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.

Intratumoural immune cell landscape in germinoma reveals multipotent lineages and exhibits prognostic significance.

AIMS: Alterations in microenvironments are a hallmark of cancer, and these alterations in germinomas are of particular significance. Germinoma, the most common subtype of central nervous system germ cell tumours, often exhibits massive immune cell infiltration intermingled with tumour cells. The role of these immune cells in germinoma, however, remains unknown. METHODS: We investigated the cellular constituents of immune microenvironments and their clinical impacts on prognosis in 100 germinoma cases. RESULTS: Patients with germinomas lower in tumour cell content (i.e. higher immune cell infiltration) had a significantly longer progression-free survival time than those with higher tumour cell contents (P = 0.03). Transcriptome analyses and RNA in-situ hybridization indicated that infiltrating immune cells comprised a wide variety of cell types, including lymphocytes and myelocyte-lineage cells. High expression of CD4 was significantly associated with good prognosis, whereas elevated nitric oxide synthase 2 was associated with poor prognosis. PD1 (PDCD1) was expressed by immune cells present in most germinomas (93.8%), and PD-L1 (CD274) expression was found in tumour cells in the majority of germinomas examined (73.5%). CONCLUSIONS: The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.

Survival outcomes after surgical resection of pulmonary metastases of head and neck tumours.

BACKGROUND: There is limited information available regarding the benefits and outcomes of resection of pulmonary metastases arising from head and neck cancers. METHODS: A retrospective review was performed of 21 patients who underwent resection of pulmonary metastases of primary head and neck malignancies at Hamamatsu University Hospital. Clinical staging, treatment methods, pathological subtype (particularly squamous cell carcinoma), disease-free interval and overall survival were evaluated. RESULTS: The 5- and 10-year overall survival rates of the study participants were 67.0 per cent and 55.0 per cent, respectively, as determined by the Kaplan-Meier method. The prognosis for patients with a disease-free interval of less than 24 months was poor compared to those with a disease-free interval of greater than 24 months (p = 0.0234). CONCLUSION: Patients with short disease-free intervals, and possibly those who are older than 60 years, should be categorised as having severe disease. However, pulmonary metastases from head and neck malignancies are potentially curable by surgical resection.

Relationship between the Peripheral Lymphocyte Response to Mycophenolic Acid in vitro and the Level of ATP in Peripheral CD4+ Lymphocytes before and after Renal Transplantation.

OBJECTIVE: The lymphocyte immunosuppressant sensitivity test has been used to predict the pharmacodynamics of immunosuppressive drugs for the purpose of preventing acute rejection and infection after renal transplantation. On the other hand, measuring the ATP levels in peripheral CD4+ lymphocytes is also able to monitor the risks of rejection and infection in transplant recipients. In the present study, we examined the relationship between the mycophenolic acid pharmacodynamics and the ATP levels in peripheral lymphocytes before and after renal transplantation. METHODS: We examined both the pharmacological efficacy of mycophenolic acid and the lymphocyte ATP levels before and 2, 4 and 6 weeks after the operation in 20 renal transplant recipients. The drug's pharmacological efficacy was evaluated by the 50% inhibitory concentration of the drug against the in vitro proliferation of peripheral blood lymphocytes activated by T cell mitogen. The ATP levels in peripheral CD4+ lymphocytes were measured by the Immuknow assay kit. The relationships between the mycophenolic acid pharmacodynamics and ATP levels in peripheral lymphocytes were examined in these recipients. RESULTS: The immunosuppressive effects of mycophenolic acid against mitogen-activated lymphocyte proliferation were significantly and positively correlated with the lymphocyte ATP levels, but only at 6 weeks after transplantation. The relationship was not significant before or at 2 or 4 weeks after the operation. CONCLUSION: Our present data raised the possibility that evaluating the pharmacological efficacy of mycophenolic acid pre-transplantation and monitoring the ATP level 6 weeks after transplantation can predict the risk of rejection and/or infection in renal transplant recipients.

Negative regulation of NaF-induced apoptosis by Bad-CAII complex.

Fluoride is used to prevent caries in dentistry. However, its mechanism of cytotoxicity induction is unclear. This study was undertaken to determine whether sodium fluoride (NaF) induces apoptosis in human oral cells and if so, whether Bad protein is involved in the process. NaF showed higher cytotoxicity and apoptosis-inducing activity against human oral squamous cell carcinoma cells (HSC-2) than against human gingival fibroblasts (HGF). Western blot analysis showed that NaF enhanced the expression and dephosphorylation of Bad protein. This study demonstrates for the first time that Bad protein forms a complex with carbonic anhydrase II (CAII), and NaF stimulates the detachment of CAII from the Bad-CAII complex and the replacement by the formation of Bad-Bcl-2 complex. Knockdown of Bad and CAII mRNA by siRNA inhibited and enhanced the NaF-induced caspase activation, respectively. The present study suggests that CAII negatively regulates the NaF-induced apoptosis by forming a complex with Bad.

Over-expression of the LTC4 synthase gene in mice reproduces human aspirin-induced asthma.

BACKGROUND: The pathogenesis of aspirin-induced asthma (AIA) is presumed to involve the aspirin/non-steroidal anti-inflammatory drug (NSAID)-induced abnormal metabolism of arachidonic acid, resulting in an increase in 5-lipoxygenase (5-LO) metabolites, particularly leukotriene C(4) (LTC(4) ). However, the role of LTC(4) in the development of AIA has yet to be conclusively demonstrated. OBJECTIVE: The aim of this study was to evaluate the contribution of the lipid product LTC(4) secreted by the 5-LO pathway to the pathogenesis of AIA. METHODS: To evaluate antigen-induced airway inflammation, the concentrations of T-helper type 2 cytokine in bronchoalveolar lavage fluid (BALF) obtained from LTC(4) synthase-transgenic (Tg) and wild-type (WT) mice after challenge with ovalbumin were measured. Subsequently, the ex vivo and in vivo effects of the NSAID sulpyrine were investigated in these Tg and WT mice by measuring the secretion of LTC(4) from sulpyrine-treated BAL cells and the levels of LTC(4) in BALF following challenge with sulpyrine. Finally, the sulpyrine-induced airway response by the administration of pranlukast, an antagonist of the cysteinyl (cs)-LT1 receptor, was analysed. RESULTS: The concentrations of IL-4, -5, and -13 in BALF from Tg mice were significantly higher than those in WT mice. In addition, sulpyrine augmented the secretion of LTC(4) in BALF and by BAL cells in Tg mice, but not in WT mice. Additionally, the increased airway resistance induced by sulpyrine could be reduced by treatment with pranlukast. Furthermore, the secretion of LTC(4) from mast cells, eosinophils, and macrophages was increased in the allergen-stimulated LTC(4) synthase gene Tg mice, even in the absence of sulpyrine, as well as in BAL cells after sulpyrine. CONCLUSION AND CLINICAL RELEVANCE: The over-expression of the LTC(4) synthase in a mouse asthma model also replicates the key features of AIA. And our study supports that cys-LTs play a major role in the pathogenesis of AIA in patients with chronic asthma.

Exposure to aflatoxins in Japan: risk assessment for aflatoxin B1.

The intake of total aflatoxins (AFT) and aflatoxin B(1) (AFB(1)) from food in Japan was estimated from AFT and AFB(1) concentration and frequency data in 24 foods (884 samples) from a 3-year retail market survey from the summer of 2004 to the winter of 2006, and by food consumption data from the National Health and Nutrition Survey performed in 2005. The AFT and AFB(1) survey revealed that peanut, peanut products, cocoa, chocolate, pistachio, white pepper, red pepper, almond, job's tears, buckwheat and corn grits are considered to be contributors of AFT (or AFB(1)) intake in Japan (maximum AFB(1) (AFT) levels ranged from 0.21 to 28.0 microg kg(-1) (from 0.21 to 9.0 microg kg(-1))) in AFT-contaminated food. A probabilistic approach using the Monte Carlo method was carried out to simulate an estimate of the AFT (or AFB(1)) intake distributions in each age group in Japan. In this study, AFB(1) intake ranged from 0.003 to 0.004 ng kg(-1) body weight day(-1) (from lower to upper limits), and the potential risk for cancer using a formula devised by the Joint Food and Agricultural Organization/World Health Organization (FAO/WHO) Expert Committee on Food Additives (JECFA) was estimated at 0.00004-0.00005 person/year/100,000 persons, even though this was in the higher levels (95.0th percentile) of the consumer population. The results suggest that the current dietary intake of AFB(1) in Japan has no appreciable effect on health.

Combining the EndoFlex tube with fiberoptic bronchoscopy in difficult intubation.

We applied a combination technique using the EndoFlex tube with fiberoptic bronchoscopy for a 69-year-old man presenting with limited mouth opening and neck movement. Awake nasotracheal intubation was performed under conscious sedation with propofol and fentanyl. After positioning the tip of the EndoFlex tube in the oropharynx, the fiberoptic bronchoscope was inserted into the tube until the tip reached the bevel of the tube. Anterior flexion of the distal tip of the EndoFlex tube facilitated uncomplicated insertion of the tube into the trachea without impingement on the arytenoids. Fiberoptic visualization confirmed that the distal-tip flexing mechanism of the EndoFlex tube corrected the direction of the tube tip anteriorly, allowing entry into the trachea. We present a case where this technique proved valuable for tracheal intubation in a patient with limitations of mouth opening and neck movement.

Postoperative refraction changes in phacoemulsification cataract surgery with implantation of different types of intraocular lens.

PURPOSE: To examine postoperative refraction changes following phacoemulsification cataract surgery and to assess their influential factors, including intraocular lens (IOL) materials and anterior chamber depth (ACD) of the implanted IOL. METHODS: In this prospective study, 339 eyes were randomly assigned to receive a rigid polymethylmethacrylate (PMMA) IOL (811C or 824C), an acrylic IOL (MA60BM), or a silicone IOL (AQ110NV). All patients were followed for 48 weeks after surgery. Postoperative spherical equivalent refraction and ACD were measured by a refractometer and by an anterior eye segment image analyzer, respectively. RESULTS: In the silicone IOL group, statistically significant myopic shift was observed at 8 weeks after the surgery and continued throughout the follow-up period. Mean myopic shift at the end (48 weeks) was -0.53 D. Concomitantly shortened ACD was also confirmed at 12 weeks after the surgery. In the other groups, postoperative refraction and IOL position did not change after surgery. CONCLUSIONS: The eyes with silicone IOL caused postoperative myopic shift due to the anterior IOL movement. It is important to be aware of the characteristics of each IOL and to take myopic shift into consideration when silicone IOL is implanted. Preferably the A-constant for silicone IOL should be reconsidered to obtain rather accurate postoperative refraction.

Atypical teratoid/rhabdoid tumour in sella turcica in an adult.

Although atypical teratoid rhabdoid tumours preferentially arise in the posterior fossa of infants, we encountered a 56 year old woman with an atypical teratoid rhabdoid tumour located in the sella. She presented with right abducent and oculomotor nerve paresis. Magnetic resonance imaging demonstrated an intrasellar tumour impinging on the right cavernous sinus. Microscopically, the tumour was composed of cells with rhabdoid features; we observed atypia, eccentric nuclei, and intracytoplasmic inclusion bodies. The Ki-67 labeling index was around 30%. The tumour cells were positive for vimentin, epithelial membrane antigen, and neurofilament, but negative for INI1. Despite extended local brain and whole-spine irradiation she died of neural axis dissemination.

Centrosome amplification induced by survivin suppression enhances both chromosome instability and radiosensitivity in glioma cells.

Glioblastoma is characterised by invasive growth and a high degree of radioresistance. Survivin, a regulator of chromosome segregation, is highly expressed and known to induce radioresistance in human gliomas. In this study, we examined the effect of survivin suppression on radiosensitivity in malignant glioma cells, while focusing on centrosome aberration and chromosome instability (CIN). We suppressed survivin by small interfering RNA transfection, and examined the radiosensitivity using a clonogenic assay and a trypan blue exclusion assay in U251MG (p53 mutant) and D54MG (p53 wild type) cells. To assess the CIN status, we determined the number of centrosomes using an immunofluorescence analysis, and the centromeric copy number by fluorescence in situ hybridisation. As a result, the radiosensitisation differed regarding the p53 status as U251MG cells quickly developed extreme centrosome amplification (=CIN) and enhanced the radiosensitivity, while centrosome amplification and radiosensitivity increased more gradually in D54MG cells. TUNEL assay showed that survivin inhibition did not lead to apoptosis after irradiation. This cell death was accompanied by an increased degree of aneuploidy, suggesting mitotic cell death. Therefore, survivin inhibition may be an attractive therapeutic target to overcome the radioresistance while, in addition, proper attention to CIN (centrosome number) is considered important for improving radiosensitivity in human glioma.

Pleomorphic xanthoastrocytoma: a comparative pathological study between conventional and anaplastic types.

AIMS: To facilitate the understanding and correct diagnosis of the anaplastic variant of pleomorphic xanthoastrocytoma (PXA). METHODS AND RESULTS: Twelve cases of PXA were divided into six conventional and six anaplastic types. Three anaplastic PXAs developed in recurrent tumours and three occurred as the primary tumour. Anaplastic PXAs were microscopically characterized by monotonous proliferation of atypical cells, increased mitotic activity, necrosis and microvascular proliferation. Characteristic features of conventional PXA are also variously included in all anaplastic PXAs. No remarkable differences were detected in the immunohistochemical profiles including the neuronal phenotype between the conventional and anaplastic types. Ki67 labelling indices of the anaplastic type were significantly higher than those of the conventional type, whereas p53 showed no difference. Immunohistochemical and fluorescence in situ hybridization analyses on epidermal growth factor receptor did not demonstrate overexpression or gene amplification. CONCLUSIONS: The anaplastic PXA, which occurs de novo or through recurrence, should be distinguished from glioblastoma by identifying the salient microscopic features of conventional PXA even in the anaplastic areas; and by demonstrating the expression of neuronal markers, in that the former is expected to have longer survival.

MR findings of pseudoneoplastic lesions in the uterine cervix mimicking adenoma malignum.

Pseudoneoplastic glandular lesions are benign lesions that are often histologically and radiographically confused with adenoma malignum, which is a rare variant of mucinous adenocarcinoma of the uterine cervix. 15 cases of pseudoneoplastic glandular lesions, characterized by multilocular cystic masses in the uterine cervix, were investigated; these lesions included endocervical glandular hyperplasia, deep nabothian cysts and tunnel cluster. All lesions were proven by conization or hysterectomy. The MR findings correlated closely to the histopathological specimens. As a result, MR findings of pseudoneoplastic glandular lesions were almost identical to those of adenoma malignum; hence, it was almost impossible to differentiate between the two pathologies. Radiologists should be aware that these two conditions are quite similar in morphology.

Single-action implantation of SA60AT with Monarch II.

PURPOSE: The authors have invented a method to implant the AcrySof model SA60AT intraocular lens (IOL) with a single action to avoid complications in the recommended method. METHODS: After inversely inserting the SA60AT into the Monarch II cartridge, the optic of the SA60AT is held with IOL forceps and rotated 90 degrees counterclockwise. At this point, the haptics of the SA60AT are placed on the upper side of the optic within the cartridge. Next, the cartridge is inserted into the anterior chamber, and the main body of the Monarch II injector rotated by 180 degrees prior to pushing the plunger gradually. Once the front area of the SA60AT is inserted into the capsular bag, the remainder of the SA60AT can be slowly injected into the capsular bag. Aspiration of viscoelastic substances enables the haptics to expand in the capsular bag. The authors examined the complications in the invented method. RESULTS: The authors successfully implanted the SA60AT into the capsular bag in 226 consecutive patients (170 patients with cataract surgery alone and 56 patients with combined vitreous surgery) using the single-action method without any complications. CONCLUSIONS: The method is simple and useful for the implantation of SA60AT with Monarch II injector.

Magnetic resonance findings of clear-cell adenocarcinofibroma of the ovary.

We report the magnetic resonance (MR) findings of clear-cell adenocarcinofibroma of the ovary. A huge multilocular cystic tumor with solid components was seen in the lower abdominal and pelvic cavity. Thickened cyst wall had low intensity on T2-weighted images, which suggested abundant fibrous tissue. Its mural nodules were strongly enhanced on contrast enhancement, which reflected malignant epithelial growth. Adenocarcinofibroma of the ovary is a rare tumor, but MR findings may be helpful to reach the correct diagnosis.

DUSP22/LMW-DSP2 regulates estrogen receptor-alpha-mediated signaling through dephosphorylation of Ser-118.

In the previous study, we demonstrated the involvement of dual specificity phosphatase 22 (DUSP22/LMW-DSP2) in regulating the leukemia inhibitory factor/interleukin-6/signal transducer and activator of transcription 3-mediated signaling pathway. In this study, we show beta-estradiol (E2)-induced DUSP22 mRNA expression in estrogen receptor alpha (ERalpha)-positive breast cancer cells, whereas E2-induced phosphorylation and activation of ERalpha was suppressed by overexpression of DUSP22 but not catalytically inactive mutants. Furthermore, small-interfering RNA-mediated reduction of DUSP22 expression enhanced ERalpha-mediated transcription and endogenous gene expression. In fact, DUSP22 associated with ERalpha in vivo and both endogenous proteins interacted in ERalpha-positive breast cancer T47D cells. These results strongly suggest that DUSP22 acts as a negative regulator of the ERalpha-mediated signaling pathway.

Differing effects of clarithromycin and azithromycin on cytokine production by murine dendritic cells.

Summary The macrolide antibiotics are now well known to have anti-inflammatory effects. Because dendritic cells (DCs) orchestrate immune responses, we examined the in vitro effects of clarithromycin (CAM), azithromycin (AZM) and midecamycin (MDM) on the expression of co-stimulatory molecules and production of cytokines [interleukin (IL)-10, IL-6, interferon (IFN)-gamma, IL-12p40, tumour necrosis factor (TNF)-alpha] of murine bone marrow-derived DCs by lipopolysaccharide (LPS) stimulation. A 15-membered macrolide, AZM, and a 14-membered macrolide, CAM, significantly enhanced the intensity of a co-stimulatory molecule, CD80, on DCs but not CD86 and CD40. AZM significantly increased the production of IL-10 and CAM significantly inhibited the production of IL-6 by DCs. However, a 16-membered macrolide, MDM, did not have any significant effect on these surface markers and cytokine productions. Moreover, AZM increased IL-10 and CAM decreased IL-2 productions significantly, when naive T cells derived from spleen were co-cultured with DCs treated in advance with LPS and these macrolides. These findings suggest that 14-membered and 15-membered, but not 16-membered macrolides play as anti-inflammatory agents, at least in part, through modulating the functions of DCs. However, each macrolide affects them in different ways.

Intraocular lymphoma metastasis from larynx.

PURPOSE: To present a rare case of primary larynx diffuse large B cell lymphoma non-Hodgkin's lymphoma (NHL), disseminated to the cerebellum and the intraocular tissue. METHODS: A 69-year-old man noticed blurred vision in both eyes. The vitreous contained infiltrating cells bilaterally, and floating opacities were increased. We performed vitrectomy to recover the vision and diagnose for both eyes. RESULTS: The authors discovered diffuse large B cell NHL with cytopathologic examination from vitreous specimen in this case, which was identical with diffuse large B cell NHL of the larynx and cerebellum, and therefore could diagnose the intraocular lesion as the metastasis of NHL. Although the vision improved, the patient had remarkable visual disturbance in both eyes at 6 months after surgery because of the chorioretinal lesion. The authors treated by the combined curative chemotherapy and radiotherapy to ocular tissue, since providing sufficient evidence that the chorioretinal lesion was to predict the metastasis of diffuse large B cell NHL After those treatments, chorioretinal lesions have disappeared in both eyes and the vision has recovered. CONCLUSIONS: Increased attention to the possibility of dissemination of laryngeal NHL to the intraocular tissue is needed.

Investigation of the stability of one-piece acrylic intraocular lenses in cataract surgery and in combined vitrectomy surgery.

BACKGROUND: To compare the degrees of intraocular lens (IOL) movement between eyes that received a one-piece acrylic IOL and those that received a three-piece acrylic IOL after cataract surgery, and also among eyes that received a one-piece acrylic IOL after a combined vitrectomy surgery for cataract. METHODS: In the first study, we report on 50 patients who were implanted with a one-piece acrylic IOL in one eye and a three-piece acrylic IOL in the contralateral eye for senile cataract. In the second study, we report on 50 patients who were implanted with a one-piece acrylic IOL in combined vitrectomy surgery for cataract and retinal diseases. The degree of IOL decentration and tilt, and anterior chamber depth (ACD) were measured using Scheimpflug video photography at 1 week, 1 month, 3 months and 6 months after surgery in both the studies. The postoperative refractive status was also examined. RESULTS: The mean decentration and tilt showed no marked changes during the follow-up in eyes with either IOL implanted, and no marked differences were noted in either study throughout the follow-up. The ACD did not change after surgery with one-piece IOL implantation, for either the cataract surgery group or the combined surgery group, except for 1 week after surgery in eyes requiring gas tamponade. In contrast, marked shallowing in ACD was observed in the three-piece group after cataract surgery. The spherical equivalent did not change markedly in either study. CONCLUSIONS: The one-piece acrylic IOL was stable in the capsular bag, both horizontally and vertically, after cataract surgery, and also after combined surgery.