29 research outputs found

    Lentiviral Vectors That Express UGT1A1 in Liver and Contain Mir-142 Target Sequences Normalize Hyperbilirubinemia in Gunn Rats

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    Background & AimsCrigler–Najjar type 1 (CN-I) is an inherited liver disease caused by an absence of bilirubin–uridine 5′-diphosphate–glucuronosyltransferase (UGT1A1) activity. It results in life-threatening levels of unconjugated bilirubin, and therapeutic options are limited. We used adult Gunn rats (an animal model of the disease) to evaluate the efficiency of lentiviral-based gene therapy to express UGT1A1 in liver. Methods Gunn rats were given intraportal injections of VSVG-pseudotyped lentiviral vectors that encode UGT1A1 under the control of a liver-specific transthyretin promoter (mTTR.hUGT1A1); this vector does not contain target sequences for miR-142, a microRNA that is expressed specifically in hematopoietic cells. Rats were also injected with the vector mTTR.hUGT1A1.142T, which contains 4 copies of the miR-142 target sequences; its messenger RNA should be degraded in antigen-presenting cells. Bilirubinemia was monitored, and the presence of transduced hepatocytes was analyzed by quantitative polymerase chain reaction. Vector expression was tested in vitro in rat hematopoietic cells. Results In Gunn rats, bilirubin levels normalized 2 weeks after administration of mTTR.hUGT1A1. However, hyperbilirubinemia resumed 8 weeks after vector administration, concomitant with the induction of an immune response. In contrast, in rats injected with mTTR-UGT1A1.142T, bilirubin levels normalized for up to 6 months and transduced cells were not eliminated. Conclusions Lentiviral vectors that express UGT1A1 reduce hyperbilirubinemia in immunocompetent Gunn rats for at least 6 months. The immune response against virally expressed UGT1A1 can be circumvented by inclusion of miR-142 target sequences, which reduce vector expression in antigen-presenting cells. This lentiviral-based gene therapy approach might be developed to treat patients with CN-I

    Expanding horizons of cross-linguistic research on reading: The Multilingual Eye-movement Corpus (MECO)

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    Scientific studies of language behavior need to grapple with a large diversity of languages in the world and, for reading, a further variability in writing systems. Yet, the ability to form meaningful theories of reading is contingent on the availability of cross-linguistic behavioral data. This paper offers new insights into aspects of reading behavior that are shared and those that vary systematically across languages through an investigation of eye-tracking data from 13 languages recorded during text reading. We begin with reporting a bibliometric analysis of eye-tracking studies showing that the current empirical base is insufficient for cross-linguistic comparisons. We respond to this empirical lacuna by presenting the Multilingual Eye-Movement Corpus (MECO), the product of an international multi-lab collaboration. We examine which behavioral indices differentiate between reading in written languages, and which measures are stable across languages. One of the findings is that readers of different languages vary considerably in their skipping rate (i.e., the likelihood of not fixating on a word even once) and that this variability is explained by cross-linguistic differences in word length distributions. In contrast, if readers do not skip a word, they tend to spend a similar average time viewing it. We outline the implications of these findings for theories of reading. We also describe prospective uses of the publicly available MECO data, and its further development plans

    Text reading in English as a second language: Evidence from the Multilingual Eye-Movements Corpus

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    Research into second language (L2) reading is an exponentially growing field. Yet, it still has a relatively short supply of comparable, ecologically valid data from readers representing a variety of first languages (L1). This article addresses this need by presenting a new data resource called MECO L2 (Multilingual Eye Movements Corpus), a rich behavioral eye-tracking record of text reading in English as an L2 among 543 university student speakers of 12 different L1s. MECO L2 includes a test battery of component skills of reading and allows for a comparison of the participants' reading performance in their L1 and L2. This data resource enables innovative large-scale cross-sample analyses of predictors of L2 reading fluency and comprehension. We first introduce the design and structure of the MECO L2 resource, along with reliability estimates and basic descriptive analyses. Then, we illustrate the utility of MECO L2 by quantifying contributions of four sources to variability in L2 reading proficiency proposed in prior literature: reading fluency and comprehension in L1, proficiency in L2 component skills of reading, extralinguistic factors, and the L1 of the readers. Major findings included (a) a fundamental contrast between the determinants of L2 reading fluency versus comprehension accuracy, and (b) high within-participant consistency in the real-time strategy of reading in L1 and L2. We conclude by reviewing the implications of these findings to theories of L2 acquisition and outline further directions in which the new data resource may support L2 reading research

    Metastatic hypervascular lymph nodes in malignant glomus vagale tumor: Angiography findings

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    Malignant vagal paraganglioma is very uncommon and the diagnosis of malignancy is made on the basis of presence of distant metastasis rather than the histological findings. We report angiography findings of metastatic cervical lymph nodes in a case of malignant vagal paraganglioma. (C) 2001 Elsevier Science Inc. All rights reserved

    Hymen Sparing Surgery for Imperforate Hymen: Case Reports and Review of Literature

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    Background: Imperforate hymen, with an incidence between 0.1% and 0.05%, is the most common obstructive congenital abnormality of the female genital tract. 'Standard' surgical treatment of imperforate hymen involves hymenectomy after a cruciate, plus, or X-shaped hymenotomy incision. Cases: Two cases with imperforate hymen treated with a simple vertical incision are presented. A few oblique sutures were used to prevent refusion. Postoperative follow up was uneventful. Summary and Conclusion: The importance of the integrity of hymen changes in different cultures and religious groups. Option of a hymen sparing procedure is readily preferred by most of these patients and families. Also preservation of hymenal tissue, hence the perception of 'integrity' of female genitalia, might be an alternative treatment option. © 2009 North American Society for Pediatric and Adolescent Gynecology

    Sonographic and MRI findings in prepubertal adnexal hemorrhagic cyst with torsion

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    Adnexal torsion is rare before menarche. We report the case of a 10-year-old girl with persistent left lower quadrant pain proven by surgery to be caused by adnexal torsion due to a hemorrhagic cyst. Sonography showed a well-defined, complex, predominantly solid mass with some sound through-transmission and a small amount of fluid. The left ovary could not be distinguished from the mass; the right ovary appeared normal. Doppler sonography demonstrated no blood flow within the mass. MRI revealed a circumferential region of high signal intensity in the periphery of the mass and multiple hyperintense foci in the left ovary. (C) 2001 John Wiley & Sons, Inc

    Mammographic and sonographic findings in the diagnosis of idiopathic granulomatous mastitis

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    The aim of this study was to describe the mammographic and sonographic findings of idiopathic granulomatous mastitis which is a rare inflammatory disease of the breast of unknown etiology. The clinical, radiologic, and pathologic features of 12 cases with idiopathic granulomatous mastitis were retrospectively reviewed. Mammography was performed in all cases, 8 of which showed a focal asymmetric density, 3 had a mass with irregular margins, and I had no abnormality. Sonography was performed in 10 cases, and a focal area with inhomogeneous and hypoechoic pattern was depicted in 6 cases, 4 of which were associated with internal tubular hypoechoic structures. One case revealed a hypoechoic mass consistent with malignancy. In 1 case sonography showed an edematous pattern involving nearly the entire breast. Two patients had normal sonograms. If a focal asymmetric density is seen in mammography and inhomogeneous hypoechogenity with internal hypoechoic tubular structures accompany ultrasonographically, these findings should suggest the possibility of idiopathic granulomatous mastitis; however, very often idiopathic granulomatous mastitis mimics a breast carcinoma clinically and the final diagnosis should be reached histopatologically due to high false-positive and false-negative mammographic appearances

    Transient neonatal hypoglycemia: cranial US and MRI findings

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    A case of transient neonatal hypoglycemia with patchy hyperechogenic white matter abnormalities in the frontal and parietooccipital lobes on cranial US is presented. An MRI examination revealed T1 and T2 shortening of the lesions in the occipital and frontal white matter. Follow-up cranial US demonstrated recovery of white matter changes in the patient with normal neurological outcome

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