97 research outputs found

    Viewing Targets in Infantile Nystagmus

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    The aim of this study was to propose a new pathophysiological hypothesis for involuntary eye oscillation in infantile nystagmus (IN): patients with IN exhibit impaired gaze fixation, horizontal smooth pursuit and optokinetic nystagmus (OKN) and use saccadic eye movements for these underlying impairments. In order to induce saccades, they make enough angle between gaze and target by precedent exponential slow eye movements. IN consists of the alternate appearance of the saccade and the slow eye movements. Unlike most previous theories, IN is therefore considered a necessary strategy allowing for better vision and not an obstacle to clear vision. In five patients with IN, eye movements were analyzed during the smooth pursuit test, saccadic eye movement test, OKN test and vestibulo-ocular reflex (VOR) test. Their gaze fixation, horizontal smooth pursuit, OKN and the last half of the slow phase of VOR were impaired. The lines obtained by connection of the end eye positions of fast phase of nystagmus coincided with the trajectories of targets. The findings indicate that patients followed the target by the fast but not the slow phase of nystagmus, which supports our hypothesis. By setting the direction of slow phase of nystagmus opposite to the direction of the OKN stimulation, enough angle can be effectively made between the gaze and target for the induction of saccade. This is the mechanism of reversed OKN response. In darkness and when eyes are closed, IN weakens because there is no visual target and neither the saccade for catching up the target or slow phase for induction of the saccade is needed

    IL-10 Inhibits Transforming Growth Factor-ß-Induction of Type I Collagen mRNA Expression via Both JNK and p38 Pathways in Human Lung Fibroblasts

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    Transforming growth factor-ß (TGF-ß) is a key factor for understanding the pathogenesis of fibrotic disorders such as idiopathic pulmonary fibrosis (IPF). We have demonstrated that interleukin-10 (IL-10) suppresses TGF-ß-induced expression of type I collagen (COL1) mRNA in a human lung fibroblast cell line (WI-38). However, the inhibitory mechanism has not yet been clearly elucidated. Thus, in the current study, we investigate the effects of IL-10 blockade of TGF-ß signaling which regulates COL1 mRNA expression. In WI-38 cells, IL-10 inhibits TGF-ß-mediated phosphorylation of both, c-Jun HN2-terminal kinase (JNK) and p38, but does not suppress TGF-ß- mediated phosphorylation of Smad2 or affect TGF-ß-upregulation of Smad7 mRNA expression. In addition, SP600125 and SB203580, specific inhibitors of JNK and p38, respectively, attenuate TGF-ß-induced COL1 mRNA expression in WI-38 cells. These results suggest that IL-10 inhibits TGF-ß-induced COL1 mRNA expression via both JNK and p38 pathways but not Smad pathways in WI-38 cells. This inhibitory mechanism may provide a novel insight into therapeutic strategies for fibrotic disorders such as IPF

    Isoform D of vascular endothelial growth factor in systemic capillary leak syndrome : a case report

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    Background: Systemic capillary leak syndrome is a rare condition characterized by episodic attacks of hypovolemia due to systemic capillary hyperpermeability, which results in profound hypotension and edema. Although the implication of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 has been suggested, the pathogenesis of systemic capillary leak syndrome remains unclear. In this report, we describe a case of systemic capillary leak syndrome in which serum isoform D of vascular endothelial growth factor was elevated. To the best of our knowledge, this is the first reported case of systemic capillary leak syndrome in which isoform D of vascular endothelial growth factor is suggested as the plausible biomarker. Case presentation: A 41-year-old Japanese man was transferred to our emergency department. He was hypotensive, tachycardic, and edematous over the trunk and all four limbs. He received aggressive intravenous fluid therapy and underwent fasciotomy of the right forearm to prevent muscle necrosis. A diagnosis of systemic capillary leak syndrome was suspected. The presence of serum monoclonal immunoglobulin G and κ light chain supported this diagnosis. Prevention of hypotensive crises was unsuccessfully attempted with theophylline, intravenous immunoglobulin, high-dose dexamethasone, bortezomib, melphalan, and prednisolone; however, the patient’s attacks dramatically disappeared after the introduction of thalidomide. The serum of the patient was stored soon after the onset of hypotensive crisis and analyzed to profile possible mediators responsible for the capillary leak. The concentration of vascular endothelial growth factor, angiopoietin-2, and C-X-C motif chemokine 10 were all within normal ranges. Meanwhile, we found that isoform D of vascular endothelial growth factor was elevated, which was normalized after the introduction of thalidomide. Conclusions: In our patient, isoform D of vascular endothelial growth factor (instead of vascular endothelial growth factor) may have been a causative factor of hypotensive crises, since isoform D contributes to vascular endothelial growth factor receptor-2 signaling, which is the major mediator of the permeability-enhancing effects of vascular endothelial growth factor. We suggest the measurement of isoform D of vascular endothelial growth factor in patients with systemic capillary leak syndrome in whose serum vascular endothelial growth factor is not elevated

    Significance of Ki-67 Expression and Risk Category (St. Gallen 2007) in Elderly Breast Cancer Patients, with Emphasis on the Need for Postoperative Adjuvant Therapy

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    Breast cancer is increasing in the elderly. Although elderly breast cancer patients frequently receive less invasive therapy, its appropriateness is debatable. Ki-67 expression is a controversial prognostic factor and predictor of the efficacy of postoperative adjuvant therapy. This study investigated the value of the Ki-67 labeling index (LI) in elderly breast cancer patients, especially with respect to adjuvant therapy. This retrospective study investigated 82 primary breast cancer patients aged 70 years who underwent surgery between 1995 and 2005. Their clinicopathological findings were reviewed and their Ki-67 LIs were determined. The patients\u27 mean age was 78 years, the mean observation period was 53.8 months, and 60 patients (73.2%) underwent adjuvant therapy. The St. Gallen (2007) risk category and the Ki-67 LI (mean, 15.3%) were both significantly correlated with relapse and prognosis. In the 31 cases with a low Ki-67 LI (< 10%), 1 patient who underwent adjuvant treatment relapsed, but there were no deaths. Among the intermediate- and high-risk patients, Ki-67 was low in 15; 1 patient who underwent adjuvant treatment relapsed, but there were no deaths. For elderly breast cancer patients aged 70 years categorized low risk by St. Gallen (2007) or with a low Ki-67 LI, the risk of relapse and death appears to be low regardless of adjuvant therapy. Though further investigation is needed to determine a method of measuring the Ki-67 LI and determining a cut-off value, our findings suggest that the Ki-67 LI helps with the selection of adjuvant therapy in elderly patients

    Targeting Notch-1 positive acute leukemia cells by novel fucose-bound liposomes carrying daunorubicin

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    Complete remission by induction therapy in acute myelogenous leukemia (AML) can be achieved due to improvements in supportive and optimized therapy. However, more than 20% of patients will still need to undergo salvage therapy, and most will have a poor prognosis. Determining the specificity of drugs to leukemia cells is important since this will maximize the dose of chemotherapeutic agents that can be administered to AML patients. In turn, this would be expected to lead to reduced drug toxicity and its increased efficacy. We targeted Notch-1 positive AML cells utilizing fucose-bound liposomes, since activation of Notch-1 is required for O-fucosylation. Herein, we report that intravenously injected, L-fucose-bound liposomes containing daunorubicin can be successfully delivered to AML cells that express fucosylated antigens. This resulted in efficient tumor growth inhibition in tumor-bearing mice and decreased proliferation of AML patient-derived leukemia cells. Thus, biological targeting by fucose-bound liposomes that takes advantage of the intrinsic characteristics of AML cells could be a promising new strategy for Notch-1 positive-AML treatment

    Pre-flight optical test and calibration for the Cosmic Infrared Background ExpeRiment 2 (CIBER-2)

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    The total integrated emission from galaxies, known as the Extragalactic Background Light (EBL), is an important observable for understanding the history of star formation over the history of the universe. Spatial fluctuations in the infrared EBL as measured by the Cosmic Infrared Background ExpeRiment (CIBER), Spitzer and AKARI exceed the predicted signal from galaxy clustering alone. The CIBER-2 project seeks to extend CIBER observa- tions of the EBL throughout the near infrared into the optical, through measurements above Earth's atmosphere during a suborbital sounding rocket flight. The experiment has a LN2-cooled 28.5 cm Cassegrain telescope along with three optical paths and dichroic beamsplitters, which are used to obtain three wide-field images in six broad spectral bands between 0.5-2.0 μm. The three focal planes also contain linear variable filters (LVFs) which simultaneously take spectra with resolution R=20 across the same range. CIBER-2 is scheduled to y multiple times on a Black Brant IX sounding rocket from White Sands Missile Range in the New Mexico desert. For the first flight, scheduled for early 2021, we have completed a variety of pre-flight optical tests, which we use to make focus adjustments, spectral response measurements, and absolute photometric calibrations. In this paper, we describe the methods behind these tests and present their results for pre-flight performance evaluation. In particular, we present measurements of the PSF for each broad spectral band, along with absolute calibration factors for each band and the LVF. Through monochromator scans, we also measure the spectral responsivity of each LVF as a function of position
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