tbuckley/cabot-search huggingface dataset:
Respiratory muscles as a target for adenovirus-mediated gene therapy
Authors: BJ Petrof
Journal: European Respiratory Journal (1998)

The protein dystrophin is absent in the muscles of patients with Duchenne muscular dystrophy (DMD) as well as dystrophin-deficient mice with muscular dystrophy (mdx mice). The mdx mouse diaphragm closely resembles the human DMD phenotype and thus provides a useful model for studies of dystrophin gene replacement. Recombinant adenovirus vectors (AdVs) hold promise as a means for delivering a functional dystrophin gene to muscle. As an initial step toward this goal, we have determined the efficiency and functional consequences of AdV-mediated reporter gene transfer to the diaphragm in both normal and mdx adult mice. At 1 week after AdV administration, there was a high level of transgene expression in the diaphragm. One month later, however, elimination of transgene expression was observed along with a significant decrease in force production by both normal and mdx diaphragms. Immunosuppression with cyclosporine did not augment the level of transgene expression, but a beneficial effect on diaphragm force-generating capacity was observed in both groups of animals. In order to further elucidate the cellular mechanisms underlying these findings, the effects of AdV gene inactivation (by ultraviolet (UV) irradiation) and interference with host T-lymphocyte subsets were examined. Both UV-inactivation of AdV and CD8+ T-cell deficiency were found to significantly alleviate AdV-induced reductions in diaphragm force-generating capacity. Brief (2 day) administration of a neutralizing antibody against host CD4+ T-cells also produced a trend towards mitigation of AdV-induced contractile dysfunction. In addition, transgene expression one month after AdV delivery was significantly enhanced with inhibition of either CD4+ or CD8+ T-cell function. The data suggest two major sources of reduced force generation after recombinant adenovirus vector-mediated gene transfer to muscle: 1) a cytotoxic component associated with recombinant adenovirus vector transcriptional activity; and 2) an immune-based component of more delayed onset that is primarily dependent upon CD8+ T-cell activity. These results have important implications for the design of future generation vectors and the potential need for immunosuppressive therapy after recombinant adenovirus vector mediated dystrophin gene transfer to Duchenne muscular dystrophy patients.
P722 PERFORMANCE AND VALUE OF IFN-LAMBDA3 AND IFN-LAMBDA4 GENOTYPING IN PATIENTS WITH CHRONIC HEPATITIS C (CHC) GENOTYPE 2/3 IN A REAL WORLD SETTING
Authors: S.B. Wiegand, B. Heidrich, S. Susser, A. Stoehr, K.H.W. Böker, N. Grigorian, R. Zachoval, R. Link, U. Naumann, C. John, A. Lohse, P. Malfertheiner, H. Carls, M.P. Manns, H. Wedemeyer, C. Sarrazin, M. Cornberg
Journal: Journal of Hepatology (2014)
Long-term expression of murine activated factor VII is safe, but elevated levels cause premature mortality
Authors: Majed N. Aljamali, Paris Margaritis, Alexander Schlachterman, Shing Jen Tai, Elise Roy, Ralph Bunte, Rodney M. Camire, Katherine A. High
Journal: Journal of Clinical Investigation (2008)

Intravenous infusion of recombinant human activated Factor VII (FVIIa) has been used for over a decade in the successful management of bleeding episodes in patients with inhibitory antibodies to Factor VIII or Factor IX. Previously, we showed that expression of murine FVIIa (mFVIIa) from an adeno-associated viral (AAV) vector corrected abnormal hemostatic parameters in hemophilia B mice. To pursue this as a therapeutic approach, we sought to define safe and effective levels of FVIIa for continuous expression. In mice transgenic for mFVIIa or injected with AAV-mFVIIa, we analyzed survival, expression levels, in vitro and in vivo coagulation tests, and histopathology for up to 16 months after birth/mFVIIa expression. We found that continuous expression of mFVIIa at levels at or below 1.5 microg/ml was safe, effective, and compatible with a normal lifespan. However, expression levels of 2 microg/ml or higher were associated with thrombosis and early mortality, with pathologic findings in the heart and lungs that were rescued in a low-factor X (low-FX) mouse background, suggesting a FX-mediated effect. The findings from these mouse models of continuous FVIIa expression have implications for the development of a safe gene transfer approach for hemophilia and are consistent with the possibility of thromboembolic risk of continuously elevated FVIIa levels.
Indomethacin increases plasma lithium.
Authors: J C Frolich, R Leftwich, M Ragheb, J A Oates, I Reimann, D Buchanan
Journal: BMJ (1979)

The effects of indomethacin on plasma lithium concentrations and renal lithium clearance were investigated in three psychiatric patients and four normal volunteers. After steady-state plasma lithium concentrations had been reached, the subjects received indomethacin placebo for three to seven days, indomethacin (50 mg thrice daily) for seven days, and placebo again for three to seven days. Indomethacin increased plasma lithium concentrations by 59% in the psychiatric patients and 30% in the volunteers. Renal lithium clearance was reduced by indomethacin by 31% in the group as a whole, and prostaglandin synthesis, determined by measuring the major metabolite of PGE2 with mass spectrometry, was reduced by 55%. These results show that indomethacin reduces renal lithium clearance to an extent which may be clinically important. They also suggest that the renal clearance may be affected by a prostaglandin-dependent mechanism, possibly located in the distal tubule.
Ethnic Differences in the Prognostic Value of Stress Technetium-99m Tetrofosmin Gated Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging
Authors: Leslee J. Shaw, Robert C. Hendel, Manuel Cerquiera, Jennifer H. Mieres, Naomi Alazraki, Elizabeth Krawczynska, Salvador Borges-Neto, Jamshid Maddahi, C. Noel Bairey Merz
Journal: Journal of the American College of Cardiology (2005)
Transcriptome Analysis Reveals that p53 and β-Catenin Alterations Occur in a Group of Aggressive Adrenocortical Cancers
Authors: Bruno Ragazzon, Rossella Libé, Sébastien Gaujoux, Guillaume Assié, Amato Fratticci, Pierre Launay, Eric Clauser, Xavier Bertagna, Frédérique Tissier, Aurélien de Reyniès, Jérôme Bertherat
Journal: Cancer Research (2010)

Adrenocortical carcinoma (ACC) is a rare disease with an overall poor but heterogeneous prognosis. This heterogeneity could reflect different mechanisms of tumor development. Gene expression profiling by transcriptome analysis led to ACC being divided into two groups of tumors with very different outcomes. Somatic inactivating mutations of the tumor suppressor gene TP53 and activating mutations of the proto-oncogene β-catenin (CTNNB1) are the most frequent mutations identified in ACC. This study investigates the correlation between p53 and β-catenin alterations and the molecular classification of ACC by transcriptome analysis of 51 adult sporadic ACCs. All TP53 and CTNNB1 mutations seemed to be mutually exclusive and were observed only in the poor-outcome ACC group. Most of the abnormal p53 and β-catenin immunostaining was also found in this group. Fifty-two percent of the poor-outcome ACC group had TP53 or CTNNB1 mutations and 60% had abnormal p53 or β-catenin immunostaining. Unsupervised clustering transcriptome analysis of this poor-outcome group revealed three different subgroups, two of them being associated with p53 or β-catenin alterations, respectively. Analysis of p53 and β-catenin target gene expressions in each cluster confirmed a profound and anticipated effect on tumor biology, with distinct profiles logically associated with the respective pathway alterations. The third group had no p53 or β-catenin alteration, suggesting other unidentified molecular defects. This study shows the important respective roles of p53 and β-catenin in ACC development, delineating subgroups of ACC with different tumorigenesis and outcomes.
IMPACT OF LOW–PROFILE SHEATHS ON VASCULAR COMPLICATION AND BLEEDING DURING TRANSFEMORAL TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Marco Barbanti, Ronald Binder, Melanie Freeman, David Wood, Jonathon Leipsic, Anson Cheung, Jian Ye, Stefan Toggweiler, John Webb
Journal: Journal of the American College of Cardiology (2013)
The Case for Social Medicine
Authors: Komal Kothari
Journal: JAMA (2014)

The first patient I ever interviewed as a medical student was a middle-aged woman named Barbara. Wearing my crisp new white coat, the pockets yet unburdened with a physician’s paraphernalia, I walked in with only the intention of having a conversation. I discovered that Barbara had kidney failure and needed dialysis three times a week, which restricted her to working part-time. Barbara now had a systemic infection, for the third time in the past few months, which required an emergency department visit and a week-long hospitalization. She would be following up with her primary care physician and nephrologist, who are in different locations from the dialysis center she attends. A few weeks later, I met Lisa in the emergency department. She suffered from an acute exacerbation of chronic pancreatitis and was in excruciating pain. After gathering her medical history, I asked Lisa where she lived. Holding back tears, she said that she had been a nurse, but now lived in a homeless shelter with her 8-year old daughter.
Antinuclear Antibodies in Systemic Lupus Erythematosus
Authors: MERRILL D. BENSON
Journal: Annals of Internal Medicine (1970)

A new method for performing the antinuclear antibody test using antibody labeled with horseradish peroxidase is described. Rabbit antibody to human IgG was conjugated to horseradish peroxidase and used to demonstrate adherence of antinuclear antibodies to the nuclei of mouse liver. Localization of the enzyme was demonstrated by its reaction with 3,3′ diaminobenzidine, which gives an insoluble brown reaction product. Sera from patients with systemic lupus erythematosus and other connective tissue diseases were tested. Thirty-four of 36 patients with systemic lupus erythematosus, 8 of 25 patients with rheumatoid arthritis, and 6 of 11 patients with progressive systemic sclerosis had demonstrable antinuclear antibodies by the peroxidase technique as compared with none of 17 normal controls. These results correlated well with the standard test using antibody labeled with fluorescein isothiocyanate. Sera from patients with systemic lupus erythematosus generally had a higher titer of antinuclear antibody than sera from patients with rheumatoid arthritis or progressive systemic sclerosis. Patterns of nuclear staining were observed in the peroxidase technique and appeared to correlate with the patterns obtained by the fluorescent antibody method. Advantages of peroxidase-labeled antibody included reproducibility of the technique, ease of standardization, lack of nonspecific staining, and use of conventional light microscope.
Life or Death—Whose Decision?
Authors: William P. Williamson
Journal: JAMA (1966)

Nineteen hundred years ago, Seneca, a Roman philosopher, said, "Death is sometimes a punishment, often a gift, and to many, is a favor." As physicians, we naturally become deeply involved in matters of life and death. Most of us believe, and essentially all religions hold, that the life of each individual is a creation of the Almighty, that supreme mastery over life belongs to the Creator, and that it is man's obligation to conserve human life as one of the noblest creations of God. Yet, whether he likes it or not, the physician's skills, decisions, and the treatments he renders, often determine life or death for his patient. <h3>The Problem</h3> This problem has become more complex because of the tremendous strides made by modern medicine. Improved understanding of body physiology and chemistry, potent drugs, remarkably efficient mechanical respirators, pacemakers, and artificial organs, combined with aggressive medical and nursing care, have
Incidence of antiarrhythmic drug use in aicd patients with high defibrillation thresholds
Authors: Andrew Epstein, G.Neal Kay, Sharon Dailey, Vance Plumb, Kenneth Ellenbogen, Andra Thomas, David Cannom, Peter Chapman, Debra Echt, Richard Fogoros, John Hummel, Joseph Levine, James Maloney, Gerald Naccarelli, Enrico Veltri
Journal: Journal of the American College of Cardiology (1991)
Increase in acute admissions and deaths after closing a geriatric day hospital.
Authors: P N Berrey
Journal: BMJ (1986)

In 1978 the normal function of a large geriatric day hospital was halted by 16 weeks of industrial action. Comparing affected patients with a matched control population for the years 1974-80 showed an appreciable increase in acute hospital admissions and deaths of those affected by the stoppage, which suggests an obvious benefit for those who are selected for attendance at a geriatric day hospital. Neither the number of acute admissions nor the number of deaths during the two months after normal services were resumed differed appreciably from those in the control years. No single cause predominates among those reported for acute admission or death during the affected year. These findings are relevant given the recent closure of several day hospitals by health authorities to cut costs. There are no published figures showing unequivocal benefits for attendance at day hospitals, and many clinicians remain unaware of their function. Yet adequate provision for day hospitals may ease the pressure on more costly acute hospital beds.
In situ identification and enumeration of T lymphocytes in cutaneous T-cell lymphomas by demonstration of granular activity of acid non-specific esterase
Authors: WOLFRAM STERRY, GERD-KLAUS STEIGLEDER, HELMUT PULLMANN
Journal: British Journal of Dermatology (1980)

Journal Article In situ identification and enumeration of T lymphocytes in cutaneous T‐cell lymphomas by demonstration of granular activity of acid non‐specific esterase Get access WOLFRAM STERRY, WOLFRAM STERRY Department of Dermatology, University of Cologne, Germany Dr Wolfram Sterry, Universitäts‐Hautklinik Koln, Joseph‐Stelzmann‐Str. 9, D‐5000 Koln 41, Federal Republic of Germany. Search for other works by this author on: Oxford Academic Google Scholar GERD‐KLAUS STEIGLEDER, GERD‐KLAUS STEIGLEDER Department of Dermatology, University of Cologne, Germany Search for other works by this author on: Oxford Academic Google Scholar HELMUT PULLMANN HELMUT PULLMANN Department of Dermatology, University of Cologne, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 103, Issue 1, 1 July 1980, Pages 67–72, https://doi.org/10.1111/j.1365-2133.1980.tb15839.x Published: 01 July 1980
Transformation of interleukin-3–dependent cells without participation of Stat5/bcl-xL: cooperation of akt with raf/erk leads to p65 nuclear factor κB–mediated antiapoptosis involving c-IAP2
Authors: Vasily M. Gelfanov, Gem S. Burgess, Sara Litz-Jackson, Alastair J. King, Mark S. Marshall, Harikrishna Nakshatri, H. Scott Boswell
Journal: Blood (2001)
Preferential X chromosome loss but random inactivation characterize primary biliary cirrhosis†
Authors: Monica Miozzo, Carlo Selmi, Barbara Gentilin, Francesca R. Grati, Silvia Sirchia, Sabine Oertelt, Massimo Zuin, M. Eric Gershwin, Mauro Podda, Pietro Invernizzi
Journal: Hepatology (2007)

Recent work has demonstrated enhanced X monosomy in women with primary biliary cirrhosis (PBC) as well as two other female-predominant autoimmune diseases, systemic sclerosis and autoimmune thyroid disease. To further our understanding of these events, we have investigated the mechanisms of X chromosome loss and X chromosome inactivation (XCI) in 166 women with PBC and 226 rigorously age-matched healthy and liver disease controls. X chromosome analysis and determination of loss pattern was performed by quantitative fluorescent polymerase chain reaction (QF-PCR) with 4 X-linked short tandem repeats. Further definition of the XCI was based on analysis of methylation-sensitive restriction sites. Importantly, in PBC the X chromosome loss occurs not only more frequently but also in a preferential fashion. This observation supports our thesis that the enhanced X monosomy involves only one parentally derived chromosome and is not secondary to a constitutive non random pattern of XCI. In fact, in the presence of monosomy, the lost X chromosome is necessarily the inactive homologue. Conclusion: The finding that the X chromosome loss is preferential suggests the critical involvement of X chromosome gene products in the female predisposition to PBC and also emphasizes the need to determine the parental origin of the maintained chromosome to investigate the role of imprinting. (HEPATOLOGY 2007.)
In vivo X-ray fluorescence of lead in bone: review and current issues.
Authors: A C Todd, D R Chettle
Journal: Environmental Health Perspectives (1994)

Bone lead measurements can assess long-term lead dosimetry because the residence time of lead in bone is long. Bone lead measurements thus complement blood and plasma lead measurements, which reflect more short-term exposure. Although the noninvasive, in vivo measurement of lead in bone by X-ray fluorescence (XRF) has been under development since the 1970s, its use is still largely confined to research institutions. There are three principal methods used that vary both in the how lead X-rays are fluoresced and in which lead X-rays are fluoresced. Several groups have reported the independent development of in vivo measurement systems, the majority adopting the 109Cd K XRF method because of its advantages: a robust measurement, a lower detection limit (compared to 57Co K XRF), and a lower effective (radiation) dose (compared to L XRF) when calculated according to the most recent guidelines. These advantages, and the subsequent widespread adoption of the 109Cd method, are primarily consequences of the physics principles of the technique. This paper presents an explanation of the principles of XRF, a description of the practical measurement systems, a review of the human bone lead studies performed to date; and a discussion of some issues surrounding future application of the methods.
The novel arsenical Darinaparsin circumvents BRG1-dependent, HO-1-mediated cytoprotection in leukemic cells
Authors: N Garnier, L A Petruccelli, M F Molina, M Kourelis, S Kwan, Z Diaz, H M Schipper, A Gupta, S V del Rincon, K K Mann, W H Miller
Journal: Leukemia (2013)
Facts and Artifacts About Anemia and Preterm Delivery
Authors: Ellice Lieberman
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Klebanoff et al,<sup>1</sup>in the July 28 issue of<i>JAMA</i>, examined hematocrit and preterm birth to determine if that association is an artifact related to changes in maternal hematocrit during pregnancy. We appreciate their efforts in attempting to resolve this difficult issue. In our initial consideration of this problem,<sup>2,3</sup>we also were concerned about possible artifact and examined the literature and our data to determine if changes in maternal hematocrit during pregnancy were a likely explanation for our results. In the literature, we did not find support for the substantial increases in hematocrit between 25 to 30 weeks and term suggested by Klebanoff et al. Several articles<sup>4-6</sup>report changes of 1.1 percent or less between 25 to 30 weeks and term. Nilsen et al,<sup>7</sup>who Klebanoff et al cite as noting larger changes, actually found maximum hemoglobin level increases of 5 g/L (a
Lymphomatoid granulomatosis presenting with ornithosis pneumonia.
Authors: R M Graham, I W Fawcett
Journal: BMJ (1984)

Publication du 6eme cas connu de granulomatose lymphomatoide dans le Royaume Uni. On observe en meme temps une pneumopathie ornithosique (inclusions intracytoplasmiques de Levinthal-Coles-Lillie)
The Role of Viruses in the Etiology of Cancer and Leukemia
Authors: Ludwik Gross
Journal: JAMA (1974)

This paper describes the development of the concept of "vertical transmission" of oncogenic viruses from one generation to another; the introduction of newborn mice for bioassay of oncogenic viruses; the discovery of the viral etiology of mouse leukemia and the isolation of the mouse leukemia virus; the clarification of the epidemiology of mouse leukemia on the basis of experimental demonstration that the mouse leukemia virus is transmitted from one generation to another directly through the embryos; the demonstration that radiation-induced leukemia in mice is caused by a virus; and the fortuitous isolation of a previously unknown and unsuspected oncogenic virus, the polyoma virus in mice. (<i>JAMA</i>230:1029-1032, 1974)
The promise of an ecological, evolutionary approach to culture and language
Authors: Edward Kako
Journal: Behavioral and Brain Sciences (2001)

Dichotomous definitions of culture and language do not generate productive questions. Instead, more progress can be made by identifying components of each that other animals might plausibly possess. The evolutionary, ecological approach advocated by Rendell and Whitehead holds great promise for helping us to understand the conditions under which natural selection can favor similar capacities in differently organized brains.
Interval Brain Scanning With Sodium Pertechnetate Tc 99m for Tumor Detectability
Authors: Gary F. Gates
Journal: JAMA (1971)

Brain scans were performed on patients during the first hour following injection of sodium pertechnetate Tc 99m, and selected patients were rescanned 1 to 24 hours later. Eighty brain tumors were found among nearly 1,500 patients scanned during a two-year period. Diagnoses were established for 74 through histological examination, and for 6, through clinical, scan, and neuroradiological findings. Forty were scanned twice, and in 15 the early scans were normal or equivocal. Fourteen of these 15 had abnormal findings upon rescanning. Twenty-six nondiagnostic to moderately abnormal early scans increased in their degree of abnormality upon rescanning. The detectability of brain tumors improved from 80% with routine early scanning, to 93% with rescanning. The optimal time for repeated scanning is three to four hours following tracer injection.
Relationships of serum plant sterols (phytosterols) and cholesterol in 595 hypercholesterolemic subjects, and familial aggregation of phytosterols, cholesterol, and premature coronary heart disease in hyperphytosterolemic probands and their first-degree relatives
Authors: Charles J. Glueck, James Speirs, Trent Tracy, Patricia Streicher, Ellen Illig, Janet Vandegrift
Journal: Metabolism (1991)
'I'll have mine with a twist of lemon'. Quinine photosensitivity from excessive intake of tonic water
Authors: G.H. Wagner, B.L. Diffey, F.A. Ive
Journal: British Journal of Dermatology (1994)

Journal Article 'I'll have mine with a twist of lemon'. Quinine photosensitivity from excessive intake of tonic water Get access G.H. Wagner, G.H. Wagner Department of Dermatology, Dryburn Hospital, Durham DH1 5TW, U. K. Search for other works by this author on: Oxford Academic Google Scholar B.L. Diffey, B.L. Diffey Department of Medical Physics, Dryburn Hospital, Durham DH1 5TW, U. K. Search for other works by this author on: Oxford Academic Google Scholar F.A. Ive F.A. Ive Department of Dermatology, Dryburn Hospital, Durham DH1 5TW, U. K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 131, Issue 5, 1 November 1994, Pages 734–735, https://doi.org/10.1111/j.1365-2133.1994.tb04995.x Published: 01 November 1994
Is inflammation the missing link between low fat mass and low survival in hemodialysis patients?
Authors: G. Tsirpanlis, S. Chatzipanagiotou, F. Boufidou, V. Kordinas, F. Alevyzaki, M. Zoga, A. Fatourou, N. Sabanis, A. Ioannidis, C. Nicolaou
Journal: Kidney International (2006)