tbuckley/cabot-search huggingface dataset:
Mutation in<i>DSG1</i>causing autosomal dominant striate palmoplantar keratoderma
Authors: M. Zamiri, F.J.D. Smith, L.E. Campbell, L. Tetley, R.A.J. Eady, M.B. Hodgins, W.H.I. McLean, C.S. Munro
Journal: British Journal of Dermatology (2009)

Journal Article Mutation in DSG1 causing autosomal dominant striate palmoplantar keratoderma Get access M. Zamiri, M. Zamiri Alan Lyell Centre for Dermatology, Glasgow, U.K.Section of Dermatology, Division of Cancer Sciences and Molecular Pathology, Robertson Building, University of Glasgow, Glasgow G12 8QQ, U.K. Search for other works by this author on: Oxford Academic Google Scholar F.J.D. Smith, F.J.D. Smith Epithelial Genetics Group, Human Genetics Unit, University of Dundee, Dundee, U.K. Search for other works by this author on: Oxford Academic Google Scholar L.E. Campbell, L.E. Campbell Epithelial Genetics Group, Human Genetics Unit, University of Dundee, Dundee, U.K. Search for other works by this author on: Oxford Academic Google Scholar L. Tetley, L. Tetley Section of Infection and Immunology, University of Glasgow, Glasgow, U.K. Search for other works by this author on: Oxford Academic Google Scholar R.A.J. Eady, R.A.J. Eady St John's Institute of Dermatology, St Thomas' Hospital, London, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.B. Hodgins, M.B. Hodgins Section of Dermatology, Division of Cancer Sciences and Molecular Pathology, Robertson Building, University of Glasgow, Glasgow G12 8QQ, U.K. Search for other works by this author on: Oxford Academic Google Scholar W.H.I. McLean, W.H.I. McLean Epithelial Genetics Group, Human Genetics Unit, University of Dundee, Dundee, U.K. Search for other works by this author on: Oxford Academic Google Scholar C.S. Munro C.S. Munro Alan Lyell Centre for Dermatology, Glasgow, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 161, Issue 3, 1 September 2009, Pages 692–694, https://doi.org/10.1111/j.1365-2133.2009.09316.x Published: 01 September 2009
Aortobronchial Fistula following Aortic Valve Surgery
Authors: Mathew Ninan, Steven Hunter, D John Parker
Journal: Journal of the Royal Society of Medicine (1994)

We report the case of a 54-year-old man with an aortobronchial fistula following aortic valve replacement for prosthetic endocarditis. He presented with massive haemoptysis and the diagnosis was made following computerized tomography of the chest. Effective treatment was achieved by adhering to the basic principles of fistula management. The patient remains well at 1 year follow-up.
Leukotriene B4 mediates shear rate-dependent leukocyte adhesion in mesenteric venules.
Authors: K Bienvenu, J Russell, D N Granger
Journal: Circulation Research (1992)

Previous studies have demonstrated that low shear rates promote leukocyte adherence to microvascular endothelium in postcapillary venules. The objective of this study was to determine whether an accumulation of inflammatory mediators such as platelet activating factor and leukotriene B4 is responsible for shear rate-dependent leukocyte-endothelial cell adhesion. Postcapillary venules (25-39 microns in diameter) in cat mesentery were studied by intravital microscopy. Venular wall shear rate was varied over a wide range by graded occlusion of the mesenteric artery. Red blood cell velocity, vessel diameter, leukocyte rolling velocity, and the numbers of rolling and adherent leukocytes were measured at each shear rate. In one series of experiments, shear rate-dependent leukocyte adherence was monitored at different superfusion rates (1.0 and 2.5 ml/min). At the lower superfusion rate, the number of adherent leukocytes was significantly higher at any given shear rate when compared with results obtained at the higher superfusion rate. This suggests that reduced washout of inflammatory mediators contributes to shear rate-dependent leukocyte adhesion. Pretreatment with different platelet activating factor receptor antagonists (WEB 2086 or WEB 2170) had no effect on the number of adherent leukocytes normally observed at lower shear rates, suggesting that platelet activating factor does not play a major role in this process. However, shear rate-dependent leukocyte adhesion was largely prevented by pretreatment with either a leukotriene B4 receptor antagonist (SC-41930) or a leukotriene synthesis inhibitor (L663,536). The results of this study indicate that a reduced washout of leukotriene B4 is responsible for the enhanced leukocyte adherence that occurs at low venular wall shear rates.
Toward a Genetic Dissection of Cortical Circuits in the Mouse
Authors: Z. Josh Huang
Journal: Neuron (2014)

The mammalian neocortex gives rise to a wide range of mental activities and consists of a constellation of interconnected areas that are built from a set of basic circuit templates. Major obstacles to understanding cortical architecture include the diversity of cell types, their highly recurrent local and global connectivity, dynamic circuit operations, and a convoluted developmental assembly process rooted in the genome. With our increasing knowledge of gene expression and developmental genetic principles, it is now feasible to launch a program of genetic dissection of cortical circuits through systematic targeting of cell types and fate mapping of neural progenitors. Strategic design of even a modest number of mouse driver lines will facilitate efforts to compile a cell type parts list, build a Cortical Cell Atlas, establish experimental access to modern tools, integrate studies across levels, and provide coordinates for tracing developmental trajectory from circuit assembly to functional operation.
Air pollution, human health, climate change and you
Authors: G. Thurston
Journal: Thorax (2007)

The “co-benefits” of reducing air pollution on climate change and human health

The study by Ko et al 1 in this issue of Thorax ( see page 779 ) provides an important new contribution to the growing body of evidence that the severe adverse health effects of air pollution, so well documented in Europe and North America, are also occurring in Asia. Indeed, a recent report by the Health Effects Institute (HEI) surveyed the available published literature on this topic as part of its Public Health and Air Pollution in Asia-Science Access on the Net (PAPA-SAN) study. They found hundreds of published studies showing adverse health effects of air pollution in Asia and summarised the results on the web (http://www.healtheffects.org/Asia/papasan-home.htm). These results show that a wide range of health effects are significantly associated with air pollution exposures in Asia, including studies of respiratory and cardiovascular morbidity and mortality in a number of cities across Asia. In fact, the HEI report identified 69 published studies of the effects of air pollution on the health of populations in Mainland China, 16 in Hong Kong, 56 in Taipei, China, 8 in Indonesia, 2 in Malaysia, 6 in Singapore, 13 in Thailand, …
Allogeneic MHC Gene Transfer Enhances an Effective Antitumor Immunity in the Early Period of Autologous Hematopoietic Stem Cell Transplantation
Authors: Akihiko Kobayashi, Hidehiko Hara, Masaki Ohashi, Takeshi Nishimoto, Kimiko Yoshida, Nobuhiro Ohkohchi, Teruhiko Yoshida, Kazunori Aoki
Journal: Clinical Cancer Research (2007)

In autologous hematopoietic stem cell transplantation (HSCT), lymphopenia-induced homeostatic proliferation of T cells is driven by the recognition of self-antigens, and there is an opportunity to skew the T-cell repertoire during the T-cell recovery by engaging tumor-associated antigens, leading to a break of tolerance against tumors. However, the homeostatic proliferation-driven antitumor responses seem to decline rapidly in association with tumor growth. We hypothesized that a tumor-specific immune response induced by an immune gene therapy could enhance and sustain homeostatic proliferation-induced antitumor immunity.The antitumor effect of allogeneic MHC (alloMHC) gene transfer was examined at the early phase of the immune reconstitution after syngeneic HSCT.Syngeneic HSCT showed significant tumor growth inhibition of syngeneic colon cancer cells within a period of 30 days; however, the tumor then resumed rapid growth and the survival of the mice was not prolonged. In contrast, when the alloMHC plasmid was intratumorally injected at the early phase after syngeneic HSCT, the established tumors were markedly regressed and the survival of recipient mice was prolonged without significant toxicities, whereas no survival advantage was recognized in recipient mice injected with a control plasmid. This tumor suppression was evident even in the other tumors that were not injected with the alloMHC plasmid. The antitumor response was characterized by the development of tumor-specific T cell- and natural killer cell-mediated cytotoxicities.The results suggest the efficacy and safety of integrating intratumoral alloMHC gene transfer with an autologous HSCT for the treatment of solid cancers.
Polyamines on the Reproductive Landscape
Authors: Pavine L. C. Lefèvre, Marie-France Palin, Bruce D. Murphy
Journal: Endocrine Reviews (2011)

The polyamines are ubiquitous polycationic compounds. Over the past 40 yr, investigation has shown that some of these, namely spermine, spermidine, and putrescine, are essential to male and female reproductive processes and to embryo/fetal development. Indeed, their absence is characterized by infertility and arrest in embryogenesis. Mammals synthesize polyamines de novo from amino acids or import these compounds from the diet. Information collected recently has shown that polyamines are essential regulators of cell growth and gene expression, and they have been implicated in both mitosis and meiosis. In male reproduction, polyamine expression correlates with stages of spermatogenesis, and polyamines appear to function in promoting sperm motility. There is evidence for polyamine involvement in ovarian follicle development and ovulation in female mammals, and polyamine synthesis is required for steroidogenesis in the ovary. Studies of the embryo indicate a polyamine requirement that can be met from maternal sources before implantation, whereas elimination of polyamine synthesis abrogates embryo development at gastrulation. Polyamines play roles in embryo implantation, in decidualization, and in placental formation and function, and polyamine privation during gestation results in intrauterine growth retardation. Emerging information implicates dietary arginine and dietary polyamines as nutritional regulators of fertility. The mechanisms by which polyamines regulate these multiple and diverse processes are not yet well explored; thus, there is fertile ground for further productive investigation.
Nucleotide compositional constraints on genomes generate alanine-, glycine-, and proline-rich structures in transcription factors
Authors: Y. Nakachi, T. Hayakawa, H. Oota, K. Sumiyama, L. Wang, S. Ueda
Journal: Molecular Biology and Evolution (1997)

Correlation between amino acid composition and nucleotide composition is examined. Class III POU transcription factors having higher third GC contents showed higher contents of alanine, glycine, and proline residues encoded by GC-rich nucleotides, and vice versa. This correlation was observed even among various types of transcription factors from vertebrates and invertebrates regardless of functional and structural constraints inherent to each protein. Furthermore, reptile class III POU sequences revealed no evolutionary directionality increasing the GC contents from cold- to warm-blooded vertebrates.
Multicomponent indices to predict survival in COPD: the COCOMICS study
Authors: Jose M. Marin, Inmaculada Alfageme, Pere Almagro, Ciro Casanova, Cristobal Esteban, Juan J. Soler-Cataluña, Juan P. de Torres, Pablo Martínez-Camblor, Marc Miravitlles, Bartolome R. Celli, Joan B. Soriano
Journal: European Respiratory Journal (2012)

Guidelines recommend defining chronic obstructive pulmonary disease (COPD) by airflow obstruction and other factors, but no studies have evaluated the ability of existing multicomponent indices to predict mortality up to 10 years. We conducted a patient-based pooled analysis. Survival analysis and C statistics were used to determine the best COPD index/indices according to several construct variables and by varying time-points. Individual data of 3633 patients from 11 COPD cohorts were collected, totalling the experience of 15 878 person-years. Overall, there were 1245 death events within our cohorts, with a Kaplan–Meier survival of 0.963 at 6 months, which was reduced to 0.432 at 10 years. In all patients, ADO (age, dyspnoea and forced expiratory volume in 1 s), BODE (body mass index, airflow obstruction, dyspnoea and exercise capacity) and e-BODE (BODE plus exacerbations) were the best indices to predict 6-month mortality. The ADO index was the best to predict 12-month (C statistic 0.702), 5-year (C statistic 0.695) and 10-year mortality (C statistic 0.698), and was significantly better than BODE (all p&lt;0.05). The best indices to predict death by C statistics when adjusting by age were e-BODE, BODEx (substitution of exacerbations for exercise capacity) and BODE. No index predicts short-term survival of COPD well. All BODE modifications scored better than ADO after age adjustment. The ADO and BODE indices are overall the most valid multicomponent indices to predict time to death in all COPD patients.
Preoperative Multimodality Therapy Improves Disease-Free Survival in Patients With Carcinoma of the Rectum: NSABP R-03
Authors: Mark S. Roh, Linda H. Colangelo, Michael J. O'Connell, Greg Yothers, Melvin Deutsch, Carmen J. Allegra, Morton S. Kahlenberg, Luis Baez-Diaz, Carol S. Ursiny, Nicholas J. Petrelli, Norman Wolmark
Journal: Journal of Clinical Oncology (2009)

Purpose Although chemoradiotherapy plus resection is considered standard treatment for operable rectal carcinoma, the optimal time to administer this therapy is not clear. The NSABP R-03 (National Surgical Adjuvant Breast and Bowel Project R-03) trial compared neoadjuvant versus adjuvant chemoradiotherapy in the treatment of locally advanced rectal carcinoma. Patients and Methods Patients with clinical T3 or T4 or node-positive rectal cancer were randomly assigned to preoperative or postoperative chemoradiotherapy. Chemotherapy consisted of fluorouracil and leucovorin with 45 Gy in 25 fractions with a 5.40-Gy boost within the original margins of treatment. In the preoperative group, surgery was performed within 8 weeks after completion of radiotherapy. In the postoperative group, chemotherapy began after recovery from surgery but no later than 4 weeks after surgery. The primary end points were disease-free survival (DFS) and overall survival (OS). Results From August 1993 to June 1999, 267 patients were randomly assigned to NSABP R-03. The intended sample size was 900 patients. Excluding 11 ineligible and two eligible patients without follow-up data, the analysis used data on 123 patients randomly assigned to preoperative and 131 to postoperative chemoradiotherapy. Surviving patients were observed for a median of 8.4 years. The 5-year DFS for preoperative patients was 64.7% v 53.4% for postoperative patients (P = .011). The 5-year OS for preoperative patients was 74.5% v 65.6% for postoperative patients (P = .065). A complete pathologic response was achieved in 15% of preoperative patients. No preoperative patient with a complete pathologic response has had a recurrence. Conclusion Preoperative chemoradiotherapy, compared with postoperative chemoradiotherapy, significantly improved DFS and showed a trend toward improved OS.
Plasmin-Mediated Activation of Contact System in Response to Pharmacological Thrombolysis
Authors: Gregory A. Ewald, Paul R. Eisenberg
Journal: Circulation (1995)

Background Thrombin activity increases in patients treated with coronary thrombolysis for acute myocardial infarction, but the mechanisms are not well defined. We have shown that thrombin activity increases in plasma and whole blood incubated with plasminogen activators and appears to be plasmin mediated and dependent on activity of the factor VIIIa/IXa complex. Methods and Results In the present study, increases in thrombin activity induced by incubation of recalcified citrated plasma with 0.16 to 0.5 μmol/L plasmin at 37°C were markedly attenuated in recalcified citrated plasma deficient in factors XI or XII, prekallikrein, or high molecular weight kininogen, as well as in plasma incubated with plasmin in the presence of 3.5 μmol/L corn trypsin inhibitor, a specific factor XIIa inhibitor. Increases in thrombin activity also occurred in nonanticoagulated whole blood incubated with pharmacological concentrations of plasminogen activators and were markedly attenuated in the presence of corn trypsin inhibitor. Plasmin-mediated (0.25 μmol/L) activation of purified factor XII occurred in 0.05 mol/L Tris-HCl and 0.012 mol/L NaCl (pH 7.8) at 37°C, resulting in equimolar quantities of two fragments that corresponded to cleavage of factor XII at Arg 353 -Val 354 , the site involved in kallikrein-mediated activation of factor XII, and cleavage at Lys 346 -Ser 347 , an apparently novel site of plasmin-mediated hydrolysis of factor XII. Contact activation was also demonstrated in plasma samples from patients after treatment with fibrinolytic agents for myocardial infarction, by demonstrating cleavage of high molecular weight kininogen from its one-chain to its two-chain form by ligand blotting with 125 I-prekallikrein. Conclusions Plasmin-mediated activation of the contact system of coagulation appears to account, at least in part, for increases in procoagulant activity in patients treated with fibrinolytic agents. It may also explain hypotension, by release of bradykinin from high molecular weight kininogen, and complement activation, by activated factor XII, that has been demonstrated in these patients.
Jewish Medical Ethics
Authors: A. Jotkowitz, Y. Jakobovits
Journal: BMJ (2009)

This year marks the 50th anniversary of the publication of this work by the former UK chief rabbi, Immanuel Jakobovits. The work was originally submitted as Lord Jakobovits’s doctoral thesis, and with it was launched the new field of Jewish medical ethics. Although Jewish teachings governing medical ethics were already well developed, they were not collected or organised to allow non-experts easy access to its many directives. 

In the second half of the 20th century medical knowledge exploded, and new technologies such as artificial reproduction and organ transplantation called for an ethical response. Daniel Callahan, the philosopher of medical ethics and cofounder of the Hastings Center …
Have We Forgotten the Purpose of Phase III Studies?
Authors: Joseph M. Flynn, John C. Byrd
Journal: Journal of Clinical Oncology (2007)

Experimental design of cancer therapeutics involves wellaccepted phases designed to establish safe dosing, assess efficacy, and determine relative effectiveness compared with standard regimens. Phase I testing allows identification of tolerable dosing and an administration schedule that is followed by phase II testing in a specific disease to examine safety and early efficacy. If acceptable toxicity and efficacy is observed in phase II testing, development may proceed down two different pathways to obtain regulatory approval for marketing within the United States. One pathway involves performance of phase III study(s) comparing the respectivenewagentwiththeacceptedstandardtreatment.Thisrandomized phase III design provides the best opportunity to examine patientbenefitwithrespecttoimprovementinremissionduration, survival, and disease symptoms along with early and late toxicities associated with each treatment. The second pathway is most appropriateforuseinconditionswherenogoodstandardoralternative therapy exists. These single-arm phase II studies are of sufficient size to adequately assess patient safety and provide evidence of patient benefit. However, this nonrandomized design lacks a control comparison, thereby introducing biases that can overestimatethebenefitofthetherapeuticagent.Asaconsequence
Advice to use topical or oral ibuprofen for chronic knee pain in older people: randomised controlled trial and patient preference study
Authors: Martin Underwood, Deborah Ashby, Pamela Cross, Enid Hennessy, Louise Letley, Jeannett Martin, Shahrul Mt-Isa, Suzanne Parsons, Madge Vickers, Ken Whyte
Journal: BMJ (2007)

<b>Objective</b> To determine whether older patients with chronic knee pain should be advised to use topical or oral non-steroidal anti-inflammatory drugs (NSAIDs). <b>Design</b> Randomised controlled trial and patient preference study. <b>Setting</b> 26 general practices. <b>Participants</b> People aged ≥50 with knee pain: 282 in randomised trial and 303 in preference study. <b>Interventions</b> Advice to use topical or oral ibuprofen. <b>Primary outcome measures</b> WOMAC (Western Ontario and McMaster Universities) osteoarthritis index, major and minor adverse effects. <b>Results</b> Changes in global WOMAC scores at 12 months were equivalent. In the randomised trial the difference (topical minus oral) was two points (95% confidence interval −2 to 6); in the preference study, it was one point (−4 to 6). There were no differences in major adverse effects in the trial or study. The only significant differences in secondary outcomes were in the randomised trial. The oral group had more respiratory adverse effects (17% <i>v</i> 7%,95% confidence interval for difference −17% to −2%), the change in serum creatinine was 3.7 mmol/l less favourable (0.9 µmol/l to 6.5 µmol/l); and more participants changed treatments because of adverse effects (16% <i>v</i> 1%, −16% to −5%). In the topical group more participants had chronic pain grade III or IV at three months, and more participants changed treatment because of ineffectiveness. <b>Conclusions</b> Advice to use oral or topical preparations has an equivalent effect on knee pain over one year, and there are more minor side effects with oral NSAIDs. Topical NSAIDs may be a useful alternative to oral NSAIDs. <b>Trial registration</b> ISRCTN 79353052.
Transcatheter Coil Occlusion of Surgical Fenestration After Fontan Operation
Authors: Robert J. Sommer, Michael Recto, Richard J. Golinko, Randall B. Griepp
Journal: Circulation (1996)

Background Fenestration of the Fontan circulation that results in a residual right-to-left shunt has improved operative survival rates among high-risk patients. Late closure of the fenestration by use of a transcatheter umbrella device has achieved separation of the systemic and pulmonary venous circulations, “completing” the Fontan pathway. Because use of umbrella devices is restricted, many institutions continue to perform only nonfenestrated Fontan procedures. Methods and Results Five children 3.5 to 8.3 years old (mean, 5.1 years) underwent cardiac catheterization 0.5 to 24 months (mean, 10 months) after operation for the purpose of occluding a persistently patent Fontan fenestration. Once candidacy was determined, an 8-mm×10-cm Gianturco coil was delivered to straddle the fenestration with established techniques for coil occlusion of patent ductus arteriosus. Complete occlusion occurred in 4 of 5 patients, in 2 of the 4 before they left the catheterization laboratory. One patient had a residual angiographic shunt but had complete closure within 24 hours by echocardiography. In 1 patient who had a residual shunt at 24 hours, the fenestration was completely closed at 1 month after coil placement. One patient had residual shunting at 2 months but saturations have increased 15% to 17% since coil placement. No embolizations (early or late), clinical hemolysis, thromboembolic events, or hemodynamic deterioration occurred among patients during 1- to 14-month follow-up periods. Conclusions A persistently patent fenestration after Fontan operation may be closed with a Gianturco coil. This universally available alternative to umbrella devices may make the fenestrated Fontan a more appealing option to centers that had not previously considered its use.