No abstract available.
Bronchopulmonary Sequestration*

Campomelic dysplasia (CD; OMIM #114290), a rare form of congenital short-limbed dwarfism, is due to mutations in SOX9, a member of the SOX (SRY-related HMG box) gene family. Multiparous mother at 38 weeks' gestation delivered a 3,272 g baby boy with characteristic phenotypes including bowing of the lower limbs, a narrow thoracic cage, 11 pairs of ribs, hypoplastic scapulae, macrocephaly, flattened supraorbital ridges and nasal bridge, cleft palate, and micrognathia. He underwent a tracheostomy at the age of three months for severe laryngomalacia after a number of repeated hospitalizations due to respiratory problems and died at the age of four months from progressive respiratory failure. He was diagnosed as having CD based on a novel frameshift mutation (p.Gln458ArgfsX12) in the SOX9 gene, the mutation which has not yet been reported in Korea.
Campomelic Dysplasia/*diagnosis/genetics/radiography ; Disorders of Sex Development/genetics ; Frameshift Mutation ; Humans ; Infant ; Male ; Respiratory Insufficiency/complications ; SOX9 Transcription Factor/*genetics ; Sequence Analysis, DNA

D-chiro-inositol (DCI) is a secondary messenger in insulin signal transduction. It is produced in vivo from myo-inositol via action of epimerase. In this study, we evaluated antitumor activity of DCI against human breast cancer both in vitro and in vivo. In order to determine the inhibitory effects of DCI on growth of human breast cancer cells (MDA-MB-231), two different assessment methods were implemented: MTT assay and mouse xenograft assay. MTT assay demonstrated downturn in cell proliferation by DCI treatment (1, 5, 10, 20 and 40 mM) groups by 18.3% (p<0.05), 17.2% (p<0.05), 17.5% (p<0.05), 18.4% (p<0.05), and 24.9% (p<0.01), respectively. Also, inhibition of tumor growth was investigated in mouse xenograft model. DCI was administered orally at the dose of 500 mg/kg and 1000 mg/kg body weight to treat nude mouse for 45 consecutive days. On the 45th day, tumor growth of DCI (500 mg/kg and 1000 mg/kg) groups was suppressed by 22.1% and 67.6% as mean tumor volumes were 9313.8 ± 474.1 mm³ and 3879.1 ± 1044.1 mm³, respectively. Furthermore, breast cancer stem cell (fCSC) phenotype (CD44⁺/CD24⁻) was measured using flow cytometry. On the 46th day, CSC ratios of DCI (500 mg/kg) and co-treatment with doxorubicin (4 mg/kg) and DCI (500 mg/kg) group decreased by 24.7% and 53.9% (p<0.01), respectively. Finally, from tumor recurrence assay, delay of 5 days in the co-treatment group compared to doxorubicin (4 mg/kg) alone group was observed. Based on these findings, we propose that DCI holds potential as an anti-cancer drug for treatment of breast cancer.
Animals ; Body Weight ; Breast Neoplasms* ; Breast* ; Cell Proliferation ; Doxorubicin ; Flow Cytometry ; Heterografts ; Humans ; In Vitro Techniques ; Insulin ; Mice ; Mice, Nude ; Neoplastic Stem Cells ; Phenotype ; Recurrence* ; Signal Transduction ; Stem Cells

PURPOSE: Osteopontin is one of the major non-collagenous protein of hard tissue. Use of peptide domain of biologically active protein has some advantages. The objective of this experimental study is evaluation of periodontal regenerative potency of synthetic peptide gel which containing collagen binding domain of osteopontin in the degree III periodontal defect of beagle dogs. MATERIAL AND METHODS: Experimental degree III furcation defect was made in the mandibular third and fourth premolar of beagles. Regenerative material was applied during flap operation. 8 weeks after regenerative surgery, all animals were sacrificed and histomorphometric measurement was performed to calculate the linear percentage of the new cementum formation and the volume percentage of new bone formation. RESULT: The linear percent of new cementum formation was 41.6% at control group and 67.1% at test group and there was statistically significant difference. The volume percent of new bone formation was 52.1% at control group and 58.9% at test group. CONCLUSION: As the results of present experiment, synthetic peptide gel containing collagen binding domain of osteopontin significantly increase new bone and cementum formation in the degree III furcation defect of canine mandible.
Animals ; Bicuspid ; Collagen ; Dental Cementum ; Furcation Defects ; Mandible ; Osteogenesis ; Osteopontin ; Protein Structure, Tertiary ; Regeneration

PURPOSE: Following tooth extraction caused by severe periodontitis, alveolar ridge dimension lose their original volume. To reduce the alveolar ridge dimension, the ridge preservation technique has been introduced and tested in many clinical studies with membrane alone or membrane plus graft, achieving reduced ridge loss compared to extraction only. The aim of the present clinical study was to compare the post-extraction dimensional changes in the membrane exposure group to non-exposure group during healing period following ridge preservation technique. METHODS: Ridge preservation was performed in 44 extraction sites. After extraction, deproteinized bovine bone mineral coated with synthetic oligopeptide (Ossgen-X15(R)) or deproteinized bovine bone mineral (Bio-Oss(R)) was implanted into the socket. A collagen membrane (Bio-Gide(R)) was trimmed to cover the socket completely and applied to the entrance of the socket. Four clinical parameters were compared between baseline and 6 months. RESULTS: During healing period, membrane exposure was observed at 19 sites. At the re-entry, hard newly formed tissue were observed at the ridge preservation site. The grafted socket sites were well preserved in their volume dimension. In both groups, horizontal ridge width was reduced and vertical height was increased. There were not statistically significant differences in horizontal (-1.32 mm vs -1.00 mm) and vertical ridge change (2.24 mm vs 2.37 mm at buccal crest, 1.36 mm vs. 1.53 mm at lingual crest) between two groups. CONCLUSIONS: The ridge preservation approach after tooth extraction effectively prevented resorption of hard tissue ridge in spite of membrane exposure during healing period.
Alveolar Process ; Bone Substitutes ; Collagen ; Membranes ; Periodontitis ; Tooth Extraction ; Tooth Socket ; Transplants

OBJECTIVE: Interleukin-12 is well known to induce cellular immune response materials and suppress the tumor growth. HPV infection has significant roles in cervical carcinogenesis, and HPV oncoprotein E6 and E7 are important roles in formation and maintenance of cervical cancer. E7 specific immune response was detected in cervical cancer patients, and this shows that E7 protein would be important in potential immunetherapy in cervical cancer. This study is aimed to investigate antitumor effect and E7 immune response by injection of adenovirus IL-12 and E7 in cervical cancer animal model. METHODS: In the cervical cancer animal model using C57BL/6 mice and HPV16 E7 immortalized hosts, 5 X 10(8) pfu/100 ul of PBS, AdLacZ, AdE7 and AdIL-12 were injected into the tumor mass when the tumor sized is increased to 7-8 mm. After the injection, the tumor size was caliperated every 2-3 days, and pathologic and blood studies were done on day 1, 3, 5, 7, 11, 12, and 21 days. The expression level of IL-12 and INF- and E7 specific immune response were measured by ELISA. RESULTS: After the injection of AdIL-12 into the tumor mass, 45% of tumor growth suppression was noted in comparison with control group. In the cases of combination injections of AdIL-12 and AdE7, 80% growth suppression was observed, and complete regression was shown in 40% of the study group. After injection of AdIL-12, the expression of IL-12 in the tumor mass was 9 time higher than that of control group, and 6 times higher in blood sample in comparison with control group. In the group with combined AdIL-12 and AdE7, the highest expression of INF- was noted in comparison with single injection of AdIL-12 or control group. IgGI and IgG2b isotype expression level increased 2.5 times and 2.2 times respectively 3 weeks after adenovirus injection. CONCLUSION: In cervical cancer animal model, IL-12 and E7 application using Adenovirus vector is significant antitumor effect and this demonstrates the potential immunotherapy in near future.
Adenoviridae ; Animals ; Carcinogenesis ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunity, Cellular ; Immunoglobulin G ; Immunotherapy ; Interleukin-12* ; Mice ; Models, Animal ; Uterine Cervical Neoplasms ; Vaccination*

BACKGROUND: Despite the many advantages of recombinant subunit vaccines, they have critical weaknesses that include a low efficacy for promoting cellular and humoral immune responses against antigens because of their poor immunogenicity, and a rapidly cleared properties as a result of proteolytic enzymes in the body. To circumvent these problems, we developed mannan-decorated inulin acetate microparticles (M-IA MPs) that functioned as carriers and adjuvants for immunization with the recombinant foot-and-mouth disease multi-epitope subunit vaccine (M5BT). METHODS: The M5BT-loaded M-IA MPs were obtained by a double-emulsion solvent-evaporation method. Their properties including morphology, size and release ability were determined by field emission scanning electron microscope, dynamic light-scattering spectrophotometer and spectrophotometer. To assess the immunization efficacy of the MPs, mice were immunized with MPs and their sera were analyzed by ELISA. RESULTS: The M-IA MPs obtained by a double-emulsion solvent-evaporation method were spherical and approximately 2–3 µm, and M5BT was encapsulated in the M-IA MPs. The M5BT-loaded M-IA MPs showed higher antigen-specific IgG, IgG1, IgG2a and anti-FMDV antibodies than the M5BT-loaded IA MPs and the Freund’s adjuvant as a control. CONCLUSION The M-IA MPs showed a powerful and multifunctional polymeric system that combined two toll-like receptor agonists compared to the conventional adjuvant.

BACKGROUND: Despite the many advantages of recombinant subunit vaccines, they have critical weaknesses that include a low efficacy for promoting cellular and humoral immune responses against antigens because of their poor immunogenicity, and a rapidly cleared properties as a result of proteolytic enzymes in the body. To circumvent these problems, we developed mannan-decorated inulin acetate microparticles (M-IA MPs) that functioned as carriers and adjuvants for immunization with the recombinant foot-and-mouth disease multi-epitope subunit vaccine (M5BT). METHODS: The M5BT-loaded M-IA MPs were obtained by a double-emulsion solvent-evaporation method. Their properties including morphology, size and release ability were determined by field emission scanning electron microscope, dynamic light-scattering spectrophotometer and spectrophotometer. To assess the immunization efficacy of the MPs, mice were immunized with MPs and their sera were analyzed by ELISA. RESULTS: The M-IA MPs obtained by a double-emulsion solvent-evaporation method were spherical and approximately 2–3 µm, and M5BT was encapsulated in the M-IA MPs. The M5BT-loaded M-IA MPs showed higher antigen-specific IgG, IgG1, IgG2a and anti-FMDV antibodies than the M5BT-loaded IA MPs and the Freund’s adjuvant as a control. CONCLUSION The M-IA MPs showed a powerful and multifunctional polymeric system that combined two toll-like receptor agonists compared to the conventional adjuvant.

Several barriers such as gastric pH, enzymatic degradation and rapid transit should be overcome to orally deliver antigens for taking up by epithelial microfold cells in Peyer's patches of small intestine. To solve the above mentioned problems, we designed pH-sensitive and mucoadhesive polymeric microparticles (MPs) prepared by double emulsion technique using cellulose acetate phthalate (CAP) to enhance immune response of foot-and-mouth disease (FMD) virus (FMDV) subunit vaccine. Thiolation of CAP improved mucoadhesive property of CAP to prolong the MPs transit time through the gastrointestinal tract. Thiolated CAP (T-CAP) also slowed down antigen release in acidic pH of stomach but released more antigens in neutral pH of small intestine due to the pH-sensitivity of the T-CAP. Oral immunization of a chimerical multi-epitope recombinant protein as the FMD subunit vaccine via T-CAP MPs effectively delivered the vaccine to Peyer's patches eliciting mucosal IgA response. It will make a step forward into a promising oral subunit vaccine development in livestock industry.
Animals ; Cellulose ; Foot-and-Mouth Disease ; Gastrointestinal Tract ; Hydrogen-Ion Concentration ; Immunization ; Immunoglobulin A ; Intestine, Small ; Livestock ; Peyer's Patches ; Polymers ; Staphylococcal Protein A ; Stomach

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.