PURPOSE: Most studies on immune tolerance of mesenchymal stem cells (MSCs) have been performed using MSCs derived from bone marrow, cord blood, or adipose tissue. MSCs also exist in the craniofacial area, specifically in teeth. The purpose of this study was to evaluate the mechanisms of immune tolerance of dental pulp-derived MSC (DP-MSC) in vitro and in vivo. MATERIALS AND METHODS: We isolated DP-MSCs from human dental pulp and co-cultured them with CD4⁺ T-cells. To evaluate the role of cytokines, we blocked TGF-β and IL-10, separately and together, in co-cultured DP-MSCs and CD4⁺ T-cells. We analyzed CD25 and FoxP3 to identify regulatory T-cells (Tregs) by fluorescence-activated cell sorting (FACS) and real-time PCR. We performed alloskin grafts with and without DP-MSC injection in mice. We performed mixed lymphocyte reactions (MLRs) to check immune tolerance. RESULTS: Co-culture of CD4⁺ T-cells with DP-MSCs increased the number of CD4⁺CD25⁺FoxP3⁺ Tregs (p<0.01). TGF-β or/and IL-10 blocking suppressed Treg induction in co-cultured cells (p<0.05). TGF-β1 mRNA levels were higher in co-cultured DP-MSCs and in co-cultured CD4⁺ T-cells than in the respective monocultured cells. However, IL-10 mRNA levels were not different. There was no difference in alloskin graft survival rate and area between the DP-MSC injection group and the non-injection group. Nonetheless, MLR was reduced in the DP-MSC injected group (p<0.05). CONCLUSION: DP-MSCs can modulate immune tolerance by increasing CD4⁺CD25⁺FoxP3⁺ Tregs. TGF-β1 and IL-10 are factors in the immune-tolerance mechanism. Pure DP-MSC therapy may not be an effective treatment for rejection, although it may module immune tolerance in vivo.
Adipose Tissue ; Animals ; Bone Marrow ; Coculture Techniques ; Cytokines ; Dental Pulp ; Fetal Blood ; Flow Cytometry ; Graft Survival ; Humans* ; Immune Tolerance* ; In Vitro Techniques ; Interleukin-10* ; Lymphocyte Culture Test, Mixed ; Mesenchymal Stromal Cells* ; Mice ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; T-Lymphocytes ; T-Lymphocytes, Regulatory* ; Tooth ; Transplants

BACKGROUND: Herpes zoster (HZ) is caused by reactivation of latent varicella-zoster virus (VZV) infection. HZ-associated aseptic meningitis, a rare complication of HZ, can require hospitalization and a long treatment period. OBJECTIVE: A retrospective study was performed to identify potential factors associated with HZ-associated aseptic meningitis development. METHODS: We included all outpatients and patients admitted in the neurology and dermatology departments of a single tertiary center, who were diagnosed with HZ for two years. Among 818 patients, 578 patients were eligible for analysis. RESULTS: The demographics and potential risk factors were compared between the uncomplicated HZ group (n=554) and aseptic meningitis group (n=24). Among the potential factors, the dermatological distribution of skin rash and gender showed statistically significantly different between the two groups. Patients with craniocervical distribution of HZ accounted for 87.5% (n=21) of the aseptic meningitis group and 54.3% (n=301) of the uncomplicated HZ group (p=0.043). The aseptic meningitis group had more men (66.7%, n=16) than the uncomplicated HZ group (42.8%, n=237, p=0.033). Patients with craniocervical distribution had an odds ratio (OR) of 5.884 (p=0.001) for developing aseptic meningitis when compared with the other dermatome involvements. Additional logistic regression analysis resulted in a fading between gender difference (p=0.050) and craniocervical involvement having an OR of 5.667 for aseptic meningitis (p=0.006). CONCLUSION: In HZ patients, skin rash with craniocervical distribution and male gender were associated with a higher risk of aseptic meningitis.
Demography ; Dermatology ; Exanthema ; Herpes Zoster* ; Herpesvirus 3, Human ; Hospitalization ; Humans ; Logistic Models ; Male ; Meningitis ; Meningitis, Aseptic* ; Neurology ; Odds Ratio ; Outpatients ; Retrospective Studies ; Risk Factors*

Diagnostic exome sequencing (DES) is a powerful tool to analyze the pathogenic variants leading to development delay (DD) and intellectual disability (ID). Recently, heterozygous de novo mutation of the histone acetyltransferase encoding gene KAT6B has been recognized as causing a syndrome with congenital anomalies and intellectual disability, namely Say-Barber-Biesecker-Young-Simpson (SBBYS) syndrome. Here we report a case of SBBYS syndrome in a third generation Korean family affected with a missense mutation in KAT6B, c.2292C>T p.(His767Tyr) identified by DES. This is the first confirmed familial inherited mutation of the KAT6B reported worldwide. Our case emphasizes again the importance of basic physical examination and taking a family history. Furthermore, advances in genetic diagnostic tools are becoming key to identifying the etiology of DD and ID. This allows a physiatrist to predict the disease's clinical evolution with relative certainty, and offer an appropriate rehabilitation plan for patients.
Exome* ; Family Characteristics* ; Histone Acetyltransferases ; Humans ; Intellectual Disability ; Mutation, Missense ; Physical Examination ; Rehabilitation

Orthodontic treatment of a complex case that involves retained deciduous mandibular second molars with missing permanent successors is challenging. Usually, congenitally missing teeth are manifested with other dental anomalies that further complicate orthodontic treatment, such as retained deciduous teeth, impactions, transpositions and peg-shaped lateral incisors. Even though the long term prognosis of the retained deciduous tooth is not fully predictable, if the teeth are in good condition, the patient and clinician may incline towards a decision to preserve the deciduous teeth as long as possible. This case report demonstrates that deciduous teeth, in this case the mandibular second molars and maxillary canine, can be incorporated into final occlusion with clinically stable long-term results.
Humans ; Incisor ; Molar* ; Prognosis ; Tooth ; Tooth, Deciduous

Inhibitor of nuclear factor kappa-B kinase beta (IKKβ) plays a critical role in cell proliferation and inflammation in various cells by activating NF-κB signaling. However, the interrelationship between peroxisome proliferator-activated receptor α (PPARα) and IKKβ in cell proliferation is not clear. In this study, we investigated the possible role of PPARα in the hepatic cell death in the absence of IKKβ gene using liver-specific Ikkb-null (Ikkb(F/F-AlbCre)) mice. To examine the function of PPARα activation in hepatic cell death, wild-type (Ikkb (F/F)) and Ikkb F/F-AlbCre mice were treated with PPARα agonist Wy-14,643 (0.1% w/w chow diet) for two weeks. As a result of Wy-14,643 treatment, apoptotic markers including caspase-3 cleavage, poly (ADP-ribose) polymerase (PARP) cleavage and TUNEL-positive staining were significantly decreased in the Ikkb(F/F-AlbCre) mice. Surprisingly, Wy-14,643 increased the phosphorylation of p65 and STAT3 in both Ikkb and Ikkb(F/F-AlbCre) mice. Furthermore, BrdU-positive cells were significantly increased in both groups after treatment with Wy-14,643. Our results suggested that IKKβ-derived hepatic apoptosis could be altered by PPARα activation in conjunction with activation of NF-κB and STAT3 signaling.
Animals ; Apoptosis ; Caspase 3 ; Cell Proliferation ; Hepatocytes* ; Inflammation ; Mice* ; NF-kappa B ; Peroxisomes ; Phosphorylation ; Phosphotransferases

Individual differences in drug responses are associated with genetic and epigenetic variability of pharmacogene expression. We aimed to identify the relevant miRNAs which regulate pharmacogenes associated with drug responses. The miRNA and mRNA expression profiles derived from data for normal and solid tumor tissues in The Cancer Genome Atlas (TCGA) Research Network. Predicted miRNAs targeted to pharmacogenes were identified using publicly available databases. A total of 95 pharmacogenes were selected from cholangiocarcinoma and colon adenocarcinoma, as well as kidney renal clear cell, liver hepatocellular, and lung squamous cell carcinomas. Through the integration analyses of miRNA and mRNA, 35 miRNAs were found to negatively correlate with mRNA expression levels of 16 pharmacogenes in normal bile duct, liver, colon, and lung tissues (p<0.05). Additionally, 36 miRNAs were related to differential expression of 32 pharmacogene mRNAs in those normal and tumorigenic tissues (p<0.05). These results indicate that changes in expression levels of miRNAs targeted to pharmacogenes in normal and tumor tissues may play a role in determining individual variations in drug response.
Adenocarcinoma ; Bile Ducts ; Carcinoma, Squamous Cell ; Cholangiocarcinoma ; Colon ; Epigenomics ; Genome* ; Individuality ; Kidney ; Liver ; Lung ; MicroRNAs* ; Pharmacogenetics ; RNA, Messenger

BACKGROUND/AIMS: Levofloxacin resistance is increasing rapidly, and widely limits its application in Helicobacter pylori eradication. This study aimed to evaluate the efficacy of a clarithromycin- versus gemifloxacin-containing triple therapy regimen in first-line eradication of H. pylori infection. MATERIALS AND METHODS: This was an open-label, prospective, non-randomized two-armed pilot study in which treatment-naïve subjects with active H. pylori infection received a seven-day triple therapy with rabeprazole 20 mg bid (twice daily), gemifloxacin 320 mg qd (once daily), and amoxicillin 500 mg bid (n=70) or seven-day triple therapy with rabeprazole 20 mg bid (twice daily), clarithromycin 500 mg bid (twice daily), and amoxicillin 500 mg bid (n=83). H. pylori infection status was checked in all patients at enrollment and at least 8 weeks after the end of therapy by the urea breath test. RESULTS: Intention-to-treat eradication rates were 71.1% and 74.3% for clarithromycin-containing triple therapy and gemifloxacin- containing triple therapy, respectively (P=0.398). The corresponding per-protocol eradication rates were 76.6% and 76.1% (P=0.624). The gemifloxacin-containing triple therapy was associated with a lower incidence of adverse events (2.9% vs. 18.5%, P=0.003). CONCLUSIONS: Although the seven-day gemifloxacin-containing triple therapy regimen showed a more favorable safety profile, there was no significant difference in eradication rates between the gemifloxacin-containing and clarithromycin-containing triple regimens, and both regimens had eradication rates slightly lower than acceptable efficacy for the Korean population. Therefore, the gemifloxacin-containing regimen might be useful as an alternative regimen for patients showing severe side effects of clarithromycin due to poor tolerance. Further studies on the efficacy of gemifloxacin in the Korean population are warranted.
Amoxicillin ; Breath Tests ; Clarithromycin ; Helicobacter pylori* ; Helicobacter* ; Humans ; Incidence ; Levofloxacin ; Pilot Projects* ; Prospective Studies ; Rabeprazole ; Treatment Outcome* ; Urea

PURPOSE: The impact of postoperative ipsilateral neck radiotherapy (INRT) versus bilateral neck radiotherapy (BNRT) on the clinical outcomes of patients with tonsillar squamous cell carcinoma was analyzed retrospectively. MATERIALS AND METHODS: Between October 2001 and June 2012, 241 patients with T1-2 and N0-N2b tonsillar carcinoma from 16 institutes underwent postoperative INRT (n=84) or BNRT (n=157) following a tonsillectomy. Seventy patients were identified from each group by propensity score matching and compared in terms of the overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates calculated using the Kaplan-Meier method with a log-rank test. RESULTS: The median follow-up was 55 months (range, 3 to 133 months). The survival outcomes in the INRT and BNRT groups were similar: 5-year OS (92.8% vs. 94.0%, p=0.985), DFS (80.5% vs. 94.2%. p=0.085), LRRFS (88.1% vs. 97.1%, p=0.083), and DMFS (92.7% vs. 97.0%, p=0.370). Subgroup analysis revealed no contralateral neck recurrence in 61 patients with T1-2N0-2a regardless of the treatment groups. For 79 patients with N2b, contralateral neck recurrence was more common in the INRT group than in the BNRT group (7.9% vs. 0.0%), but the difference was not significant (p=0.107). The overall grade ≥ 2 toxicities were lower in the INRT group: acute (45.7% vs. 74.3%, p=0.001) and late (4.3% vs. 31.4%, p < 0.001), respectively. CONCLUSION: INRT is an attractive strategy for patients with T1-2N0-2a tonsillar carcinoma compared to BNRT. For patients with N2b, there was a small risk of contralateral neck recurrence when treated with INRT, but its impact on the OS was limited with successful salvage treatment.
Academies and Institutes ; Carcinoma, Squamous Cell* ; Disease-Free Survival ; Epithelial Cells* ; Follow-Up Studies ; Humans ; Methods ; Neck* ; Palatine Tonsil* ; Propensity Score* ; Radiotherapy* ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Salvage Therapy ; Tonsillar Neoplasms ; Tonsillectomy

PURPOSE: To evaluate the effectiveness of optical coherence tomography angiography (OCTA) in investigating changes in the area of the foveal avascular zone (FAZ) in patients with diabetic retinopathy (DR) and normal subjects. METHODS: Eighty-five eyes of 50 DR patients and 50 eyes of 25 normal subjects were included. OCTA images of the FAZ were acquired using the split-spectrum amplitude decorrelation angiography algorithm of Optovue Avanti RTVue XR OCT. Patients were divided into three groups according to DR severity: mild-to-moderate non-proliferative diabetic retinopathy (NPDR) group, severe NPDR group, and proliferative DR group. The area of the FAZ was measured using built-in software and was compared between the patients and normal subjects and among the three groups. RESULTS: The area of the FAZ in patients with diabetic retinopathy (0.46 mm²) was significantly larger than that in normal subjects (0.30 mm², p = 0.001). A significant difference was observed depending on DR severity: 0.40 mm² in the mild-to-moderate NPDR group, 0.45 mm² in the severe NPDR group, and 0.53 mm² in the PDR group (p = 0.03). Correlation between area of the foveal avascular zone and visual acuity showed a tendency toward reduction in visual acuity (p = 0.002). CONCLUSIONS: OCTA effectively detected changes in the FAZ area in DR patients. OCTA has the potential to be used for noninvasive quantification and monitoring of the FAZ.
Angiography ; Diabetic Retinopathy* ; Humans ; Tomography, Optical Coherence ; Visual Acuity

BACKGROUND/AIMS: The detection of multifocal lesions is important for the successful management of gastric neoplasms. We investigated the characteristics of missed simultaneous lesions and the reason for the missed diagnoses. METHODS: A total of 140 patients who underwent repeat endoscopy before endoscopic resection between June 2013 and June 2014 were retrospectively reviewed. We classified simultaneous lesions into three groups based on a review of earlier images: group 1, no images of the location of simultaneous lesions were taken; group 2, no corresponding lesion was evident in the previous images; and group 3, simultaneous lesions were visible in the earlier images but a biopsy was not performed. RESULTS: Simultaneous lesions were found in 12 patients (8.6%) with 13 lesions, comprising 10 dysplasia (76.9%) and three adenocarcinoma (23.1%). Regarding the reasons for missed diagnoses, seven lesions (53.8%) were classified as group 3, five (38.5%) as group 1, and the remaining lesion (7.7%) as group 2. There were no significant differences in the characteristics of the patients with and without simultaneous lesions. CONCLUSIONS: Lesions disregarded or unnoticed during endoscopic examination were the main reason for missed diagnosis of simultaneous lesions. Endoscopists should consider the possibility of simultaneous lesions and attempt to meticulously evaluate the entire gastric mucosa.
Adenocarcinoma ; Biopsy ; Diagnosis ; Endoscopy ; Gastric Mucosa ; Humans ; Retrospective Studies ; Stomach Neoplasms