tbuckley/cabot-search huggingface dataset:
Correction of Neurological Disease of Mucopolysaccharidosis IIIB in Adult Mice by rAAV9 Trans-Blood–Brain Barrier Gene Delivery
Authors: Haiyan Fu, Julianne DiRosario, Smruti Killedar, Kimberly Zaraspe, Douglas M McCarty
Journal: Molecular Therapy (2011)

The greatest challenge in developing therapies for mucopolysaccharidosis (MPS) IIIB is to achieve efficient central nervous system (CNS) delivery across the blood–brain barrier (BBB). In this study, we used the novel ability of adeno-associated virus serotype 9 (AAV9) to cross the BBB from the vasculature to achieve long-term global CNS, and widespread somatic restoration of α-N-acetylglucosaminidase (NAGLU) activity. A single intravenous (IV) injection of rAAV9-CMV-hNAGLU, without extraneous treatment to disrupt the BBB, restored NAGLU activity to normal or above normal levels in adult MPS IIIB mice, leading to the correction of lysosomal storage pathology in the CNS and periphery, and correction of astrocytosis and neurodegeneration. The IV delivered rAAV9 vector also transduced abundant neurons in the myenteric and submucosal plexus, suggesting peripheral nervous system (PNS) targeting. While CNS entry did not depend on osmotic disruption of the BBB, it was significantly enhanced by pretreatment with an IV infusion of mannitol. Most important, we demonstrate that a single systemic rAAV9-NAGLU gene delivery provides long-term (>18 months) neurological benefits in MPS IIIB mice, resulting in significant improvement in behavioral performance, and extension of survival. These data suggest promising clinical potential using the trans-BBB neurotropic rAAV9 vector for treating MPS IIIB and other neurogenetic diseases. The greatest challenge in developing therapies for mucopolysaccharidosis (MPS) IIIB is to achieve efficient central nervous system (CNS) delivery across the blood–brain barrier (BBB). In this study, we used the novel ability of adeno-associated virus serotype 9 (AAV9) to cross the BBB from the vasculature to achieve long-term global CNS, and widespread somatic restoration of α-N-acetylglucosaminidase (NAGLU) activity. A single intravenous (IV) injection of rAAV9-CMV-hNAGLU, without extraneous treatment to disrupt the BBB, restored NAGLU activity to normal or above normal levels in adult MPS IIIB mice, leading to the correction of lysosomal storage pathology in the CNS and periphery, and correction of astrocytosis and neurodegeneration. The IV delivered rAAV9 vector also transduced abundant neurons in the myenteric and submucosal plexus, suggesting peripheral nervous system (PNS) targeting. While CNS entry did not depend on osmotic disruption of the BBB, it was significantly enhanced by pretreatment with an IV infusion of mannitol. Most important, we demonstrate that a single systemic rAAV9-NAGLU gene delivery provides long-term (>18 months) neurological benefits in MPS IIIB mice, resulting in significant improvement in behavioral performance, and extension of survival. These data suggest promising clinical potential using the trans-BBB neurotropic rAAV9 vector for treating MPS IIIB and other neurogenetic diseases.
TIME DELAY FROM SYMPTOM ONSET-TO-REPERFUSION AND LABORATORY EFFICACY OF P2Y12 INHIBITORS IN PATIENTS WITH STE: MYOCARDIAL INFARCTION TREATED WITH PRIMARY PCI
Authors: Zuzana Motovska, Ondrakova Martina, Teodora Vichova, Jiri Knot, Frantisek Bednar, Jaroslav Ulman
Journal: Journal of the American College of Cardiology (2014)
Health-Policy Issues and the Predicament in Poland
Authors: Thomas G. Webster
Journal: New England Journal of Medicine (1982)

When I visited Poland in May and June of 1981, I was struck by the contrast between two strong forces that fed into the stream of Poland's daily existence: one, the great tide of enthusiasm over Solidarity's independent sweep into so many corners of Polish life, including health care; the other, the almost palpable air of apprehension and resignation born of the nation's tortured history, its legacy of wars and oppression, and the present-day realities.Even then, six months before the government declared martial law on December 13, many Poles whom I met were troubled with uncertainty and despair. Physicians . . .
Antibody Protein Synthesis by Lymph Nodes Homotransplanted to a Hypogammaglobulinemic Adult
Authors: Christopher M. Martin, John B. Waite, Norman B. McCullough
Journal: Journal of Clinical Investigation (1957)

After showing that normal skin homografted upon a congenitally agammaglobulinemic child survived for a prolonged period (1), Good and Varco further demonstrated that within certain limits hypogammaglobulinemic patients might be artificially endowed with a system of active im- munity through homotransplantation of a reticulo- endothelial tissue (2, 3).The present study was designed both to explore the therapeutic possibilities of lymph node homo- transplantation and to take advantage of the unique antibody-synthesizing defect in hypogammaglobulinemia to quantitate the immune response of hu- man lymphoid tissue.This paper presents the results of measurements of antibody protein synthesis, during primary and secondary immune responses, by normal lymph nodes homotransplanted to a hypogammaglobulinemic adult, together with qualitative observa- tions of the interplay of recipient and transplant during and after the 150-to 160-day period of survival of the lymph nodes. MATERIALS AND METHODSChallenge antigen.Because it is potent, reliable, and rapidly productive of antibodies susceptible to accurate measurement, typhoid vaccine was selected as the anti- gen with which to test the reactivity of the transplant.The preparation employed' to challenge both recipient and donor contained 1,000 million heat-killed organisms of the Panama 58 strain per ml., and was of the type ordinarily stimulating production of H and 0 (but not V,) antibodies.Titration of typhoid H-and 0-agglutinins.Agglutinins were measured on coded specimens by one observer at one time, and expressed as the mean of four determina- tions on recipient sera and two on donor sera, by the slide agglutination method devised by Welch and Stuart (4) and improved by Diamond (5).Single pooled batches of commercial (Lederle) Salmonella Group D 'Typhoid Vaccine, Eli Lilly and Co., Lot No. 7289-
Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ)
Authors: Pier Luigi Zinzani, Monica Tani, Alessandro Pulsoni, Marco Gobbi, Alessio Perotti, Stefano De Luca, Alberto Fabbri, Alfonso Zaccaria, Maria Teresa Voso, Pierpaolo Fattori, Luciano Guardigni, Sonia Ronconi, Maria Giuseppina Cabras, Luigi Rigacci, Amalia De Renzo, Enrica Marchi, Vittorio Stefoni, Mariapaola Fina, Cinzia Pellegrini, Gerardo Musuraca, Enrico Derenzini, Stefano Pileri, Stefano Fanti, Pier Paolo Piccaluga, Michele Baccarani
Journal: The Lancet Oncology (2008)
Abstract 514: Relationship between loss of heterozygosity of HLA-A gene and HLA class I expression in gastric cancer
Authors: Mami Yoshii, Hiroaki Tanaka, Katsunobu Sakurai, Hisashi Nagahara, Kenjiro Kimura, Ryosuke Amano, Eiji Noda, Naoshi Kubo, Kazuya Muguruma, Nobuya Yamada, Masakazu Yashiro, Kiyoshi Maeda, Tetsuji Sawada, Masaichi Ohira, Tetsuro Ishikawa, Kosei Hirakawa
Journal: Cancer Research (2012)

Abstract [Introduction]Human leukocyte antigen (HLA), located on 6p21.3, encodes for genes involved in antigen processing and presentation. Loss of heterozygosity (LOH) at 6p21.3 may cause downregulation of HLA class I, and may provide tumor cells with an immune-escape tumor phenotype. The aim of this study is to examine HLA class I expression in gastric cancer tissues and cell lines, to clarify the clinical impact of HLA-A dawnregulation on progression of gastric cancer. [Materials and methods]We examined HLA class I expression in clinical samples from 206 patients by immunohistochemical staining. By flow cytometric analysis, we analyzed the expression of HLA class I antigen in gastric cancer cell lines. Furthermore, we performed HLA-A typing in gastric cancer cell lines by PCR-SBT method. [Results]We observed that HLA class I expression was downregulated in metastatic lymph node compared with in primary lesion. HLA class I expression in primary lesion was associated with ly factors and histological types. Furthermore, patients with negative expression of HLA class I showed significantly poorer prognosis. In vitro, we observed the downregulation of HLA class I antigen in OCUM-2MLN cells which have a high potential for lymph node metastasis. By PCR-SBT method, we detected loss of heterozigosity of HLA-A gene in OCUM-2MLN. [Conclusion]We observed that HLA class I expression was associated with poor prognosis of gastric cancer and LOH of HLA-A was recognized in cancer cell line which has potential to develop lymph node metastasis. Our findings suggested that LOH of HLA-A gene would result in provide cancer cells with capacity to metastasize into lymph nodes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 514. doi:1538-7445.AM2012-514
Reiter's Syndrome and Aortic Insufficiency
Authors: Gerald P. Rodnan, Thomas G. Benedek, James A. Shaver, Robert H. Fennell
Journal: JAMA (1964)

Two men with Reiter's syndrome are described who developed aortic insufficiency with no evidence of syphilis or rheumatic heart disease. One patient, who had complete heart block and died of cardiac failure, was found to have mesoaortic disease and dilatation of the aortic valve with rolling of the free margins of the semilunar cusps. The other patient is living but has angina pectoris and exertional dyspnea. Cardiac catheterization in this case revealed severe aortic regurgitation. The clinical and pathological changes in these and other cases of Reiter's syndrome with aortic insufficiency appear to be similar to those described in patients with ankylosing spondylitis and aortic root and valvular disease.
Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway
Authors: Andrew L Kung, Sonya D Zabludoff, Dennis S France, Steven J Freedman, Elizabeth A Tanner, Annelisa Vieira, Susan Cornell-Kennon, Jennifer Lee, Beqing Wang, Jamin Wang, Klaus Memmert, Hans-Ulrich Naegeli, Frank Petersen, Michael J Eck, Kenneth W Bair, Alexander W Wood, David M Livingston
Journal: Cancer Cell (2004)
Mediastinal Mass in a Patient With Liver Disease
Authors: Val Dunn
Journal: JAMA (1982)

History  A 20-year-old woman was examined for a mediastinal mass detected on chest roentgenograms. Biopsy diagnosis of chronic active hepatitis had been made at age 12 years, three years after an episode of acute infectious hepatitis. Three episodes of significant hemorrhage from esophageal varices were documented. Bleeding hemorrhoids, peptic ulcer disease, and easy bruising were also reported. She had been receiving immune suppression therapy with prednisone and azathioprine (Imuran) for two years. On admission, splenomegaly and thrombocytopenia were noted. Erect posteroanterior (PA) and lateral chest x-ray films (Fig 1) and a contrast-enhanced computed tomographic scan of the lower thorax (Fig 2) were obtained.  Diagnosis  Esophageal varices and venous collateral secondary to portal hypertension.  Lateral and PA chest x-ray films showed a retrocardiac mediastinal mass (Fig 1). The azygous vein appeared normal on erect films but was enlarged on supine tomography. On lateral tomograms, the superior margin of the mass corresponded
Hyper-SUMOylation of the Kv7 Potassium Channel Diminishes the M-Current Leading to Seizures and Sudden Death
Authors: Yitao Qi, Jingxiong Wang, Valerie C. Bomben, De-Pei Li, Shao-Rui Chen, Hao Sun, Yutao Xi, John G. Reed, Jinke Cheng, Hui-Lin Pan, Jeffrey L. Noebels, Edward T.H. Yeh
Journal: Neuron (2014)
Reviews, Notes, and Listings: Pulmonary Medicine: The Diagnosis and Treatment of Pulmonary Hypertension
Authors: David Langleben
Journal: Annals of Internal Medicine (1993)

Literature of Medicine15 April 1993Reviews, Notes, and Listings: Pulmonary Medicine: The Diagnosis and Treatment of Pulmonary HypertensionDavid Langleben, MDDavid Langleben, MDSir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Quebec, H3T 1E2, Canada.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-8-199304150-00052 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Diagnosis and Treatment of Pulmonary HypertensionE. Kenneth Weir, Stephen L. Archer, and John T. Reeves; eds. 395 pages. Mount Kisco, New York: Futura Publishing Company Inc.; 1992. $69.00.Until recently, the diagnosis and treatment of pulmonary hypertension have, to a great degree, been exercises in frustration. For the internist, who has often borne the responsibility for early detection when the only initial symptom may be mild dyspnea, the rapid decline to death in many patients with pulmonary hypertension has been a most sobering experience. This book, dedicated to Robert Grover, an enduring pioneer in pulmonary hypertension research, will be useful ... Author, Article, and Disclosure InformationAffiliations: Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Quebec, H3T 1E2, Canada. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 April 1993Volume 118, Issue 8Page: 656KeywordsForecastingHemodynamicsHistologyLung transplantationMagnetic resonance imagingPopulation statisticsPulmonary hypertensionPulmonary medicineSclerodermaVasodilators ePublished: 15 August 2000 Issue Published: 15 April 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A Retrospective Study of Reintroduction of Oxaliplatin in Patients with Advanced or Recurrent Colorectal Cancer
Authors: N. Nakayama, K. Nishimura, T. Kenmochi, T. Egawa, T. Sasaki, K. Shimada, S. Akatsuka, Y. Takinishi, K. Kobayashi, S. Sato
Journal: Annals of Oncology (2013)
Allergic Granulomatosis with Massive Gastric Involvement
Authors: Murray R. Abell, Richard V. Limond, William E. Blamey, William Martel
Journal: New England Journal of Medicine (1970)

ALTHOUGH granulomatous reactions had been observed in association with allergic states, it was Churg and Strauss1 who, in 1951, defined allergic granulomatosis as a clinicopathological syndrome. Asthma preceded the onset of the disease, which was usually characterized by weight loss, fever, anemia, a marked increase in blood eosinophilic leukocytes and a declivitous course resulting in death. The histologic hallmark was the presence of distinctive allergic granulomas in connective and muscular tissues, particularly of lung, cardiovascular system and kidney and subcutaneously. These were usually microscopic in size, but some of them had become confluent, forming gross nodules.A variety of granulomatous . . .
TREATMENT OF OPEN OR COMPOUND FRACTURES.Read in the Section on Surgery and Anatomy, at the Forty-fifth Annual Meeting of the American Medical Association, held at San Francisco, June 5-8, 1894.
Authors: HENRY H. MUDD
Journal: JAMA (1894)

An open wound communicating with a fractured bone is a serious complication. Every effort is directed to its closure by sound healing. Its importance and the difficulty of its management is determined largely by the amount of injury inflicted upon the soft tissues about the fracture, and by the extent of the comminution of the bone. This open wound is usually determined by the violence which inflicts the fracture, but may result from ulceration. An oblique fracture where the skin has been torn by the sharp angling of the bone, with or without impact against an external object, offers a good opportunity to convert a compound into a simple fracture. Fractures by direct violence which is not crushing, even if the bone is comminuted, present often good opportunity for the immediate closure of the wound. The soft parts are not necessarily much injured by such a fracture. This is especially
On specification and the senses
Authors: Thomas A. Stoffregen, Benoît G. Bardy
Journal: Behavioral and Brain Sciences (2001)

In this target article we question the assumption that perception is divided into separate domains of vision, hearing, touch, taste, and smell. We review implications of this assumption for theories of perception and for our understanding of ambient energy arrays (e.g., the optic and acoustic arrays) that are available to perceptual systems. We analyze three hypotheses about relations between ambient arrays and physical reality: (1) that there is an ambiguous relation between ambient energy arrays and physical reality, (2) that there is a unique relation between individual energy arrays and physical reality, and (3) that there is a redundant but unambiguous relation, within or across arrays, between energy arrays and physical reality. This is followed by a review of the physics of motion, focusing on the existence and status of referents for physical motion. Our review indicates that it is not possible, in principle, for there to be a unique relation between physical motion and the structure of individual energy arrays. We argue that physical motion relative to different referents is specified only in the global array, which consists of higher-order relations across different forms of energy. The existence of specificity in the global array is consistent with the idea of direct perception, and so poses a challenge to traditional, inference-based theories of perception and cognition. However, it also presents a challenge to much of the ecological approach to perception and action, which has accepted the assumption of separate senses.
B3-04: Gefitinib (IRESSA) versus vinorelbine in chemonaïve elderly patients with advanced non-small-cell lung cancer (INVITE): a randomized Phase II study
Authors: Lucio Crinò, Petr Zatloukal, Martin Reck, Milos Pesek, Joyce Thomson, Hugo Ford, Fred Hirsch, Emma Duffield, Alison Armour, Michael Cullen
Journal: Journal of Thoracic Oncology (2007)
Cancer in adolescence
Authors: C A Stiller
Journal: BMJ (1994)

secretory diarrhoea, diarrhoea associated with amyloidosis, and diabetic diarrhoea has been reported, but no controlled trials have been performed.15The agents have no effect on the diarrhoea of cholera.Octreotide has shown some promise in the management of refractory diarrhoea related to AIDS, especially in patients without identifiable pathogens.'6After years of mostly uncontrolled studies, a series of randomised controlled trials is defining the clinical applications of octreotide.'7Nevertheless, analogues of somato- statin with special affinities for the different classes of somatostatin receptors are needed.Now that the sequences of many of the somatostatin receptor subtypes are being described,'8 the synthesis of analogues targeted for specific clinical applications should be possible.
Eccrine syringofibroadenomatosis associated with hidrotic ectodermal dysplasia
Authors: None Simpson, None Styles, None Cockerell
Journal: British Journal of Dermatology (1998)

Eccrine syringofibroadenoma (ES) is generally regarded as a solitary benign adnexal neoplasm of the skin. Recently, the epithelial and stromal changes of this lesion have been recognized as being a reaction pattern in certain settings. We describe two individuals in whom this process was a manifestation of hidrotic ectodermal dysplasia. In both cases, the diagnosis had been missed for many years and the process had been thought to be a manifestation of an inflammatory dermatosis of the palms and soles. In both instances, other family members were found to be affected. Thus, ES may be manifested clinically as erythematous erosive plaques, especially of the palms and soles. It is important that clinicians be familiar with this disorder and be aware that it may exhibit unusual cutaneous manifestations.
A Novel Technique for Endoscopic Snare Polypectomy Using a Duodenoscope in Combination with a Colonoscope for the Inaccessible Colonic Polyp
Authors: G. Dafnis
Journal: Endoscopy (2006)

Colonoscopic polypectomy, introduced by H. Shinya in 1969, is now a well-established technique [1]. Although polypectomy may not be limited by the size of the lesion [2] [3] [4] [5], the location of the polyp can present problems. Some polyps are so situated that they are impossible to remove using a colonoscope, and laparoscopy, either alone or in combination with colonoscopy, has been proposed for the management of such patients [6] [7]. This report describes a novel technique for removing these really difficult polyps entirely endoscopically, by using a duodenoscope in combination with a colonoscope. To my knowledge this is the first published report of this technique.
Abstract 3107: Runt-related transcription factor 1 (RUNX1) is involved in transcriptional repression by estrogen receptor and breast cancer cell proliferation.
Authors: Ka Liu, Richard L. Smith, Trang Nguyen-Vu, Nicholes R. Candelaria, Colin M. Rogerson, W. Evan Johnson, Edwin Cheung, Boris R. Jankovic, Wail Ba alawi, Jinsong Zhang, Vladimir B. Bajic, Chin-Yo Lin
Journal: Cancer Research (2013)

Abstract In the majority of breast cancers, estrogen and its cellular receptor, estrogen receptor (ER), are involved in regulating tumor cell proliferation. ER is both a prognostic marker and a therapeutic target in the management of hormone-dependent tumors. Current research efforts and the paradigm of ER transcriptional regulatory functions in breast cancer have focused on the role of ER in activating target gene transcription. Microarray studies and whole-genome ER binding site mapping experiments indicate, however, that ER can alternatively directly repress the expression of a significant subset of target genes. We posit that transcriptional repression by ER likely involves interactions with other co-regulatory transcription factors found in the proximity of ER binding sites in the cis-regulatory regions of repressed target genes and have identified the runt-related transcription factor 1 (RUNX1), a key regulator of hematopoiesis and leukemogenesis, as a candidate co-regulatory factor involved in transcriptional repression by ER. Here, we demonstrate that RUNX1 interacts with ER, specifically the ligand-binding domain, and is involved in the repression of ER target genes and estrogen-dependent and -independent proliferation of breast cancer cells. We also show that putative ER-RUNX1 target genes are associated with disease outcome in breast cancer patients. These findings not only provide the first evidence for the involvement of RUNX1 in hormonal carcinogenesis and additional insights into mechanisms of transcriptional regulation by ER but may potentially lead to more effective strategies for targeting ER and estrogen signaling in the prevention and treatment of breast cancer. Citation Format: Ka Liu, Richard L. Smith, Trang Nguyen-Vu, Nicholes R. Candelaria, Colin M. Rogerson, W. Evan Johnson, Edwin Cheung, Boris R. Jankovic, Wail Ba alawi, Jinsong Zhang, Vladimir B. Bajic, Chin-Yo Lin. Runt-related transcription factor 1 (RUNX1) is involved in transcriptional repression by estrogen receptor and breast cancer cell proliferation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3107. doi:10.1158/1538-7445.AM2013-3107