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1.
Br J Oral Maxillofac Surg ; 60(2): 128-133, 2022 02.
Article in English | MEDLINE | ID: mdl-34815100

ABSTRACT

Controversy exists regarding the influence of the graft placement site in the mandible on the success of non-vascularised bone grafts. In this study, we examine the association between the compartment of the mandibular defect and the bone graft failure rate. A systematic literature review and meta-analysis was performed using MEDLINE, Embase, and Cochrane databases. Failure rates according to the compartment of mandibular defect were extracted and analysed by meta-analysis. The Newcastle-Ottawa Scale was used to assess the quality of the studies, and publication bias was evaluated using funnel plots. The search strategy identified 27 publications. After screening, five were selected for review. Based on the result of comparison among these five, we found no significant statistical association between the bone graft failure rate and compartment of mandibular defect, although further investigation of prospective randomised cohort studies is required.


Subject(s)
Mandibular Reconstruction , Bone Transplantation , Humans , Mandible/surgery , Postoperative Complications , Prospective Studies
2.
Sci Adv ; 5(8): eaax2476, 2019 08.
Article in English | MEDLINE | ID: mdl-31489377

ABSTRACT

Endochondral ossification during long bone development and natural fracture healing initiates by mesenchymal cell condensation, directed by local morphogen signals and mechanical cues. Here, we aimed to mimic development for regeneration of large bone defects. We hypothesized that engineered human mesenchymal condensations presenting transforming growth factor-ß1 (TGF-ß1) and/or bone morphogenetic protein-2 (BMP-2) from encapsulated microparticles promotes endochondral defect regeneration contingent on in vivo mechanical cues. Mesenchymal condensations induced bone formation dependent on morphogen presentation, with BMP-2 + TGF-ß1 fully restoring mechanical function. Delayed in vivo ambulatory loading significantly enhanced the bone formation rate in the dual morphogen group. In vitro, BMP-2 or BMP-2 + TGF-ß1 initiated robust endochondral lineage commitment. In vivo, however, extensive cartilage formation was evident predominantly in the BMP-2 + TGF-ß1 group, enhanced by mechanical loading. Together, this study demonstrates a biomimetic template for recapitulating developmental morphogenic and mechanical cues in vivo for tissue engineering.


Subject(s)
Bone Development/physiology , Bone and Bones/physiology , Morphogenesis/physiology , Osteogenesis/physiology , Animals , Biomimetics/methods , Bone and Bones/metabolism , Cells, Cultured , Humans , Male , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/physiology , Rats , Tissue Engineering , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1/metabolism
3.
Br J Oral Maxillofac Surg ; 57(2): 185-187, 2019 02.
Article in English | MEDLINE | ID: mdl-30612837

ABSTRACT

Autologous fat has long been used as a filler in the face, and has recently gained popularity in plastic surgery with a wound infection rate of 1% - 5%. The incidence of mycobacterial infections has increased over recent decades, which is attributed in part to the increased popularity of these procedures.2 Infections by non-tuberculosis mycobacteria often cause chronic inflammation and progressive infection that may eventually manifest themselves as severe scars, fistulas, and hollows, and irregular facial contours. However, few cases of mycobacterial infection have been reported to have been caused by plastic surgery. We present a rare case of non-tuberculosis mycobacterial infection after transfer of autologous fat to the face.


Subject(s)
Mycobacterium Infections, Nontuberculous , Surgery, Plastic , Face , Humans , Nontuberculous Mycobacteria
4.
Vox Sang ; 2018 Jul 13.
Article in English | MEDLINE | ID: mdl-30003551

ABSTRACT

BACKGROUND AND OBJECTIVES: Despite safety measures to minimize the risk of transfusion-transmitted infections, a residual risk remains. To trace and review some such cases, we ask donors to notify the blood centre if they are diagnosed with an infection after they donate blood. MATERIALS AND METHODS: We analysed all data on postdonation cases of hepatitis A reported between 2007 and 2012. Archived specimens from these donors were tested for hepatitis A virus (HAV) using anti-HAV IgM/IgG and HAV-PCR as markers. If any of the test results were positive, we reviewed the medical records of the recipients and, if necessary, tested them for hepatitis A. RESULTS: Fifteen blood donors notified the blood centres of having been diagnosed with hepatitis A after donation. All archived samples except for one were HAV-PCR-positive and anti-HAV IgM/IgG-negative. Of the donated components, four RBCs and 14 FFPs had not been transfused to patients and were recalled. Among 26 recipients of the implicated components, fourteen were still alive when they were notified. Two patients showed clinical symptoms of hepatitis A and had positive results with anti-HAV IgM. CONCLUSION: Transfusion-transmitted hepatitis A is rare but exists. To reduce the risk, donors should be told to notify the blood centre if they are diagnosed with blood-borne diseases after they donate blood. Physicians should consider the possibility of transfusion-transmitted hepatitis A if a transfused patient has hepatitis A but no history of travel or route of faecal-oral infection.

5.
Int J Oral Maxillofac Surg ; 47(10): 1250-1257, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29655817

ABSTRACT

The purpose of this study was to determine the influence of insurance status on treatment and outcomes in oral cavity cancer. Patients were identified in the National Cancer Database (NCDB). Data were collected and analyzed using χ2 tests, Kaplan-Meier methods, and multivariable Cox regression models. Those uninsured or on Medicaid were more likely to be younger (P<0.001), minority race (P<0.001), have a lower median household income (P<0.001), lower educational attainment (P<0.001), not undergo primary resection (P<0.001), present with higher T (P<0.001),N (P<0.001), and M (P<0.001) stage of disease, and have a higher tumor grade (P<0.001). On univariate analysis, those with private insurance had significantly better overall survival than those uninsured (hazard ratio (HR) 1.481), under Medicaid (HR 2.006), or on Medicare (HR 1.921). On multivariable Cox regression analysis, insurance status remained an independent prognosticator even after accounting for multiple demographic, socioeconomic, treatment, and clinicopathological factors. These data suggest that insurance status is associated with treatment and outcomes in patients with oral cavity cancer. Being uninsured or on Medicaid was found to be associated with a higher risk of a poorer prognosis when compared to private insurance, and the data suggest the need to expand comprehensive medical coverage and optimize access to adequate medical care in vulnerable patient populations.


Subject(s)
Carcinoma, Squamous Cell/therapy , Insurance Coverage , Mouth Neoplasms/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Demography , Female , Humans , Male , Medicaid/statistics & numerical data , Medically Uninsured/statistics & numerical data , Medicare/statistics & numerical data , Middle Aged , Survival Analysis , Treatment Outcome , United States
6.
Eur J Cancer Care (Engl) ; 27(2): e12814, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29333736

ABSTRACT

This study examined how patients with cancer estimate caregiver burden (CB) and the association between their underestimation of CB and their caregivers' self-ratings of their quality of life (CQOLC-K; Korean version of the Caregiver Quality of Life Index-Cancer), depression and anxiety (Korean version of the Hospital Anxiety and Depression Scale). Participants consisted of 990 patient-caregiver dyads recruited from a nationwide cross-sectional survey conducted in South Korea. Medical baseline data were retrieved from the hospital information systems of the participating centres. The patients with cancer who underestimated CB ranged from 18.62% (for physical CB) to 23.33% (for social CB). They had less advanced cancer, a lower income, were the caregiver's spouse, reported higher levels of family avoidance of communication about cancer, and had female caregivers. The patients' underestimation of CB was significantly related to lower CQoL and higher levels of caregiver depression and anxiety. The current study provides empirical evidence for the link between the underestimation of CB by patients with cancer and compromised caregiving experiences of cancer caregivers. Open family communication about cancer was discussed as one of several practical strategies for decreasing patients' underestimation of CB.


Subject(s)
Anxiety Disorders/etiology , Caregivers/psychology , Depressive Disorder/etiology , Neoplasms/psychology , Quality of Life , Attitude to Health , Communication , Cost of Illness , Cross-Sectional Studies , Family Relations , Female , Humans , Male , Middle Aged
7.
J Vet Pharmacol Ther ; 40(5): 561-568, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28205288

ABSTRACT

Ribavirin (RBV) is a synthetic guanosine analog that is used as a drug against various viral diseases in humans. The in vitro antiviral effects of ribavirin against porcine viruses were demonstrated in several studies. The purposes of this study were to evaluate the adverse effects and pharmacokinetics of ribavirin following its intramuscular (IM) injection in pigs. Ribavirin was formulated as a double-oil emulsion (RBV-DOE) and gel (RBV-Gel), which were injected into the pigs as single-dose IM injections. After injection of RBV, all of the pigs were monitored. The collected serum and whole blood samples were analyzed by liquid chromatography-tandem mass spectrometry and complete blood count analysis, respectively. All of the ribavirin-treated pigs showed significant decreases in body weight compared to the control groups. Severe clinical signs including dyspnea, anorexia, weakness, and depression were present in ribavirin-treated pigs until 5 days postinjection (dpi). The ribavirin-treated groups showed significant decrease in the number of red blood cells and hemoglobin concentration until 8 dpi. The mean half-life of the RBV-DOE and RBV-Gel was 27.949 ± 2.783 h and 37.374 ± 3.502 h, respectively. The mean peak serum concentration (Cmax ) and area under the serum concentration-time curve from time zero to infinity (AUCinf ) of RBV-DOE were 8340.000 ± 2562.577 ng/mL and 16 0095.430 ± 61 253.400 h·ng/mL, respectively. The Cmax and AUCinf of RBV-Gel were 15 300.000 ± 3764.306 ng/mL and 207526.260 ± 63656.390 h·ng/mL, respectively. The results of this study provided the index of side effect and pharmacokinetics of ribavirin in pigs, which should be considered before clinical application.


Subject(s)
Antiviral Agents/pharmacokinetics , Ribavirin/pharmacokinetics , Swine/metabolism , Animals , Antiviral Agents/adverse effects , Humans , Injections, Intramuscular/veterinary , Ribavirin/adverse effects
8.
Int J Health Plann Manage ; 32(2): e206-e217, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27412878

ABSTRACT

OBJECTIVES: The aim of this study was to examine the impacts of a government-directed palliative care demonstration (PCD) project, Per-diem Payment System (PDPS), on length of stay (LOS), hospital costs, resource usage and healthcare quality during the searched period from January in 2009 to December in 2010. STUDY DESIGN: A retrospective claim data review. METHODS: Individuals who had been eligible for the palliative care payment policy, PDPS, during 2 years (from 2009 to 2010) were assigned to the case group including seven hospitals (n = 3117). Those (seven hospitals) who were not come eligible for the palliative care payment policy were assigned to the control group (n = 2347) with fee for service. The data used in this study were electronically submitted requests of payment to the Health Insurance Review Agency during the period January 2009 to December 2010. RESULTS: After the PCD project, the length of stay for palliative patients with cancer diseases decreased by 2.56% (ß = -0.026; p-value = 0.0001) among patients hospitalized in a PCD project compared with patients hospitalized in seven hospitals that was not designed as a PCD project. Compared with costs before the PCD project, costs decreased by 0.76% (ß = 0.013; p-value = 0.0001). CONCLUSIONS: We provided evidence regarding the change in the societal burden due to palliative care. Although there was a reduction of direct medical costs reported in limited number of hospitals, in the long term, we can anticipate an expanding impact on medical costs in all palliative hospitals. Copyright © 2016 John Wiley & Sons, Ltd.


Subject(s)
Health Expenditures , Hospitalization/economics , Length of Stay/economics , Palliative Care/economics , Reimbursement Mechanisms , Aged , Aged, 80 and over , Female , Health Policy , Health Resources/statistics & numerical data , Health Services Research , Humans , Male , Middle Aged , Quality of Health Care , Republic of Korea , Retrospective Studies
9.
Br J Surg ; 102(12): 1567-73, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26312601

ABSTRACT

BACKGROUND: There is a lack of information regarding the oncological safety of robotic intersphincteric resection (ISR) with coloanal anastomosis. The objective of this study was to compare the long-term feasibility of robotic compared with laparoscopic ISR. METHODS: Between January 2008 and May 2011, consecutive patients who underwent robotic or laparoscopic ISR with coloanal anastomosis from seven institutions were included. Propensity score analyses were performed to compare outcomes for groups in a 1 : 1 case-matched cohort. The primary endpoint was 3-year disease-free survival. RESULTS: A total of 334 patients underwent ISR with coloanal anastomosis, of whom 212 matched patients (106 in each group) formed the cohort for analysis. The overall rate of conversion to open surgery was 0.9 per cent in the robotic ISR group and 1.9 per cent in the laparoscopic ISR group. Nine patients (8.5 per cent) in the laparoscopic group and three (2.8 per cent) in the robotic ISR group still had a stoma at last follow-up (P = 0.075). Total mean hospital costs were significantly higher for robotic ISR (€ 12,757 versus € 9223 for laparoscopic ISR; P = 0.037). Overall 3-year local recurrence rates were similar in the two groups (6.7 per cent for robotic and 5.7 per cent for laparoscopic resection; P = 0.935). The combined 3-year disease-free survival rates were 89.6 (95 per cent c.i. 84.1 to 95.9) and 90.5 (85.4 to 96.6) per cent respectively (P = 0.298). CONCLUSION: Robotic ISR with coloanal anastomosis for rectal cancer has reasonable oncological outcomes, but is currently too expensive with no short-term advantages.


Subject(s)
Adenocarcinoma/surgery , Anal Canal/surgery , Colectomy/methods , Laparoscopy/methods , Postoperative Complications/epidemiology , Rectal Neoplasms/surgery , Robotics/methods , Adenocarcinoma/diagnosis , Adenocarcinoma/mortality , Anastomosis, Surgical/methods , Conversion to Open Surgery , Disease-Free Survival , Female , Follow-Up Studies , Humans , Male , Neoplasm Recurrence, Local/epidemiology , Neoplasm Staging , Rectal Neoplasms/diagnosis , Rectal Neoplasms/mortality , Republic of Korea/epidemiology , Survival Rate/trends , Time Factors
10.
J Appl Microbiol ; 119(2): 465-74, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26033289

ABSTRACT

AIMS: We investigated the effect of ozone treatment of apple juice at different pH levels for inactivation of Escherichia coli O157:H7, Salmonella Typhimurium and Listeria monocytogenes. METHODS AND RESULTS: Apple juice (pH 3.0, 4.0 and 5.0) inoculated with the three pathogens were treated with gaseous ozone (3.0 l min(-1) flow rate and 2.0-3.0 g m(-3) ) for up to 4 min. Ozone treatment (4 min) of pH 3.0 apple juice resulted in >5.36 log CFU ml(-1) reduction of E. coli O157:H7. Ozone treatment of pH 4.0 and 5.0 apple juice for 4 min reduced this pathogen by 5.12 log CFU ml(-1) and 1.86 log CFU ml(-1) respectively. The combination of low pH and ozone showed a great antimicrobial effect in apple juice. Salm. Typhimurium and L. monocytogenes showed a reduction trend similar to E. coli O157:H7. There were no significant changes of colour values when apple juice was treated with ozone, except for b values. Among all ozone treated samples, the browning index was lower than that of nontreated samples and there were no significant differences in total phenolic contents. CONCLUSIONS: In conclusion, ozone treatment of low pH apple juice was significantly effective in inactivation of foodborne pathogens while maintaining acceptable apple juice quality. SIGNIFICANCE AND IMPACT OF THE STUDY: The antimicrobial effect of ozone treatment on foodborne pathogens in apple juice can be reinforced by lowering the pH of apple juice.


Subject(s)
Beverages/microbiology , Escherichia coli O157/drug effects , Food Preservation/methods , Malus/microbiology , Ozone/pharmacology , Beverages/analysis , Escherichia coli O157/growth & development , Hydrogen-Ion Concentration , Listeria monocytogenes/drug effects , Listeria monocytogenes/growth & development , Ozone/chemistry , Salmonella typhimurium/drug effects , Salmonella typhimurium/growth & development
11.
Nutr Metab Cardiovasc Dis ; 25(7): 677-85, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26026212

ABSTRACT

BACKGROUND AND AIMS: Low bilirubin and high gamma-glutamyltransferase (GGT), which are endogenous markers of oxidative stress, confer a higher risk of cardiovascular disease (CVD). We investigated associations between serum concentrations of bilirubin, GGT and coronary atherosclerosis. METHODS AND RESULTS: A cross-sectional analysis was performed on 1520 subjects who underwent multidetector computed tomography scans. Coronary atherosclerosis was assessed by coronary artery calcium score (CACS) and obstructive coronary artery disease (OCAD), was defined as the presence of coronary artery stenosis of ≥50%. Total bilirubin (TB) level was negatively correlated with CACS and coronary stenosis whereas GGT level was positively correlated with CACS in men. However, there was no correlation between TB, GGT levels and either CACS or coronary artery stenosis in women. In a multivariate-adjusted model, TB level was inversely associated with a CACS > 100 [odds ratio (OR) per log standard deviation (SD), 0.67; 95% confidence interval (CI), 0.52-0.87], and OCAD (OR per log SD, 0.77; 95% CI, 0.62-0.95) in men. By contrast, GGT level was positively associated with a CACS > 100 (OR per log SD, 1.35; 95% CI, 1.05-1.73) but not with OCAD. Adding TB and GGT to the conventional risk factors increased predictive accuracy for CACS > 100 (net reclassification improvement index [NRI] = 13.1%, P = 0.026; integrated discrimination index [IDI] = 0.024, P = 0.001) and for OCAD (NRI = 12.6%, P = 0.026; IDI = 0.010, P = 0.013). CONCLUSIONS: Low TB and high GGT levels were concomitantly associated with coronary atherosclerosis in Korean men. Future studies are needed to elucidate the causal associations of TB and GGT with CVD.


Subject(s)
Bilirubin/blood , Coronary Artery Disease/blood , gamma-Glutamyltransferase/blood , Adult , Coronary Stenosis/diagnostic imaging , Coronary Vessels/diagnostic imaging , Cross-Sectional Studies , Fatty Liver/blood , Female , Humans , Male , Middle Aged , Multidetector Computed Tomography , Republic of Korea , Retrospective Studies , Risk Factors , Sex Characteristics , Vascular Calcification/blood , Vascular Calcification/pathology
12.
Eye (Lond) ; 29(8): 1051-9, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25998944

ABSTRACT

PURPOSE: To determine the preoperative anatomic factors in macular holes and their correlation to hole closure. METHODS: Forty-six eyes with consecutive unilateral macular hole who had undergone surgery and followed up for at least 6 months were enrolled. Optical coherence tomography images and best-corrected visual acuity (BCVA) within 2 weeks prior to operation and 6 months after surgery were analyzed. The maximal hole dimension, foveal degeneration factors (inner nuclear layer cysts, outer segment (OS) shortening) and the widest foveolar floor size of the fellow eyes were measured. For overcoming preoperative individual variability of foveal morphology, an 'adjusted' hole size parameter (the ratio between the hole size and the fellow eye foveolar floor size) was used based on the fact that both eyes were morphologically symmetrical. RESULTS: Mean preoperative BCVA (logMAR) was 1.03±0.43 and the mean postoperative BCVA was 0.50±0.38 at 6 months. Preoperative BCVA is significantly associated with postoperative BCVA (P=0.0002). The average hole diameter was 448.9±196.8 µm and the average fellow eye foveolar floor size was 461.3±128.4 µm. There was a correlation between hole diameter and the size of the fellow eye foveolar floor (Pearson's coefficient=0.608, P<0.0001). The adjusted hole size parameter was 0.979±0.358 (0.761-2.336), which was a strong predictor for both anatomic (P=0.0281) and visual (P=0.0016) outcome. CONCLUSION: When determining the extent of preoperative hole size, we have to take into consideration the foveal morphologic variations among individuals. Hole size may be related to the original foveal shape, especially in relation to the centrifugal retraction of the foveal tissues.


Subject(s)
Fovea Centralis/pathology , Retinal Perforations/pathology , Retinal Perforations/surgery , Vitrectomy , Aged , Aged, 80 and over , Analysis of Variance , Female , Humans , Male , Middle Aged , Retinal Perforations/physiopathology , Retrospective Studies , Tomography, Optical Coherence , Visual Acuity/physiology , Vitrectomy/methods
13.
Hum Exp Toxicol ; 34(9): 869-77, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25504686

ABSTRACT

Cigarette smoke (CS) is a major risk factor for emphysema, which causes cell death in structural cells of the lung by mechanisms that are still not completely understood. We demonstrated previously that CS extract (CSE) induces caspase activation in MRC-5 human lung fibroblasts, activated protein kinase C-η (PKC-η), and translocated PKC-η from the cytosol to the membrane. The objective of this study was to investigate the involvement of PKC-η activation in a CSE-induced extrinsic apoptotic pathway. We determined that CSE increases expression of caspase 3 and 8 cleavage in MRC-5 cells and overexpression of PKC-η significantly increased expression of caspase 3 and 8 cleavage compared with control LacZ-infected cells. In contrast, dominant negative (dn) PKC-η inhibited apoptosis in MRC-5 cells exposed to CSE and decreased expression of caspase 3 and 8 compared with control cells. Exposure to 10% CSE for >8 h significantly increased lactate dehydrogenase release in PKC-η-infected cells compared with LacZ-infected cells. Additionally, PKC-η-infected cells had an increased number of Hoechst 33342 stained nuclei compared with LacZ-infected cells, while dn PKC-η-infected cells exhibited fewer morphological changes than LacZ-infected cells under phase-contrast microscopy. In conclusion, PKC-η activation plays a pro-apoptotic role in CSE-induced extrinsic apoptotic pathway in MRC-5 cells. These results suggest that modulation of PKC-η may be a useful tool for regulating the extrinsic apoptosis of MRC-5 cells by CSE and may have therapeutic potential in the treatment of CS-induced lung injury.


Subject(s)
Apoptosis/drug effects , Nicotiana/toxicity , Protein Kinase C/drug effects , Smoke/adverse effects , Caspase 3/metabolism , Caspase 8/metabolism , Cell Line , Cell Survival/drug effects , Fibroblasts/drug effects , Humans , L-Lactate Dehydrogenase/metabolism , Lac Operon/drug effects , Lung/pathology , Pulmonary Disease, Chronic Obstructive/pathology , beta-Galactosidase/metabolism
14.
Oncogene ; 33(47): 5434-41, 2014 Nov 20.
Article in English | MEDLINE | ID: mdl-24240688

ABSTRACT

Gene fusion is involved in the development of various types of malignancies. Recent advances in sequencing technology have facilitated identification of gene fusions and have stimulated the research of this field in cancer. In the present study, we performed next-generation transcriptome sequencing in order to discover novel gene fusions in gastric cancer. A total of 282 fusion transcript candidates were detected from 12 gastric cancer cell lines by bioinformatic filtering. Among the candidates, we have validated 19 fusion transcripts, which are 7 inter-chromosomal and 12 intra-chromosomal fusions. A novel DUS4L-BCAP29 fusion transcript was found in 2 out of 12 cell lines and 10 out of 13 gastric cancer tissues. Knockdown of DUS4L-BCAP29 transcript using siRNA inhibited cell proliferation. Soft agar assay further confirmed that this novel fusion transcript has tumorigenic potential. We also identified that microRNA-coding gene PVT1, which is amplified in double minute chromosomes in SNU-16 cells, is recurrently involved in gene fusion. PVT1 produced six different fusion transcripts involving four different genes as fusion partners. Our findings provide better insight into transcriptional and genetic alterations of gastric cancer: namely, the tumorigenic effects of transcriptional read-through and a candidate region for genetic instability.


Subject(s)
Gene Fusion , Cell Line, Tumor , Gene Expression Profiling , High-Throughput Nucleotide Sequencing , Humans , Membrane Proteins/genetics , Oxidoreductases/genetics , RNA, Long Noncoding/genetics , Reproducibility of Results , Stomach Neoplasms/genetics
15.
Transl Psychiatry ; 3: e321, 2013 Oct 29.
Article in English | MEDLINE | ID: mdl-24169640

ABSTRACT

Whole-genome expression profiling in postmortem brain tissue has recently provided insight into the pathophysiology of schizophrenia. Previous microarray and RNA-Seq studies identified several biological processes including synaptic function, mitochondrial function and immune/inflammation response as altered in the cortex of subjects with schizophrenia. Now using RNA-Seq data from the hippocampus, we have identified 144 differentially expressed genes in schizophrenia cases as compared with unaffected controls. Immune/inflammation response was the main biological process over-represented in these genes. The upregulation of several of these genes, IFITM1, IFITM2, IFITM3, APOL1 (Apolipoprotein L1), ADORA2A (adenosine receptor 2A), IGFBP4 and CD163 were validated in the schizophrenia subjects using data from the SNCID database and with quantitative RT-PCR. We identified a co-expression module associated with schizophrenia that includes the majority of differentially expressed genes related to immune/inflammation response as well as with the density of parvalbumin-containing neurons in the hippocampus. The results indicate that abnormal immune/inflammation response in the hippocampus may underlie the pathophysiology of schizophrenia and may be associated with abnormalities in the parvalbumin-containing neurons that lead to the cognitive deficits of the disease.


Subject(s)
Hippocampus/immunology , RNA, Messenger/analysis , Schizophrenia/immunology , Adult , Antigens, CD/genetics , Antigens, CD/immunology , Antigens, Differentiation/genetics , Antigens, Differentiation/immunology , Antigens, Differentiation, Myelomonocytic/genetics , Antigens, Differentiation, Myelomonocytic/immunology , Apolipoprotein L1 , Apolipoproteins/genetics , Apolipoproteins/immunology , Case-Control Studies , Female , Gene Expression Profiling , Hippocampus/metabolism , Humans , Inflammation/genetics , Insulin-Like Growth Factor Binding Protein 4/genetics , Insulin-Like Growth Factor Binding Protein 4/immunology , Lipoproteins, HDL/genetics , Lipoproteins, HDL/immunology , Male , Membrane Proteins/genetics , Membrane Proteins/immunology , Middle Aged , Oligonucleotide Array Sequence Analysis , RNA-Binding Proteins/genetics , RNA-Binding Proteins/immunology , Receptor, Adenosine A2A/genetics , Receptor, Adenosine A2A/immunology , Receptors, Cell Surface/genetics , Receptors, Cell Surface/immunology , Reverse Transcriptase Polymerase Chain Reaction , Schizophrenia/genetics , Up-Regulation
16.
Ann Oncol ; 24(8): 2080-7, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23559152

ABSTRACT

BACKGROUND: The mechanism of primary resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small-cell lung cancer (NSCLC) has not been clearly understood. PATIENTS AND METHODS: Eleven patients exhibiting primary resistance (disease progression <3 months) were identified among 197 consecutive NSCLC patients with TKI-sensitive EGFR mutations who received EGFR TKIs at Seoul National University Hospital. Treatment-naïve tumors were examined for concurrent genetic alterations using fluorescence in situ hybridization and targeted deep sequencing of cancer-related genes. Deletion polymorphism of Bcl-2-interacting mediator of cell death (BIM) gene was examined to validate its predictive role for TKI outcome. RESULTS: The median progression-free survival (PFS) for patients receiving EGFR TKIs was 11.9 months, and the response rate 78.8%. Among the 11 patients exhibiting primary resistance, a de novo T790M mutation was identified in one patient, and two exhibited mesenchymal-epithelial transition amplification and anaplastic lymphoma kinase fusion. Targeted deep sequencing identified no recurrent, coexistent drivers of NSCLC. Survival analysis revealed that patients with recurrent disease after surgery had a longer PFS than those with initial stage IV disease. However, BIM deletion polymorphism, line of treatment, EGFR genotype, and smoking were not predictive of PFS for EGFR TKIs. CONCLUSIONS: We identified coexistent genetic alterations of cancer-related genes that could explain primary resistance in a small proportion of patients. Our result suggests that the mechanism of primary resistance might be heterogeneous.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Adult , Aged , Aged, 80 and over , Apoptosis Regulatory Proteins/genetics , Base Sequence , Bcl-2-Like Protein 11 , Carcinoma, Non-Small-Cell Lung/genetics , Cell Transdifferentiation/genetics , Disease-Free Survival , Drug Resistance, Neoplasm , Erlotinib Hydrochloride , Female , Gefitinib , Genotype , Humans , Lung Neoplasms/genetics , Male , Membrane Proteins/genetics , Middle Aged , Mutation , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-bcl-2/genetics , Quinazolines/therapeutic use , Sequence Analysis, DNA , Sequence Deletion/genetics
17.
Cancer Gene Ther ; 20(3): 186-94, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23392203

ABSTRACT

As hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, development of novel therapeutic approaches for HCC is urgently needed. Two different genes, LETM1 and CTMP, which target mitochondrial functions, were chosen and linked using 2A-peptide sequence. Successful self-cleavage of 2A-peptide induced synergistic antitumor effect in the liver of H-ras12V, the HCC model mice, by simultaneous activation of LETM1 (Leucine zipper/EF hand-containing transmembrane-1) and CTMP (carboxyl-terminal modulator protein). Overexpression of LETM1 and CTMP significantly reduced the incidence of tumorigenesis, which were confirmed by gross and microscopic observations. Morphological changes in mitochondria, such as swelling and loss of cristae, were significant, and the prolonged activation of defects in mitochondrial function led to mitochondria-mediated apoptosis. Furthermore, with CTMP as a direct binding partner of Akt1, and LETM1 as a binding partner of CTMP, LETM1-2A-CTMP downregulated the Akt1 pathway at both Ser473 and Thr308 sites of phosphorylation. Proliferation and angiogenesis, which are important in cancer prognosis, were reduced in tumor sites after introduction of LETM1-2A-CTMP. Taken together, the results indicate that introduction of the mitochondria-targeting genes, LETM1 and CTMP, and self-processing capacity of 2A-peptide sequence exerts an antitumor effect in liver of H-ras12V mice, suggesting its potential as a tool for gene therapy.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Calcium-Binding Proteins/genetics , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Membrane Proteins/genetics , Plasmids/administration & dosage , Thiolester Hydrolases/genetics , Animals , Apoptosis/genetics , Carcinoma, Hepatocellular/blood supply , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Cell Proliferation , Disease Models, Animal , Disease Progression , Gene Expression , Gene Order , Humans , Liver Neoplasms/blood supply , Liver Neoplasms/metabolism , Mice , Mitochondria/genetics , Mitochondria/metabolism , Neovascularization, Pathologic/genetics , Peptides/genetics , Polyethyleneimine/analogs & derivatives , Polyethyleneimine/chemistry , Proto-Oncogene Proteins c-akt/metabolism , Recombinant Fusion Proteins/genetics , Tumor Burden/genetics
18.
Vox Sang ; 102(4): 362-4, 2012 May.
Article in English | MEDLINE | ID: mdl-22211799

ABSTRACT

Deferral of blood donors taking teratogenic drugs is critical. From March 2008 to January 2009, we analysed stored blood specimens from donors who had taken teratogenic drugs and whose blood was transfused to women of childbearing age to determine the plasma concentration at the time of donation using high-performance liquid chromatography. In total, 167 specimens were examined. The numbers of specimens exceeding the quantification limit were 7, 39, 4, 2 and 1 for finasteride, isotretinoin, acitretin, etretinate and dutasteride, respectively. Finasteride was beyond the recommended drug deferral period in one specimen. These results may help create practical deferral policies.


Subject(s)
Blood Donors , Teratogens/analysis , Transfusion Reaction , Acitretin/blood , Adult , Etretinate/blood , Female , Finasteride/blood , Humans , Young Adult
19.
Chemosphere ; 82(9): 1268-76, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21196025

ABSTRACT

Persistent organic pollutants (POPs), xenobiotics that accumulate in fat tissue, may impair bone metabolism. We studied (1) the association of bone mineral density (BMD) with POPs and (2) whether associations of fat mass (FM) or lean mass (LM), two components of body composition, with BMD differed depending on levels of POPs. Participants aged ≥ 20 in the National Health and Nutrition Examination Survey 1999-2004 were included (n=2769). Eight POPs with detection rate ≥ 80% and three skeletal subregions (left arm, pelvis, and right leg) were selected. All analyses were stratified by gender and age (cutpoint 50 years or more). POPs at background concentrations were mostly unassociated with BMD. However, the associations of FM and LM with BMD depended on POPs concentrations, in particular with BMD of the left arm (usually not weight-bearing) in postmenopausal women. When POPs concentrations were low, FM showed inverse associations with BMD while LM showed positive associations. However, when POPs levels were high, FM showed positive associations with BMD while the positive associations between LM and BMD weakened. POPs may biologically modify the associations of FM and LM with BMD, especially among postmenopausal women, possibly explaining inconsistent associations between FM and BMD in previous epidemiological studies.


Subject(s)
Body Mass Index , Bone Density/drug effects , Environmental Exposure/statistics & numerical data , Environmental Pollutants/blood , Organic Chemicals/blood , Adipose Tissue/metabolism , Adult , Aged , Body Composition , Dioxins/blood , Dioxins/toxicity , Environmental Exposure/analysis , Environmental Pollutants/metabolism , Environmental Pollutants/toxicity , Female , Humans , Male , Middle Aged , Nutrition Surveys , Organic Chemicals/metabolism , Organic Chemicals/toxicity , Pesticides/blood , Pesticides/toxicity , Polychlorinated Biphenyls/blood , Polychlorinated Biphenyls/toxicity , United States
20.
Article in English | MEDLINE | ID: mdl-21096350

ABSTRACT

This paper is about a glass-type wireless bio-signal transmitter that can monitor the user's health state in daily life. The device implemented in this study consists of the transmission part and the receiving part. The transmission part includes a photoplethysmography(PPG) sensor for detecting pulse wave signals, accelerometer for detecting kinetic signals, and a wireless controller for transmitting acquired bio-information. The receiving part is designed to check and process transmitted data through interoperation with a PC. In the experiments, we collected data during a sitting posture and repeated sit-to-stand motion in laboratory environment, and analyzed the data. As to accuracy, the correlation between the peak-to-peak intervals in the signals of the Biopac equipment and the developed device measured in a sitting posture was 97.5%, and that measured in sit-to-stand motion was 87%. In addition, when bio-signals were transmitted through wireless communication, the transmission was successful 100% without any error. When pulse wave signals and kinetic signals were obtained and compared, the results proved the accuracy and daily applicability of the developed device, and the glass-type wireless bio-signal transmission system is expected to be applicable to unobtrusive health monitoring for the user.


Subject(s)
Diagnosis, Computer-Assisted/instrumentation , Eyeglasses , Monitoring, Ambulatory/instrumentation , Photoplethysmography/instrumentation , Telemetry/instrumentation , Adult , Equipment Design , Equipment Failure Analysis , Female , Humans , Male , Young Adult
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