Multi-institutional feasibility study of intensity-modulated radiotherapy with chemotherapy for locally advanced non-small cell lung cancer

International Journal of Clinical Oncology - This multi-institutional clinical trial evaluated the feasibility of intensity-modulated radiotherapy (IMRT) for patients with locally advanced...     

Teeth contacting habit as a contributing factor to chronic pain in patients with temporomandibular disorders

Many different factors are known to cause and perpetuate the symptoms of temporomandibular disorders (TMD). However, the roles of parafunctional factors have not been clearly elucidated. We found one of these habits in the clinical setting. This parafunctional habit involves daily light touching of the upper and lower teeth, when the mouth is closed. We named this habit Teeth Contacting Habit (TCH). [OBJECTIVES] To investigate the following hypotheses: 1) TCH is associated with perpetuation of chronic pain of TMD patients; 2) TCH is associated with other behavioral factors. [METHODS] Two hundred and twenty-nine TMD outpatients with chronic pain were analyzed with multivariate logistic regression models. [RESULTS] TCH was found in 52.4% of patients. Patients with TCH and pain lasting for more than four months were less likely to experience improvements in pain at the first visit (OR = 1.944, p = 0.043). Other factors associated with TCH were as follows: unilateral chewing (OR = 2.802) and involvement in a precision job (OR = 2.195). [CONCLUSION] TCH can prolong TMD pain and is associated with other behavioral factors.     

A figurative proverb test for dementia: rapid detection of disinhibition,excuse and confabulation,causing discommunication

Background: Communicative disability is regarded as a prominent symptom of demented patients, and many studies have been devoted to analyze deficits of lexical‐semantic operations in demented patients. However, it is often observed that even patients with preserved lexical‐semantic skills might fail in interactive social communication. Whereas social interaction requires pragmatic language skills, pragmatic language competencies in demented subjects have not been well understood. We propose here a brief stress‐free test to detect pragmatic language deficits, focusing on non‐literal understanding of figurative expression. We hypothesized that suppression of the literal interpretation was required for figurative language interpretation. Methods: We examined 69 demented subjects, 13 subjects with mild cognitive impairment and 61 healthy controls aged 65 years or more. The subjects were asked the meaning of a familiar proverb categorized as a figurative expression. The answers were analyzed based on five factors, and scored from 0 to 5. To consider the influence of cognitive inhibition on proverb comprehension, the scores of the Stroop Colour–Word Test were compared concerning correct and incorrect answers for each factor, respectively. Furthermore, the characteristics of answers were considered in the light of excuse and confabulation qualitatively. Results: The proverb comprehension scores gradually decreased significantly as dementia progressed. The literal interpretation of the proverb, which showed difficulties in figurative language comprehension, was related to disinhibition. The qualitative analysis showed that excuse and confabulation increased as the dementia stage progressed. Conclusions: Deficits in cognitive inhibition partly explains the difficulties in interactive social communication in dementia. With qualitative analysis, asking the meaning of a proverb can be a brief test applied in a clinical setting to evaluate the stage of dementia, and to illustrate disinhibition, confabulation and excuse, which might cause discommunication and psychosocial maladjustment in demented patients.     

Elevated circulating levels of tumor necrosis factor in patients with mitral valve disease and ventricular septum defect

Summary Elevated levels of circulating tumor necrosis factor (TNF)-α have been reported in patients with decreased left ventricular ejection fraction. Also, TNF has been reported to depress myocardial contractility. In our previous study, no correlation was found between the plasma level of TNF and clinical parameters in patients with cardiomyopathy. In the present study, we detected elevated levels of circulating TNF-α in 5 out of 15 patients with mitral valve disease and in 1 patient with ventricular septal defect whose left ventricular ejection fraction was within the normal range. The levels of TNF-α were not correlated with any hemodynamic parameters. Further studies are necessary to clarify the mechanisms of the regulation and effects of TNF-α in patients with chronic heart failure.     

Presenilin 1 associates with glycogen synthase kinase-3β and its substrate tau

Families bearing mutations in the presenilin 1 (PS1) gene develop Alzheimer’s disease. Previous studies have shown that the Alzheimer-associated mutations in PS1 increase production of amyloid β protein (Aβ_1–42). We now show that PS1 also regulates phosphorylation of the microtubule-associated protein tau. PS1 directly binds tau and a tau kinase, glycogen synthase kinase 3β (GSK-3β). Deletion studies show that both tau and GSK-3β bind to the same region of PS1, residues 250–298, whereas the binding domain on tau is the microtubule-binding repeat region. The ability of PS1 to bring tau and GSK-3β into close proximity suggests that PS1 may regulate the interaction of tau with GSK-3β. Mutations in PS1 that cause Alzheimer’s disease increase the ability of PS1 to bind GSK-3β and, correspondingly, increase its tau-directed kinase activity. We propose that the increased association of GSK-3β with mutant PS1 leads to increased phosphorylation of tau.     

Effect of the free radical scavenger edaravone on peripheral nerve ischemia–reperfusion injury

We investigated the effects of edaravone, a free radical scavenger, on peripheral nerve ischemia–reperfusion injury caused by ligation of vessels supplying the sciatic and tibial nerves in rats. The control group was administered a placebo, the standard‐dose group was given 3 mg/kg of edaravone intraperitoneally every 24 hours, and the low‐dose group was given 1 mg/kg of edaravone. At 7 days after reperfusion, neurological and electrophysiological parameters were improved in the standard‐dose group as compared with the control group. After 14 days, however, these differences were no longer observed. After 21 days, persistent edema and nerve fiber degeneration were noted in the standard‐dose group, but not in the control or low‐dose groups. Edaravone was effective during the early reperfusion period, but chronic inhibition of reactive oxygen species may be detrimental for nerve regeneration after ischemia–reperfusion injury. Further studies are necessary to confirm the long‐term influence of edaravone. Muscle Nerve, 2009     

Expression of sphingosine kinase 2 in synovial fibroblasts of rheumatoid arthritis contributing to apoptosis by a sphingosine analogue, FTY720

Gene expression profiles in synovial tissues from rheumatoid arthritis (RA) patients have yielded useful information on the pathogenetic process of the synovitis. In one group of them, sphingosine kinase 2 (SPHK2), a nuclear protein regulating cell proliferation, seemed to be highly expressed, undergoing a different pathogenetic process of synovitis. In the present study it was clarified that SPHK2 was expressed in the synovial fibroblasts of the synovial tissues obtained from the knee joints of the RA patients. In the cultured synovial fibroblasts from these patients, SPHK2 was more highly expressed than that in the human macrophage cell line, THP-1 and human dermal fibroblasts. SPHK2 was expressed in and around the nucleus and transferred to the cytoplasm and cell surface by the administration of epidermal growth factor, associated with the increased expression of sphingosine-1-phosphate. A sphingosine analogue, FTY720, which is activated by phosphorylation specifically by SPHK2, mediated apoptotic signaling of the cultured synovial fibroblasts. These findings suggest that SPHK2 may regulate the autonomous proliferation of synovial fibroblasts as one of the predisposing genes to RA and could be a target for a novel therapeutic strategy for RA.