The Yeast Tor Signaling Pathway Is Involved in G2/M Transition via Polo-Kinase

The target of rapamycin (Tor) protein plays central roles in cell growth. Rapamycin inhibits cell growth and promotes cell cycle arrest at G1 (G0). However, little is known about whether Tor is involved in other stages of the cell division cycle. Here we report that the rapamycin-sensitive Tor complex 1 (TORC1) is involved in G2/M transition in S. cerevisiae. Strains carrying a temperature-sensitive allele of KOG1 (kog1-105) encoding an essential component of TORC1, as well as yeast cell treated with rapamycin show mitotic delay with prolonged G2. Overexpression of Cdc5, the yeast polo-like kinase, rescues the growth defect of kog1-105, and in turn, Cdc5 activity is attenuated in kog1-105 cells. The TORC1-Type2A phosphatase pathway mediates nucleocytoplasmic transport of Cdc5, which is prerequisite for its proper localization and function. The C-terminal polo-box domain of Cdc5 has an inhibitory role in nuclear translocation. Taken together, our results indicate a novel function of Tor in the regulation of cell cycle and proliferation

Relationship Between the Severity of Oral and Maxillofacial Injuries and Helmet Use by Type in Motorcycle Accidents

Helmets are known to be effective in reducing the severity of head injuries in motorcycle accidents. Although, to our knowledge, few reports have examined the relationship between the severity of oral and maxillofacial injuries and helmet use by type in motorcycle accidents. We retrospectively analyzed 54 patients with oral and maxillofacial injuries from motorcycle accidents and attempted to clarify the relationship between injury severity and the protective effects of a helmet. We studied 40 men and 14 women with a mean age of 26.1±15.0 years (range, 15 to 79 years) who sustained oral and maxillofacial injuries in motorcycle accidents treated in Dokkyo University Hospital from 1994 through 2003. In each case, we examined the mechanism of injury, type of helmet the injury severity score, the 1990 revision of the Abbreviated Injury Scale (AIS-90) score, and the length of hospitalization. Of these 54 patients, 47 patients wore a helmet. Of these 47 patients, 8 (14.8%) wore a full-face type of helmet and 39 (72.2%) wore an open-face type of helmet. The injury severity scores and the Abbreviated Iniurv Scale scores for head and neck were not significantly different by helmet use or type of helmet. However, the AIS-90 scores for facial injuries were significantly decreased with helmet use. The scores for facial injuries in the patients who wore the full-face type of helmets (1.4±0.5) were significantly lower than those in the patients who wore the open-face type of helmets (1.8 ±0.4, p<0.05) and in patients without helmets (1.9±0.4, p<0.05). Wearing a helmet effectively prevented oral and maxillofacial injuries; although, it could not fully prevent all oral and maxillofacial injuries in motorcyclists. These injuries may have been caused by indirect forces transmitted through the helmet

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

コウクウ ヘンペイ ジョウヒ ガン ノ シツジュン ヨウシキ ニ タイスル サンジゲンテキ カイセキ

口腔扁平上皮癌において浸潤様式が治療成績に関連することは,これまでにも多数報告されているが,すべての症例で浸潤様式と治療成績が相関するとは限らず検討課題の一つとなっている.そこで,口腔扁平上皮癌23例を対象に,その連続標本の三次元画像をコンピュータグラフィクスにより再構築し,腫瘍の浸潤様式を検討するとともに,治療成績との関係ならびに従来より用いられている二次元解析法の山本・小浜分類(以下Y・K分類)との関係について比較検討した.三次元的解析による浸潤様式を形態的特徴から,連続型と非連続型の二つに大別し,さらに連続型は圧迫型と索状型の二つに分類した.腫瘍制御,非制御別では,非連続型は連続型に比較し有意に不良で,また,それらとY・K分類との関係では,比較的予後が良好とされるY・K分類2型でも非連続型の場合には制御不良であったのに対し,予後が不良とされる4C,4D型では連続型の場合には制御良好であった.三次元解析法では腫瘍の浸潤様式を立体的に再現できること,連続型と非連続型の2つに大別されるため判定が容易であること,さらに治療成績と有意に関連することなどから臨床において有用な方法と思われた.It has been described in many previous reports that mode of invasion is associated with prognosis in oral squamous cell carcinoma (OSCC). However, there is not necessarily correlation between mode of invasion and prognosis clinically. Although we have evaluated the grade for mode of invasion in OSCC by two-dimensional view from H-E section, in this study, we tried three-dimensional analysis for mode of invasion in OSCC. We performed three-dimensional reconstruction of mode of invasion in OSCC by computer graphics, and compared with that of two-dimensional evaluation and examined the relationship between three-dimensional analysis and prognosis. Mode of invasion in OSCC was classified into two types by three-dimensional analysis as follows; 1) continuous type, and 2) discontinuous type. Furthermore, continuous type was subclassified into a) solid type, and b) cord type. The cases of continuous type were recognized in all grade type of mode of invasion according to Yamamoto and Kohama classification, but the cases of discontinuous type were recognized in only 2, 4C, and 4D grade types. In continuous type, thirteen out of fifteen cases (86.7%) were controlled, where in discontinuous type only 4 out of 8 cases (50.0%) were controlled. The control rate of local recurrence in the patients with discontinuous type was significantly lower than that with the continuous type (p=0.0429). We suggest that three-dimensional analysis is useful clinically, because we could judge mode of invasion easily and reconstruct whole structure of OSCC more exactly, and furthermore, this analysis is associated with prognosis of OSCC