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1.
J Dent Res ; 102(7): 825-834, 2023 07.
Article in English | MEDLINE | ID: mdl-37246809

ABSTRACT

The enamel knot (EK), located at the center of cap stage tooth germs, is a transitory cluster of nondividing epithelial cells. The EK acts as a signaling center that provides positional information for tooth morphogenesis and regulates the growth of tooth cusps. To identify species-specific cuspal patterns, this study analyzed the cellular mechanisms in the EK that were related to bone morphogenetic protein (Bmp), which plays a crucial role in cell proliferation and apoptosis. To understand the cellular mechanisms in the EK, the differences between 2 species showing different cuspal patterning, mouse (pointy bunodont cusp) and gerbil (flat lophodont cusp), were analyzed with quantitative reverse transcriptase polymerase chain reaction and immunofluorescent staining. Based on these, we performed protein-soaked bead implantation on tooth germs of the 2 different EK regions and compared the cellular behavior in the EKs of the 2 species. Many genes related with cell cycle, cell apoptosis, and cell proliferation were involved in BMP signaling in the EK during tooth development. A comparison of the cell proliferation and apoptosis associated with Bmp revealed distinctive patterns of the cellular mechanisms. Our findings indicate that the cellular mechanisms, such as cell proliferation and apoptosis, in the EK are related to Bmp4 and play an important role in tooth morphogenesis.


Subject(s)
Tooth , Animals , Mice , Dental Enamel/metabolism , Odontogenesis/genetics , Tooth Germ , Bone Morphogenetic Proteins/metabolism , Cell Proliferation , Apoptosis , Bone Morphogenetic Protein 4/metabolism
2.
Eur Rev Med Pharmacol Sci ; 25(11): 4051-4063, 2021 06.
Article in English | MEDLINE | ID: mdl-34156683

ABSTRACT

OBJECTIVE: Buerger's disease is a rare disease that causes critical limb ischemia; however, the underlying pathophysiological mechanism remains unclear. Therefore, we investigated the interaction between interleukin (IL)-17 and high-mobility group protein B 1 (HMGB1) and determined whether A disintegrin and metalloproteinase 10 (ADAM10) inhibit this interaction. PATIENTS AND METHODS: The study population included 15 patients with Buerger's disease and 10 healthy donors without a history of giving peripheral blood samples. Cytokine levels were measured using a luminex multiplex assay in plasma. Flow cytometry was used to analyze the subtypes of helper T (Th) cells among peripheral blood mononuclear cells (PBMCs). The effect of ADAM10 on PBMCs was analyzed in vitro. RESULTS: The levels of inflammatory cytokines and production of pathogenic Th cells were found to be higher in Korean patients with Buerger's disease. IL-17 treatment induced HMGB1 associated molecules. HMGB1 also induced IL-17 and Th17 associated transcription factors in Buerger's patients. We observed that ADAM10 regulates the interaction between IL-17 and HMGB1 via advanced glycation end products (RAGE)/nuclear factor-kappa B (NF-kB) pathway in patients with Buerger's disease. CONCLUSIONS: This study suggests that IL-17 and HMGB1 cytokines contribute to the pathogenesis of Buerger's disease. These results indicate that ADAM10 alleviates inflammation in Buerger's disease via the HMGB1 and RAGE/NF-κB signaling pathway and provides insights into the molecular basis of and a potential therapeutic strategy for Buerger's disease.


Subject(s)
Cytokines/immunology , HMGB1 Protein/immunology , Thromboangiitis Obliterans/immunology , ADAM10 Protein/immunology , Adult , Amyloid Precursor Protein Secretases/immunology , Cells, Cultured , Cytokines/blood , Cytokines/genetics , Female , HMGB1 Protein/blood , HMGB1 Protein/genetics , Humans , Leukocytes, Mononuclear/immunology , Male , Membrane Proteins/immunology , Middle Aged , NF-kappa B/immunology , Nuclear Receptor Subfamily 1, Group F, Member 3/genetics , Receptor for Advanced Glycation End Products/genetics , Thromboangiitis Obliterans/blood , Thromboangiitis Obliterans/genetics
4.
Epidemiol Infect ; 149: e90, 2021 04 05.
Article in English | MEDLINE | ID: mdl-33814028

ABSTRACT

Invasive meningococcal disease has high morbidity and mortality, with infants and young children among those at greatest risk. This phase III, open-label, randomised study in toddlers aged 12-23 months evaluated the immunogenicity and safety of meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT), a tetanus toxoid conjugated vaccine against meningococcal serogroups A, C, W and Y, when coadministered with paediatric vaccines (measles, mumps and rubella [MMR]; varicella [V]; 6-in-1 combination vaccine against diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b [DTaP-IPV-HepB-Hib] and pneumococcal conjugate vaccine [PCV13])(NCT03205371). Immunogenicity to each meningococcal serogroup was assessed by serum bactericidal antibody assay using human complement (hSBA). Vaccine safety profiles were described up to 30 days post-vaccination. A total of 1183 participants were enrolled. The proportion with seroprotection (hSBA ≥1:8) to each meningococcal serogroup at Day 30 was comparable between the MenACYW-TT and MenACYW-TT + MMR + V groups (≥92 and ≥96%, respectively), between the MenACYW-TT and MenACYW-TT + DTaP-IPV-HepB-Hib groups (≥90% for both) and between the MenACYW-TT and MenACYW-TT + PCV13 groups (≥91 and ≥84%, respectively). The safety profiles of MenACYW-TT, and MMR + V, DTaP-IPV-HepB-Hib, and PCV13, with or without MenACYW-TT, were generally comparable. Coadministration of MenACYW-TT with paediatric vaccines in toddlers had no clinically relevant effect on the immunogenicity and safety of any of the vaccines.


Subject(s)
Meningococcal Infections/prevention & control , Meningococcal Vaccines/immunology , Neisseria meningitidis/immunology , Antibodies, Bacterial/blood , Antibodies, Viral/blood , Chickenpox Vaccine/administration & dosage , Chickenpox Vaccine/immunology , Diphtheria-Tetanus-Pertussis Vaccine/administration & dosage , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Female , Haemophilus Vaccines/administration & dosage , Haemophilus Vaccines/immunology , Hepatitis B Vaccines/administration & dosage , Hepatitis B Vaccines/immunology , Humans , Immunogenicity, Vaccine , Infant , Male , Measles-Mumps-Rubella Vaccine/administration & dosage , Measles-Mumps-Rubella Vaccine/immunology , Pneumococcal Vaccines/administration & dosage , Pneumococcal Vaccines/immunology , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Inactivated/immunology , Safety , Serogroup , Vaccines, Combined/administration & dosage , Vaccines, Combined/immunology
5.
J Infect Dis ; 218(1): 95-108, 2018 06 05.
Article in English | MEDLINE | ID: mdl-29767739

ABSTRACT

Background: A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Methods: Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. Results: 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. Clinical Trials Registration: NCT00543543; NCT00943722.


Subject(s)
Papillomaviridae/classification , Papillomaviridae/isolation & purification , Papillomavirus Infections/prevention & control , Papillomavirus Infections/virology , Papillomavirus Vaccines/adverse effects , Papillomavirus Vaccines/immunology , Adolescent , Adult , Antibodies, Viral/blood , Asia/epidemiology , Child , Double-Blind Method , Drug-Related Side Effects and Adverse Reactions/epidemiology , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Genitalia, Female/virology , Humans , Male , Papillomaviridae/genetics , Papillomavirus Infections/epidemiology , Papillomavirus Vaccines/administration & dosage , Treatment Outcome , Young Adult
6.
Biotech Histochem ; 92(7): 536-544, 2017.
Article in English | MEDLINE | ID: mdl-28925723

ABSTRACT

Age-related hearing loss (ARHL) is characterized by an age-dependent decline of auditory function characterized by with loss of sensory hair cells, spiral ganglion neurons, and stria vascularis (SV) cells in the cochlea of the inner ear. Aging and age-related diseases result from accumulated oxidative damage caused by reactive oxygen species (ROS) generated by mitochondria. The isocitrate dehydrogenase (IDH) family includes three enzymes in human cells: IDH1, IDH2, and IDH3. Although all three enzymes catalyze the same enzymatic reaction, that is, oxidative decarboxylation of isocitrate to produce α-ketoglutarate, each IDH enzyme has unique features. We identified and characterized IDH expression in the cochlea and vestibule of the murine inner ear. We examined the mRNA expression levels of Idh family members in the cochlea and vestibule using reverse transcription-PCR (RT-PCR) and detected expression of IDH family members in both tissues. We also used immunohistochemistry to localize IDH family members within the cochlea and vestibule of the adult mouse inner ear. IDH1 was detected throughout the cochlea. IDH2 was expressed specifically in the hair cells, spiral ganglion, and stria vascularis. IDH3α was found in the cell bodies of neurons of the spiral ganglion, the stria vascularis, and in types II, IV, and V cells of the spiral ligament in a pattern that resembled the location of the Na+, K+-ATPase ion channel. We postulate that the IDH family participates in transporting K+ ions in the cochlea. In the vestibule, all IDH family members were detected in both hair cells and the vestibular ganglion. We hypothesize that IDH1, IDH2, and IDH3 function to protect proteins in the inner ear from oxidative stress during K+ recycling.


Subject(s)
Ear, Inner , Isocitrate Dehydrogenase/metabolism , Animals , Ear, Inner/enzymology , Ear, Inner/metabolism , Female , Humans , Immunohistochemistry , Isocitrate Dehydrogenase/genetics , Male , Mice , Reverse Transcriptase Polymerase Chain Reaction
7.
Genet Mol Res ; 16(2)2017 Apr 13.
Article in English | MEDLINE | ID: mdl-28407192

ABSTRACT

The Japanese oak silkmoth, Antheraea yamamai Guérin-Méneville, 1861 (Lepidoptera: Saturniidae), is an important natural resource of industrial value for silk fiber production. Owing to a lack of geographic and population genetic information, systematic domestication of An. yamamai has not been possible yet. In this study, 10 microsatellite markers developed using next-generation sequencing and two mitochondrial DNA (mtDNA) gene sequences (COI and ND4) were used to investigate the genetic variation and geographic structure of An. yamamai populations in South Korea. The two mtDNA gene sequences revealed very low total genetic variation and, consequently, low geographic variation, validating the use of more variable molecular markers. Genotyping of 76 An. yamamai individuals from nine localities in South Korea showed that the observed number of alleles at each locus ranged from 3 to 26, the polymorphism information content was 0.2990-0.9014, the observed and expected heterozygosities were 0.3252-0.9076 and 0.2500-0.9054, respectively, and FIS was -0.654-0.520. The population-based FIS, FST, RST, and global Mantel tests all suggested that the An. yamamai populations were overall well-interconnected, suggesting that any population can be used as a genetic source for domestication. Nevertheless, STRUCTURE analyses using microsatellite data and mtDNA sequences indicated the presence of two genetic pools in many populations, although a plausible explanation for this observation requires further studies.


Subject(s)
Bombyx/genetics , DNA, Mitochondrial/genetics , Microsatellite Repeats , Polymorphism, Genetic , Animals , Gene Pool
8.
J Vet Intern Med ; 31(2): 335-342, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28064467

ABSTRACT

BACKGROUND: A high prevalence of cholestatic disease, including gallbladder mucocele (GBM), has been reported in dogs with naturally occurring pituitary-dependent hyperadrenocorticism (PDH). HYPOTHESIS/OBJECTIVES: Differences exist in the clinical features of dogs with PDH and concurrent cholestatic disease, and also is the management of these dogs with trilostane. ANIMALS: Sixty-five client-owned dogs with naturally occurring PDH. METHODS: This was a retrospective, observational case series. Each dog was treated with trilostane for at least 3 months before the study, and had a good clinical response, as determined by owners. Statistical comparisons of clinical signs, results of routine blood tests, basal and post-ACTH cortisol concentration, and optimal trilostane dosage were made after dogs were separated into the following 3 groups by ultrasonographic imaging: normal on ultrasound (NOU) group, cholestasis group, and GBM group. RESULTS: The GBM group had more severe clinical signs and significantly different total serum cholesterol concentration and post-ACTH stimulation cortisol concentration at the time of diagnosis. Dogs that weighed <6 kg had a significantly higher prevalence of cholestatic disease than did the other dogs (P = .003). The optimal trilostane dosages for the GBM and cholestasis groups were 2.5 and 1.5 times the dosage of the NOU group, respectively (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Gallbladder disease associated with cholestatic disease is correlated with PDH in dogs, in both its clinical features and drug management. These findings may be associated with hypercholesterolemia, unidentified genetic factors, and the hydrophobic nature of trilostane.


Subject(s)
Dihydrotestosterone/analogs & derivatives , Dog Diseases/physiopathology , Gallbladder Diseases/veterinary , Mucocele/veterinary , Pituitary ACTH Hypersecretion/veterinary , Adrenocorticotropic Hormone/blood , Animals , Body Weight , Dihydrotestosterone/administration & dosage , Dog Diseases/diagnostic imaging , Dog Diseases/drug therapy , Dogs , Female , Gallbladder Diseases/complications , Gallbladder Diseases/diagnostic imaging , Gallbladder Diseases/physiopathology , Hydrocortisone/blood , Male , Mucocele/complications , Mucocele/diagnostic imaging , Mucocele/physiopathology , Pituitary ACTH Hypersecretion/complications , Pituitary ACTH Hypersecretion/drug therapy , Pituitary ACTH Hypersecretion/physiopathology , Retrospective Studies
9.
Clin Microbiol Infect ; 22(10): 880-886, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27475739

ABSTRACT

Given the mode of transmission of Middle East respiratory syndrome (MERS), healthcare workers (HCWs) in contact with MERS patients are expected to be at risk of MERS infections. We evaluated the prevalence of MERS coronavirus (CoV) immunoglobulin (Ig) G in HCWs exposed to MERS patients and calculated the incidence of MERS-affected cases in HCWs. We enrolled HCWs from hospitals where confirmed MERS patients had visited. Serum was collected 4 to 6 weeks after the last contact with a confirmed MERS patient. We performed an enzyme-linked immunosorbent assay (ELISA) to screen for the presence of MERS-CoV IgG and an indirect immunofluorescence test (IIFT) to confirm MERS-CoV IgG. We used a questionnaire to collect information regarding the exposure. We calculated the incidence of MERS-affected cases by dividing the sum of PCR-confirmed and serology-confirmed cases by the number of exposed HCWs in participating hospitals. In total, 1169 HCWs in 31 hospitals had contact with 114 MERS patients, and among the HCWs, 15 were PCR-confirmed MERS cases in study hospitals. Serologic analysis was performed for 737 participants. ELISA was positive in five participants and borderline for seven. IIFT was positive for two (0.3%) of these 12 participants. Among the participants who did not use appropriate personal protective equipment (PPE), seropositivity was 0.7% (2/294) compared to 0% (0/443) in cases with appropriate PPE use. The incidence of MERS infection in HCWs was 1.5% (17/1169). The seroprevalence of MERS-CoV IgG among HCWs was higher among participants who did not use appropriate PPE.


Subject(s)
Coronavirus Infections/epidemiology , Infectious Disease Transmission, Patient-to-Professional/statistics & numerical data , Middle East Respiratory Syndrome Coronavirus/immunology , Adolescent , Adult , Aged , Coronavirus Infections/immunology , Female , Health Personnel , Health Surveys , Humans , Incidence , Male , Middle Aged , Population Surveillance , Seroepidemiologic Studies , Young Adult
10.
Public Health ; 139: 178-182, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27406975

ABSTRACT

OBJECTIVES: Metabolic syndrome (MS), as a precursor of diabetes mellitus (DM) and cardiovascular disease, is increasing steadily worldwide. We examined the preventive effects of lifestyle intervention on the occurrence of DM and acute myocardial infarction (AMI) in MS. STUDY DESIGN: Observational study on disease occurrence after lifestyle intervention. METHODS: The lifestyle intervention was administered to subjects with MS participating in a metropolitan lifestyle intervention program for 1 year. The same numbers of non-participating age- and sex-matched subjects with MS were randomly extracted from national health examination data. After intervention or examination, new occurrences of hypertension, DM, and AMI were identified through the national health insurance claims data during 1 year. For DM and AMI, multivariate logistic regression analysis for the factors affecting each disease was performed. RESULTS: In the intervention group and the control group (14,918 in each group), the occurrence of hypertension was 555 (6.07%) and 751 (8.33%), the occurrence of DM was 324 (2.55%) and 488 (3.89%), the occurrence of dyslipidemia was 321 (2.59%) and 373 (2.72%), and the occurrence of AMI was 13 (0.09%) and 26 (0.17%), respectively. In multivariate logistic regression analysis, adjusted odds ratios for intervention were 0.752 (95% confidence interval [CI]: 0.644-0.879) and 0.499 (95% CI: 0.251-0.992) for DM and AMI, respectively, indicating that lifestyle intervention has a preventive effect. CONCLUSIONS: Lifestyle intervention in MS has preventive effects on the occurrence of DM and AMI, and long-term follow-up is needed to evaluate these preventive effects in more detail.


Subject(s)
Diabetes Mellitus/epidemiology , Life Style , Metabolic Syndrome/epidemiology , Myocardial Infarction/epidemiology , Preventive Health Services , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Program Evaluation , Republic of Korea/epidemiology
11.
Int J Oral Maxillofac Surg ; 45(9): 1074-80, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27156429

ABSTRACT

This study was performed to evaluate the long-term changes in mandibular width, lower facial width, and ramus angulation after intraoral vertical ramus osteotomy (IVRO) and to identify the factors influencing these changes. This retrospective study included 53 consecutive patients with mandibular prognathism who underwent IVRO with (n=33) or without (n=20) Le Fort I osteotomy. Postero-anterior cephalograms and frontal facial photographs obtained before, 1 month after, and at least 24 months after IVRO were used for measurements. A linear mixed model and paired t-tests were used to analyze temporal changes and the associated influencing factors. The mandibular width increased immediately after surgery (P<0.05), but decreased continuously thereafter. The ramus angulation showed negligible change within the first month (P>0.05) and decreased thereafter up to approximately 36 months. The amounts of mandibular setback and posterior impaction and the length of time postoperative influenced these changes. The lower facial width changed, although inconsistently, within 3mm over time (P>0.05). In conclusion, the mandibular width increased after IVRO but seemed to normalize within approximately 3 years. The lower facial width did not reflect underlying skeletal changes. Therefore, long-term transverse changes after IVRO can be considered clinically irrelevant.


Subject(s)
Mandible/surgery , Osteotomy, Sagittal Split Ramus/methods , Prognathism/surgery , Adult , Cephalometry , Female , Follow-Up Studies , Humans , Male , Mandible/anatomy & histology , Retrospective Studies , Young Adult
12.
For Pathol ; 46(2): 164-167, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27087782

ABSTRACT

Raffaelea quercus-mongolicae is a fungus associated with oak wilt and deemed to cause extensive oak mortality in South Korea. Since the discovery of this fungus on a dead Mongolian oak (Quercus mongolica) in 2004, the mortality continued to spread southwards in South Korea. Despite continued expansion of the disease and associated significant impacts on forest ecosystems, information is lacking about the origin and genetic diversity of R. quercus-mongolicae. Restriction-site-Associated DNA (RAD) sequencing was used to assess genetic diversity and population structure among five populations (provinces) of R. quercus-mongolicae in South Korea. In total, 179 single nucleotide polymorphisms (SNPs) were identified among 2,639 RAD loci across the nuclear genome of the 54 R. quercus-mongolicae isolates (0.0012 SNPs per bp), which displayed an overall low expected heterozygosity and no apparent population structure. The low genetic diversity and no apparent population structure among South Korean populations of this ambrosia beetle-vectored fungus supports the hypothesis that this fungus was introduced to South Korea.

14.
Br J Surg ; 103(1): 126-35, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26572697

ABSTRACT

BACKGROUND: This study aimed to investigate whether radiofrequency ablation (RFA) is an alternative to surgical resection for hepatocellular carcinoma (HCC) within the context of current guidelines. METHODS: This retrospective study included patients with normal portal pressure and serum bilirubin level who initially underwent liver resection or RFA for a single HCC of maximum size 3 cm. Between-group differences in cumulative rates of survival and recurrence specific for HCC were analysed in the entire cohort and in a propensity score-matched cohort. RESULTS: A total of 604 patients were enrolled, 273 in the liver resection group and 331 in the RFA group. The 5- and 10-year HCC-specific survival rates for the resection and RFA groups were 87·6 versus 82·1 per cent and 59·0 versus 61·2 per cent respectively (P = 0·214), whereas overall 5- and 10-year recurrence-free survival rates for the corresponding groups were 60·6 versus 39·4 per cent and 37·5 versus 25·1 per cent respectively (P < 0·001). In the propensity score-matched cohort (152 pairs), there were no differences in HCC-specific survival (hazard ratio (HR) 1·03 for RFA versus resection; P = 0·899), whereas recurrence-free survival again differed between the treatment groups (HR 1·75; P < 0·001). RFA was independently associated with poorer outcomes in terms of treatment-site recurrence-free survival (adjusted HR 1·66; P = 0·026), but not non-treatment-site recurrence-free survival (adjusted HR 1·15; P = 0·354). CONCLUSION: Although RFA carries a higher risk of treatment-site recurrence than hepatic resection, it provides comparable overall survival in patients with a single small HCC without portal hypertension or a raised bilirubin level.


Subject(s)
Carcinoma, Hepatocellular/surgery , Catheter Ablation , Hepatectomy , Liver Neoplasms/surgery , Adult , Aged , Carcinoma, Hepatocellular/mortality , Female , Follow-Up Studies , Humans , Liver Neoplasms/mortality , Male , Middle Aged , Neoplasm Recurrence, Local , Propensity Score , Retrospective Studies , Survival Analysis , Treatment Outcome
15.
Am J Transplant ; 16(1): 157-70, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26372830

ABSTRACT

ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the largest single-center experience of ABO-incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in-hospital mortality. The cumulative 3-year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO-compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody-mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized.


Subject(s)
ABO Blood-Group System/immunology , Blood Group Incompatibility , Desensitization, Immunologic , Graft Rejection/immunology , Liver Transplantation , Living Donors , Rituximab/pharmacology , Adolescent , Adult , Aged , Female , Humans , Immunosuppressive Agents/pharmacology , Liver Diseases/immunology , Liver Diseases/surgery , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Young Adult
16.
Oncogene ; 35(10): 1314-23, 2016 Mar 10.
Article in English | MEDLINE | ID: mdl-26028023

ABSTRACT

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and is on the rise in the United States. Previous studies showed that the matricellular protein CCN1 (CYR61) is induced during hepatic injuries and functions to restrict and resolve liver fibrosis. Here, we show that CCN1 suppresses hepatocarcinogenesis by inhibiting carcinogen-induced compensatory hepatocyte proliferation, thus limiting the expansion of damaged and potentially oncogenic hepatocytes. Consistent with tumor suppression, CCN1 expression is downregulated in human HCC. Ccn1(ΔHep) mice with hepatocyte-specific deletion of Ccn1 suffer increased HCC tumor multiplicity induced by the hepatocarcinogen diethylnitrosamine (DEN). Knockin mice (Ccn1(dm/dm)) that express an integrin α6ß1-binding defective CCN1 phenocopied Ccn1(ΔHep) mice, indicating that CCN1 acts through its α6ß1 binding sites in this context. CCN1 effectively inhibits epidermal growth factor receptor (EGFR)-dependent hepatocyte proliferation through integrin α6-mediated accumulation of reactive oxygen species (ROS), thereby triggering p53 activation and cell cycle block. Consequently, Ccn1(dm/dm) mice exhibit diminished p53 activation and elevated compensatory hepatocyte proliferation, resulting in increased HCC. Furthermore, we show that a single dose of the EGFR inhibitor erlotinib delivered prior to DEN-induced injury was sufficient to block compensatory proliferation and annihilate development of HCC nodules observed 8 months later, suggesting potential chemoprevention by targeting CCN1-inhibitable EGFR-dependent hepatocyte proliferation. Together, these results show that CCN1 is an injury response protein that functions not only to restrict fibrosis in the liver, but also to suppress hepatocarcinogenesis by inhibiting EGFR-dependent hepatocyte compensatory proliferation.


Subject(s)
Carcinogenesis/metabolism , Carcinoma, Hepatocellular/pathology , Cysteine-Rich Protein 61/metabolism , Liver Neoplasms/pathology , Animals , Carcinogenesis/chemically induced , Cell Line, Tumor , Cell Proliferation/drug effects , Cysteine-Rich Protein 61/genetics , Diethylnitrosamine/pharmacology , ErbB Receptors/antagonists & inhibitors , Gene Expression Regulation, Neoplastic/drug effects , Humans , Liver/drug effects , Liver/pathology , Male , Mice , Mice, Inbred C57BL , Mutation , Reactive Oxygen Species/metabolism , Tumor Suppressor Protein p53/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
17.
Article in English | WPRIM (Western Pacific) | ID: wpr-630722

ABSTRACT

Heterotopic bone formation is a very rare event in the gastrointestinal tract including in the appendix. Here we report three cases of heterotopic ossification in appendiceal mucinous neoplasms, one occurring in an appendiceal mucinous cystadenoma, another in a low-grade appendiceal mucinous neoplasm, and the third occurring in an appendiceal mucinous adenocarcinoma. The clinicopathologic characteristics of these three present cases and two previously reported cases are discussed in detail. The mechanism of heterotopic ossification in appendiceal mucinous neoplasm is still unclear, but mucin extravasation and subsequent calcification may be predisposing events.

19.
Transplant Proc ; 47(3): 576-9, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25891689

ABSTRACT

BACKGROUND: For deceased-donor liver graft retrieval, the warm dissection technique of hilar dissection before perfusion had been the standard procedure in the early period of liver transplantation. Thereafter, the cold dissection technique of in situ flushing and hilar dissection after perfusion has been preferred in many transplantation centers for rapid procurement of multiple organs. This study intended to assess the safety and usefulness of the warm dissection technique used in deceased-donor liver transplantation. METHODS: This study analyzed a single surgeon's experience of the warm dissection technique for 165 cases of liver graft retrieval, regarding the prolongation of retrieval operation time, retrieval-associated graft injury, and recipient outcomes. RESULTS: An additional 20 to 40 minutes was required for warm dissection. The incidence of retrieval-associated graft injury was 13 (7.9%), in which hepatic parenchymal injury was detected in 7 (capsular tear in 6 and subcapsular hematoma in 1) and vascular injury in 6 (celiac axis injury in 5 and common hepatic artery injury in 1). There was no other episode of injury at the branch artery, vena cava, portal vein, and bile duct. There was no significant difference of 1-year graft survival rates between liver grafts with and without graft injury (83% vs 83.3%, P = .73). CONCLUSIONS: When the vital signs of deceased donor are stable, the warm dissection technique may be helpful to decrease the cold ischemic preservation time because the risk of graft injury is acceptably low and it provides more time for recipient preparation, thus giving potential advantages for marginal liver grafts.


Subject(s)
Dissection/adverse effects , Dissection/methods , Liver , Temperature , Tissue and Organ Harvesting/methods , Adult , Bile Ducts/injuries , Female , Graft Survival , Hepatic Artery/injuries , Humans , Liver/injuries , Liver Transplantation , Male , Middle Aged , Perfusion , Portal Vein/injuries , Safety , Tissue Donors , Tissue and Organ Harvesting/adverse effects
20.
Transplant Proc ; 47(3): 580-3, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25891690

ABSTRACT

BACKGROUND: The number of deceased organ donors in Korea has been gradually increased to reach 8 per million population. This study intended to analyze the updated status of urgent deceased-donor liver transplantation in a Korean high-volume liver transplantation center. METHODS: A retrospective study was performed with a 4-year study period from 2010 to 2013. RESULTS: During the study period, 328 adult patients were enrolled at the Asan Medical Center for urgent orthotopic liver transplantation (OLT) with Korean Network for Organ Sharing status 1 in 56 (17.1%) and status 2A in 272 (82.9%). Of them, 201 (61.3%) were allocated for OLT and 195 (58.2%) actually underwent OLT after exclusion of 6 cases of spontaneous withdrawal. In KONOS status 1, liver grafts were initially allocated to 33 (58.9%), but 6 were withdrawn owing to clinical improvement, so 27 (48.2%) actually underwent OLT. In status 2A, 168 (61.8%) underwent OLT within 2 weeks of priority waiting period. According to ABO blood groups in recipients, the allocation probability was 68% (68 of 100) in group A, 60.6% (60 of 99) in group B, 64.1% (25 of 39) in group AB, and 53.3% (48 of 90) in group O. Mean waiting period for OLT was 5.7 ± 2.1 days. CONCLUSIONS: Deceased donor incidence of ∼8 per million population contributed to meeting ∼60% of the demand for urgent deceased-donor liver transplantation in a Korean transplantation center, so further increasing deceased organ donor numbers is necessary to improve the current status of organ shortage.


Subject(s)
Hospitals, High-Volume , Liver Transplantation/statistics & numerical data , Tissue Donors/supply & distribution , Transplant Recipients/classification , Transplants/supply & distribution , ABO Blood-Group System , Adult , Aged , Female , Humans , Male , Middle Aged , Probability , Republic of Korea , Retrospective Studies
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