Study on the Pathogenesis of Foreign Body Granulomatous Inflammation in the Livers of Sprague-Dawley Rats

Focal granulomatous inflammation developed in the livers of five 10-week-old male Sprague-Dawley rats. The characteristic features of this lesion were the presence of foreign body multinucleated giant cells engulfing calcium deposits and site-specific development in a fissure formed in a sub-lobation in the left lobe or interlobar fissure of the medial lobe of the liver. To clarify the pathogenesis of this lesion, rat livers showing abnormal sub-lobation or lobar atrophy, rat livers in an acute dermal toxicity study and guinea pig livers in a skin sensitization test were also examined histologically. Consequently, the present lesion was considered to be a reactive change against calcium that was dystrophically deposited in the area of hepatocellular necrosis due to delayed circulatory disturbance caused by external pressure or extension force. Granulomatous lesions like in the present cases should be differentiated from those caused by evident exogenous pathogens such as chemicals or microorganisms

Interleukin-6 is required for cell cycle arrest and activation of DNA repair enzymes after partial hepatectomy in mice

BACKGROUND: Interleukin-6 (IL-6) has been shown to be vital for liver regeneration, however the specific mechanisms and factors involved remain incompletely defined. The present study aimed to investigate whether IL-6 exerts its protective effects via arresting the cell cycle allowing base excision and repair of oxidized DNA after hepatectomy. RESULTS: Following seventy percent partial hepatectomy (PH) in wild type (WT) mice IL-6 serum levels increased reaching peak levels at 3 hours. This was associated with markers of cell cycle arrest as p21 expression was increased and cyclin D1 and proliferating cell nuclear antigen (PCNA) expression decreased. In the absence of IL-6, markers of cell cycle arrest were absent and the number of bromodeoxyuridine (BrdU) positive cells was significantly higher at 28, 32 and 36 hours after PH. The mRNAs for DNA repair enzymes, including Neil-1, 8-oxodGTPase, OGG1, Apex1, and UDG (DNA glycosylase) were increased 2 to 4 fold in WT mice at 6 and/or 12 hours after PH compared to IL-6 knockout (KO) mice. The protein levels of Neil1 and OGG1 were also significantly increased in WT mice compared to KO mice. Pathological changes were far greater and survival was less in IL-6 KO mice than in WT mice. Administration of IL-6 in KO mice restored p21 and DNA repair enzyme expression to wild-type levels and survival was improved. CONCLUSIONS: IL-6 caused cell cycle arrest and delayed proliferation during the first day after PH. This delay was associated with the activation of DNA repair enzymes resulting in accurate replication and restoration of hepatic mass

Retrospective analysis of definitive radiotherapy for neck node metastasis from unknown primary tumor: Japanese Radiation Oncology Study Group study

Objective: To investigate the optimal treatment method and risk factor of neck node metastasis from unknown primary tumors (NUP) treated by radiotherapy. Methods: Retrospective case study based on a multi-institutional survey was conducted by the Japanese Radiation Oncology Study Group. Patients pathologically diagnosed as having NUP from 1998 to 2007 were identified. Univariate and multivariate analyses of overall survival (OS), progression free survival (PFS), neck progression free survival (NPFS) and mucosal progression free survival (MPFS) were evaluated. Results: In total, 130 patients with median age of 65 years were included. Nodal stages N1, N2a, N2b and N2c were observed for 10, 26, 43, 12 and 39 patients, respectively. All the patients received radiotherapy (RT) with neck dissection in 60 and with chemotherapy in 67 cases. The median doses to the metastatic nodes, prophylactic neck and prophylactic mucosal sites were 60.0, 50.4 and 50.4 Gy, respectively. The median follow-up period for surviving patients was 42 months. Among 12 patients, occult primary tumors in the neck region developed after radiotherapy. The 5-year OS, PFS, NPFS and MPFS were 58.1%, 42.4%, 47.3% and 54.9%, respectively. Univariate analysis showed that lower N stage (N1?2b), non-bulky node (<6 cm) and negative extracapsular extension (ECE) status were the factors associated with favorable OS, PFS, NPFS and MPFS. Radical surgery proved to be a favorable factor of OS, NPFS and MPFS. On multivariate analysis, lower N stage and negative ECE status were correlated with improved survival. Conclusions: Lower nodal stage and negative ECE status showed a favorable impact on survival and disease control in patients with NUP treated by radiotherapy

Influence of temperature on twitch potentiation following submaximal voluntary contractions in human plantar flexor muscles

Abstract This study aimed to clarify the influence of temperature on post‐activation twitch potentiation, a possible indicator of fast‐twitch fiber activation during a preceding voluntary contraction. Ten healthy males immersed their left lower leg in water of different temperatures (cold: 0°C, neutral: 32–35°C, hot: ~43°C) for 20 min each. In each temperature condition, they performed submaximal (10%–50% of maximal voluntary contraction torque measured before water immersion) and maximal plantar flexions. Immediately after each voluntary contraction, twitch contractions were evoked with supramaximal stimulation of the posterior tibial nerve. The magnitude of twitch potentiation, defined as a percent increase in twitch torque following a voluntary contraction, increased with the intensity of the preceding voluntary contraction. The magnitude of twitch potentiation after the maximal voluntary contraction was smaller in Cold than in the other temperature conditions. However, temperature had no influence on the relative magnitude of twitch potentiation following the submaximal contractions. In addition, there was no difference in electromyographic activity between the gastrocnemius and soleus muscles in any temperature conditions. Collectively, the temperature dependence was not observed when using twitch potentiation or electromyographic amplitude as an indicator of fast‐twitch fiber activation during brief submaximal voluntary contractions

Effects of Reduced Carbohydrate Intake after Sprint Exercise on Breath Acetone Level

Assessment of breath acetone level may be an alternative procedure to evaluate change in fat metabolism. The purpose of the present study was to investigate the effect of insufficient carbohydrate (CHO) intake after sprint exercise on breath acetone level during post-exercise. Nine subjects conducted two trials, consisting of either reduced CHO trial (LOW trial) or normal CHO trial (NOR trial). In each trial, subjects visited to laboratory at 7:30 following an overnight fast to assess baseline breath acetone level. They commenced repeated sprint exercise from 17:00. After exercise, isoenergetic meals with different doses of CHO (LOW trial; 18% for CHO, 27% for protein, 55% for fat, NOR trial; 58% for CHO, 14% for protein, 28% for fat) were served. Breath acetone level was also monitored immediately before and after exercise, 1 h, 3 h, 4 h, and 15 h (on the following morning) after completing exercise. A significant higher breath acetone level was observed in LOW trial than in NOR trial 4 h after completion of exercise (NOR trial; 0.66 ppm, LOW trial; 0.9 ppm). However, breath acetone level did not differ on the following morning between two trials. Therefore, CHO intake following an exhaustive exercise affects breath acetone level during early phase of post-exercise

Bach1 Deficiency and Accompanying Overexpression of Heme Oxygenase-1 Do Not Influence Aging or Tumorigenesis in Mice

Oxidative stress contributes to both aging and tumorigenesis. The transcription factor Bach1, a regulator of oxidative stress response, augments oxidative stress by repressing the expression of heme oxygenase-1 (HO-1) gene (Hmox1) and suppresses oxidative stress-induced cellular senescence by restricting the p53 transcriptional activity. Here we investigated the lifelong effects of Bach1 deficiency on mice. Bach1-deficient mice showed longevity similar to wild-type mice. Although HO-1 was upregulated in the cells of Bach1-deficient animals, the levels of ROS in Bach1-deficient HSCs were comparable to those in wild-type cells. Bach1−/−; p53−/− mice succumbed to spontaneous cancers as frequently as p53-deficient mice. Bach1 deficiency significantly altered transcriptome in the liver of the young mice, which surprisingly became similar to that of wild-type mice during the course of aging. The transcriptome adaptation to Bach1 deficiency may reflect how oxidative stress response is tuned upon genetic and environmental perturbations. We concluded that Bach1 deficiency and accompanying overexpression of HO-1 did not influence aging or p53 deficiency-driven tumorigenesis. Our results suggest that it is useful to target Bach1 for acute injury responses without inducing any apparent deteriorative effect

Clinical outcomes of stage I and IIA non-small cell lung cancer patients treated with stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system.

Purpose: To investigate the clinical outcomes of stage I and IIA non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT) using a real-time tumor-tracking radiotherapy (RTRT) system. Materials and methods: Patterns-of-care in SBRT using RTRT for histologically proven, peripherally located, stage I and IIA NSCLC was retrospectively investigated in four institutions by an identical clinical report format. Patterns-of-outcomes was also investigated in the same manner. Results: From September 2000 to April 2012, 283 patients with 286 tumors were identified. The median age was 78 years (52-90) and the maximum tumor diameters were 9 to 65 mm with a median of 24 mm. The calculated biologically effective dose (10) at the isocenter using the linear-quadratic model was from 66 Gy to 126 Gy with a median of 106 Gy. With a median follow-up period of 28 months (range 0-127), the overall survival rate for the entire group, for stage IA, and for stage IB + IIA was 75%, 79%, and 65% at 2 years, and 64%, 70%, and 50% at 3 years, respectively. In the multivariate analysis, the favorable predictive factor was female for overall survival. There were no differences between the clinical outcomes at the four institutions. Grade 2, 3, 4, and 5 radiation pneumonitis was experienced by 29 (10.2%), 9 (3.2%), 0, and 0 patients. The subgroup analyses revealed that compared to margins from gross tumor volume (GTV) to planning target volume (PTV) ≥ 10 mm, margins < 10 mm did not worsen the overall survival and local control rates, while reducing the risk of radiation pneumonitis. Conclusions: This multi-institutional retrospective study showed that the results were consistent with the recent patterns-of-care and patterns-of-outcome analysis of SBRT. A prospective study will be required to evaluate SBRT using a RTRT system with margins from GTV to PTV < 10mm