Method to classify dental arch forms.

INTRODUCTION: The aim of this study was to propose a method to classify dental arch forms of subjects with normal occlusion into several types that can ensure both goodness of fit and clinical application. METHODS: We selected 306 subjects with normal occlusion from 15,836 young adults, recorded 14 reference points that defined the distance between 2 arch forms as the area between 2 arches, and then classified the dental arch forms by using the partitioning around medoids clustering and silhouette method. We measured tooth size, arch width, basal arch width, arch depth, mesiodistal angulations, and buccolingual inclinations. RESULTS: We identified 3 types of arch forms, and cross-classification of the maxillary by mandibular arch forms showed a more frequent distribution in the diagonal elements than in the off-diagonal elements. The 3 arch forms showed differences in tooth size, arch width, basal arch width, and inclination of the posterior teeth. CONCLUSIONS: By defining area discrepancies as distance measures and applying them to the cluster method by using medoids, the dental arch form can be classified keeping control for the extremes without bias. It is hoped that this method will have possible clinical applications in determining the shape and number of preformed orthodontic arch forms.

Variation of the intermaxillary tooth-size relationship in normal occlusion.

The purpose of this study was to explore the intermaxillary tooth-size relationship that is attributed to normal occlusion using multivariate cluster analysis, while simultaneously incorporating the full dentition as a data set. From the central incisor to the second molar, the tooth sizes of 307 subjects (188 males and 119 females; mean age ± standard deviation, 19.9 ± 3.3 years) with normal occlusion were investigated. Tooth-size data were analysed separately for the maxilla and the mandible. When clustering, the partitioning around medoids (PAM) algorithm was performed with the transformed data based on principal component analysis (PCA). After the subjects were classified into four groups, the cluster memberships were cross-classified, and the distribution pattern and intermaxillary tooth-size relationships were explored. Bolton tooth ratio showed a relatively wide range, and this was indicative of the variability in tooth size in subjects with a normal occlusion. However, the patterns of the intermaxillary tooth-size relationship were similar for males and females, and this result was concordant with the findings of the classic Bolton analysis. Using the multivariate approach to analyse the tooth-size data set of an individual patient and then comparing the results with the normal occlusion cluster has possible clinical applications in determining the amount and location of tooth-size control in orthodontics.

Oral administration of 1,4-aryl-2-mercaptoimidazole inhibits T-cell proliferation and reduces clinical severity in the murine experimental autoimmune encephalomyelitis model.

T cells play a pivotal role in the initiation and progression of multiple sclerosis. We have found that 1,4-aryl-2-mercaptoimidazole (KRM-III) inhibited T-cell antigen receptor- and phorbol myristate acetate/ionomycin-induced activation of nuclear factor of activated T cells (NFAT) and T-cell proliferation with an IC(50) of 5 microM. The KRM-III-mediated inhibitory effect was specific for NFAT activation but not for nuclear factor kappaB. Oral administration of 90 mg/kg KRM-III resulted in complete abrogation of anti-CD3 antibody-induced T-cell activation and a 45.8% reduction in footpad swelling in bovine serum albumin-induced delayed-type hypersensitivity. In the murine experimental autoimmune encephalomyelitis (EAE) model, oral administration of KRM-III significantly attenuated the severity of disease when given before or after disease onset. Draining lymph node cells from KRM-III-treated mice showed markedly reduced proliferation in response to myelin oligodendrocyte glycoprotein peptide. Histological analysis indicated that KRM-III reduced the infiltration of inflammatory cells to the white matter of spinal lumbar cords. These results demonstrate that KRM-III efficiently inhibits T-cell activation and inflammatory responses and lessens EAE clinical signs, which suggest KRM-III as a potential lead compound for the treatment of T-cell-driven autoimmune diseases.

Susceptibility of cancer cells to beta-lapachone is enhanced by ionizing radiation.

PURPOSE: To reveal the interaction between beta-lapachone (beta-lap) and ionizing radiation (IR) in causing clonogenic death in cancer cells and to elucidate the potential usefulness of beta-lap treatment in combination with radiotherapy of cancer. METHODS AND MATERIALS: FSaII tumor cells of C3H mice were used. The cytotoxicity of beta-lap alone or in combination with IR in vitro was determined using clonogenic survival assay method. The IR-induced changes in the expression and the enzymatic activity of NAD(P)H:quinone oxidoreductase (NQO1), a mediator of beta-lap cytotoxicity, were elucidated and the relationship between the NQO1 level and the sensitivity of cells to beta-lap was investigated. The combined effect of IR and beta-lap to suppress tumor growth was studied using FSaII tumors grown subcutaneously in the thigh of C3H mice. RESULTS: beta-Lap caused clonogenic death of FSaII tumor cells in vitro in a dose- and time-dependent manner. When cells were treated first with beta-lap and then exposed to IR in vitro, the resultant cell death was only additive. On the contrary, exposing cells to IR at 2.5 Gy first and then treating the cells with beta-lap killed the cells in a synergistic manner. Importantly, the 2.5 Gy cells were sensitive to beta-lap as long as 10 h after irradiation, which was long after the sublethal radiation damage was repaired. Irradiation of FSaII cells in vitro with 2.5 Gy significantly increased the expression and enzymatic activity of NQO1. The growth delay of FSaII tumors caused by an intraperitoneal injection of beta-lap in combination with 20 Gy irradiation of tumor was significantly greater than that caused by beta-lap or 20 Gy irradiation alone. CONCLUSION: The sensitivity of cells to beta-lap is dependent on NQO1 activity. IR caused a long-lasting increase in NQO1 activity in cancer cells, thereby sensitizing cells to beta-lap and treatment of experimental mouse tumors with IR and beta-lap suppressed tumor growth in a synergistic manner. The combination of beta-lap and radiotherapy is a potentially effective regimen for the treatment of human cancer.

Effect of pH on radiation-induced p53 expression.

PURPOSE: In most tumors, the intratumor environment is acidic. The purpose of this study was to elucidate the effect of acidic extracellular environment on the radiation-induced expression of p53 and related molecular signals. METHODS AND MATERIALS: Cultured RKO.C human colorectal cancer cells carrying wild-type p53 were used. Cells grown in pH 7.5 medium or pH 6.6 medium were irradiated with gamma-rays, and the expression of p53 and p53 mRNA, as well as the degradation rate of the molecules, was determined. The transcriptional activity for p53 was investigated using cells transfected with a p53 reporter construct. The expression of Mdm2 and the phosphorylation of p53, essential factors for p53 degradation, were also investigated. RESULTS: The pH 6.6 environment prolonged the radiation-induced expression of p53 and p53 mRNA. The radiation-induced increase in transcriptional activity of p53 lasted longer in pH 6.6 medium than in pH 7.5 medium. The degradation of p53 was delayed at pH 6.6. The radiation-induced expression of Mdm2 was markedly suppressed, whereas the phosphorylation of p53 was markedly increased after irradiation in pH 6.6 medium. CONCLUSION: Acidic environment significantly enhances the radiation-induced expression of p53, partly by increasing the formation of p53 and also partly by slowing down the degradation of p53 through inhibiting p53-Mdm2 complex formation. The potential implication of acidic intratumor microenvironment for the response of tumors to radiotherapy remains to be elucidated.

Role of sphingomyelin-MAPKs pathway in heat-induced apoptosis.

The role of sphingomyelinase (SMase) activation and mitogen activated protein kinases (MAPKs) activation in cellular apoptosis was investigated during the hyperthermic treatment of HL-60 human leukemia cells. Treating the cells for 1 h at 43(o)C caused more than 50% of cellular apoptosis within several hours. The neutral-SMase activity in the cells treated for 1 h at 42(o)C was slightly increased but decreased in the cells treated at 43(o)C or 44(o)C for the same period whereas the acid SMase activity was slightly increased after heating the cells at 42(o)C and 43(o)C and markedly increased at 44(o)C for 1 h. Treatment of cells with inhibitors of SMase activation and ceramide formation significantly reduced the heat-induced apoptosis. Three major families of mitogen-activated protein kinases (MAPKs), i.e. ERK1/2, p38 and JNK, were activated by the hyperthermic treatment of cells. Inhibition of ERK1/2 with PD98059 exerted little effect on the heat-induced apoptosis and p38 inhibition with SB203580 slightly lessened apoptosis whereas, inhibition of JNK with SP600125 markedly suppressed the heat-induced apoptosis. These results indicate that heat-shock induced the activation of SMase, particularly acid-SMase, thereby causing apoptosis and that JNK played a pivotal role in heat-induced apoptosis in HL-60 leukemia cells.

Development of peer-group-classification criteria for the comparison of cost efficiency among general hospitals under the Korean NHI program.

OBJECTIVES: To classify general hospitals into homogeneous systematic-risk groups in order to compare cost efficiency and propose peer-group-classification criteria. DATA SOURCES: Health care institution registration data and inpatient-episode-based claims data submitted by the Korea National Health Insurance system to the Health Insurance Review and Assessment Service from July 2007 to December 2009. STUDY DESIGN: Cluster analysis was performed to classify general hospitals into peer groups based on similarities in hospital characteristics, case mix complexity, and service-distribution characteristics. Classification criteria reflecting clustering were developed. To test whether the new peer groups better adjusted for differences in systematic risks among peer groups, we compared the R(2) statistics of the current and proposed peer groups according to total variations in medical costs per episode and case mix indices influencing the cost efficiency. DATA COLLECTION: A total of 1,236,471 inpatient episodes were constructed for 222 general hospitals in 2008. PRINCIPAL FINDINGS: New criteria were developed to classify general hospitals into three peer groups (large general hospitals, small and medium general hospitals treating severe cases, and small and medium general hospitals) according to size and case mix index. CONCLUSIONS: This study provides information about using peer grouping to enhance fairness in the performance assessment of health care providers.

Development of a predictive model for type 2 diabetes mellitus using genetic and clinical data.

OBJECTIVES: Recent genetic association studies have provided convincing evidence that several novel loci and single nucleotide polymorphisms (SNPs) are associated with the risk of developing type 2 diabetes mellitus (T2DM). The aims of this study were: 1) to develop a predictive model of T2DM using genetic and clinical data; and 2) to compare misclassification rates of different models. METHODS: We selected 212 individuals with newly diagnosed T2DM and 472 controls aged in their 60s from the Korean Genome and Epidemiology Study. A total of 499 known SNPs from 87 T2DM-related genes were genotyped using germline DNA. SNPs were analyzed for significant association with T2DM using various classification algorithms including Quest (Quick, Unbiased, Efficient, Statistical tree), Support Vector Machine, C4.5, logistic regression, and K-nearest neighbor. RESULTS: We tested these models using the complete Korean Genome and Epidemiology Study cohort (n = 10,038) and computed the T2DM misclassification rates for each model. Average misclassification rates ranged at 28.2-52.7%. The misclassification rates for the logistic and machine-learning algorithms were lower than the statistical tree algorithms. Using 1-to-1 matched data, the misclassification rate of the statistical tree QUEST algorithm using body mass index and SNP variables was the lowest, but overall the logistic regression performed best. CONCLUSIONS: The K-nearest neighbor method exhibited more robust results than other algorithms. For clinical and genetic data, our "multistage adjustment" model outperformed other models in yielding lower rates of misclassification. To improve the performance of these models, further studies using warranted, strategies to estimate better classifiers for the quantification of SNPs need to be developed.

Synergistic effect of ionizing radiation and beta-Lapachone against RKO human colon adenocarcinoma cells.

PURPOSE: To reveal the interaction between beta-Lapachone (beta-lap) and ionizing radiation in causing cell death in RKO human colon adenocarcinoma cells, and to elucidate the potential usefulness of combined beta-lap treatment and radiotherapy for cancer treatment. MATERIALS AND METHODS: The cytotoxicities of various treatments were determined in vitro using clonogenic and apoptotic cell death. The changes in cell cycle distribution were studied using flow cytometry and an in vitro kinase assay. The tumor growth was studied using RKO tumors grown s.c. in the hind leg BALB/c- nuslc nude mice. RESULTS: beta-Lap caused clonogenic cell death and rapid apoptosis in RKO cells in vitro, in a dose dependent manner. The repair of sublethal radiation damage was almost completely inhibited when cells were maintained in beta-lap during the interval between the two-dose irradiation. Flow cytometry study demonstrated that beta-lap induced apoptosis, independent of the cell cycle phase, and completely prohibited the induction of radiation-induced G2 arrest in irradiated cells. The prohibition of radiation-induced G2 arrest is unclear, but may be related to the profound suppression of the p53, p21 and cyclin B1-Cdc2 kinase activities observed in cells treated with beta-lap. The combination of beta-lap and radiation markedly enhanced the radiation-induced growth suppression of tumors. CONCLUSION: beta-Lap is cytotoxic against RKO cells, both in vitro and in vivo, and also sensitized cells to ionizing radiation by inhibiting sublethal radiation damage repair. beta-lap is potentially useful as a potent anti-cancer chemotherapy drug and potent radiosensitizer against cancer cells.

A preliminary results of a randomized trial comparing monthly 5-flourouracil and cisplatin to weekly cisplatin alone combined with concurrent radiotherapy for locally advanced cervical cancer.

PURPOSE: To determine the superior chemotherapeutic regimen between monthly 5-FU plus cisplatin (FP) and weekly cisplatin alone in concurrent chemoradiotherapy for locally advanced cervical cancer, the compliance of treatment, response, survival and toxicities were analyzed between the two arms. MATERIALS AND METHODS: Between March 1998 and December 2001, 61 patients with locally advanced cervical cancer (stage IIB through IVA) and negative para-aortic lymph nodes were randomly assigned to either 'monthly FP' (arm I, n=34) or 'weekly cisplatin' (arm II, n=27) with concurrent radiotherapy. The patients of arm I received FP (5-FU 1,000 mg/m(2)/day + cisplatin 20 mg/m(2)/day, for 5 days, for 3 cycles at 4 week intervals) and those of arm II received cisplatin (30 mg/m(2)/day, for 6 cycles at 1 week intervals) with concurrent radiotherapy. The radiotherapy consisted of 41.4 approximately 50.4 Gy external beam irradiation in 23 approximately 28 fractions to the whole pelvis, with high dose rate brachytherapy delivering a dose of 30 approximately 35 Gy in 6 approximately 7 fractions to point A. During the brachytherapy, a parametrial boost was delivered. The median follow-up period for survivors was 44 months. RESULTS: The compliance of treatment in monthly FP weekly cisplatin arms were 62 and 81%, respectively. The complete response rates at 3 months were 96 and 88% in arms I and II, respectively. The 4-year overall survival and disease free survival rates were 64 and 54% in the arm I and 77 and 66% in the arm II, respectively. The incidence of hematologic toxicity more than grade 2 was 29% in the arm I and 15% in the arm II. Only one patient in arm I experienced grade 3 gastrointestinal toxicity. No severe genitourinary toxicity was observed. CONCLUSION: No significant difference was observed in the compliance, responses, survival rates and acute toxicities between the two treatment arms. More patients and further follow up will be required.