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ABSTRACT: Tricho-rhino-phalangeal syndrome type I (TRPSI) is a rare autosomal dominant hereditary disorder characterized by sparse hair, bulbous nose, long philtrum, thin upper lip, and skeletal abnormalities including cone-shaped epiphyses, shortening of the phalanges, and short stature. TRPSI is caused by mutations in the TRPS1 gene. Herein, we report two Korean cases of TRPSI. Although both patients (a 17-year-old-female and a 14-year-old male) had typical clinical findings, Patient 1 had an additional growth hormone (GH) deficiency. Treatment with recombinant human growth hormone (rhGH) 0.7 IU/kg/week led to an increase in growth velocity. Over 10 years of GH therapy, the mean growth velocity was 5.7±0.9 cm/year. However, the patient 2 did not show apparent GH deficiency by GH stimulation test, had a poor response with rhGH therapy and GH therapy was discontinued after 6 months. Upon genetic analysis of the TRPS1 gene, two mutations were found. Patient 1 had a heterozygous mutation c.2520dupT (p.Arg841LysfsX3) which had not been previously reported. Patient 2 had a known nonsense mutation c.1630C>T (p.Arg544X). In summary, we were the first to report Korean patients with mutation of TRPS1.
Annals of clinical and laboratory science 01/2012; 42(3):307-12. · 0.96 Impact Factor
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ABSTRACT: Many clinical situations necessitate highly sensitive and reliable molecular assays; however, the achievement of such assays remains a challenge due to the inherent limitations of molecular testing methods. Here, we describe a simple and inexpensive enrichment technique that we call mutant enrichment with 3'-modified oligonucleotides (MEMO). The method is based on the use of a 3'-modified oligonucleotide primer that blocks extension of the normal allele but enables extension of the mutated allele. The performance of the technique was evaluated with respect to its ability to detect common cancer mutations in the EGFR, KRAS, BRAF, TP53, JAK2, and NPM1 genes. We achieved sensitivities of 10(-2) to 10(-6) using downstream Sanger sequencing, depending on the concentrations and thermodynamics of the primers. MEMO may be applicable to the quantitative real-time PCR platform and other downstream assays. This technique may be practically applicable to various medical situations.
The Journal of molecular diagnostics: JMD 11/2011; 13(6):657-68. · 3.48 Impact Factor
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ABSTRACT: To evaluate the localization of osteopontin (OPN) and osterix in periodontal tissue during experimental tooth movement with heavy force in rats.
Nickel-titanium closed-coil springs were used to create a 100 g mesial force to the maxillary first molars. On days 3, 7, 10, and 14 after force application, histological changes in periodontium were examined by immunohistochemistry using proliferating cell nuclear antigen (PCNA), OPN, and osterix.
PCNA-positive cells were found close to the alveolar bone and cementum on both sides. OPN-positive cells were observed along the cementing line of the cementum and bone on both sides and also were visible along with newly formed fibers in the periodontal ligament on the tension side. Osterix-positive cells were strongly detected on the surface of the alveolar bone and cementum on both sides.
During tooth movement, periodontal remodeling occurs on both sides. These results indicate that OPN and osterix may play an important role of differentiation and osteoblasts and cementoblasts matrix formation during periodontal tissue remodeling.
The Angle Orthodontist 08/2011; 82(1):107-14. · 1.21 Impact Factor
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ABSTRACT: To investigate thyroid-stimulating hormone receptor (TSHR) and thyroid peroxidase (TPO) mutations in Korean patients with primary congenital hypothyroidism (CH).
Congenital hypothyroidism is a common genetic disorder in which the majority of mutations occur in the TSHR and TPO genes.
We examined the frequencies of TSHR and TPO mutations among Korean patients with primary CH. Furthermore, we explored the relationships between imaging findings and mutation status.
A total of 193 paediatric patients with nonsyndromic CH were enrolled in the present study.
Patients with decreased (99m) Tc uptake were screened for TSHR mutations using Sanger sequencing, and those with increased uptake were screened for TPO mutations. The relationships between scintigraphic and ultrasonographic findings and mutation status were analysed.
Thirteen (16·5%) of 79 patients with decreased (99m) Tc uptake were found to harbour TSHR mutations including G132R, G245S, R450H, R519C and F525S. The R450H mutation was present in 13 (72·2%) of 18 disease alleles. Seven (10·3%) of 68 patients with increased (99m) Tc uptake harboured TPO mutations including R189Q, K439E, G493S, C808LfsX72, A863T, R875Hfs and P883S. The TSHR and TPO mutations were observed only in patients with normal to slightly enlarged thyroid glands.
This study identified underlying TSHR and TPO mutations in Korean patients with CH and revealed a possible relationship between imaging findings and mutation status. In addition, the low rate of mutation positivity suggests significant genetic heterogeneity of CH in the Korean population.
Clinical Endocrinology 06/2011; 75(5):715-21. · 3.17 Impact Factor
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ABSTRACT: Congenital central hypoventilation syndrome (CCHS), also known as Ondine's curse, is characterized by idiopathic failure of autonomic breathing and is often associated with neurocristopathies such as Hirschsprung disease (HSCR). CCHS is caused by mutations in the paired-like homeobox 2B (PHOX2B) gene, often manifest as polyalanine repeat expansions. Herein, we report the cases of two unrelated Korean patients with Ondine-Hirschsprung disease. The patient's clinical manifestations were apnea and cyanosis requiring immediate endotracheal intubation, recurrent hypoventilation with hypercapnia, hypoxia after ventilator removal, and abdominal distension since birth. Intestinal biopsies were performed and the absence of ganglion cells in the colon was consistent with HSCR. We performed direct sequencing analysis in the PHOX2B and RET genes and fluorescence polymerase chain reaction in order to determine the polyalanine tract expansion in exon 3 of the PHOX2B gene. Expansion mutations were detected in both patients; one had 20/24 repeats and the other had 20/27 repeats. The 20/24 genotype has not been previously described in severe CCHS phenotypes and associated HSCR. We believe that the information in this report will improve our understanding of the phenotypic and genotypic heterogeneities of CCHS and HSCR.
European Journal of Pediatrics 03/2011; 170(10):1267-71. · 1.88 Impact Factor
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Jeeyun Lee,
Jin Won Seo,
Hyun Jung Jun,
Chang-Seok Ki,
Se Hoon Park,
Young Suk Park,
Ho Yeong Lim,
Min Gew Choi,
Jae Moon Bae,
Tae Sung Sohn,
Jae Hyung Noh,
Sung Kim,
Hey-Lim Jang, Ji-Youn Kim,
Kyoung-Mee Kim,
Won Ki Kang,
Joon Oh Park
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ABSTRACT: Identification of critical genes which play pivotal roles in controlling tumor growth and survival will establish the basis for developing therapeutic targets. With the aim of establishing personalized medicine for treatment of solid tumors, we focused on MET amplification in gastric cancer patients, given the extreme sensitivity to c-Met inhibitor in MET amplified gastric cancer cell lines. We tested MET amplification and activation of c-Met in various gastric cancer cell lines and tissue samples from 482 gastric cancer patients who underwent curative surgery. Gastric cancer cell lines with MET amplification by quantitative real-time PCR (qPCR) and FISH predicted sensitivity to PHA-665,752, a selective c-Met kinase inhibitor. Of the 472 patients who had DNA sample available for qPCR analysis, 100 patients (21.2%) had a MET copy number greater than 4.0 copies and demonstrated poorer survival following curative surgery with statistical significance (5-year OS; 50.0 vs. 59.1%; MET amplification (+) vs. MET amplification (-); P = 0.0134). These results suggest that the increased MET copy number measured by qPCR plays an important role in determining prognosis in gastric cancer patients. However, the predictive role of MET amplification for treatment response should be further explored in upcoming clinical trials.
Oncology Reports 03/2011; 25(6):1517-24. · 1.84 Impact Factor
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ABSTRACT: LHX8 (LIM-homeobox gene 8) is known as an important regulating factor in tooth morphogenesis. Odontoma is a mixed odontogenic tumor where epithelium and mesenchyme differentiated together, resulting in anomalous tooth structures. In this study, gene and protein expressions of LHX8 were analyzed in human odontoma-derived mesenchymal cells (HODC) compared to adult dental mesenchymal stem cells (aDSC), as well as morphological and histological characteristics of odontoma were analyzed.
aDSCs were isolated from normal teeth, and HODCs were isolated from surgically removed odontoma mass. Morphological and histological evaluations were performed to compare between compound odontomas and normal premolars. RT-PCR and real-time PCR were performed to identify LHX8 mRNA expression in the HODCs and aDSCs. LHX8 protein expression levels were observed by immunoblotting and immunofluorescent staining.
The compound odontoma was composed of multiple tooth-like structures, which contained disorganized but recognizable enamel matrix, dentin, pulp, and cementum. LHX8 mRNA and LHX8 protein expressions were all higher in HODCs compared to those in aDSCs examined by RT-PCR, immunoblot, and immunofluorescent staining. Especially, real-time PCR showed 2.77-fold higher LHX8 expression in HODCs than in normal periodontal ligament stem cells (PDLSCs), while alveolar bone marrow stem cells (ABMSCs) expressed 0.12-fold LHX8 than PDLSCs.
Based on these observations, LHX8 might play an important role in odontoma formation. This is the first report regarding the comparison of LHX8 expression between HODC and normal aDSCs and its overexpression in human samples. The specific mechanism of LHX8 in odontoma morphogenesis awaits further study.
Journal of Oral Pathology and Medicine 03/2011; 40(3):250-6. · 1.63 Impact Factor
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ABSTRACT: To prospectively assess the reliability of US-guided diffuse optical tomography (US-DOT) using interobserver agreement for the diagnosis of breast lesions with individual real-time imaging and to assess the interobserver agreement of conventional sonography (US) combined with US-DOT for differentiation between benignity and malignancy breast lesions.
An Institutional Review Board approved this study, and all subjects provided written informed consent. 122 breast lesions in 111 patients evaluated with US-guided core biopsy were included. Assessments with US and US-DOT for cases subjected to biopsy were obtained by two radiologists using individual real-time imaging prior to biopsy and were prospectively recorded by each performer. With DOT, the total haemoglobin concentration (THC) for each breast lesion was measured. Histopathological results from US-guided biopsies were used as a reference standard. To assess measurement interobserver agreement, the intraclass correlation coefficient (ICC) and the Bland-Altman plot were used for THC in US-DOT and the kappa values and ROC analysis were used to evaluate the diagnostic performances of the US BI-RADS final assessment in US and combined US and US-DOT.
Of 122 US-guided core biopsied lesions, 83 (68.0%) were diagnosed as benign, and 39 (32.0%) as malignant. Excellent correlation was seen in the THC in US-DOT (ICC score 0.796; 95% confidence interval, 0.708-0.857). The interobserver agreement in BI-RADS final assessment with US and US-DOT (almost perfect; κ = 0.8618) was improved compared with that of US (substantial agreement, κ = 0.6574). However, the overall areas under the ROC curve did not show significant differences between US and combined US and US-DOT, 0.8894 and 0.8975, respectively (P = 0.981).
The reliability of THC in US-DOT showed excellent correlation in overall real-time performance. Although the inter-observer agreement for BI-RADS final assessment of US was improved by using US-DOT, the performances of radiologists with respect to the characterization of breast masses as benign or malignant were not significantly improved with US-DOT.
European Radiology 01/2011; 21(7):1353-63. · 3.22 Impact Factor
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ABSTRACT: To evaluate the most accurate criteria using ultrasound (US) and contrast-enhanced computed tomography (CT) in predicting lateral lymph node metastasis in patients with papillary thyroid carcinoma (PTC).
A total of 122 lateral cervical lymph nodes of 113 patients diagnosed with PTC underwent preoperative US-guided fine-needle aspiration biopsy (US-FNAB) and CT. Degree of enhancement (DOE) was calculated by the differences of Hounsfield units (HU) between the lymph node and the ipsilateral sternocleiomastoideus muscle. Standard reference was set by surgical pathology results. Diagnostic performances of US, CT, and cutoff value for DOE were analyzed.
Seventy lymph nodes (57.4%) were metastases, and 52 (42.6%) were benign. The cutoff value of DOE on CT was 35.7 HU. Diagnostic performance of CT including DOE of 35.7 HU was lower than US, but without significance (P = 0.321). When any suspicious CT feature was combined with the combination of suspicious US features, values of the area under the receiver operating characteristic curve decreased compared to the combinations of suspicious US features alone, 0.785 to 0.741, respectively (P = 0.225).
Contrast-enhanced CT does not greatly improve diagnostic values of US in the diagnosis of metastatic lateral cervical lymph nodes in patients with PTC.
Annals of Surgical Oncology 01/2011; 18(6):1734-41. · 4.17 Impact Factor
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ABSTRACT: Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial myopathy commonly caused by deleterious changes in the mitochondrial DNA (mtDNA). We describe a 45-year-old man who was referred to us for investigation of progressive ptosis. We performed a multiplex ligation-dependent probe amplification (MLPA) assay of mtDNA from muscle tissue and peripheral blood leukocytes, and followed up with gap-polymerase chain reaction (PCR) and direct sequence analysis. Results showed a deletion of a 4,407 bp segment in the mtDNA region, ranging from nucleotide position 8,577 in the MT-ATP6 gene to nucleotide position 12,983 in the MT-ND5 gene. To the best of our knowledge, this is the first report of a CPEO patient with a large novel deletion of mtDNA genetically confirmed by MLPA assay. MLPA can be a feasible platform for clinical laboratories to detect large deletion mutations in the mtDNA for suspected cases.
Annals of clinical and laboratory science 01/2011; 41(4):385-9. · 0.96 Impact Factor
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ABSTRACT: Nucleic acid-based amplification tests allow the rapid detection of Mycobacterium tuberculosis. Recently, a real-time PCR assay for M. tuberculosis complex, the Cobas TaqMan MTB test (Roche Diagnostics, Basel, Switzerland), was introduced. We performed a prospective study to evaluate the diagnostic performance of the Cobas TaqMan MTB test system. A total of 406 specimens collected from 247 patients were simultaneously tested by conventional culture, Cobas Amplicor MTB PCR, and TaqMan MTB PCR. The cross-reactivity with other Mycobacterium species and the detection limit were also evaluated. Among 406 specimens, a total of 24 specimens (5.9%) were culture positive: 14 specimens were positive by both TaqMan and Amplicor MTB PCRs, while 5 specimens were positive by only TaqMan PCR. The remaining five specimens were negative by both PCR methods. Seven specimens with negative culture results were positive by TaqMan PCR, but five of these were negative by Amplicor MTB PCR. The sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were 79.1%, 98.2%, 73.1%, and 98.7% for TaqMan and 58.3%, 99.5%, 87.5%, and 97.4% for the Amplicor MTB PCR test, respectively. There was no cross-reactivity with M. tuberculosis and nontuberculous mycobacterial species. The detection limit for the Cobas TaqMan MTB PCR test was 4.0 copies/μl. The Cobas TaqMan MTB PCR test showed higher sensitivity for detection of the M. tuberculosis complex without disturbing the specificity and NPV than the Amplicor MTB PCR test.
Journal of clinical microbiology 11/2010; 49(1):173-6. · 4.16 Impact Factor
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ABSTRACT: Ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) is an accurate, reliable, and simple procedure to perform, and it is nowadays accepted as a standard diagnostic method for the differential diagnosis of thyroid nodules. However, a major limitation of US-FNAB is indeterminate cytology results at a thyroid nodule. This study investigated the clinical and US characteristics that predict malignancy, as well as the role of intraoperative frozen sections (FS) in the treatment of thyroid nodules with indeterminate cytology.
From September 2002 to December 2007, the medical records of 181 patients (185 nodules) with indeterminate FNAB cytology results were retrospectively reviewed. Among them, 99 patients (M:F = 13:86; mean age, 43.71 years) with 99 thyroid nodules underwent subsequent surgery with pathologic confirmation. Seventy-eight patients (78.8%) underwent intraoperative FS. US findings of the surgically proven thyroid nodules were retrospectively reviewed. US features, clinical characteristics, and FS results were compared to the surgically proven pathologic results.
Nineteen nodules (19.2%) with indeterminate FNAB cytology were diagnosed as malignant. Lesion size varied from 4 to 70 mm (mean, 27.0 mm). Male patients (46.2%) were more significantly associated with malignancy than female patients (15.1%, P < 0.05). Microlobulated or ill-defined margins (87.5%), microcalcifications (50.0%), and taller-than-wide shape (80.0%) were US features showing correlations with malignancy (P < 0.05). Intraoperative FS significantly predicted malignancy (P < 0.05). Of the 78 cases with FS, 29 cases (37.2%) were deferred. Among the remaining 49 cases, 4 (5.1%) were malignant on FS and subsequent surgical pathology. Forty-five cases (57.7%) were diagnosed as benign on FS, but only two cases were diagnosed as malignant on surgical pathology.
Ultrasound is a feasible method in predicting malignancy in thyroid nodules with indeterminate FNAB cytology. Also, intraoperative FS is a supportive method with high specificity that may guide the treatment of thyroid nodule with indeterminate cytology.
Annals of Surgical Oncology 03/2010; 17(8):2147-55. · 4.17 Impact Factor
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ABSTRACT: The beneficial effects of growth hormones (GHs) on wound healing have been reported. Although the mechanism of how GH promotes wound healing is unclear, there are reports showing that the principal factor lies in the GH-stimulated production of IGF-1 in topical wounds. In this study, a human primary cell model was devised to examine how the topical application of GHs affects fibroblast proliferation and keratinocyte migration, which play fundamental roles in wound healing.
The fibroblasts were cultured in media with different concentrations of GH. The amount of fibroblast proliferation was assessed using a tetrazolium-based colourimetric assay (MTT assay). The amount of newly formed IGF-I mRNA was measured by reverse transcription and polymerase chain reaction (RT-PCR). Keratinocyte migration was compared using a migration assay.
Fibroblast proliferation was significantly higher in the experimental group than in the control group (the absorbance of 2.5IU L(-1) GH applied group: 0.3954+/-0.056, control group: 0.2943+/-0.0554, P<0.05), and the promotion of IGF-I formation by fibroblasts was observed. There was more keratinocyte migration in the experimental group than in the control group (the remaining gap in the 2.5IU L(-1) GH applied group after keratinocyte migration: 46.57+/-2.22% of the primary gap, control group: 75.14+/-3.44%, P<0.05).
GH enhances the local formation of IGF-1, which activates fibroblast proliferation and keratinocyte migration. These results highlight the potential of the topical application of GHs in the treatment of wounds.
Journal of Plastic Reconstructive & Aesthetic Surgery 12/2009; 63(4):e364-9. · 1.49 Impact Factor
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ABSTRACT: Investigations of naturally occurring mutations, such as the deletional thalassaemias and hereditary persistence of fetal haemoglobins (HPFHs), have brought many insights into human globin switching, but limited data have been reported so far. We selected 15 individuals with elevated fetal haemoglobin (HbF) levels (>5%) from a previous screening of 27 006 Korean individuals and analysed dosage changes of the globin gene cluster using multiplex ligation-dependent probe amplification (MLPA). Dosage changes detected by the MLPA probes were followed up with gap-polymerase chain reaction and sequence analysis. Three subjects were found to have deletions in the globin gene cluster, including a beta-thalassaemia due to deletion of HBB (beta-globin gene), an HPFH due to deletions of HBD (delta-globin gene) and HBB, and an HPFH due to a novel HBG2-HBG1 fusion gene consisting of exons 1 and 2 of HBG2 ((G)gamma-globin gene) and exon 3 of HBG1 ((A)gamma-globin gene). The case with the HBG2-HBG1 fusion suggested the existence of another mechanism for the reactivation of HBG2 and HBG1. The IVS2 of HBG2 and HBG1might play a role in HbF regulation, and combinations of specific polymorphisms could influence the reactivation of these genes in adults.
British Journal of Haematology 10/2009; 148(1):154-60. · 4.94 Impact Factor
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ABSTRACT: In rodents, a circumvallate papilla (CVP) develops with dynamic changes in epithelial morphogenesis during early tongue development. Molecular and cellular studies of CVP development revealed that there would be two different mechanisms in the apex and the trench wall forming regions with specific expression patterns of Wnt11 and Shh. Molecular interactions were examined using in vitro organ culture with over-expression of Shh, important signalling molecules and various inhibitors revealed that there are two significant different mechanisms in CVP formation by Wnt11 and Shh expressions. Wnt, a well known key molecule to initiate taste papillae, would govern Rho activation and cytoskeleton formation in the apex epithelium of CVP. In contrast, Shh regulates the cell proliferation to differentiate taste buds and to invaginate the epithelium for development of von Ebner's gland (VEG). Based on these results, we suggest that these different molecular signalling cascades of Wnt11 and Shh would play crucial roles in specific morphogenesis and pattern formation of CVP during early mouse embryo development.
Developmental Biology 12/2008; 325(1):273-80. · 4.07 Impact Factor
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ABSTRACT: The regeneration of wounded stratified epithelium is accomplished via the migration of keratinocytes from the margins of the wound. However, the process of keratinocyte migration on the wound surface and the role of epithelial stem cells during re-epithelialization remain to be elucidated. Therefore, we administered BrdU to embryonic mice and generated epithelial defects on the buccal mucosa of these mice at two weeks after birth, using CO(2) laser irradiation, with which we removed the entire thickness of the epithelium. In the unwounded epithelium, cytokeratin 14, p63, and BrdU were localized within the basal layer of the epithelium, but the majority of cells within the regenerated epithelium were immunopositive for these proteins. PCNA-negative and BrdU-positive basal keratinocytes, which evidence a slow cell cycle, were localized solely within the basal layer of the unwound epithelium facing the tips of dermal papillae. After laser irradiation, these basal keratinocytes facing the tips of the papillae evidenced positive immunoreactivity for PCNA, in addition to BrdU. These results indicate that epithelial stem cells of oral mucosa may be localized in the basal layer of the epithelium facing the tips of dermal papillae, and may migrate laterally with other basal keratinocytes in response to external stimuli.
Histochemie 10/2008; 130(6):1165-75. · 2.59 Impact Factor
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ABSTRACT: To evaluate imaging findings of diffuse pancreatic ductal adenocarcinoma.
We included 14 patients (4 men and 10 women; mean age, 64.5 years) with diffuse pancreatic ductal adenocarcinoma on the basis of retrospective radiological review. Two radiologists retrospectively reviewed 14 CT scans in consensus with respect to the following: tumor site, peripheral capsule-like structure, dilatation of intratumoral pancreatic duct, parenchymal atrophy, and ancillary findings. Eight magnetic resonance (MR) examinations with MR cholangiopancreatography (MRCP) and seven endoscopic retrograde cholangiopancreatography (ERCP) were also reviewed, focusing on peripheral capsule-like structure and dilatation of intratumoral pancreatic duct.
CT revealed tumor localization to the body and tail in 11 (79%) patients and peripheral capsule-like structure in 13 (93%). The intratumoral pancreatic duct was not visible in 13 (93%). Pancreatic parenchymal atrophy was not present in all 14 patients. Tumor invasion of vessels was observed in all 14 patients and of neighbor organs in 8 (57%). On contrast-enhanced T1-weighted MR images, peripheral capsule-like structure showed higher signal intensity in five patients (71%). In all 11 patients with MRCP and/or ERCP, the intratumoral pancreatic duct was not dilated.
Diffuse pancreatic ductal adenocarcinoma has characteristic imaging findings, including peripheral capsule-like structure, local invasiveness, and absence of both dilatation of intratumoral pancreatic duct and parenchymal atrophy.
European Journal of Radiology 09/2008; 67(2):321-8. · 2.61 Impact Factor
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ABSTRACT: Although Hertwig's epithelial root sheath (HERS) performs an important function in the formation of the tooth root, the developmental mechanisms that control HERS growth and differentiation remain to be thoroughly elucidated. Bone morphogenetic protein 4 (BMP4), which is secreted by mesenchymal cells, acts on the dental epithelium as a regulator of cell differentiation during crown formation. In an effort to determine whether BMP4 specifically regulates the development of HERS in the dental epithelium, we assessed the localizations of BMP4, BMP receptor-IB (BMPR-IB), and BMPR-II during molar root formation in the mouse. HERS cells were shown to express BMPR-IB and BMPR-II. BMP4-positive cells were detected densely in the dental papillae around HERS, thereby suggesting that BMP4 participated in HERS formation. Beads soaked in BMP4, NOGGIN, or phosphate-buffered saline (PBS) were implanted into the pulp cavity under culture conditions, and the length of HERS was evaluated with regard to the proliferating cells. After 12 h, both groups exhibited a similar HERS developmental pattern, with the length and shape of HERS bearing a close resemblance to one another. However, after 48 h, the observed HERS elongation was significantly shorter in the BMP4-treated group. In addition, proliferative cell nuclear antigens were detectable only in the NOGGIN- and PBS-treated groups. These findings demonstrate that mesenchymally expressed BMP4 regulates HERS development by preventing elongation and maintaining cell proliferation. BMP4 may, therefore, prove useful as a root-formation regulatory agent in a variety of tissue-engineering applications.
Cell and Tissue Research 09/2008; 333(3):503-9. · 3.11 Impact Factor
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Thrombosis Research 07/2008; 123(2):412-7. · 2.44 Impact Factor
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Ji Youn Kim MD,
Eun Joo Chung MD,
PhD Won Yong Lee MD,
Hee Young Shin MD,
PhD Gyeong Han Lee MD,
PhD Yearn-Seong Choe MD,
Yong Choi PhD,
PhD Byeong Joon Kim MD, Ji Youn Kim,
Eun Joo Chung,
Won Yong Lee,
Hee Young Shin,
Gyeong Han Lee,
Yearn‐Seong Choe,
Yong Choi,
Byeong Joon Kim
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ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential therapeutic tool in Parkinson's disease (PD). However, the therapeutic value and/or the placebo effect of rTMS on PD remain to be elucidated. To investigate the therapeutic value and/or placebo effect of rTMS in PD, we compared the motor section of unified PD rating scale (UPDRS III) and the amount of extracellular dopamine concentration using [11C] raclopride PET before and after two sessions of rTMS in 9 PD patients. During a consecutive 2 days while off-medication, two series of 15 trains of 5 Hz-frequency rTMS (intensity, 90% of the resting motor threshold) were applied to the hand area of more severely symptomatic motor cortex (MC). After unilateral rTMS of MC, mean raclopride binding potentials (BPs) were reduced not only in putaminal and caudate areas on the stimulated side (−4.9% and −6.5%, respectively) (P > 0.05) but also in putaminal and caudate areas of nonstimulated hemispheres (−6.6%, P > 0.05 and −12.1%, P = 0.049, respectively). UPDRS III scores were significantly decreased (35.0 ± 14.1 to 32.0 ± 13.4, P = 0.049). A reduction of raclopride BP in nonstimulated ventral striatum by unilateral rTMS supports the placebo response during rTMS. © 2007 Movement Disorder Society
Movement Disorders 01/2008; 23(2):207 - 211. · 4.51 Impact Factor
