Comparison of quality of life and psychological distress in patients with tongue cancer undergoing a total/subtotal glossectomy or extended hemiglossectomy and free flap transfer: a prospective evaluation.

The aim of this study was to assess changes in the quality of life and psychological distress of patients with tongue cancer undergoing total/subtotal glossectomy (TG) or extended hemiglossectomy (HG) and free flap transfer. Differences between the two groups were compared using the Short Form 8-Item Health Survey (SF-8) and Hospital Anxiety and Depression Scale (HADS). Of the 43 patients with tongue cancer, 24 (56%) underwent TG and 19 (44%) underwent HG. The general health and social functioning scores in the SF-8 and depression in the HADS were significantly worse in the TG group than in the HG group at 12 months after surgery, indicating that patients in the TG group may experience social isolation and psychological distress, and have difficulty in employability even 12 months after surgery. In contrast, all items of the SF-8 in the HG group were nearly equal to those in the general population. Due to the extensive psychological impact on patients with tongue cancer who are planned for an extended resection, curative surgery with free flap transfer and multidisciplinary psychiatric support are essential to improve quality of life and manage psychological distress.

High-power laser experiment on developing supercritical shock propagating in homogeneously magnetized plasma of ambient gas origin.

A developing supercritical collisionless shock propagating in a homogeneously magnetized plasma of ambient gas origin having higher uniformity than the previous experiments is formed by using high-power laser experiment. The ambient plasma is not contaminated by the plasma produced in the early time after the laser shot. While the observed developing shock does not have stationary downstream structure, it possesses some characteristics of a magnetized supercritical shock, which are supported by a one-dimensional full particle-in-cell simulation taking the effect of finite time of laser-target interaction into account.

Oral medicine psychiatric liaison clinic: study of 1202 patients attending over an 18-year period.

Patients with orofacial pain and discomfort often suffer from psychiatric disorders. However, few studies involving a large sample have examined the diagnostic results of patients with orofacial pain or discomfort in relation to psychiatric disorders. The purpose of this study was to summarize and clarify the characteristics and demographic data of 1202 patients attending the psychiatric liaison clinic at Aichi Gakuin University Hospital. Psychiatric diagnosis was performed by psychiatrists for all patients, based on the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Among the 1202 patients, 992 (82.5%) were female. The average age of the patients was 57.2±15.0years. The predominant broad categories of orofacial pain and discomfort seen were burning mouth syndrome (n=484, 40.3%), persistent idiopathic facial pain (n=258, 21.5%), and oral dysesthesia (n=215, 17.9%). The predominant broad categories of psychiatric diagnoses seen were somatic symptoms and related disorders (n=934, 77.7%) and depressive disorders (n=76, 6.3%). Among the 934 patients with somatic symptoms and related disorders, 678 had a somatic symptom disorder with predominant pain. The results confirmed that most patients with orofacial pain and discomfort were middle-aged and elderly women suffering from a somatic symptom disorder with predominant pain.

Transcriptome Reveals Cathepsin K in Periodontal Ligament Differentiation.

Periodontal ligaments (PDLs) play an important role in remodeling the alveolar bond and cementum. Characterization of the periodontal tissue transcriptome remains incomplete, and an improved understanding of PDL features could aid in developing new regenerative therapies. Here, we aimed to generate and analyze a large human PDL transcriptome. We obtained PDLs from orthodontic treatment patients, isolated the RNA, and used a vector-capping method to make a complementary DNA library from >20,000 clones. Our results revealed that 58% of the sequences were full length. Furthermore, our analysis showed that genes expressed at the highest frequencies included those for collagen type I, collagen type III, and proteases. We also found 5 genes whose expressions have not been previously reported in human PDL. To access which of the highly expressed genes might be important for PDL cell differentiation, we used real-time polymerase chain reaction to measure their expression in differentiating cells. Among the genes tested, the cysteine protease cathepsin K had the highest upregulation, so we measured its relative expression in several tissues, as well as in osteoclasts, which are known to express high levels of cathepsin K. Our results revealed that PDL cells express cathepsin K at similar levels as osteoclasts, which are both expressed at higher levels than those of the other tissues tested. We also measured cathepsin K protein expression and enzyme activity during cell differentiation and found that both increased during this process. Immunocytochemistry experiments revealed that cathepsin K localizes to the interior of lysosomes. Last, we examined the effect of inhibiting cathepsin K during cell differentiation and found that cathepsin K inhibition stimulated calcified nodule formation and increased the levels of collagen type I and osteocalcin gene expression. Based on these results, cathepsin K seems to regulate collagen fiber accumulation during human PDL cell differentiation into hard tissue-forming cells.

The Piccolo Intronic Single Nucleotide Polymorphism rs13438494 Regulates Dopamine and Serotonin Uptake and Shows Associations with Dependence-Like Behavior in Genomic Association Study.

Piccolo (PCLO) inhibits methamphetamine-induced neuropharmacological effects via modulation of dopamine (DA) uptake and regulation of the transport of synaptic vesicles in neuronal cells. Clinical studies have recently suggested that the single nucleotide polymorphism (SNP) rs13438494 in the intron 24 of the PCLO gene is associated with psychiatric disorder, in the meta-analysis of GWAS. Therefore, in this study, we attempted to evaluate the possible role of the PCLO SNP in the mechanisms of uptake of monoamines. To characterize rs13438494 in the PCLO gene, we constructed plasmids carrying either the C or A allele of the SNP and transiently transfected them into SH-SY5Y cells to analyze genetic effects on the splicing of PCLO mRNA. The C and A allele constructs produced different composition of the transcripts, indicating that the intronic SNP does affect the splicing pattern. We also transfected DA and serotonin (5-hydroxytryptamine; 5- HT) transporters into cells and analyzed their uptakes to elucidate the association to psychiatric disorders. In the cells transfected with the C allele, both the DA and 5-HT uptake were enhanced compared to the A allele. We also conducted a clinical study, in order to clarify the genetic associations. PCLO rs13438494 exhibits a relationship with the symptoms of drug dependence or related parameters, such as the age of first exposure to methamphetamine, eating disorders, tobacco dependence and fentanyl requirement. Our findings suggest that rs13438494 is associated with drug abuse and contributes to the pathogenesis of psychiatric disorders via modulation of neurotransmitter turnover.

Genome-wide association study identifies a potent locus associated with human opioid sensitivity.

Opioids, such as morphine and fentanyl, are widely used as effective analgesics for the treatment of acute and chronic pain. In addition, the opioid system has a key role in the rewarding effects of morphine, ethanol, cocaine and various other drugs. Although opioid sensitivity is well known to vary widely among individual subjects, several candidate genetic polymorphisms reported so far are not sufficient for fully understanding the wide range of interindividual differences in human opioid sensitivity. By conducting a multistage genome-wide association study (GWAS) in healthy subjects, we found that genetic polymorphisms within a linkage disequilibrium block that spans 2q33.3-2q34 were strongly associated with the requirements for postoperative opioid analgesics after painful cosmetic surgery. The C allele of the best candidate single-nucleotide polymorphism (SNP), rs2952768, was associated with more analgesic requirements, and consistent results were obtained in patients who underwent abdominal surgery. In addition, carriers of the C allele in this SNP exhibited less vulnerability to severe drug dependence in patients with methamphetamine dependence, alcohol dependence, and eating disorders and a lower 'Reward Dependence' score on a personality questionnaire in healthy subjects. Furthermore, the C/C genotype of this SNP was significantly associated with the elevated expression of a neighboring gene, CREB1. These results show that SNPs in this locus are the most potent genetic factors associated with human opioid sensitivity known to date, affecting both the efficacy of opioid analgesics and liability to severe substance dependence. Our findings provide valuable information for the personalized treatment of pain and drug dependence.

Iron plays a key role in the cytodifferentiation of human periodontal ligament cells.

BACKGROUND AND OBJECTIVE: The periodontal ligament (PDL) is vital to maintaining the homeostasis of the tooth and periodontal tissue. The influence of iron levels on the cytodifferentiation of PDL cells has not been studied, despite evidence that iron overload or deficiency can have adverse effects on alveolar bone density. The purpose of this study was to examine the effects of altered iron levels on cytodifferentiation in human PDL cells. MATERIAL AND METHODS: Human PDL cells were incubated with culture media supplemented with 10-50 µm ammonium ferric citrate or 5 µm deferoxamine (an iron chelator) during differentiation. Intracellular iron status was assessed by measuring changes in the expression of ferritin RNA and protein. PDL cell differentiation and function were evaluated by measuring osteoblast differentiation gene markers and the capacity of cultures to form mineralized nodules. RESULTS: Iron accumulation resulted in upregulation of light and heavy chain ferritin proteins. Concurrently, osteoblast differentiation gene markers and mineralized nodule formation were suppressed. Iron deficiency resulted in downregulation of light and heavy chain ferritin proteins, suppression of alkaline phosphatase activity and formation of mineralized nodules during PDL cell differentiation. CONCLUSION: We conclude that iron is critical for normal cell differentiation of human PDL cells.

Amelogenin enhances the osteogenic differentiation of mesenchymal stem cells derived from bone marrow.

Amelogenins are the major constituent of developing extracellular enamel matrix proteins and are understood to have an exclusively epithelial origin. Recent studies have demonstrated that amelogenins can be detected in other tissues, including bone marrow mesenchymal stem cells (MSCs), but the role of amelogenins in MSCs remains unclear. The purpose of this study was to examine the effect of recombinant human full-length amelogenin (rh174) on the osteogenic differentiation of cultured human MSCs. MSCs isolated from human bone marrow were cultured in osteoblastic differentiation medium with 0, 10 or 100 ng/ml rh174. The mRNA levels of bone markers were examined by real-time PCR analysis. Alkaline phosphatase (ALP) activity and calcium concentration were determined. Mineralization was evaluated by alizarin red staining. The mRNA levels of ALP, type I collagen, osteopontin and bone sialoprotein in the MSCs treated with rh174 became significantly higher than those in non-treated controls. Treatment of MSCs with rh174 also enhanced ALP activity and calcium concentration, resulting in enhanced mineralization, as denoted by high intensity of alizarin red staining. In conclusion, the present study showed that rh174 enhances the mineralization accompanied by the upregulation of bone markers in human bone marrow MSCs during osteogenic differentiation, suggesting a certain role of amelogenin in the modulation of osteogenic differentiation of MSCs.

Reduction of insulin signaling upregulates angiopoietin-like protein 4 through elevated free fatty acids in diabetic mice.

BACKGROUND: Angiopoietin-like protein 4 (Angptl4) is thought to cause an increase in serum triglyceride levels. In the present study, we elucidated Angptl4 expression in the mouse models of type 1 and type 2 diabetes mellitus, and investigated the possible mechanisms involved. METHODS: Type 1 diabetes was induced in C57BL/6 J mice by treating them with streptozotocin (STZ). Type 2 diabetes was induced by feeding the mice a high-fat diet (HFD) for 18 weeks. RESULTS: The levels of Angptl4 mRNA expression in liver, white adipose tissue (WAT), and brown adipose tissue (BAT) were found to increase in the STZ diabetic mice relative to control mice. This effect was attenuated by insulin administration. In the HFD diabetic mice, the Angptl4 mRNA expression levels were increased in liver, WAT, and BAT. Treatment with metformin for 4 weeks attenuated the increased levels of Angptl4 mRNA. Fatty acids (FAs) such as palmitate and linoleate induced Angptl4 mRNA expression in H4IIE hepatoma cells and 3T3-L1 adipocytes. Treatment with insulin but not metformin attenuated FA-induced Angptl4 mRNA expression in H4IIE. Both insulin and metformin did not influence the effect of FAs in 3T3-L1 cells. CONCLUSION: These observations demonstrated that Angptl4 mRNA expression was increased through the elevated free FAs in diabetic mice.

Immunolocalization of ghrelin in the stomach of Sprague-Dawley rat.

To investigate the distribution of ghrelin in different regions of stomach in Sprague-Dawley rat, and attempt to compare with those of humans and other mammalian species in this study, the stomach of rats was divided into five sections, cardia, fundus, greater curvature, lesser curvature and pylorus. Immunohistochemistry and Western blotting were performed to investigate the ghrelin-producing cells. The immunolocalization and protein levels of ghrelin differed significantly in different regions of stomach in rats. It was present at a high level in the greater curvature of the pars glandularis, and the lesser curvature. In the fundus and pylorus, no ghrelin immunoreactive cells were detected. In this study, we elucidated the distribution of ghrelin-producing cells in different regions of rat stomach in detail for the first time. It is further considered that the differences of ghrelin distribution in stomach of different species may induce different stimulatory effects on fat accumulation and metabolism.

Direct density measurement of shock-compressed iron using hard x rays generated by a short laser pulse.

We present the application of short-pulse laser-driven hard x rays (>40 keV) for the direct density measurement of iron compressed by a laser-driven shock. By using an on-shot calibration of the spectral absorption, we are able to obtain line densities with 5%-10% precision, although the x-ray source is not monochromatic. We also discuss possibilities for increasing the precision, which would be an improvement for equation of state measurements.

Association study between casein kinase 1 epsilon gene and methamphetamine dependence.

Casein kinase 1 epsilon (CKIepsilon) is a component of the DARPP-32 in second-messenger pathway. CKIepsilon phosphorylates and activates DARPP-32, a key molecule in various complex signaling pathways, including dopamine and glutamine signaling, which have both been demonstrated to be main pathways in substance dependence. A recent clinical study showed that rs135745, a noncoding single nucleotide polymorphism of the 3'-untranslated region of the CSNK1E gene, was associated with the intensity of the subjective response to an oral amphetamine dose in normal volunteers. Differences in sensitivity to the drug should affect development of dependence to it. Hence, we genotyped rs135745 of the CSNK1E (MIM 600863) gene in 215 patients with methamphetamine dependence and 274 age- and gender-matched normal controls. No significant differences in genotype and allele frequencies were observed between the patients with methamphetamine dependence and controls. There was also no significant association between rs135745 and the clinical characteristics of methamphetamine dependence and co-morbid methamphetamine psychosis (e.g., age of first consumption, latency of psychosis, prognosis of psychosis after therapy, spontaneous relapse of psychotic symptoms, and poly-substance abuse status). The present findings suggest that having a genetic variant of the CSNK1E gene did not affect susceptibility to methamphetamine dependence or psychosis, at least in a Japanese population.

Tranilast inhibits glucose-induced insulin secretion from pancreatic beta-cells.

Tranilast, N-(3,4-demethoxycinnamoyl)-anthranilic acid, is an anti-allergic agent identified as an inhibitor of mast cell degranulation. Recently, tranilast was shown to decrease albuminuria in a rat model of diabetic nephropathy and to ameliorate vascular hypertrophy in diabetic rats, suggesting that it may be clinically useful in the treatment of diabetic complications. However, the effects of tranilast on glucose tolerance have not been elucidated. Thus, the aim of this study is to investigate the effect of tranilast on insulin secretion in pancreatic beta-cells. Treatment with tranilast significantly suppressed insulin secretion in INS-1E cells and rat islets induced by 16.7 mmol/l glucose. Furthermore, tranilast inhibited tolbutamide-induced insulin secretion. Treatment with tranilast increased (86)Rb (+) efflux from COS-1 cells in which pancreatic beta-cell-type ATP-sensitive K (+) (K (ATP)) channels were reconstructed and suppressed the cytosolic ATP/ADP ratio in INS-1E cells. Interestingly, treatment with tranilast enhanced glucose uptake in INS-1E cells. In the present study, we demonstrated that tranilast inhibited glucose- and tolbutamide-induced insulin secretion through the activation of K (ATP) channels in pancreatic beta-cells.

Two adult cases of coronary artery aneurysms secondary to Kawasaki disease.

Kawasaki disease (KD) is an acute, self-limiting vasculitis that occurs in children of all ages, which was first described by Kawasaki in 1967. The fatal complication of KD is coronary artery involvement resulting in coronary artery aneurysms. We report on two adult cases with coronary artery aneurysms secondary to childhood KD who underwent coronary artery bypass grafting (CABG) using multiple arterial grafts. There have been few reports of cardiovascular surgery in adult survivors of KD.

Endovascular stent-graft repair for spontaneous rupture of the nonaneurysmal thoracic aorta in a patient with Takayasu's arteritis.

Takayasu's arteritis is a disease of unknown etiology with a constellation of clinical findings primarily resulting from stenotic lesions on the aorta and its branches. Although aneurysmal degeneration is observed frequently in patients with Takayasu's arteritis, non-aneurysmal spontaneous aortic rupture is extremely rare. We report a case of endovascular stent grafting for spontaneous rupture of a non-aneurysmal thoracic aorta in Takayasu's arteritis.

[Successful administration of nifekalant hydrochloride for postoperative junctional ectopic tachycardia in congenital cardiac surgery].

Two episode of junctional ectopic tachycardia (JET) caused hemodynamic deterioration early after tetralogy of Fallot repair in an 8-month-old infant. Sinus rhythm resumed in each of the episodes immediately after intravenous administration of nifekalant hydrochloride (NIF), a newly developed Vaughan-Williams class III antiarrhythmic drug in Japan. Although QT interval was modestly prolonged with NIF, no life-threatening ventricular arrhythmia (i.e., torsades de pointes) occurred. NIF might be an effective alternative in the treatment of postoperative JET in congenital cardiac surgery.

Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia.

Pituitary adenylate cyclase-activating polypeptide (PACAP, ADCYAP1: adenylate cyclase-activating polypeptide 1), a neuropeptide with neurotransmission modulating activity, is a promising schizophrenia candidate gene. Here, we provide evidence that genetic variants of the genes encoding PACAP and its receptor, PAC1, are associated with schizophrenia. We studied the effects of the associated polymorphism in the PACAP gene on neurobiological traits related to risk for schizophrenia. This allele of the PACAP gene, which is overrepresented in schizophrenia patients, was associated with reduced hippocampal volume and poorer memory performance. Abnormal behaviors in PACAP knockout mice, including elevated locomotor activity and deficits in prepulse inhibition of the startle response, were reversed by treatment with an atypical antipsychotic, risperidone. These convergent data suggest that alterations in PACAP signaling might contribute to the pathogenesis of schizophrenia.

Association study of the tumor necrosis factor-alpha gene and its 1A receptor gene with methamphetamine dependence.

Recent preclinical findings that repeated treatment with methamphetamine (METH) induced an increase in tumor necrosis factor-alpha (TNF-alpha) mRNA in some brain regions and that TNF-alpha blocked METH neurotoxicity and rewarding effects suggest TNF-alpha, a multifunctional pro-inflammatory cytokine, may be involved in METH dependence. We hypothesized that genetic polymorphisms of the TNF-alpha gene and its receptor genes may be associated with vulnerability to METH dependence. Genetic association of -308G>A and -857C>T in the promotor region of the TNF-alpha gene, and 36A>G in exon 1 of the TNF receptor 1A gene (TNFR-SF1A), were analyzed in patients with METH dependence (n = 185) and healthy controls (n = 221) in a Japanese population. No significant association of alleles or haplotypes of the TNF-alpha or TNFR-SF1A genes with METH dependence was found. Neither was any significant association of clinical phenotype with METH dependence found. These results suggest that genetic variations in the TNF-alpha gene and its receptor genes may not be involved in individual vulnerability to METH dependence.

Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-kappaB phosphorylation and nuclear factor-kappaB transcriptional activity through nicotinic acetylcholine receptor alpha7.

Macrophages/monocytes and the proinflammatory mediators, such as tumour necrosis factor (TNF)-alpha, prostaglandin E(2) (PGE(2)), macrophage inflammatory protein (MIP)-1alpha and MIP-1alpha, play a critical role in the progression of immunological disorders including rheumatoid arthritis, Behçet's disease and Crohn's disease. In addition, the nicotinic acetylcholine receptor-alpha7 (alpha7nAChR) subunit is an essential regulator of inflammation. In this study, we evaluated the expression of the alpha7nAChR subunit on human peripheral monocytes and the effect of nicotine on the production of these proinflammatory mediators by activated monocytes. Fluorescein isothiocyanate (FITC)-labelled alpha-bungarotoxin demonstrated the cell surface expression of the alpha7nAchR subunit. Pretreatment with low-dose nicotine caused inhibition of TNF-alpha, PGE(2), MIP-1alpha and MIP-1alpha production, and mRNA expression of TNF-alpha, MIP-1alpha and MIP-1alpha and COX-2 in lipopolysaccharide (LPS)-activated monocytes. These suppressive effects of nicotine were caused at the transcriptional level and were mediated through alpha7nAChR. Nicotine suppressed the phosphorylation of I-kappaB, and then inhibited the transcriptional activity of nuclear factor-kappaB. These immunosuppressive effects of nicotine may contribute to the regulation of some immune diseases.