Association of ultrasound-based measures of fetal body composition with newborn adiposity.

BACKGROUND: Newborns exhibit substantial variation in gestational age-adjusted and sex-adjusted fat mass proportion. The antecedent characteristics of fetal body composition that are associated with newborn fat mass proportion are poorly understood. OBJECTIVE: The aim of this study was to determine whether a composite measure of fetal fat mass is prospectively associated with newborn adiposity. METHODS: In a longitudinal study of 109 low-risk pregnancies, fetal ultrasonography was performed at approximately 12, 20 and 30 weeks gestation. Estimated fetal adiposity (EFA) was derived by integrating cross-sectional arm and thigh per cent fat area and anterior abdominal wall thickness. Newborn per cent body fat was quantified by Dual Energy X-Ray Absorptiometry. The association between EFA and newborn per cent body fat was determined by multiple linear regression. RESULTS: After controlling for confounding factors, EFA at 30 weeks was significantly associated with newborn per cent body fat (standardized ß = 0.41, p < 0.001) and explained 24.0% of its variance, which was substantially higher than that explained by estimated fetal weight (8.1%). The observed effect was driven primarily by arm per cent fat area. CONCLUSIONS: A composite measure of fetal adiposity at 30 weeks gestation may constitute a better predictor of newborn per cent body fat than estimated fetal weight by conventional fetal biometry. Fetal arm fat deposition may represent an early indicator of newborn adiposity. After replication, these findings may provide a basis for an improved understanding of the ontogeny of fetal fat deposition, thereby contributing to a better understanding of its intrauterine determinants and the development of potential interventions.

Magnesium sulphate and perinatal mortality and morbidity in very-low-birthweight infants born between 24 and 32 weeks of gestation in Japan.

OBJECTIVE: Maternal exposure to magnesium sulphate has a neuroprotective effect in premature infants. This study aimed to examine this neuroprotective effect and the dose-response relationship in very-low-birthweight infants born between 24 and 32 weeks of gestation. STUDY DESIGN: A retrospective cohort study compared the rates of mortality and brain damage between three groups: no magnesium sulphate, low-dose (<50g) magnesium sulphate and high-dose (≥50g) magnesium sulphate. RESULTS: Japanese maternal and neonatal databases were linked using six key parameters from 2003 to 2007. Of 298,514 deliveries, 9101 were very-low-birthweight infants. Among these, full matching was possible for 5562 infants. Of the fully-matched infants, 3763 were born between 24 and 32 weeks of gestation, and 1813 (48%) were followed-up beyond 18 months. A multivariate analysis of the data, including gestational age, sex, fetal growth restriction, antenatal steroids and low pH (<7.1), showed that the low-dose group had no beneficial effects in terms of a reduction in mortality or incidence of brain damage (cerebral palsy or mental retardation). The high-dose group showed a significantly higher mortality rate [odds ratio (OR) 1.9, 95% confidence interval (CI) 1.2-2.9]. A stratified subgroup analysis of infants born between 28 and 32 weeks of gestation showed that survivors in the low-dose group had significantly lower rates of cerebral palsy (OR 0.4, 95% CI 0.2-0.98) and brain damage (OR 0.2, 95% CI 0.1-0.9), while the high-dose group did not show any significant changes. CONCLUSION: This study found that antepartum exposure to magnesium sulphate did not reduce the infant mortality rate or influence neurological outcomes. However, among infants born between 28 and 32 weeks of gestation, rates of cerebral palsy and brain damage were found to be significantly lower among survivors in the low-dose group.

Gap-junction-mediated communication in human periodontal ligament cells.

Periodontal tissue homeostasis depends on a complex cellular network that conveys cell-cell communication. Gap junctions (GJs), one of the intercellular communication systems, are found between adjacent human periodontal ligament (hPDL) cells; however, the functional GJ coupling between hPDL cells has not yet been elucidated. In this study, we investigated functional gap-junction-mediated intercellular communication in isolated primary hPDL cells. SEM images indicated that the cells were in contact with each other via dendritic processes, and also showed high anti-connexin43 (Cx43) immunoreactivity on these processes. Gap-junctional intercellular communication (GJIC) among hPDL cells was assessed by fluorescence recovery after a photobleaching (FRAP) analysis, which exhibited dye coupling between hPDL cells, and was remarkably down-regulated when the cells were treated with a GJ blocker. Additionally, we examined GJs under hypoxic stress. The fluorescence recovery and expression levels of Cx43 decreased time-dependently under the hypoxic condition. Exposure to GJ inhibitor or hypoxia increased RANKL expression, and decreased OPG expression. This study shows that GJIC is responsible for hPDL cells and that its activity is reduced under hypoxia. This is consistent with the possible role of hPDL cells in regulating the biochemical reactions in response to changes in the hypoxic environment.

Endoscopic submucosal dissection allows less-invasive curative resection for gastric tube cancer after esophagectomy - a case series.

Detection of early gastric tube cancers (GTCs) has increased with more detailed surveillance endoscopy using indigo carmine dye following esophagectomy. This retrospective study clarified the clinicopathological features and application of endoscopic submucosal dissection (ESD) for GTCs. Data collected for eight GTCs treated by ESD included clinical and pathological features and outcomes following ESD. Overall, eight GTCs were identified in seven (6.3 %) of 112 patients who underwent esophagectomy and gastric tube reconstruction. Almost all lesions were macroscopically type 0-IIa with mucosal to submucosal invasion, and seven GTCs were successfully resected en bloc by ESD. Submucosal invasion to > 500 microm was observed in one case with associated delayed perforation that was treated conservatively. No local recurrences of GTCs were observed. Detailed surveillance endoscopy using indigo carmine dye appears useful for diagnosing early-stage GTC. Furthermore ESD represents a feasible alternative to conventional endoscopic mucosal resection as a minimally invasive therapy for early-stage GTC.

Protein microarray analysis identifies human cellular prion protein interactors.

AIMS: To obtain an insight into the function of cellular prion protein (PrPC), we studied PrPC-interacting proteins (PrPIPs) by analysing a protein microarray. METHODS: We identified 47 novel PrPIPs by probing an array of 5000 human proteins with recombinant human PrPC spanning amino acid residues 23-231 named PR209. RESULTS: The great majority of 47 PrPIPs were annotated as proteins involved in the recognition of nucleic acids. Coimmunoprecipitation and cell imaging in a transient expression system validated the interaction of PR209 with neuronal PrPIPs, such as FAM64A, HOXA1, PLK3 and MPG. However, the interaction did not generate proteinase K-resistant proteins. KeyMolnet, a bioinformatics tool for analysing molecular interaction on the curated knowledge database, revealed that the complex molecular network of PrPC and PrPIPs has a significant relationship with AKT, JNK and MAPK signalling pathways. CONCLUSIONS: Protein microarray is a useful tool for systematic screening and comprehensive profiling of the human PrPC interactome. Because the network of PrPC and interactors involves signalling pathways essential for regulation of cell survival, differentiation, proliferation and apoptosis, these observations suggest a logical hypothesis that dysregulation of the PrPC interactome might induce extensive neurodegeneration in prion diseases.

Evaluation of combined docetaxel and nedaplatin chemotherapy for recurrent esophageal cancer compared with conventional chemotherapy using cisplatin and 5-fluorouracil: a retrospective study.

This retrospective study evaluated the safety and efficacy of combination chemotherapy using docetaxel and nedaplatin in an outpatient setting compared with those of chemotherapy using cisplatin (CDDP) and 5-Fu under hospitalization. Subjects comprised 21 patients who had been diagnosed with recurrent esophageal squamous cell carcinoma (ESCC), with 10 patients receiving combination chemotherapy comprising CDDP and 5-fluorouracil (5-Fu) under hospitalization (FP group; n = 10), and 11 patients receiving combination chemotherapy comprising docetaxel and nedaplatin in an outpatient setting (Doc/Ned group; n = 11). In the Doc/Ned group, patients received 30 mg/m(2) of docetaxel over a 1-h infusion on day 1, followed by 40 mg/m(2) of nedaplatin over a 2-h infusion on day 1 in an outpatient setting. In the Doc/Ned group, complete response was observed in two patients (18.1%), one with liver metastasis and one with abdominal lymph node metastasis, and two (18.1%) achieved partial response. In contrast, no complete responses were obtained in the FP group, and partial response was observed in only one patient (10.0%) with local recurrence. Response rates were thus 36.3% for the Doc/Ned group and 10.0% for the FP group. With a median follow-up of 234 days in the Doc/Ned group and 279 days in the FP group, median survival time (MST) was 234 days in the Doc/Ned group and 378 days in the FP group. No significant differences in MST were identified between groups. Thus regimen based on docetaxel and nedaplatin allows administration on an outpatient basis and appears feasible for recurrent ESCC as a second-line chemotherapy.

Neutrino signals from the formation of a black hole: A probe of the equation of state of dense matter.

The gravitational collapse of a nonrotating, black-hole-forming massive star is studied by nu-radiation-hydrodynamical simulations for two different sets of realistic equation of state of dense matter. We show that the event will produce as many neutrinos as the ordinary supernova, but with distinctive characteristics in luminosities and spectra that will be an unmistakable indication of black hole formation. More importantly, the neutrino signals are quite sensitive to the difference of equation of state and can be used as a useful probe into the properties of dense matter. The event will be unique in that they will be shining only by neutrinos (and, possibly, gravitational waves) but not by photons, and hence they should be an important target of neutrino astronomy.

Efficacy and safety of nurse-administered propofol sedation during emergency upper endoscopy for gastrointestinal bleeding: a prospective study.

BACKGROUND AND STUDY AIMS: Recent studies have documented the safety of propofol sedation for endoscopic procedures, but many endoscopists are reluctant to use propofol for high-risk patients because of adverse effects. The aim of this study was to demonstrate the safety and efficacy of nurse-administered propofol sedation during emergency upper endoscopy for patients with gastrointestinal bleeding. PATIENTS AND METHODS: Over a period of 18 months, 120 patients suffering from acute upper gastrointestinal bleeding received propofol sedation administered by a registered nurse. Among these, 15 patients were classified into American Society of Anesthesiologists (ASA) class IV, 84 were ASA class III, and 21 were ASA class II. Patients without gastrointestinal bleeding, who also received propofol during the same period and were matched for age, gender, and ASA class, served as controls. RESULTS: Endoscopic hemostasis was achieved in 98.3 % of patients, and 97.5 % were satisfied with the procedure. In patients with gastrointestinal bleeding, the rates of hypotension (systolic blood pressure < 90 mmHg) and hypoxemia (peripheral oxygen saturation < 90 %) were 8.3 % and 6.7 % respectively, values higher than those in the control group. However, neither mask ventilation nor endotracheal intubation was necessary. Although two patients with gastrointestinal bleeding developed pneumonia, most likely due to aspiration during the procedure, they recovered within 5 days of treatment. There were no sedation-associated severe complications or mortalities. CONCLUSION: Using a strict protocol designed to protect the patient's airway and cardiovascular function, nurse-administered propofol sedation during emergency upper gastrointestinal endoscopy is safe and appropriate in cases of acute gastrointestinal bleeding.

Pressure-pain threshold of oral mucosa and its region-specific modulation by pre-loading.

Once subjected to denture wearing, oral mucosa has to withstand mechanical loads of various levels and durations. However, how this load affects oral mucosal sensitivity is unknown. This study investigated the pressure-pain threshold (PPT) of oral mucosa with or without pre-loading. An electric pressure algometer was developed specifically for measuring the PPT of oral mucosa. Measurements of 10 dentulous maxillae showed that the baseline PPT (BPPT) of the palatal site was 4.9- and 3.7-fold greater than that of the labial or buccal sites, respectively. The PPT of the labial site decreased significantly compared with its BPPT after 2 s-100% BPPT and 5 s-100% BPPT pre-loading. The PPT of the palatal site increased after 5 s-50% BPPT and 5 s-80% BPPT and 0.2 s-100% BPPT and 2 s-100% BPPT pre-loading. The PPT of the buccal site did not change after all levels and durations of pre-loadings tested. These results indicated the disproportionate modulation of oral mucosal PPT following various loads, suggesting that oral mucosa possesses region-specific psychophysical tolerance to mechanical stimuli.

Smads regulate collagen gel contraction by human dermal fibroblasts.

BACKGROUND: Transforming growth factor (TGF)-beta induces fibroblast contraction that is implicated in efficient wound healing. The Smad family of proteins mediates signal transduction of the TGF-beta superfamily. However, its role in fibroblast contraction remains unclear. OBJECTIVES: To determine whether Smad proteins regulate fibroblast contraction. METHODS: We used an in vitro type I collagen gel contraction assay with human dermal fibroblasts infected with adenoviruses carrying Smads. RESULTS: Overexpression of Smad3, a major signal transducer in the Smad family, enhanced collagen gel contraction by fibroblasts when compared with fibroblasts overexpressing a control lacZ. Addition of a very low concentration of TGF-beta1 that did not affect the collagen gel contraction by itself enhanced the contraction by fibroblasts overexpressing Smad3. In contrast, TGF-beta1-mediated collagen gel contraction was suppressed by overexpression of Smad7, a major inhibitory regulator in the Smad family, in fibroblasts. In addition, inhibitors of the Erk and p38 pathways, PD98059 and SB203580, did not affect TGF-beta1-mediated collagen gel contraction by dermal fibroblasts. CONCLUSIONS: Modulation of Smad3 or Smad7 expression in dermal fibroblasts affected their contraction of collagen gels possibly by regulating TGF-beta signalling in fibroblasts.

The effect of whole-body hyperthermia combined with 'metronomic' chemotherapy on rat mammary adenocarcinoma metastases.

Many women diagnosed with invasive breast cancer have undetected occult metastases at the time of their primary tumour diagnosis. The development and growth of these micro-metastases relies heavily on angiogenesis. Therefore, administering an angiogenesis-blocking treatment from the time of diagnosis could reduce the incidence of metastasis and, ultimately, increase patient survival. It is hypothesized that an antiangiogenesis strategy combining fever-range whole-body hyperthermia (FR-WBH) and metronomic chemotherapy could inhibit the development of metastatic disease with minimal toxicity. To test this theory, a low, daily dose of the topoisomerase-I inhibitor irinotecan hydrochloride (CPT-11) was administered over a prolonged period of time to rats bearing the highly metastatic MTLn3 mammary adenocarcinoma primary tumour surgically excised on day 12 after implantation. The metronomic CPT-11 was combined with long-duration, low-temperature, fever-range whole body hyperthermia (FR-WBH). This systemic hyperthermia enhances chemotherapy-induced cytotoxicity as well as immunological activity. Both the group treated with FR-WBH alone and the combined FR-WBH + CPT-11 group had delayed onset and reduced incidence of axillary lymph node metastases compared to control (p < 0.05). Combination therapy of FR-WBH + CPT-11 resulted in a significantly greater inhibition of axillary lymph node metastasis volume compared to both control and CPT-11 alone (p < 0.02) at day 16. Interestingly, none of the therapies significantly affected inguinal lymph node metastases. Lung metastases were decreased by 36% at the time of death in rats treated with FR-WBH + CPT-11, by 25% in the CPT-11 alone group and by 14% in the FR-WBH alone group. Rats treated with FR-WBH, + CPT-11 survived significantly longer (35%) than control animals (p < 0.04). Neither significant body weight loss nor gastrointestinal toxicity was observed in any group. These data suggest that, after excision of the primary tumour, FR-WBH and metronomic CPT-11 can be safely combined to reduce distant lymph node and lung metastases and, thus, to increase survival.

Pressure-pain threshold determination in the oral mucosa: validity and reliability.

Fundamental knowledge of pain in the oral mucosa is lacking. We determined the validity and reliability of the pressure-pain threshold (PPT) measurement in the oral mucosa using a newly developed hand-held pressure algometer. Ten dentulous subjects were recruited, and the PPT was measured at the bilateral buccal (on the attached gingiva apical to the midline of the upper first premolars, 3 mm from the mucogingival junction) and the palatal sites (mid-point between the bilateral upper first molars). The PPT linearly increased with an increase in load-rate (P < 0.0001). The PPT yielded a high intra-individual stability both for the same-day consecutive trials and weekly sessions. The palatal site revealed a 4- to 4.65-fold greater PPT than the buccal sites (Bonferroni, P < 0.0001), whereas no difference was found between the bilateral buccal sites (P=0.663). Despite a great interindividual variation in the PPT, significant intra-individual correlations were found among the measurement sites. This suggested differences in individual sensitivity to pain in the oral mucosa, which may determine overall pain sensation specific to an individual. A pressure algometer described herein reliably assessed the PPT in the oral mucosa and sensitively discriminated PPT differences at different sites and at different load-rates, suggesting the reliability and validity of PPT measurements in the oral mucosa for clinical and research investigations.

Transforming growth factor-beta1 suppresses atopic dermatitis-like skin lesions in NC/Nga mice.

BACKGROUND: Atopic dermatitis is a chronic, relapsing inflammatory disorder characterized by pruritic and eczematous skin lesions. Transforming growth factor (TGF)-beta1 has been implicated in the suppression of inflammatory responses. OBJECTIVE: The purpose of this study is to determine whether TGF-beta1 suppresses skin lesions in a mouse model of atopic dermatitis. METHODS: We used the NC/Nga strain of mice as an in vivo model of atopic dermatitis. The effects of exogenous TGF-beta1 on atopic dermatitis-like skin lesions in NC/Nga mice were evaluated clinically, histologically and immunologically. RESULTS: Subcutaneous injection of recombinant TGF-beta1 macroscopically suppressed eczematous skin lesions in NC/Nga mice associated with reduced serum immunoglobulin E (IgE) levels. Histological analysis showed that TGF-beta1 significantly inhibited the infiltration of inflammatory cells such as mast cells and eosinophils into the skin of NC/Nga mice. Spontaneous interferon (IFN)-gamma production from splenocytes of NC/Nga mice was down-regulated by the treatment with TGF-beta1 and neutralizing antibody against IFN-gamma inhibited skin lesions in NC/Nga mice. The inhibitory effect of TGF-beta1 on the skin lesions lasted at least 1 week after cessation of the treatment. CONCLUSION: These findings indicate that TGF-beta1 suppressed atopic dermatitis-like skin lesions in NC/Nga mice at least in part through down-regulation of IFN-gamma. These results suggest that TGF-beta1 may have a therapeutic potential for atopic dermatitis.

Pathogenesis of esophageal squamous cell carcinoma with lymphoid stroma.

BACKGROUND/AIMS: Lymphocyte infiltration in esophageal cancer, especially when beneath intraepithelial carcinoma, is frequently seen. However, cases of esophageal cancer with a dense stromal infiltration of lymphocytes are rare and the pathogenesis of such cases has yet to be clearly demonstrated. The objective of this study is to clarify its pathogenesis. METHODOLOGY: Four cases of esophageal squamous cell carcinoma with lymphoid stroma were investigated by immunohistochemical staining for the detection of Epstein-Barr virus, human papillomavirus, human leukocyte antigen-DR, as well as T and B cells in cancer tissue. RESULTS: In these four cases, neither positive staining of Epstein-Barr virus nor human papillomavirus infection was detected. On the other hand, the expression of human leukocyte antigen-DR antigen was evident in all cases with dense T-cell infiltration in the tumor tissue and moderate B-cell infiltration around the tumor. CONCLUSIONS: The expression of human leukocyte antigen-DR antigen without Epstein-Barr virus or human papillomavirus infection could thus be one possible pathogenesis of patients demonstrating esophageal squamous cell carcinoma with a lymphoid stroma.

Cerebral blood flow measurement of severely head-injured patients during mild hypothermia.

In 14 patients with severe head injury, the cerebral blood flow (CBF) during mild hypothermia therapy was measured. Their Glasgow Coma Scale scores on admission were 8 or less and the intracranial pressures were greater than 20 mmHg despite conventional therapy. The CBF was measured with two-level stable xenon CT techniques. And in 11 patients, the cerebral metabolic rates for oxygen (CMRO2) was also calculated. All cases were divided into two groups according to the outcome at discharge by using the Glasgow Outcome Scale, good outcome group in 6 and poor outcome one in 8. The values of mean CBF and CMRO2 of each group were 25.6 +/- 6.6 vs 24.4 +/- 6.4 ml/100 g/min and 1.26 +/- 0.45 vs 0.79 +/- 0.31 ml/100 g/ml, respectively. There were no statistically significant differences between both groups. Single CBF measurement during this therapy may not be helpful as a factor of prognosis evaluation in patients with severe head injury.

Pancreatic Schwannoma: report of a case.

We present herein a case of solitary schwannoma of the pancreas and also review 26 previously reported cases from the English and Japanese literature. Primary schwannoma of the pancreas is a rare tumor. A 50-year-old female was discovered to have a large mass in the upper abdomen on ultrasonography. An examination by computed tomography (CT) scan, magnetic resonance imaging (MRI), and ultrasonography revealed a solid and cystic tumor in the left upper quadrant of the abdomen. A distal pancreatectomy with a splenectomy was performed to remove this tumor. A microscopic examination identified the tumor to be situated in the pancreas while it was composed of cells that originated from Schwann cells. Only 26 cases of pancreatic schwannoma have previously been reported in the English and Japanese literature. We describe in detail the characteristic findings based on image analyses, including CT scan, MRI, ultrasonography, and angiography, in these 26 cases.

[Arterial infusion therapy with implantable port for inoperable hepatobiliary tumors].

PURPOSE: To assess the clinical utility of arterial infusion therapy with implantable port for inoperable malignant hepatobiliary tumors. MATERIALS AND METHODS: Twenty-seven patients with advanced hepatobiliary tumors (M:F = 14:13, mean age 63.6, 11 cases with metastases from colon cancer, 4 cases from gastric cancer, 5 cases with gallbladder cancer, 3 cases with cholangiocarcinoma, 2 cases with cholangiocellularcarcinoma, 1 case with hepatocellular carcinoma and 1 with pancreatic cancer) were treated with arterial infusion ports which were placed via left subclavian artery or femoral artery. The regimens used were FEM for 5 cases, EEP for 2 cases and FP for 20 cases. RESULTS: Overall mean survival date was 241.8 days. The numbers of cases with CR, PR, NC and PD were 1, 6, 10 and 10, respectively, and the effective rate was 25.9%. Mean survivals of cases with cholangiocellularcarcinoma, metastases from gastric cancer and colon cancer were 715 days, 324.3 days and 245.9 days, respectively. Severe gastrointestinal side effects (> grade 3) were not observed. Serious bone marrow suppressions were frequently observed with FEM and EEP, but were rare with FP (10%). DISCUSSION: Arterial infusion therapy with implantable port is clinically useful for advanced cholangiocancer and metastases from the gastrointestinal system. This system contributes to the quality of life of patients, since the infusion procedure is simple and can be archived in the outpatient clinics.

HLA-DR antigen expression in squamous epithelial dysplasia and squamous cell carcinoma of the esophagus: an immunohistochemical study.

To clarify the biologic significance of esophageal squamous epithelial dysplasia, especially the similarity to carcinoma in situ, immunohistochemical investigation of HLA-DR antigen expression and lymphocyte infiltration was performed. HLA-DR antigen was expressed in 12 of the 35 invasive carcinomas (34.4%), 23 of the 38 intraepithelial carcinomas (60.5%), 21 of the 50 areas of dysplasia (42.0%) and only 2 of the 625 specimens of non-cancerous squamous epithelium (0.3%). The HLA-DR-positive rate of dysplasia localized continuous to HLA-DR-positive carcinoma was 68.4%, which was significantly higher than that for HLA-DR positive dysplasia localized continuous to HLA-DR negative cancer (11.1%) (p<0.05). In areas of dysplasia and intraepithelial carcinoma, T cell infiltration was significantly increased at the sites of HLA-DR antigen expression (P<0.01). B cell infiltration was also more common in areas of positive expression. These results suggest that HLA-DR antigen is associated with the local immune response to squamous epithelial dysplasia, and that HLA-DR antigen expression may prevent tumor invasion similarly to its role in intraepithelial carcinoma.

Difference in the mechanism of balancing-side disclusion between 1st and 2nd molars.

This study investigates the cusp angle and movement variables related to balancing-side disclusion and compares the characteristics between the 1st and 2nd molar regions. Fifty-six normal young adults were divided into two groups according to balancing-side contact: a disclusion group consisting of 40 subjects (80 excursions), and a non-disclusion group consisting of 16 subjects (20 excursions). Lateral excursions were measured in six-degrees of freedom, and the inclinations of the frontal paths were calculated on the working-side canine, balancing-side 1st and 2nd molars and balancing-side condylar point. The cusp angle was measured using a three-dimensional digitizer. While there were no differences between disclusion and non-disclusion groups in the inclination of the balancing-side condylar path, significant differences were found in the cusp angle and the inclination of the working-side canine path. In the non-disclusion group, the cusp angle of the 2nd molar was markedly greater than that of the 1st molar. It was concluded that the inclination of the anterior guidance and the cusp angle of related teeth have a great effect on the occurrence of balancing-side disclusion and that the mechanism of high frequent balancing-side contacts at the 2nd molar was characterized by its greater cusp angle compared to the 1st molar.