tbuckley/cabot-search huggingface dataset:
Meganuclease-mediated Virus Self-cleavage Facilitates Tumor-specific Virus Replication
Authors: Engin Gürlevik, Peter Schache, Anneliese Goez, Arnold Kloos, Norman Woller, Nina Armbrecht, Michael P Manns, Stefan Kubicka, Florian Kühnel
Journal: Molecular Therapy (2013)

Meganucleases can specifically cleave long DNA sequence motifs, a feature that makes them an ideal tool for gene engineering in living cells. In a proof-of-concept study, we investigated the use of the meganuclease I-Sce I for targeted virus self-disruption to generate high-specific oncolytic viruses. For this purpose, we provided oncolytic adenoviruses with a molecular circuit that selectively responds to p53 activation by expression of I-Sce I subsequently leading to self-disruption of the viral DNA via heterologous I-Sce I recognition sites within the virus genome. We observed that virus replication and cell lysis was effectively impaired in p53-normal cells, but not in p53-dysfunctional tumor cells. I-Sce I activity led to effective intracellular processing of viral DNA as confirmed by detection of specific cleavage products. Virus disruption did not interfere with E1A levels indicating that reduction of functional virus genomes was the predominant cause for conditional replication. Consequently, tumor-specific replication was further enhanced when E1A expression was additionally inhibited by targeted transcriptional repression. Finally, we demonstrated p53-dependent oncolysis by I-Sce I-expressing viruses in vitro and in vivo, and demonstrated effective inhibition of tumor growth. In summary, meganuclease-mediated virus cleavage represents a promising approach to provide oncolytic viruses with attractive safety profiles. Meganucleases can specifically cleave long DNA sequence motifs, a feature that makes them an ideal tool for gene engineering in living cells. In a proof-of-concept study, we investigated the use of the meganuclease I-Sce I for targeted virus self-disruption to generate high-specific oncolytic viruses. For this purpose, we provided oncolytic adenoviruses with a molecular circuit that selectively responds to p53 activation by expression of I-Sce I subsequently leading to self-disruption of the viral DNA via heterologous I-Sce I recognition sites within the virus genome. We observed that virus replication and cell lysis was effectively impaired in p53-normal cells, but not in p53-dysfunctional tumor cells. I-Sce I activity led to effective intracellular processing of viral DNA as confirmed by detection of specific cleavage products. Virus disruption did not interfere with E1A levels indicating that reduction of functional virus genomes was the predominant cause for conditional replication. Consequently, tumor-specific replication was further enhanced when E1A expression was additionally inhibited by targeted transcriptional repression. Finally, we demonstrated p53-dependent oncolysis by I-Sce I-expressing viruses in vitro and in vivo, and demonstrated effective inhibition of tumor growth. In summary, meganuclease-mediated virus cleavage represents a promising approach to provide oncolytic viruses with attractive safety profiles.
The Potentials of Inserting New Genetic Information
Authors: Karen E. Mercola, Martin J. Cline
Journal: New England Journal of Medicine (1980)

The concept that new genes can be inserted into living animals is relatively new, but the phenomenon of transmission of genetic material from one organism into the genome of another has probably existed since the early stages of evolution. Mutation of nucleotide sequences in the DNA code has long been seen as the principal mechanism of evolutionary adaptation, while transmission of genetic materials between species was considered to be a rare event. This conventional view requires revision in the light of recent knowledge about genetic elements adapted for shuttling between different regions of a single genome or between different genomes. . . .
TCT-687 A Comparison of Angiographic and Transesophageal Measurements of Left Atrial Appendage Dimensions during Catheter-Based Left Atrial Appendage Occlusion: Implications for Sizing and Safety.
Authors: Roberto Spina, John E. Boland, David Baron, Paul Roy, David W. Muller, Brendan Gunalingam
Journal: Journal of the American College of Cardiology (2013)
The Battle for Access — Health Care in Afghanistan
Authors: Brigg Reilley, Gloria Puertas, Anne-Sophie Coutin
Journal: New England Journal of Medicine (2004)

Recent rounds on the infectious disease ward in Mir Wais Hospital, in Kandahar, Afghanistan, found a young farmhand recuperating from meningitis sitting with the two friends who had accompanied him to the hospital. He had survived the disease, but only barely, and the episode had left him blind. In quiet tones, the man discussed with the medical staff whether his condition was permanent. In another room, a family of six was recovering from typhoid fever. The family members were fortunate that they had sought care early, because typhoid has a fatality rate of nearly 10 percent in Kandahar. The most . . .
Cytokines Epistasis Contributes to Childhood Asthma
Authors: I.R. Genov, A. Goncalves-Primo, A. Yambartsev, L.K. Arruda, A.S. Zampolo, V.P.L. Ferriani, D. Solé, C.K. Naspitz, M. Gerbase-DeLima, A. Morgun
Journal: Journal of Allergy and Clinical Immunology (2006)
Churchill's Illustrated Medical Dictionary
Authors: John H. Dirckx
Journal: JAMA (1989)

Medical lexicography for speakers of English has a tradition going back centuries. The major medical dictionaries currently on the market have built solid reputations through many editions, and any newcomer to the field is bound to attract intense scrutiny. It is a pleasure to report that the new<i>Churchill's Medical Dictionary</i>, vast in physical dimensions (more than 100 000 entries on more than 2100 pages), displays lexicographic brilliance in proportion. The range of terms defined in<i>Churchill's</i>provides ample coverage of the basic sciences and medical specialties as well as dentistry. Abbreviations and taxonomic terms are fully represented. Pharmaceutical terms also receive good coverage, but few proprietary drug names are included. The treatment of anatomic nomenclature is exhaustive and phenomenally precise. Variant spellings, particularly British spellings, are abundantly supplied. Achieving a just proportion among the constituent parts of a work of this size is a task to strain the resources
Authors' reply to Metcalf and Wilkin
Authors: J. J. Puder, P. Marques-Vidal, C. Schindler, L. Zahner, I. Niederer, F. Burgi, V. Ebenegger, A. Nydegger, S. Kriemler
Journal: BMJ (2012)

Childhood obesity is complex.1 We acknowledged that to change behaviour and prevent childhood obesity is difficult when acting in only one sector—in this case, schools—especially in a socially disadvantaged population.2 However, this difficulty should not prevent all sectors from playing their part. In addition, a shift of the population median by a …
Indian Supreme Court ruling makes arrest of doctors harder
Authors: Ganapati Mudur
Journal: BMJ (2005)

The Indian Supreme Court has ruled that doctors may be criminally prosecuted

only for gross negligence or a high degree of negligence and that “a simple lack of care, an error of judgment, or an accident is not proof of negligence.”

Indian doctors and some consumers' groups have hailed the judgment, which will

make the arrest of doctors for medical negligence harder but leaves intact the existing provisions for patients to claim compensation under consumer laws.

However, a representative of the People's Health Movement cautioned that the judgment needed to be followed up by action by medical …
Prolactin (PRL) and Its Receptor: Actions, Signal Transduction Pathways and Phenotypes Observed in PRL Receptor Knockout Mice
Authors: Christine Bole-Feysot, Vincent Goffin, Marc Edery, Nadine Binart, Paul A. Kelly
Journal: Endocrine Reviews (1998)

I. Introduction II.PRL A. The PRL/GH/PL family B. PRL gene and primary structure C. PRL tertiary structure D. Extrapituitary PRL III.PRL Receptor (PRLR) A. The class 1 cytokine receptor superfamily B. PRLR gene and primary structure C. PRLR tertiary structure D. PRLR binding and activation by PRL IV.Distribution of the PRLRs V. Biological Functions of PRL A. Water and electrolyte balance B
Allergic diseases in relation to vaccinations and infectious diseases: Two cross-sectional studies in schoolchildren 4 years apart
Authors: R. Pierdomenico, C. D'Ambrosio, G. Rasi, G. Lapucci, A. Torre, P.M. Matricardi, A. Carlucci, S. Bonini
Journal: Journal of Allergy and Clinical Immunology (2003)
Allen-Barker-Hines Peripheral Vascular Diseases
Authors: David I. Abramson
Journal: JAMA (1981)

As in the past, this fifth edition of one of the earliest clinical books on peripheral vascular disorders represents the combined effort of a large number of authors (41), all from various departments of the Mayo Clinic. The book consists of 35 chapters divided into five sections, and, in great part, the contents are authoritative, readable, thorough, and comprehensive in their presentation. According to the editors, the general organization and framework of the present volume closely follow those of the previous ones, a format that appears to be open to some criticism. For example, section 1 is devoted to basic considerations, and it still contains two chapters that are purely clinically oriented, one dealing with symptoms and signs of peripheral vascular disorders and the other with laboratory means of identifying their presence. The remaining three chapters are properly placed, since they concern themselves with such subjects as a detailed description
Origin and Evolution of the Chloroplast trnK (matK) Intron: A Model for Evolution of Group II Intron RNA Structures
Authors: Georg Hausner, Robert Olson, Dawn Simon, Ian Johnson, Erin R. Sanders, Kenneth G. Karol, Richard M. McCourt, Steven Zimmerly
Journal: Molecular Biology and Evolution (2005)

The trnK intron of plants encodes the matK open reading frame (ORF), which has been used extensively as a phylogenetic marker for classification of plants. Here we examined the evolution of the trnK intron itself as a model for group II intron evolution in plants. Representative trnK intron sequences were compiled from species spanning algae to angiosperms, and four introns were newly sequenced. Phylogenetic analyses showed that the matK ORFs belong to the ML (mitochondrial-like) subclass of group II intron ORFs, indicating that they were derived from a mobile group II intron of the class. RNA structures of the introns were folded and analyzed, which revealed progressive RNA structural deviations and degenerations throughout plant evolution. The data support a model in which plant organellar group II introns were derived from bacterial-like introns that had "standard" RNA structures and were competent for self-splicing and mobility and that subsequently the ribozyme structures degenerated to ultimately become dependent upon host-splicing factors. We propose that the patterns of RNA structure evolution seen for the trnK intron will apply to the other group II introns in plants.
Doctors will be key to raising productivity levels to plug shortages in workforce
Authors: C. Santry
Journal: BMJ (2012)

Demand for healthcare workers in many of the world’s major economies, including the United Kingdom, will outstrip supply by up to 29% in the next decade, analysts have predicted.

A discussion paper by the consultancy firm KPMG warns of a “widening chasm” between the growing demand for health services and declining availability of staff in the countries of the Organisation for Economic Co-operation and Development.1

The report forecasts a 22% to 29% gap between demand for and supply of health workers in the OECD by 2022. It puts this down to ageing workforces, more part time employment, and medical technologies requiring people with additional skills.

The …
Efficacy of the β3-adrenoceptor Agonist Mirabegron for the Treatment of Overactive Bladder by Severity of Incontinence at Baseline: A Post Hoc Analysis of Pooled Data from Three Randomised Phase 3 Trials
Authors: Christopher Chapple, Vik Khullar, Victor W. Nitti, Jeffrey Frankel, Sender Herschorn, Mathilde Kaper, Mary Beth Blauwet, Emad Siddiqui
Journal: European Urology (2014)
Sex, attachment, and the development of reproductive strategies
Authors: Marco Del Giudice
Journal: Behavioral and Brain Sciences (2009)

This target article presents an integrated evolutionary model of the development of attachment and human reproductive strategies. It is argued that sex differences in attachment emerge in middle childhood, have adaptive significance in both children and adults, and are part of sex-specific life history strategies. Early psychosocial stress and insecure attachment act as cues of environmental risk, and tend to switch development towards reproductive strategies favoring current reproduction and higher mating effort. However, due to sex differences in life history trade-offs between mating and parenting, insecure males tend to adopt avoidant strategies, whereas insecure females tend to adopt anxious/ambivalent strategies, which maximize investment from kin and mates. Females are expected to shift to avoidant patterns when environmental risk is more severe. Avoidant and ambivalent attachment patterns also have different adaptive values for boys and girls, in the context of same-sex competition in the peer group: in particular, the competitive and aggressive traits related to avoidant attachment can be favored as a status-seeking strategy for males. Finally, adrenarche is proposed as the endocrine mechanism underlying the reorganization of attachment in middle childhood, and the implications for the relationship between attachment and sexual development are explored. Sex differences in the development of attachment can be fruitfully integrated within the broader framework of adaptive plasticity in life history strategies, thus contributing to a coherent evolutionary theory of human development.
Use of endoscopic nasobiliary drainage tube for treating mediastinitis caused by insertion of an esophageal self-expanding metal stent
Authors: K. Soga, J. Ochiai, T. Miyajima, Y. Naito, T. Yoshikawa
Journal: Endoscopy (2011)

Self-expanding metal stents (SEMS) are relatively easy to deploy, with a high technical success rate, and provide rapid relief of dysphagia [1], which is the major factor affecting quality of life in patients not suitable for resection. Since Domschke et al. first reported the use of SEMS in 1990 [2], the technique has been widely used for malignant esophageal stenosis [3], although there have been many reports of complications associated with the combination of SEMS and chemoradiation therapy (CRT) [4] [5].
Abstract 1326: Differential cytokine-related signaling pathways responded to ionizing radiation in two lung adenocarcinoma cell lines
Authors: Yen-Chun Liu, Tzu-Pin Lu, Tzu-Hung Hsiao, Jo-Yang Lu, Feng-Ming Hsu, Jason Chia-Hsien Cheng, Pan-Chyr Yang, Liang-Chuan Lai, Eric Y Chuang, Mong-Hsun Tsai
Journal: Cancer Research (2010)

Abstract Lung cancer is the leading cause of cancer-related mortality in the world. Metastasis is the leading cause of death and an enormous therapeutic challenge for non-small cell lung cancer. Radiation therapy is a treatment of unresectable lung cancer and may palliate the symptoms, locally control tumor growth, and provide higher survival rate. Yet, the molecular mechanism of radio-sensitivity in lung cancer still remains unclear. Two lung adenocarcinoma cell lines (CL1-0 and CL1-5) with different metastatic potentials were irradiated with 10Gy γ-radiation. CL1-5 showed more radio-sensitive than CL1-0 since the surviving fractions in CL1-5 were ten times lower than CL1-0 by clonogenic assays. Gene expression profiles were also analyzed using microarray in order to better understand differential gene expression between these two cell lines after radiation. Total RNAs for whole genome gene expression analysis were extracted from these two cell lines at 0, 1, 4, 9 and 24 h after 10Gy irradiation. Gene Set Enrichment Analysis (GSEA) revealed the pathways of death, cytokine, cell adhesion, IL1R, NF-κB, and TNFR had differences between these two cell lines following 10Gy radiation exposure. Tumor necrosis factor (TNF) cytokine family and interleukin-1 (IL1) was up-regulated in CL1-5 after irradiation. The expression level of TNF-α validated by quantitative real time PCR was increased in CL1-5 and was not detected in CL1-0. Therefore, TNF-α released into the culture medium in CL1-5 after irradiation might be a death signal to activate the NF-κB pathway and cause more cell death. Moreover, the different responses of NF-κB-related pathways induced by radiation between the two cell lines might contribute the different survival. These cytokine modulations might provide promising targets for further investigation regarding radiation treatment in lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1326.
Current Management of Acute Gastrointestinal Hemorrhage
Authors: Eddy D. Palmer
Journal: JAMA (1977)

This is a brief, rather superficial review of upper gastrointestinal bleeding, with some mention of lower tract bleeding. The coverage is spotty. Pathology is presented as a series of photographs of gross specimens. The chapter on barium studies, likewise, is composed of a large group of films illustrating lesions of the tract, including those with a bleeding potential and those without. The chapter on ulcer disease is concerned mainly with the pathophysiology of the crater. The reader will have trouble with some of the teachings, such as the statements that when there is esophagitis there invariably is a hiatus hernia, and that ulcers develop from erosions. (Forgive us, Konjetzny!) Wilson's chapter on arteriography is excellent, well worth review by all gastroenterologists and general surgeons. It is full of excellent detail and good sense.
Human Metapneumovirus in Lung Transplant Recipients and Comparison to Respiratory Syncytial Virus
Authors: Peter Hopkins, Keith McNeil, Fiona Kermeen, Michael Musk, Emily McQueen, Ian Mackay, Terry Sloots, Michael Nissen
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Human metapneumovirus is a newly described virus isolated in 2001 from children with acute respiratory viral infection. It has subsequently been reported globally, although there are limited data in lung transplant recipients.Objectives: To prospectively analyze whether human metapneumovirus was circulating in our adult lung transplant community and assess the morbidity of this infection and to compare the clinical presentation and outcome after intravenous ribavirin of human metapneumovirus with that of respiratory syncytial virus (RSV).Methods: Lung transplant patients with clinical features of respiratory viral infection underwent nasopharyngeal aspirates. Patients with a positive specimen for RSV or human metapneumovirus by reverse transcriptase–polymerase chain reaction analysis and graft dysfunction received intravenous ribavirin and pulse steroid therapy.Measurements and Main Results: Eighty-nine patients had 199 visits for aspirate studies. A viral cause was determined for 62 visits in 47 patients (19 human metapneumovirus, 18 RSV, 13 parainfluenza, 9 influenza A, 2 adenovirus, and 1 influenza B). A significant percentage of patients with metapneumovirus (63%) and RSV (72%) developed graft dysfunction, with average declines in FEV1 of 30 ± 12.4% and 25.9 ± 11.2%, respectively. In these patients, bronchiolitis obliterans syndrome onset or progression occurred in no patients with human metapneumovirus compared with 5 of 13 (38%) patients with RSV at 6 months.Conclusions: Human metapneumovirus is a leading cause of acute respiratory tract illness in lung transplant recipients. The incidence and clinical spectrum at presentation are similar to RSV, although the latter seems to be associated with a higher risk of chronic rejection. We recommend testing of nasopharyngeal aspirates for human metapneumovirus with polymerase chain reaction to assess local epidemiologic patterns.
UK health officials launch “five in one” vaccine for babies
Authors: Roger Dobson
Journal: BMJ (2004)

A “five in one” vaccine for babies is being introduced throughout the United Kingdom from the end of September.

The vaccine, which will give protection against whooping cough, diphtheria, tetanus, polio, and Haemophilus influenzae type B (Hib), has already been adopted in Canada. The vaccine replaces the four in one vaccine, which excludes polio vaccine (currently given orally).

Government ministers and health officials emphasised that the move, one of several changes in the childhood immunisation programme, will make immunisation safer and more efficient.

Professor Elizabeth Miller, head of …
Abstract 2450: Surface molecule CD229 represents a possible target for the treatment of multiple myeloma
Authors: Djordje Atanackovic, Jens Panse, York Hildebrandt, Adam Jadczak, Tim Luetkens, Sebastian Kobold, Nesrine Lajmi, Axel R. Zander, Yanran Cao, Carsten Bokemeyer, Nicolaus Kroeger
Journal: Cancer Research (2010)

Abstract BACKGROUND AND OBJECTIVES: The majority of patients with multiple myeloma (MM) will eventually relapse and succumb to their disease even after high dose chemotherapy and autologous stem cell transplantation, possibly due to the persistence of BM-residing myeloma stem cells. Therefore, new treatment strategies incorporating new therapeutic targets - ideally to be expressed by the bulk of end-stage myeloma cells and their dormant progenitors - are needed to improve the outcome of myeloma patients. DESIGN AND METHODS: We screened myeloma cell lines for the presence of a large number of immunoreceptors and verified expression of potential target molecules on cell lines and patient samples. The function of the respective proteins was evaluated using gene knockdown and their potential as targets for antibody therapies was investigated using in vitro cytotoxicity assays. RESULTS: Of all immunoreceptors analyzed, SLAM family member CD229 showed the strongest expression and was also found on myeloma precursors. Primary myeloma cells of myeloma patients uniformly evidenced CD229 surface expression while the molecule was absent from most healthy human tissues. Flow cytometric analysis of CD229 expression facilitated the detection of myeloma cells in the bone marrow. CD229 seemed to promote the survival of myeloma cells while CD229 silencing increased their susceptibility towards chemotherapy. Importantly, targeting CD229 with a monoclonal antibody resulted in specific lysis of the tumor cells. CONCLUSIONS: These results suggest that CD229 might represent an attractive diagnostic and therapeutic target for the treatment of MM. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2450.