Lack of association between adolescent idiopathic scoliosis and previously reported single nucleotide polymorphisms in MATN1, MTNR1B,TPH1, and IGF1 in a Japanese population

Adolescent idiopathic scoliosis (AIS) is a spinal deformity most commonly arising in apparently healthy girls around puberty. AIS has a strong genetic predisposition. Several genetic associations between AIS and single nucleotide polymorphisms (SNPs) have been reported; common SNPs in the genes for matrilin 1 (MATN1), melatonin receptor 1B (MTNR1B), tryptophan hydroxylase 1 (TPH1), and insulin‐like growth factor 1 (IGF1) are reported to be associated with AIS in Chinese. However, these associations have not been replicated so far. To confirm the associations, we compared these SNPs with AIS predisposition and curve severity in a population of Japanese females consisting of 798 AIS patients and 1,239 controls. All the subjects were genotyped using the PCR‐based Invader assay. We found no association of any of the SNPs with AIS predisposition or curve severity. Considering the statistical power and sample size of the present study, we concluded that these SNPs are not associated with either AIS predisposition or curve severity in Japanese. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29: 1055–1058, 2011     

The full stomach test as a novel diagnostic technique for identifying patients at risk of Brugada syndrome

INTRODUCTION: Autonomic modulation, particularly high vagal tone, plays an important role in the occurrence of ventricular tachyarrhythmias in the Brugada syndrome. Food intake modulates vagal activity. We assessed the usefulness of a novel diagnostic technique, the "full stomach test," for identifying a high-risk group in patients with a Brugada-type electrocardiogram (ECG). METHODS AND RESULTS: In 35 patients with a Brugada-type ECG, we assessed 12-lead ECGs before and after a large meal, a pilsicainide pharmacological test, spontaneous ST-segment change, late potentials by signal-averaged ECG, microvolt T-wave alternans, and four other ECG parameters. These patients were divided into two groups (i.e., high-risk group [n = 17] and indeterminate risk group [n = 18]). The full stomach test was defined as positive when augmentation of characteristic ECG abnormalities was observed after meals. Thirteen patients had a prior history of life-threatening events such as aborted sudden death and syncope, with a total of 30 episodes. These episodes had a circadian pattern, at night and after meals. The full stomach test was positive in 17 of the study patients (49%). A positive test outcome was characterized by a higher incidence of a history of life-threatening events than a negative test outcome (P = 0.015, odds ratio = 7.1). In comparison between the two groups, the incidence (82%) of positive outcomes in the high-risk group was significantly higher than that (17%) in the indeterminate risk group (P = 0.0002). CONCLUSIONS: Characteristic ECG changes diagnostic of Brugada syndrome are augmented by a large meal. These data are associated with a history of life-threatening events in Brugada syndrome.     

Bone morphogenetic protein 2 induced differentiation toward superficial epithelial cells in the gastric mucosa

Background Epithelial–mesenchymal interactions are important for maintenance of the gastrointestinal tract mucosa. Moreover, diffusible factors from the underlying mesenchyme control the proliferation and differentiation of the epithelial cells. However, the details of the associated signaling remain unknown. Methods Two novel cell lines, designated MSE1 (mouse stomach epithelium) and MSMF1 (mouse stomach myofibroblast) cells, were established from mouse glandular stomach and cocultured in three-dimensional collagen gels in vitro. Results MSE1 cells formed dramatic branching tubular structures upon coculture with MSMF1 cells. In contrast, they formed spherical cyst structures in the absence of fibroblast support or the presence of Swiss 3T3 cells. Since bone morphogenetic protein 2 (BMP2) was expressed by MSMF1 cells but not Swiss 3T3 cells, we investigated whether it induced the morphological differentiation. Addition of BMP2 to MSE1 cells induced the formation of branching tubular structures, even in the absence of MSMF1 cells. Noggin, a BMP2 antagonist, blocked the MSMF1-induced tubular branch formation by MSE1 cells. MSE1 cells were induced to express mRNA of MUC5AC, an important marker for gastric superficial epithelium in the upper part of pits, upon branching tubule formation after BMP2 addition. Coculture with MSMF1 cells or BMP2 addition induced Smad1 phosphorylation in MSE1 cells. Furthermore, BMP2 inhibited MSE1 cell proliferation in MTS assays and suppressed AKT phosphorylation. Conclusions BMP2 stimulated MSE1 cells to form branching duct-like structures and differentiate toward superficial epithelium in three-dimensional cocultures in vitro, suggesting that it may act as a morphogen and differentiation inducer in epithelial–mesenchymal interactions of gastric mucosa.     

Autonomic cardiovascular responses to heme oxygenase inhibition in conscious rats

Carbon monoxide (CO) is produced in the course of heme degradation from biliverdin by heme oxygenase (HO) in various tissues, including the central nervous system. Recent studies suggest the inhibition of HO activity increases arterial pressure mediated by the autonomic nervous system. The present study was designed to investigate the autonomic regulation of cardiovascular responses to inhibition of endogenous CO production by the HO inhibitor Zinc deuteroporphyrin 2, 4-bis glycol (ZnDPBG) by using direct sympathetic nerve recordings in conscious, chronically instrumented rats. ZnDPBG induced increases in mean arterial pressure (MAP) (P<0.05) and renal sympathetic nerve activity (RSNA) (P<0.05) but no significant change in heart rate (P>0.05) in intact rats. In atropine-treated rats, ZnDPBG also induced increases in MAP (P<0.05) and RSNA (P<0.05) but no change in heart rate (P>0.05). In sinoaortic denervated rats, ZnDPBG induced increases in MAP (P<0.05), heart rate (P<0.05), and RSNA (P<0.05). ZnDPBG shifted the baroreflex curve for RSNA upward and to the right, which was characterized by increases in the maximum and minimum response and midpoint pressure without altering the maximum gain. These results indicate that inhibition of HO activity within the central nervous system causes sympathoexcitation, resulting in an increase in arterial pressure. We conclude that the CO/HO system plays an important role in cardiovascular regulation by modulating sympathetic tone.     

Operative treatment of bilateral hip dislocations in a child with metatropic dysplasia

We present a case of bilateral hip dislocations with metatropic dysplasia. Radiographic features such as narrow thorax, dense wafer vertebral bodies, narrowing interpedicular distances, kyphoscoliosis, crescent-shaped iliac wings, dumbbell-shaped tubular bones, and inferiorly directing lesser trochanter conform to the findings of metatropic dysplasia. Hip dislocations were misdiagnosed by ultrasonographic and radiographic hip screening, owing to the severely deformed femoral heads and acetabulums. The diagnosis of hip dislocations became possible by magnetic resonance imaging. The bilateral hip dislocation was reduced by open reduction of the hip joints and femoral derotation varus osteotomies.     

Operative reconstruction of the severe sequelae of infantile septic arthritis of the hip

We retrospectively reviewed the results of operative reconstruction of 21 hips in 21 patients with severe sequelae due to infantile septic arthritis of the hip. Eleven hips were classified as Choi type IIIA, 4 as type IIIB, 1 as type IVA, and 5 as type IVB sequelae. The average age at the time of the first surgery was 4.2 years, and the average follow-up period was 8.9 years. Successful results were obtained in 8 of the 11 type IIIA hips by means of a combination of open reduction, femoral varus osteotomy, and pelvic osteotomy. However, only 2 of the 4 type IIIB hips treated by femoral valgus osteotomy and/or bone grafting and 2 of the 6 types IVA and IVB hips treated by greater trochanter arthroplasty had successful results.     

Cellular effects of manufactured nanoparticles: effect of adsorption ability of nanoparticles

Nanoparticles are important industrial materials. However, many nanoparticles show biological effects, including toxic activity. Metal ion release is the most important factor affecting the biological effects of nanoparticles. In addition, nanoparticles have large adsorption ability. The adsorption ability, in particular protein adsorption to nanoparticles, has an effect on cellular uptake and cellular metabolisms. Moreover, the adsorption ability of nanoparticles causes artificial effects in in vitro systems. Consequently, accurate determination of released or secreted proteins such as lactate dehydrogenase and cytokines adsorbed to nanoparticles is affected. In addition, artificial effects cause overestimation or underestimation of the cytotoxicity of nanoparticles. Therefore, measurement of the protein adsorption of nanoparticles is important. Some methods for the determination of the adsorption to nanoparticles have been suggested. The flow field-flow fractionation method is one of the efficient techniques for determining proteins on the surface of nanoparticles. The cellular effects caused by nanoparticles should be carefully considered.     

Chromium(III) oxide nanoparticles induced remarkable oxidative stress and apoptosis on culture cells

Chromium(III) oxide (Cr₂O₃) is used for industrial applications such as catalysts and pigments. In the classical form, namely the fine particle, Cr₂O₃ is insoluble and chemically stable. It is classified as a low‐toxicity chromium compound. Recently, industrial application of nanoparticles (a new form composed of small particles with a diameter of ≤100 nm, in at least one dimension) has been increasing. Cellular effects induced by Cr₂O₃ nanoparticles are not known. To shed light upon this, the release of soluble chromium from Cr₂O₃ nano‐ and fine‐particles in culture medium was compared. Fine Cr₂O₃ particles were insoluble in the culture medium; on the contrary, Cr₂O₃ nanoparticles released soluble hexavalent chromium into the culture medium. Cr₂O₃ nanoparticles showed severe cytotoxicity. The effect of Cr₂O₃ nanoparticles on cell viability was higher than that of fine particles. Cr₂O₃ nanoparticles showed cytotoxicity equal to that of hexavalent chromium (K₂Cr₂O₇). Human lung carcinoma A549 cells and human keratinocyte HaCaT cells showed an increase in intracellular reactive oxygen species (ROS) level and activation of antioxidant defense systems on exposure to Cr₂O₃ nanoparticles. Exposure of Cr₂O₃ nanoparticles led to caspase‐3 activation, showing that the decrease in cell viability by exposure to Cr₂O₃ nanoparticles was caused by apoptosis. Cellular responses were stronger in the Cr₂O₃ nanoparticles‐exposed cells than in fine Cr₂O₃‐ and CrCl₃‐exposed cells. Cellular uptake of Cr₂O₃ particles were observed in nano‐ and fine‐particles. The cellular influence of the extracellular soluble trivalent chromium was lower than that of Cr₂O₃ nanoparticles. Cr₂O₃ nanoparticles showed cytotoxicity by hexavalent chromium released at outside and inside of cells. The cellular influences of Cr₂O₃ nanoparticles matched those of hexavalent chromium. In conclusion, Cr₂O₃ nanoparticles have a high cytotoxic potential. © 2011 Wiley Periodicals, Inc. Environ Toxicol 2013.