tbuckley/cabot-search huggingface dataset:
Differential T cell receptor photoaffinity labeling among H-2Kd restricted cytotoxic T lymphocyte clones specific for a photoreactive peptide derivative. Labeling of the alpha-chain correlates with J alpha segment usage.
Authors: P Romero, J L Casanova, J C Cerottini, J L Maryanski, I F Luescher
Journal: The Journal of Experimental Medicine (1993)

Using a direct binding assay based on photoaffinity labeling, we studied the interaction of T cell receptor (TCR) with a Kd-bound photoreactive peptide derivative on living cells. The Kd-restricted Plasmodium berghei circumsporozoite (PbCS) peptide 253-260 (YIPSAEKI) was reacted NH2-terminally with biotin and at the TCR contact residue Lys259 with photoreactive iodo, 4-azido salicylic acid (IASA) to make biotin-YIPSAEK(IASA)I. Cytotoxic T lymphocyte (CTL) clones derived from mice immunized with this derivative recognized this conjugate, but not a related one lacking the IASA group nor the parental PbCS peptide. The clones were Kd restricted. Recognition experiments with variant conjugates, lacking substituents from IASA, revealed a diverse fine specificity pattern and indicated that this group interacted directly with the TCR. The TCR of four clones could be photoaffinity labeled by biotin-YIPSAEK(125IASA)I. This labeling was dependent on the conjugates binding to the Kd molecule and was selective for the TCR alpha (2 clones) or beta chain (1 clone), or was common for both chains (1 clone). TCR sequence analysis showed a preferential usage of J alpha TA28 containing alpha chains that were paired with V beta 1 expressing beta chains. The TCR that were photoaffinity labeled at the alpha chain expressed these J alpha and V beta segments. The tryptophan encoded by the J alpha TA28 segment is rarely found in other J alpha segments. Moreover, we show that the IASA group interacts preferentially with tryptophan in aqueous solution. We thus propose that for these CTL clones, labeling of the alpha chain occurs via the J alpha-encoded tryptophan residue.
A magnetic internal mechanism for precise orientation of the camera in wireless endoluminal applications
Authors: P. Valdastri, C. Quaglia, E. Buselli, A. Arezzo, N. Di Lorenzo, M. Morino, A. Menciassi, P. Dario
Journal: Endoscopy (2010)

The use of magnetic fields to control operative devices has been recently described in endoluminal and transluminal surgical applications. The exponential decrease of magnetic field strength with distance has major implications for precision of the remote control. We aimed to assess the feasibility and functionality of a novel wireless miniaturized mechanism, based on magnetic forces, for precise orientation of the camera.A remotely controllable endoscopic capsule was developed as proof of concept. Two intracapsular moveable permanent magnets allow fine positioning, and an externally applied magnetic field permits gross movement and stabilization. Performance was assessed in ex vivo and in vivo bench tests, using porcine upper and lower gastrointestinal tracts.Fine control of capsule navigation and rotation was achieved in all tests with an external magnet held steadily about 15 cm from the capsule. The camera could be rotated in steps of 1.8 degrees . This was confirmed by ex vivo tests; the mechanism could adjust the capsule view at 40 different locations in a gastrointestinal tract phantom model. Full 360 degrees viewing was possible in the gastric cavity, while the maximal steering in the colon was 45 degrees in total. In vivo, a similar performance was verified, where the mechanism was successfully operated every 5 cm for 40 cm in the colon, visually sweeping from side to side of the lumen; 360 degrees views were obtained in the gastric fundus and body, while antrally the luminal walls prevented full rotation.We report the feasibility and effectiveness of the combined use of external static magnetic fields and internal actuation to move small permanent intracapsular magnets to achieve wirelessly controllable and precise camera steering. The concept is applicable to capsule endoscopy as to other instrumentation for laparoscopic, endoluminal, or transluminal procedures.
Phase II Trial of Conformal Radiation Therapy for Pediatric Low-Grade Glioma
Authors: Thomas E. Merchant, Larry E. Kun, Shengjie Wu, Xiaoping Xiong, Robert A. Sanford, Frederick A. Boop
Journal: Journal of Clinical Oncology (2009)

The use of radiotherapy in pediatric low-grade glioma (LGG) is controversial, especially for young patients. We conducted a phase II trial of conformal radiation therapy (CRT) to estimate disease control by using a 10-mm clinical target volume (CTV) margin.Between August 1997 and August 2006, 78 pediatric patients with LGG and a median age of 8.9 years (range, 2.2 to 19.8 years) received 54 Gy CRT by using a 10-mm CTV and by targeting with systematic magnetic resonance imaging (MRI) registration. Tumor locations were diencephalon (n = 58), cerebral hemisphere (n = 3), and cerebellum (n = 17). Sixty-seven patients had documented or presumed WHO grade 1 tumors, 25 patients had prior chemotherapy, and 13 patients had neurofibromatosis type 1.During a median follow-up of 89 months, 13 patients experienced disease progression. One patient experienced marginal treatment failure, eight experienced local failures, and four experienced metastatic failure. The mean and standard error 5- and 10-year event-free (87.4% +/- 4.4% and 74.3% +/- 15.4%, respectively) and overall (98.5% +/- 1.6% and 95.9% +/- 5.8%, respectively) survival rates were determined. The mean and standard error cumulative incidences of local failure at 5 and 10 years were 8.7% +/- 3.5% and 16.4% +/- 5.4%, respectively. The mean and standard error cumulative incidence of vasculopathy was 4.79% +/- 2.73% at 6 years, and it was higher for those younger than 5 years of age (P = .0105) at the time of CRT.This large, prospective series of irradiated children with LGG demonstrates that CRT with a 10-mm CTV does not compromise disease control. The results suggest that CRT should be delayed in young patients to reduce the risk of vasculopathy.
Older people are not a burden, says WHO
Authors: Anne Gulland
Journal: BMJ (2015)

Older people should not be looked on as a costly burden on health systems, the World Health Organization has urged.

In its first global report on ageing and health WHO said that it was often wrongly assumed that the growing numbers of older people will put an intolerable burden on healthcare.1 “In reality, the picture is far less clear,” said WHO.

The report said that in some high income countries healthcare expenditure per person actually fell after the age of around 75, while expenditure on long term care (which includes both health and social care) increased. The report quoted an analysis of expenditure by Torbay and Southern Devon Health and Care NHS Trust which found that expenditure increased across all services as age increased, …
Rooting the eutherian tree: the power and pitfalls of phylogenomics
Authors: Hidenori Nishihara, Norihiro Okada, Masami Hasegawa
Journal: Genome biology (2007)

Abstract Background Ongoing genome sequencing projects have led to a phylogenetic approach based on genome-scale data (phylogenomics), which is beginning to shed light on longstanding unresolved phylogenetic issues. The use of large datasets in phylogenomic analysis results in a global increase in resolution due to a decrease in sampling error. However, a fully resolved tree can still be wrong if the phylogenetic inference is biased. Results Here, in an attempt to root the eutherian tree using genome-scale data with the maximum likelihood method, we demonstrate a case in which a concatenate analysis strongly supports a putatively wrong tree, whereas the total evaluation of separate analyses of different genes grossly reduced the bias of the phylogenetic inference. A conventional method of concatenate analysis of nucleotide sequences from our dataset, which includes a more than 1 megabase alignment of 2,789 nuclear genes, suggests a misled monophyly of Afrotheria (for example, elephant) and Xenarthra (for example, armadillo) with 100% bootstrap probability. However, this tree is not supported by our 'separate method', which takes into account the different tempos and modes of evolution among genes, and instead the basal Afrotheria tree is favored. Conclusion Our analysis demonstrates that in cases in which there is great variation in evolutionary features among different genes, the separate model, rather than the concatenate model, should be used for phylogenetic inference, especially in genome-scale data.
Changes in chronic respiratory symptoms in two populations of adults studied longitudinally over 13 years
Authors: M Krzyzanowski, MD Lebowitz
Journal: European Respiratory Journal (1992)

Data from two longitudinal studies conducted in Cracow, Poland, and Tucson, Arizona, USA, were used to evaluate the differences in period prevalence, incidence and remission rates of respiratory symptoms between two populations, as well as to assess the between-cities similarities in the relationships of the symptoms to age and smoking habit. The analysis was based on data from 3,082 adult Cracow residents, interviewed twice 13 yrs apart, and from 1,452 Tucson adults, with mean period between initial and final survey of 12.2 yrs. Log-linear models were used to consider possible interactions of the symptoms, age, smoking, gender and city. The relationship of the symptoms to smoking was similar in both cities, after adjustment for age and gender, with at least doubled incidence rates of most symptoms in continuous smokers compared to lifetime nonsmokers. The between-population differences in the symptoms were related to age, indicating onset of bronchitic symptoms occurring earlier in life in Cracow, and of asthmatic symptoms in Tucson. These differences were due to factors other than tobacco smoking e.g. various types of ambient air pollution.
Paternal age and reproduction
Authors: Gideon A. Sartorius, Eberhard Nieschlag
Journal: Human Reproduction Update (2009)

Due to various sociological factors, couples in developed countries are increasingly delaying childbearing. Besides ethical, economical and sociological issues, this trend presents us with several complex problems in reproduction. Although it is well-known that maternal age has a negative effect on fertility and increases the risk of adverse outcome during pregnancy and in offspring, the paternal influence on these outcomes is less well researched and not well-known. We performed a systematic search of PubMed, and retrieved original articles and review articles to update our previous survey in this journal. This review highlights the link between male age and genetic abnormalities in the germ line and summarizes the knowledge about the effects of paternal age on reproductive function and outcome. Increasing paternal age can be associated with decreasing androgen levels, decreased sexual activity, alterations of testicular morphology and a deterioration of semen quality (volume, motility, morphology). Increased paternal age has an influence on DNA integrity of sperm, increases telomere length in spermatozoa and is suggested to have epigenetic effects. These changes may, at least in part, be responsible for the association of paternal age over 40 years with reduced fertility, an increase in pregnancy-associated complications and adverse outcome in the offspring. Although higher maternal age can be an indication for intensive prenatal diagnosis, including invasive diagnostics, consideration of the available evidence suggests that paternal age itself, however, provides no rationale for invasive procedures.
Beta radiation with direct stenting: Final results of the BRIDGE trial
Authors: Patrick W. Serruys, William Wijns, Ivan de Scheerder, Paul A. van den Heuvel, Wolfgang Rutsch, Helmut D. Glogar, Carlos Macaya, Pierre H. Materne, Heike Vonhausen, Patricia C. Otto-Terlouw
Journal: Journal of the American College of Cardiology (2003)
Recombinant human interleukin-3 hastens trilineage hematopoietic recovery following high-dose (7 g/m2) cyclophosphamide cancer therapy
Authors: A.M. Gianni, S. Siena, M. Bregni, M. Di Nicola, F. Peccatori, M. Magni, F. Ravagnani, I. Sklenar, G. Bonadonna
Journal: Annals of Oncology (1993)
Overexpression of G Protein–Coupled Receptor Kinase-2 in Smooth Muscle Cells Attenuates Mitogenic Signaling via G Protein–Coupled and Platelet-Derived Growth Factor Receptors
Authors: Karsten Peppel, Anne Jacobson, Xuewei Huang, John P. Murray, Martin Oppermann, Neil J. Freedman
Journal: Circulation (2000)

Background —Neointimal hyperplasia involves activation of smooth muscle cells (SMCs) by several G protein–coupled receptor (GPCR) agonists, including endothelin-1, angiotensin II, thrombin, and thromboxane A 2 . Signaling of many GPCRs is diminished by GPCR kinase-2 (GRK2). We therefore tested whether overexpression of GRK2 in SMCs could diminish mitogenic signaling elicited by agonists implicated in the pathogenesis of neointimal hyperplasia. Methods and Results —Overexpression of GRK2 was achieved in primary rabbit aortic SMCs with a recombinant adenovirus. Control SMCs were infected with an empty vector adenovirus. Inositol phosphate responses to endothelin-1, angiotensin II, thrombin agonist peptide, and platelet-derived growth factor (PDGF) were attenuated by 37% to 72% in GRK2-overexpressing cells ( P &lt;0.01), but the response to the thromboxane A 2 analogue U46619 was unaffected. GRK2 also inhibited SMC [ 3 H]thymidine incorporation stimulated not only by these agonists (by 30% to 60%, P &lt;0.01) but also by 10% FBS (by 35%, P &lt;0.05). However, GRK2 overexpression had no effect on epidermal growth factor–induced [ 3 H]thymidine incorporation. Agonist-induced tyrosine phosphorylation of the PDGF-β receptor, but not the epidermal growth factor receptor, was reduced in GRK2-overexpressing SMCs. GRK2 overexpression also reduced SMC proliferation in response to endothelin-1, PDGF, and 10% FBS by 62%, 51%, and 29%, respectively ( P &lt;0.01), without any effect on SMC apoptosis. Conclusions —GRK2 overexpression diminishes SMC mitogenic signaling and proliferation stimulated by PDGF or agonists for several GPCRs. Gene transfer of GRK2 may therefore be therapeutically useful for neointimal hyperplasia.
Effect of a Comprehensive Surgical Safety System on Patient Outcomes
Authors: Eefje N. de Vries, Hubert A. Prins, Rogier M.P.H. Crolla, Adriaan J. den Outer, George van Andel, Sven H. van Helden, Wolfgang S. Schlack, M. Agnès van Putten, Dirk J. Gouma, Marcel G.W. Dijkgraaf, Susanne M. Smorenburg, Marja A. Boermeester
Journal: New England Journal of Medicine (2010)

Adverse events in patients who have undergone surgery constitute a large proportion of iatrogenic illnesses. Most surgical safety interventions have focused on the operating room. Since more than half of all surgical errors occur outside the operating room, it is likely that a more substantial improvement in outcomes can be achieved by targeting the entire surgical pathway.We examined the effects on patient outcomes of a comprehensive, multidisciplinary surgical safety checklist, including items such as medication, marking of the operative side, and use of postoperative instructions. The checklist was implemented in six hospitals with high standards of care. All complications occurring during admission were documented prospectively. We compared the rate of complications during a baseline period of 3 months with the rate during a 3-month period after implementation of the checklist, while accounting for potential confounders. Similar data were collected from a control group of five hospitals.In a comparison of 3760 patients observed before implementation of the checklist with 3820 patients observed after implementation, the total number of complications per 100 patients decreased from 27.3 (95% confidence interval [CI], 25.9 to 28.7) to 16.7 (95% CI, 15.6 to 17.9), for an absolute risk reduction of 10.6 (95% CI, 8.7 to 12.4). The proportion of patients with one or more complications decreased from 15.4% to 10.6% (P<0.001). In-hospital mortality decreased from 1.5% (95% CI, 1.2 to 2.0) to 0.8% (95% CI, 0.6 to 1.1), for an absolute risk reduction of 0.7 percentage points (95% CI, 0.2 to 1.2). Outcomes did not change in the control hospitals.Implementation of this comprehensive checklist was associated with a reduction in surgical complications and mortality in hospitals with a high standard of care. (Netherlands Trial Register number, NTR1943.).
Paradoxical Worsening of Tuberculosis Following Antiretroviral Therapy in Patients with AIDS
Authors: MASAHIRO NARITA, DAVID ASHKIN, ELENA S. HOLLENDER, ARTHUR E. PITCHENIK
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Transient worsening of tuberculous symptomatology and lesions following antituberculous therapy (paradoxical response) has previously been described as a rare occurrence. To determine the incidence of paradoxical responses in patients with AIDS and TB who are treated with antituberculous therapy and subsequently with combination antiretroviral therapy (ARV), we conducted a prospective study of 33 HIV-seropositive TB patients treated with anti-TB therapy and antiretroviral therapy (Group 1) compared with 55 HIV-seronegative TB patients treated with anti-TB therapy (Group 2) and 28 HIV-seropositive TB patients treated with anti-TB therapy but not on antiretrovirals (historical control; Group 3). In Group 1 patients, paradoxical responses were temporally more related to the initiation of ARV than to the initiation of anti-TB therapy (mean ± SD: 15 ± 11 d versus 109 ± 72 d [p < 0.001]) and occurred much more frequently (12 of 33; 36%) compared with Group 2 (1 of 55; 2%) (p < 0.001) or with Group 3 (2 of 28; 7%) (p = 0.013). The majority of patients who experienced paradoxical responses and received tuberculin purified protein derivative (PPD) in Group 1 had their tuberculin skin tests convert from negative to strongly positive after ARV. These observations suggest that a paradoxical response associated with enhanced tuberculin skin reactivity may occur after the initiation of ARV in HIV-infected TB patients. Furthermore, the skin test conversion after the initiation of ARV may have important public health implications.
Clinical, environmental, and genetic determinants of multiple sclerosis in children with acute demyelination: a prospective national cohort study
Authors: Brenda Banwell, Amit Bar-Or, Douglas L Arnold, Dessa Sadovnick, Sridar Narayanan, Melissa McGowan, Julia O'Mahony, Sandra Magalhaes, Heather Hanwell, Reinhold Vieth, Raymond Tellier, Thierry Vincent, Giulio Disanto, George Ebers, Katherine Wambera, Mary B Connolly, Jerome Yager, Jean K Mah, Fran Booth, Guillaume Sebire, David Callen, Brandon Meaney, Marie-Emmanuelle Dilenge, Anne Lortie, Daniela Pohl, Asif Doja, Sunita Venketaswaran, Simon Levin, E Athen MacDonald, David Meek, Ellen Wood, Noel Lowry, David Buckley, Conrad Yim, Mark Awuku, Pamela Cooper, François Grand'Maison, J Burke Baird, Virender Bhan, Ruth Ann Marrie
Journal: The Lancet Neurology (2011)
The Evolution of the Phage Shock Protein Response System: Interplay between Protein Function, Genomic Organization, and System Function
Authors: M. Huvet, T. Toni, X. Sheng, T. Thorne, G. Jovanovic, C. Engl, M. Buck, J. W. Pinney, M. P. H. Stumpf
Journal: Molecular Biology and Evolution (2010)

Sensing the environment and responding appropriately to it are key capabilities for the survival of an organism. All extant organisms must have evolved suitable sensors, signaling systems, and response mechanisms allowing them to survive under the conditions they are likely to encounter. Here, we investigate in detail the evolutionary history of one such system: The phage shock protein (Psp) stress response system is an important part of the stress response machinery in many bacteria, including Escherichia coli K12.
How to handle an over 25% increase in submissions
Authors: T Opthof
Journal: Cardiovascular Research (1998)

Recently, the number of submissions to CardioÕascular Ž .Research has increased by more than 25% Fig. 1 .We assume that this may be partly explained by the huge w x increase in impact factor over the recent years 1 from 1.47 in 1991 to 3.26 in 1996 as reported by the Institute Ž .for Scientific Information Fig. 2 .Despite the increased number of submissions Cardiow x Õascular Research has been able to maintain 2 its rapid Ž .reviewing process Fig. 3 .A grant of Knoll AG, allowing us to offer reviewers who meet our deadline a compact disk of their choice, has been of great help in this respect.
Lack of mitochondrial trifunctional protein in mice causes neonatal hypoglycemia and sudden death
Authors: Jamal A. Ibdah, Hyacinth Paul, Yiwen Zhao, Scott Binford, Ken Salleng, Mark Cline, Dietrich Matern, Michael J. Bennett, Piero Rinaldo, Arnold W. Strauss
Journal: Journal of Clinical Investigation (2001)

Mitochondrial trifunctional protein (MTP) is a hetero-octamer of four α and four β subunits that catalyzes the final three steps of mitochondrial long chain fatty acid β-oxidation. Human MTP deficiency causes Reye-like syndrome, cardiomyopathy, or sudden unexpected death. We used gene targeting to generate an MTP α subunit null allele and to produce mice that lack MTP α and β subunits. The Mtpa–/– fetuses accumulate long chain fatty acid metabolites and have low birth weight compared with the Mtpa+/– and Mtpa+/+ littermates. Mtpa–/– mice suffer neonatal hypoglycemia and sudden death 6–36 hours after birth. Analysis of the histopathological changes in the Mtpa–/– pups revealed rapid development of hepatic steatosis after birth and, later, significant necrosis and acute degeneration of the cardiac and diaphragmatic myocytes. This mouse model documents that intact mitochondrial long chain fatty acid oxidation is essential for fetal development and for survival after birth. Deficiency of MTP causes fetal growth retardation, neonatal hypoglycemia, and sudden death.
Constitutive activation of the phosphatidyl inositol 3 kinase signalling pathway in acral lentiginous melanoma
Authors: F.C. Muchemwa, D. Ma, Y. Inoue, J.A. Curtin, B.C. Bastian, H. Ihn, T. Kageshita
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, Melanoma is a common skin malignancy which, when advanced, responds poorly to chemotherapeutic agents and radiation. It is important to understand the signal transduction pathways involved in its transformation in order to develop novel therapeutic agents. Mutations in either BRAF or RAS genes result in activation of the mitogen activated protein kinase (MAPK) pathway.1, 2 The phosphatidyl inositol 3 kinase (PI3K) pathway is a direct target of activated RAS.3 Through activation of AKT, PI3K has potential antiapoptotic targets including BAD4 and caspase‐9,5 as well as one of the proapoptotic Forkhead transcription factors.6 In a previous study, we showed that the frequency of BRAF mutations in melanoma varies with anatomical site and sun‐exposure patterns.7 Melanomas on glabrous, subungual and mucosal sites had significantly lower frequencies of BRAF mutations than melanomas on the trunk and nonglabrous skin of the extremities. We then went further to investigate whether other mutations could be found in the MAPK pathway or whether other signalling pathways could be involved in the pathogenesis of these melanomas.