal hearing cats were used in this study. Cats were treated with 100 microL ouabain (1 mM) applied on the round window. After three days, compound action potential (CAP) and CM were measured and the cochlea was obtained. Pathologic change of spiral ganglion cell was evaluated under light microscope after H&E stain. Normal saline was injected for the control group. RESULTS: In the ouabain group, CAP threshold was increased in all tested frequencies (p0.05). There was significant difference between CAP and CM threshold shift (p<0.001). In the control group, there was no significant difference in CAP and CM thresholds. Light microscopic findings show that the condensed chromatin and nuclear fragments of spiral ganglion cells of an ear was exposed to ouabain, and outer hair cell and inner hair cell were not damaged. CONCLUSION: This study shows that the CAP threshold was significantly increased but the CM threshold was not changed in the ouabain group. Ouabain induced damage of spiral ganglion cells. This study is not sufficient to explain auditory neuropathy because threshold shift of CAP is not obvious, but it would be helpful to explain that selective damage of spiral ganglion cell would be the mechanism of auditory neuropathy.

A Case of Totally Lateralized Tympanic Membrane / 대한이비인후과학회지

Lateralized tympanic membrane is a complication of tympanoplasty resulting in conductive hearing loss. We describe a case of a 23-year-old patient who developed totally lateralized left tympanic membrane with hearing disturbance. The blind-pouch appearance of the left ear canal and conductive hearing loss were checked. The revision of underling tympanoplasty was performed using temporalis fascia and conchal cartilage. The ossicular chain was reconstructed with partial ossicular replacement prosthesis. Canaloplasty and split thickness skin graft were applied for the skin defect of the left external auditory meatus. Totally lateralized tympanic membrane was successfully reconstructed with cartilage tympanoplasty and canaloplasty, achieving improved hearing.

Utility of Electrically Evoked Potentials in Cochlear Implant Users / 대한이비인후과학회지

Cochlear implants (CIs) are generally used in individuals with severe to profound hearing loss. Needs for objective measures with CI users have increased due to implantation of children at younger ages and large variation in performance. To date, a significant body of research has been published that describes the general methodology used to measure electrically evoked neural responses as well as issues and stimulation paradigms relevant to the measurement of specific neural responses and several potential applications for objective measures with CI users. Objective measures of cochlear implant function have most certainly played a role in developing a better understanding of the process of electrical stimulation of the auditory nerve and the activation of the central auditory pathways. An important remaining issue in further improvements with cochlear implants is the better understanding of variability across subjects and the development of methods to improve signal processing in poor performers. The measurement of electrically evoked neural activity, both peripheral and central response, can be an important tool for accomplishing such tasks.

A Case of Acute Myeloid Leukemia Transformed from JAK2 V617F-Positive Chronic Neutrophilic Leukemia

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) characterized by persistent peripheral blood neutorphilia, bone marrow hypercellularity of neutrophilic granulocyte proliferation and hepatosplenomegaly. Acquired somatic mutation, JAK2 V617F, is the only molecular marker known to have association with classic BCR-ABL1 negative MPNs. However, JAK2 V617F has been detected occasionally in other MPNs such as CNL or other disease entities. We experienced a case of CNL with JAK2 V617F mutation. The patient was diagnosed according to the 2008 WHO classification criteria, and developed AML 9 months after the diagnosis of CNL. The JAK2 V617F was detected in the bone marrow throughout the clinical course. More cases are needed to establish the role of JAK2 V617F in the pathogenesis, prognosis and disease course of CNL.

Subpopulations of Regulatory T Cells in Rheumatoid Arthritis, Systemic Lupus Erythematosus, and Behcet's Disease

Recently, subpopulations of regulatory T (Treg) cells, resting Treg (rTreg) and activated Treg (aTreg), have been discovered. The authors investigated the relationship between the change of Treg, aTreg and rTreg and autoimmune diseases. Treg cells and those subpopulations were analyzed by using the human regulatory T cell staining kit and CD45RA surface marker for 42 rheumatoid arthritis (RA), 13 systemic lupus sclerosis (SLE), 7 Behcet's disease (BD), and 22 healthy controls. The proportion of Treg cells was significantly lower in RA (3.8% +/- 1.0%) (P < 0.001) and BD (3.3% +/- 0.5%) (P < 0.01) compared to healthy controls (5.0% +/- 1.3%). The proportion of aTreg cells was also significantly lower in RA (0.4% +/- 0.2%) (P = 0.008) and BD (0.3% +/- 0.1%) (P = 0.013) compared to healthy controls (0.6% +/- 0.3%). The rTreg cells showed no significant differences. The ratio of aTreg to rTreg was lower in RA patients (0.4% +/- 0.2%) than that in healthy controls (0.7% +/- 0.4%) (P = 0.002). This study suggests that the decrement of aTreg not rTreg cells contributes the decrement of total Treg cells in peripheral blood of RA and BD autoimmune diseases. Detailed analysis of Treg subpopulations would be more informative than total Treg cells in investigating mechanism of autoimmune disease.

Two Cases of Middle Ear Adenoma with Neuroendocrine Differentiation (Carcinoid Tumor) / 대한이비인후과학회지

Middle ear adenoma with neuroendocrine differentiation (carcinoid tumor) is a rare benign tumor of the tympanic cavity. Carcinoid tumor is generally derived from primitive stem cells in the gut wall but can be seen in other organs, including the lungs, mediastinum, thymus, liver, pancreas, bronchus, ovaries, prostate, and kidneys. This is unusual considering neuroendocrine cells have not been identified in normal or inflamed middle ear mucosa. Carcinoid tumor of the middle ear represents a class within the spectrum of adenomatous neoplasms. Immunohistochemical techniques have helped clarify that these tumors all share elements of neuroendocrine differentiation. Although histologic and biological similarities with middle ear adenoma exist, carcinoid tumor of the middle ear should be classified as a well-differentiated neuroendocrine carcinoma because the carcinoid tumor has higher rate of recurrence and incidence of metastasis than middle ear adenoma. Surgical management is the recommended treatment and long-term observation is necessary.

Down-regulation of survivin suppresses uro-plasminogen activator through transcription factor JunB

Survivin, a member of the inhibitors of apoptosis protein family, is expressed during development and in various human cancers. However, the clinical relevance of survivin in cancer is still a matter of debate. Genes induced by hepatocyte growth factor (HGF) were screened using cDNA microarray technology in the stomach cancer cell lines, NUGC3 and MKN28. The levels of JunB, survivin, and uro-plasminogen activator (uPA) were up-regulated in cells treated with HGF in a dose-dependent manner. HGF-induced up regulation of JunB, survivin, and uPA was inhibited by pre-treatment with a MEK inhibitor (PD 98059). HGF-induced up-regulation of uPA was repressed by survivin knockdown. HGF enhanced the binding activity of JunB to the survivin promoter in control cells, but not in the JunB-shRNA cells. Transfection with survivin-shRNA resulted in a decrement of cell proliferation, as determined with MTT assays. In an in vitro invasion assay, significantly fewer cells transfected with survivin shRNA than control cells were able to invade across a Matrigel membrane barrier. In conclusion, survivin appeared to play an important role in the up-regulation of uPA induced by HGF via JunB and might contribute to HGF-mediated tumor invasion and metastasis, which may serve as a promising target for gastric cancer therapy.

The Relationship between Thresholds of Electrically Evoked Compound Action Potential and Speech Perception in Children with Cochlear Implants / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Neuropathology around the cochlea could create variation from site to site in physiological thresholds of cochlear implant users. This variability would be detrimental to speech recognition with a cochlear implant for a variety of reasons, including distortion of the place code and variation in the number of neurons. The purpose of this study is to examine the relationship between thresholds of electrically evoked compound action potential (ECAP) and speech perception in children implanted with the Nucleus Freedom devices. SUBJECTS AND METHOD: Fifty-seven children implanted with the Nucleus Freedom device participated in this study. ECAP thresholds were recorded using the automated neural response telemetry test protocol. We then calculated mean threshold and three metrics to assess across-site variation within subjects: 1) the variance of T levels for all tested sites, 2) the range of T levels (highest minus lowest) across all tested sites and 3) site-to-site variation. For each subject, these measures were compared with performance on tests of word recognition. RESULTS: There was considerable across-site (within-subject) and across-subject variability in thresholds. However, we found no significant correlation between speech recognition and across-site variation of thresholds as well as mean threshold levels. CONCLUSION: These data suggest that the ECAP measures of thresholds may not be an accurate predictor of speech perception ability.

Prevalence of Metallo-beta-lactamases in Imipenem-non-susceptible Pseudomonas aeruginosa and Acinetobacter baumannii / 대한임상미생물학회지

BACKGROUND: Metallo-beta-lactamases (MBLs) have been reported in gram negative bacilli and are becoming increasingly important clinically because the enzymes hydrolyse almost all beta-lactams, including carbapenems. Thus, the present study was conducted to determine the prevalence of MBL types in imipenem-nonsusceptible Pseudomonas aeruginosa and Acinetobacter baumannii isolated from a tertiary teaching hospital. METHODS: Imipenem-nonsusceptible strains, 128 P. aeruginosa and 93 A. baumannii, were collected from clinical specimens. Identification and susceptibility tests were determined by Vitek GNI and GNS cards. MBL production was determined by modified Hodge test and imipenem-EDTA synergy test. Multiplex PCR amplification of MBL genes including blaIMP-1, blaVIM-1 and blaVIM-2 were performed. RESULTS: Thirty-one P. aeruginosa (24.2%) isolates and 3 A. baumannii (3.2%) were found to be MBL producers. In P. aeruginosa, 20 (15.6%) and 11 (8.6%) isolates were positive for blaIMP-1 and blaVIM-2, respectively whereas 1 (1.0%) and 2 (2.2%) isolates in A. baumannii, respectively. CONCLUSION: IMP-1 is more prevalent MBL type than VIM-2 among imipenem-nonsusceptible P. aeruginosa unlike in other studies. Larger numbers of isolates and sequential studies are strongly recommended for the useful evaluation and monitoring of MBL production in the hospital setting to infection-control.

The Relationship between Electrically Evoked Compound Action Potential and Speech Perception in CI24RE Implant Users / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Since performance with a cochlear implant is negatively correlated with an individual's duration of deafness prior to implantation, neural survival may be an important factor in determining outcome. To date, studies relating physiological measures such as the threshold and growth of the electrically evoked potentials have not shown clear relationships to human speech perception abilities, although there are positive results correlating these measures to nerve survival in animals. The primary goal of this study was to determine the extent to which the growth functions of electrically evoked compound action potential (ECAP) are related with speech perception performance in recent CI24RE implant users and to investigate the relationship between ECAP growth function and performance according to more limited electrodes. SUBJECTS AND METHOD: We measured ECAP growth functions to biphasic pulses using reverse neural telemetry system in 21 CI24RE implant users. For each subject, the slope of the growth function was compared with speech perception tests. In addition, this measure was also evaluated for a more limited set of electrodes. RESULTS: Significant correlations have been found between the slope of ECAP growth functions and speech performance in CI24RE implant recipients. In addition, a relatively strong correlation has been found between the slope of ECAP growth function and performance on word recognition test in the group of basal electrodes. CONCLUSION: Effectiveness of the cochlear implant can be quite variable. These results show that ECAP measure may be useful in developing a test for predicting the outcomes of using the implant.