tbuckley/cabot-search huggingface dataset:
Targeted Integration of Functional Human ATM cDNA Into Genome Mediated by HSV/AAV Hybrid Amplicon Vector
Authors: Maria L Cortés, Angelika Oehmig, Okay Saydam, Jocelyn D Sanford, Katherine F Perry, Cornel Fraefel, Xandra O Breakefield
Journal: Molecular Therapy (2007)

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by neurodegeneration, immunodeficiency, cancer predisposition, genome instability, and sensitivity to ionizing radiation (IR). We have previously shown that a herpes simplex virus type 1 (HSV-1) amplicon vector carrying the human ataxia-telangiectasia mutated (ATM) complementary DNA (cDNA) is able to correct aspects of the cellular phenotype of human A-T cells in culture, and is also able to transfer the ATM cDNA to the Atm–/– mouse cerebellum. In order to achieve stable gene replacement, we have generated an HSV/adeno-associated virus (AAV) hybrid amplicon vector carrying the expression cassettes for the ATM cDNA [(9.2 kilobases (kb)] and enhanced green fluorescent protein (EGFP), flanked by AAV inverted terminal repeats (ITRs). This hybrid vector, in the presence of AAV Rep proteins, mediates site-specific integration into the AAVS1 site on chromosome 19 in human cells and in Atm–/– mice carrying that human locus. The functional activity of the vector-derived ATM was confirmed in vitro and in vivo by ATM autophosphorylation at Ser-1981 after IR. This proof-of-principle study establishes the ability of HSV/AAV hybrid amplicon vectors to mediate functional targeted integration of the ATM cDNA into A-T cells in culture and in Atm–/– mice in vivo, thus laying a foundation for possible gene therapy approaches in the treatment of A-T patients. Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by neurodegeneration, immunodeficiency, cancer predisposition, genome instability, and sensitivity to ionizing radiation (IR). We have previously shown that a herpes simplex virus type 1 (HSV-1) amplicon vector carrying the human ataxia-telangiectasia mutated (ATM) complementary DNA (cDNA) is able to correct aspects of the cellular phenotype of human A-T cells in culture, and is also able to transfer the ATM cDNA to the Atm–/– mouse cerebellum. In order to achieve stable gene replacement, we have generated an HSV/adeno-associated virus (AAV) hybrid amplicon vector carrying the expression cassettes for the ATM cDNA [(9.2 kilobases (kb)] and enhanced green fluorescent protein (EGFP), flanked by AAV inverted terminal repeats (ITRs). This hybrid vector, in the presence of AAV Rep proteins, mediates site-specific integration into the AAVS1 site on chromosome 19 in human cells and in Atm–/– mice carrying that human locus. The functional activity of the vector-derived ATM was confirmed in vitro and in vivo by ATM autophosphorylation at Ser-1981 after IR. This proof-of-principle study establishes the ability of HSV/AAV hybrid amplicon vectors to mediate functional targeted integration of the ATM cDNA into A-T cells in culture and in Atm–/– mice in vivo, thus laying a foundation for possible gene therapy approaches in the treatment of A-T patients.
Recruiting for Primary Care
Authors: N G Levinsky
Journal: New England Journal of Medicine (1993)

It is widely agreed that for optimal delivery of health care, half or more of all doctors should be primary care physicians1,2. Nevertheless, unmoved by considerations of national need, a high and increasing proportion of graduates of U.S. medical schools are choosing to become specialists. Moreover, surveys indicate that many established primary care practitioners are unhappy with their practices3. This growing discordance between policy and reality has led policy makers, practitioners, and academics to suggest a variety of programs to increase the number of generalists. These proposals can be grouped into two categories. One group emphasizes changes . . .
WORCESTER GENERAL INFIRMARY: CASES OF FATAL OBSTRUCTION OF THE BOWEL BY CANCEROUS DEPOSIT
Authors: J. Malden, H. D. Carden
Journal: BMJ (1856)

Sneral, which should constitute a valid objection to the uee of chloroform in an operation which is advisable in such a state of health.More care may be needed in one subject than in another; but this may be said of almost every medicinal agent powerful enough to be worth anything.The " accidents", as they are called, which have happeued now and then, have arisen, in many cases, I think,-I hardly like to utter my fears-from some want of care in the person giving it.If the administration of it is intrusted to you, take care that your attention, while students, and hereafter as practitioners, of surgery, does not wander from the patient's chest, and your finger from his pulse, to the more interesting features of the case, lest you smother the patient with the napkin on which you -dropped some smal dose of the drug.Remember, such a
Treatment-Related Leukemia
Authors: Charles A. Coltman, Steve Dahlberg
Journal: New England Journal of Medicine (1990)

The majority of the published studies addressing the question of treatment-related leukemia used cohort methods of analysis in which the incidence of leukemia was measured among patients treated for primary cancer. Comparisons of the risk of leukemia have been made between patients and age- and sex-matched populations or between subsets of patients treated with different regimens. There may be bias associated with these methods,1 in that patients with Hodgkin's disease, for example, may differ from the "normal" population with respect to the risk of leukemia. The differences could include the more careful follow-up of patients with Hodgkin's disease, or more . . .
676. Local Stimulation of Articular Cartilage Repair by Transplantation of Encapsulated Chondrocytes Overexpressing Human FGF-2 In Vivo
Authors: Gunter Kaul, Magali Cucchiarini, David Zurakowski, StephenB. Trippel, Dieter Kohn, Henning Madry
Journal: Molecular Therapy (2005)

Background: Defects of articular cartilage are an unsolved problem in orthopaedics. Application of fibroblast growth factor-2 (FGF-2) protein has been demonstrated to modulate articular cartilage repair in vivo. We previously reported that overexpression of FGF-2 selectively stimulated cell proliferation in an ex vivo model of chondrocyte transplantation and that transgene expression remains present in vivo for at least 30 days when transfected chondrocytes are implanted in osteochondral cartilage defects. In the present study, we tested the hypothesis that gene transfer of human fibroblast growth factor 2 (FGF-2) via transplantation of encapsulated genetically modified articular chondrocytes stimulates chondrogenesis in cartilage defects in vivo.
Congenital Aortic Stenosis Resulting From a Unicommissural Valve
Authors: M. WAYNE FALCONE, WILLIAM C. ROBERTS, ANDREW G. MORROW, JOSEPH K. PERLOFF
Journal: Circulation (1971)

Clinical, electrocardiographic, phonocardiographic, radiographic, hemodynamic, and anatomic findings are presented in 21 adult patients with stenotic unicommissural aortic valves. Distinction between congenitally unicuspid and bicuspid aortic valves before operation or autopsy was not possible. Although the basic structure of the valve may render it inherently stenotic, the age at which a murmur was first noted (average, 19 years), the duration of a known murmur (average, 25 years), and the age of onset of first symptoms of left ventricular outflow obstruction (average, 41 years) strongly suggest that stenosis at least in part is acquired. The relationship of the true and false commissures to the coronary arterial ostia could be determined with certainty in 12 patients. The basic division of the aortic valve into left, right, and noncoronary cusps is maintained, but the raphes do not extend to the valve orifice. Because the aortic valve is attached to the ascending aorta at only one point (the true commissure), which is at the level of the orifice, valvotomy is hazardous, and valve replacement appears indicated when operative treatment becomes necessary in the adult patient with a stenotic unicommissural aortic valve.
Building-Associated Risk of Febrile Acute Respiratory Disease-Reply
Authors: John F. Brundage
Journal: JAMA (1988)

<h3>In Reply.—</h3> The letters of Drs Lipinski and Hodgson emphasize the point that many characteristics of indoor air are modified by mechanical ventilation systems. They suggest several specific components of indoor air as potential determinants of the health effects observed in our study. Since our report was based on routinely gathered surveillance data, we do not have information regarding the physical characteristics of the air inside the modern or old barracks during the study period. We recognize the practical significance of defining relationships of specific physical characteristics of indoor air with infectious and other health risks. In this regard, the letters emphasize an important point: since many characteristics of indoor air are affected by mechanical ventilation, studies of the health effects of specific components of indoor air must account for the potentially confounding effects of physical characteristics that concurrently vary. Until such technically difficult studies are done, however, attempts to
Everolimus-Eluting versus Paclitaxel-Eluting Stents in Coronary Artery Disease
Authors: Gregg W. Stone, Ali Rizvi, William Newman, Kourosh Mastali, John C. Wang, Ronald Caputo, Julie Doostzadeh, Sherry Cao, Charles A. Simonton, Krishnankutty Sudhir, Alexandra J. Lansky, Donald E. Cutlip, Dean J. Kereiakes
Journal: New England Journal of Medicine (2010)

Previous studies have established the superiority of coronary everolimus-eluting stents over paclitaxel-eluting stents with respect to angiographic findings. However, these trials were not powered for superiority in clinical end points.We randomly assigned 3687 patients at 66 U.S. sites to receive everolimus-eluting stents or paclitaxel-eluting stents without routine follow-up angiography. The primary end point was the 1-year composite rate of target-lesion failure (defined as cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization).Everolimus-eluting stents were superior to paclitaxel-eluting stents with respect to the primary end point of target-lesion failure (4.2% vs. 6.8%; relative risk, 0.62; 95% confidence interval, 0.46 to 0.82; P=0.001). Everolimus-eluting stents were also superior with respect to the major secondary end point of the 1-year rate of ischemia-driven target-lesion revascularization (P=0.001) and were noninferior with respect to the major secondary end point of the 1-year composite rate of cardiac death or target-vessel myocardial infarction (P<0.001 for noninferiority; P=0.09 for superiority). The 1-year rates of myocardial infarction and stent thrombosis were also lower with everolimus-eluting stents than with paclitaxel-eluting stents (1.9% vs. 3.1%, P=0.02 for myocardial infarction; 0.17% vs. 0.85%, P=0.004 for stent thrombosis). Target-lesion failure was consistently reduced with everolimus-eluting stents as compared with paclitaxel-eluting stents in 12 prespecified subgroups, except in the subgroup of patients with diabetes (6.4% vs. 6.9%, P=0.80).Everolimus-eluting stents, as compared with paclitaxel-eluting stents, resulted in reduced rates of target-lesion failure at 1 year, results that were consistent in all patients except those with diabetes, in whom the results were nonsignificantly different. (ClinicalTrials.gov number, NCT00307047.)
How small changes led to big profits for insulin manufacturers
Authors: D. Cohen, P. Carter
Journal: BMJ (2010)

In the first of a series of investigations by the <i>BMJ</i> and <i>Channel 4 News, </i><b>Deborah Cohen and Philip Carter</b> discover why more expensive analogue insulins are increasingly prescribed instead of cheaper human insulin despite lack of evidence of benefit for patients with type 2 diabetes
Primary Care Research
Authors: J. Jarrett Clinton
Journal: JAMA (1993)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Trichostatin A enhances proliferation and migration of vascular smooth muscle cells by downregulating thioredoxin 1
Authors: Seungjeong Song, Sang Won Kang, Chulhee Choi
Journal: Cardiovascular Research (2009)

A reduction in the level of thioredoxin 1 (Trx1) has been proposed as a possible mechanism for the tumor-specific growth arrest caused by inhibition of histone deacetylases (HDACs). In this study, we investigated the effect of trichostatin A (TSA), a potent HDAC inhibitor, on the proliferation and migration of vascular smooth muscle cells (VSMCs), and we examined the role of reduced Trx1 levels in this effect. TSA treatment time-dependently decreased Trx1 expression in rat VSMCs at both the mRNA and protein levels. It also enhanced platelet-derived growth factor (PDGF)-induced proliferation and migration of the VSMCs. By potentiating Akt phosphorylation, the siRNA-induced downregulation of Trx1 also enhanced VSMC proliferation and migration in response to PDGF or serum treatment. Consistent with these results, TSA administration increased neointimal thickening in a murine model of post-angioplastic restenosis. These data demonstrate that TSA enhances vascular proliferative activity by downregulating Trx1, thus activating an Akt-dependent pathway. Our results indicate that, in addition to its apoptotic effects in tumour cells, the downregulation of Trx1 has a proliferative role in primary VSMCs.
siRNA Targeting Hes5 Augments Hair Cell Regeneration in Aminoglycoside-damaged Mouse Utricle
Authors: Jae Yun Jung, Matt R. Avenarius, Swetlana Adamsky, Evgenia Alpert, Elena Feinstein, Yehoash Raphael
Journal: Molecular Therapy (2013)

Notch signaling is active during the development of mosaic epithelial sheets and during their turnover and regeneration. After the loss of hair cells in the mosaic sheet of the vestibular sensory epithelium, new hair cells can be spontaneously generated by transdifferentiation of supporting cells. This regenerative process involves downregulation of the Hes5 gene and is known to be limited and incomplete, especially when the lesion is severe. Here, we test whether further downregulation of Hes5 gene accomplished by the use of siRNA after a severe lesion induced by an aminoglycoside in the mouse utricle can enhance the transdifferentiation of supporting cells and lead to the increased production of new hair cells. We demonstrate that Hes5 levels in the utricle decreased after the application of siRNA and that the number of hair cells in these utricles was significantly larger than following control treatment. The data suggest that siRNA technology may be useful for inducing repair and regeneration in the inner ear and that the Notch signaling pathway is a potentially useful target for specific gene expression inhibition. Notch signaling is active during the development of mosaic epithelial sheets and during their turnover and regeneration. After the loss of hair cells in the mosaic sheet of the vestibular sensory epithelium, new hair cells can be spontaneously generated by transdifferentiation of supporting cells. This regenerative process involves downregulation of the Hes5 gene and is known to be limited and incomplete, especially when the lesion is severe. Here, we test whether further downregulation of Hes5 gene accomplished by the use of siRNA after a severe lesion induced by an aminoglycoside in the mouse utricle can enhance the transdifferentiation of supporting cells and lead to the increased production of new hair cells. We demonstrate that Hes5 levels in the utricle decreased after the application of siRNA and that the number of hair cells in these utricles was significantly larger than following control treatment. The data suggest that siRNA technology may be useful for inducing repair and regeneration in the inner ear and that the Notch signaling pathway is a potentially useful target for specific gene expression inhibition.
Development of gap junctional channels and intercellular communication in rat liver during ontogenesis
Authors: Masaki Iwai, Yoshinori Harada, Akira Muramatsu, Saiyu Tanaka, Takahiro Mori, Takeshi Okanoue, Fumitaka Katoh, Toshifumi Ohkusa, Kei Kashima
Journal: Journal of Hepatology (2000)
Pain Evaluation and Management in the Nursing Home
Authors: Bruce A. Ferrell
Journal: Annals of Internal Medicine (1995)

As many as 45% to 80% of nursing home residents have pain that contributes materially to functional impairment and decreased quality of life. Substantial barriers, including a high frequency of dementia, multiple pain problems, and increased sensitivity to drug side effects often make pain assessment and management more difficult in the nursing home setting. Logistic problems in carrying out diagnostic procedures and management interventions are also common. Pain can be alleviated in nursing homes through the careful use of analgesic drugs combined with nonpharmacologic strategies, including exercise programs and other physical therapies. Elderly nursing home residents are more sensitive to the side effects associated with many analgesic drugs, but this does not justify the failure to treat pain, especially in those who are terminally ill or near the end of life. Structured programs for routine pain assessment and treatment are needed. Physician involvement in pain assessment and management is necessary if pain control is to be improved for nursing home patients.
Diverse marrow stromal cells protect CLL cells from spontaneous and drug-induced apoptosis: development of a reliable and reproducible system to assess stromal cell adhesion-mediated drug resistance
Authors: Antonina V. Kurtova, Kumudha Balakrishnan, Rong Chen, Wei Ding, Susanne Schnabl, Maite P. Quiroga, Mariela Sivina, William G. Wierda, Zeev Estrov, Michael J. Keating, Medhat Shehata, Ulrich Jäger, Varsha Gandhi, Neil E. Kay, William Plunkett, Jan A. Burger
Journal: Blood (2009)
M26 Teaching students to prescribe oxygen safely: the impact of an e-Learning module and BTS oxygen prescription section on oxygen prescribing by medical students taking Final MBBS examinations
Authors: D Hammersley, LJE Smith, D Furmedge, C Ward, S Kennedy, LJ Restrick, A Sturrock
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> National audits show oxygen prescribing is not consistently safe, despite BTS Emergency Oxygen Guidelines. We previouslyidentified that medical students were unable to safely prescribe oxygen at final MBBS examinations.<sup>1</sup> A compulsory e-Learning module was introduced to address this unmet educational need. We assessed the impact of this intervention in 2013. <h3>Methods</h3> An Oxygen Prescribing Final MBBS OSCE station was used in 2012 and 2013. In 2013 candidates (350) completed a new compulsory oxygen e-Learning module. Candidates in 2012 (227) had not. In 2013 the exam prescription chart also included an oxygen prescription section. Each year, candidates were presented with one of two clinical scenarios. Scenario 1: 72-year-old patient with COPD, and Scenario 2: 72-year-old hypoxic patient without respiratory disease. Oxygen prescriptions were assessed against BTS standards across a number of domains. They were classified as 9safe/unsafe9 and 9perfect/imperfect9 by a respiratory nurse specialist. <h3>Results</h3> Some improvements were seen in both scenarios (See Table 1), particularly prescription of the correct target saturation range. In 2012 40% (42/105) prescribed correct range for the non-COPD scenario; in 2013 this was 98% (154/156). <h3>Conclusions</h3> Introducing an oxygen e-Learning module and BTS-recommended oxygen prescription section resulted in improved competence and safety of oxygen prescribing with significant improvement in correct target saturation ranges. However, students still have gaps in equipment knowledge and a high proportion did not prescribe oxygen safely for a patient without respiratory disease. The e-Learning module was undertaken by students at a point close to examinations; moving this earlier in the year may lead to better engagement and improve the understanding of oxygen prescribing in non-COPD patients, emphasised in the module. Safer prescribing is enabled by oxygen prescription sections with target range saturation choices but equipment education is also needed. Adverse consequences of incorrect oxygen use continue to cause patients harm. Ensuring undergraduates have the practical knowledge and skills to prescribe oxygen safely is essential. <h3>Reference</h3> D Hammersley, A Connor, C Ward, <i>et al</i>. Competence in, and safety of, oxygen prescribing by medical students taking Final MBBS as assessed by Objective Structured Clinical Examination. <i>Thorax </i>2012; 67(Suppl 2):A168
Hepatic Presentation on Bone Scintigraphy of a Patient With Acute Hepatic Failure
Authors: YUH-FENG WANG, SHIOU-CHI CHERNG, HENG-CHEN CHU, TSU-KANG JEN, WEN-SHENG HUANG
Journal: Clinical Nuclear Medicine (1999)

A 70-year-old man with possible pulmonary tuberculosis had taken antituberculosis therapy for 2 months. Dyspnea and abdominal fullness developed and he was found to have acute hepatitis. The antituberculosis drugs were discontinued and his liver enzyme levels decreased rapidly within 5 days. The patient died on the fifth day of acute hepatic failure. Bone scintigraphy done on the third day to exclude pulmonary malignancy with bone metastases showed intense hepatic uptake, probably caused by hepatic necrosis. FIGURE 1Fig. 1: (A) Tc-99m MDP whole-body bone scan and (B) the abdominal planar image of a 70-year-old patient with acute hepatitis. Nonvisualization of his left kidney was caused by severe hydronephrosis, which was confirmed by CT scan. Diffuse hepatic uptake is demonstrated. Because other patients injected with the same batch of radiopharmaceutical did not show liver radioactivity, changes possibly due to chemical purity and constitution could be excluded. Given his clinical history, laboratory biochemical data, and change in mental condition, it is likely that general hepatic necrosis from antituberculosis drug-induced hepatic failure resulted in increased hepatic radioactivity on scintigraphy (1–3). Caution must be exercised with patients who have poor hepatic function and who show hepatic uptake of a bone imaging agent (4).