Metallothionein as an Anti-Inflammatory Mediator

The integration of knowledge concerning the regulation of MT, a highly conserved, low molecular weight, cystein-rich metalloprotein, on its proposed functions is necessary to clarify how MT affects cellular processes. MT expression is induced/enhanced in various tissues by a number of physiological mediators. The cellular accumulation of MT depends on the availability of cellular zinc derived from the diet. MT modulates the binding and exchange/transport of heavy metals such as zinc, cadmium, or copper under physiological conditions and cytoprotection from their toxicities, and the release of gaseous mediators such as hydroxyl radicals or nitric oxide. In addition, MT reportedly affects a number of cellular processes, such as gene expression, apoptosis, proliferation, and differentiation. Given the genetic approach, the apparently healthy status of MT-deficient mice argues against an essential biological role for MT; however, this molecule may be critical in cells/tissues/organs in times of stress, since MT expression is also evoked/enhanced by various stresses. In particular, because metallothionein (MT) is induced by inflammatory stress, its roles in inflammation are implied. Also, MT expression in various organs/tissues can be enhanced by inflammatory stimuli, implicating in inflammatory diseases. In this paper, we review the role of MT of various inflammatory conditions

Minimax theorem and Nash equilibrium of symmetric three-players zero-sum game with two strategic variables

We consider a symmetric three-players zero-sum game with two strategic variables. Three players are Players A, B and C. Two strategic variables are ti and si, i = A;B;C. They are related by invertible functions. Using the minimax theorem by Sion (1958) and the fixed point theorem by Glicksberg (1952) we will show that Nash equilibria in the following four states are equivalent. 1. All players, Players A, B and C choose ti; i = A;B;C, (as their strategic variables). 2. Two players choose ti's, and one player chooses si. 3. One player chooses ti, and two players choose si's. 4. All players, Players A, B and C choose si; i = A;B;C

Minimax theorem and Nash equilibrium of symmetric three-players zero-sum game with two strategic variables

We consider a symmetric three-players zero-sum game with two strategic variables. Three players are Players A, B and C. Two strategic variables are ti and si, i = A;B;C. They are related by invertible functions. Using the minimax theorem by Sion (1958) and the fixed point theorem by Glicksberg (1952) we will show that Nash equilibria in the following four states are equivalent. 1. All players, Players A, B and C choose ti; i = A;B;C, (as their strategic variables). 2. Two players choose ti's, and one player chooses si. 3. One player chooses ti, and two players choose si's. 4. All players, Players A, B and C choose si; i = A;B;C

A questionnaire-based comparative study of postoperative quality of life between laryngotracheal separation and tracheoesophageal diversion

Purpose: Whether tracheoesophageal diversion (TED) is preferable to laryngotracheal separation (LTS) is unclear. This study examined the need for tracheoesophageal anastomosis by reviewing complications after TED and LTS and administering a questionnaire on postoperative quality of life.Patients and methods: Medical records of TED/LTS cases performed at a single institution from 2003 to 2015 were retrospectively reviewed and a questionnaire was administered to parents of patients at an outpatient visit.Results: A total of 40 TED and 18 LTS cases were included. Complications occurred in six TED cases and one LTS case, with no significant differences between groups (P=0.42). A total of 22 parents of patients (TED 16 cases; LTS six cases) completed the questionnaire. Voice production was reported in three TED cases and two LTS cases. Patients indicated that suctions were ‘decreased’ in 13 and ‘unchanged’ in two TED cases, but ‘decreased’ in one and ‘unchanged’ in five LTS cases (P=0.0055). Readmissions were ‘increased’ in one and ‘decreased’ in 14 TED cases, but ‘decreased’ in three and ‘unchanged’ in three LTS cases (P=0.015).Conclusion: Postoperative complication rate was equivalent between groups, and the numbers of suctions and readmissions were decreased in the TED group. Therefore, tracheoesophageal anastomosis should be performed more commonly.Keywords: complication, laryngotracheal separation, quality of life questionnaire, tracheoesophageal diversio

Amygdala Response During Anticipatory Anxiety in Patients with Tension-type Headache

Tension-type headache (TTH) is the most prevalent primary headache disorder, affecting 0.5%〜4.8% of the population worldwide. Psychological factors play an important role in the pathogenesis of TTH. For instance, depression and anxiety are thought to enhance central sensitization, and thus increase the frequency of headaches. In this study, we used the Minnesota Multiphasic Personality Inventory (MMPI) and measures of anxiety to analyze personality traits associated with TTH. Specifically, we were interested in the relationship between these variables, respiratory responses, and brain activity. Our results showed that individuals with TTH had significantly higher state anxiety scores compared with healthy controls. In addition, individuals with TTH showed a greater increase in RR during a stressful task involving anticipation of an electrical stimulation. During anticipatory anxiety, there was bilateral amygdala (AMG) activation in TTH patients, while only the right AMG was activated in healthy controls. Interestingly, patients in the TTH group with high levels of state anxiety and high scores on schizophrenia scales had the following MMPI personality traits: peculiar perception, poor familial relationship, difficulties concentrating, and lack of deep interest. We suggest that the psychological factors associated with the above-mentioned brain activation might induce peripheral muscle pressure, which then triggers headaches

High Levels of Copper, Zinc, Iron and Magnesium, but not Calcium, in the Cerebrospinal Fluid of Patients with Fahr's Disease

Patients with marked calcification of the basal ganglia and cerebellum have traditionally been referred to as having Fahr's disease, but the nomenclature has been criticized for including heterogeneous etiology. We describe 3 patients with idiopathic bilateral striatopallidodentate calcinosis (IBSPDC). The patients were a 24-year-old man with mental deterioration, a 57-year-old man with parkinsonism and dementia, and a 76-year-old woman with dementia and mild parkinsonism. The former 2 patients showed severe calcification of the basal ganglia and cerebellum, and the latter patient showed severe calcification of the cerebellum. We found significantly increased levels of copper (Cu), zinc (Zn), iron (Fe) and magnesium (Mg), using inductively coupled plasma mass spectrometry in the CSF of all these 3 patients. The increased levels of Cu, Zn, Fe and Mg reflect the involvement of metabolism of several metals and/or metal-binding proteins during the progression of IBSPDC. More numerous patients with IBSPDC should be examined in other races to clarify the common mechanism of the disease and to investigate the specific treatment

Indispensable roles of OX40L-derived signal and epistatic genetic effect in immune-mediated pathogenesis of spontaneous pulmonary hypertension

<p>Abstract</p> <p>Background</p> <p>Pulmonary hypertension (PH) refers to a spectrum of diseases with elevated pulmonary artery pressure. Pulmonary arterial hypertension (PAH) is a disease category that clinically presents with severe PH and that is histopathologically characterized by the occlusion of pulmonary arterioles, medial muscular hypertrophy, and/or intimal fibrosis. PAH occurs with a secondary as well as a primary onset. Secondary PAH is known to be complicated with immunological disorders. The aim of the present study is to histopathologically and genetically characterize a new animal model of PAH and clarify the role of OX40 ligand in the pathogenesis of PAH.</p> <p>Results</p> <p>Spontaneous onset of PAH was stably identified in mice with immune abnormality because of overexpression of the tumor necrosis factor (TNF) family molecule OX40 ligand (OX40L). Histopathological and physical examinations revealed the onset of PAH-like disorders in the C57BL/6 (B6) strain of OX40L transgenic mice (B6.TgL). Comparative analysis performed using different strains of transgenic mice showed that this onset depends on the presence of OX40L in the B6 genetic background. Genetic analyses demonstrated a susceptibility locus of a B6 allele to this onset on chromosome 5. Immunological analyses revealed that the excessive OX40 signals in TgL mice attenuates expansion of regulatory T cells the B6 genetic background, suggesting an impact of the B6 genetic background on the differentiation of regulatory T cells.</p> <p>Conclusion</p> <p>Present findings suggest a role for the OX40L-derived immune response and epistatic genetic effect in immune-mediated pathogenesis of PAH.</p

Role of the Carboxy-Terminal Region of the GluRε2 Subunit in Synaptic Localization of the NMDA Receptor Channel

AbstractThe synaptic localization of the N-methyl-D-aspartate (NMDA) type glutamate receptor (GluR) channel is a prerequisite for synaptic plasticity in the brain. We generated mutant mice carrying the carboxy-terminal truncated GluRε2 subunit of the NMDA receptor channel. The mutant mice died neonatally and failed to form barrelette structures in the brainstem. The mutation greatly decreased the NMDA receptor–mediated component of hippocampal excitatory postsynaptic potentials and punctate immunofluorescent labelings of GluRε2 protein in the neuropil regions, while GluRε2 protein expression was comparable. Immunostaining of cultured cerebral neurons showed the reduced punctate staining of the truncated GluRε2 protein at synapses. These results suggest that the carboxy-terminal region of the GluRε2 subunit is important for efficient clustering and synaptic localization of the NMDA receptor channel