tbuckley/cabot-search huggingface dataset:
Peloruside A Does Not Bind to the Taxoid Site on β-Tubulin and Retains Its Activity in Multidrug-Resistant Cell Lines
Authors: Thomas N. Gaitanos, Rubén M. Buey, J. Fernando Díaz, Peter T. Northcote, Paul Teesdale-Spittle, José M. Andreu, John H. Miller
Journal: Cancer Research (2004)

Abstract Peloruside A (peloruside), a microtubule-stabilizing agent from a marine sponge, is less susceptible than paclitaxel to multidrug resistance arising from overexpression of the P-glycoprotein efflux pump and is not affected by mutations that affect the taxoid binding site of β-tubulin. In vitro studies with purified tubulin indicate that peloruside directly induces tubulin polymerization in the absence of microtubule-associated proteins. Competition for binding between peloruside, paclitaxel, and laulimalide revealed that peloruside binds to a different site on tubulin to paclitaxel. Moreover, laulimalide was able to displace peloruside, indicating that peloruside and laulimalide may compete for the same or overlapping binding sites. It was concluded that peloruside and laulimalide have binding properties that are distinct from other microtubule-stabilizing compounds currently under investigation.
Treatment of proximal metatarsal V fractures in athletes and non-athletes
Authors: Gino M Kerkhoffs, Viktor E Versteegh, Inger N Sierevelt, Peter Kloen, C Niek van Dijk
Journal: British Journal of Sports Medicine (2012)

Since the first publication on proximal metatarsal V fractures by Jones in 1902,1 there has been a lot of controversy about the classification and ideal treatment of the proximal metatarsal V fracture. The controversy includes mainly the different anatomical,2,–,4 radiological5 and aetiological aspects.6,–,9 A proper understanding of these different aspects of the proximal metatarsal V fracture is essential, because a right interpretation of fracture type and the appropriate treatment strategy may greatly diminish the time to return to competitive sports or activities of daily living (ADL).

The purpose of this study was to evaluate the treatment strategies of the different proximal metatarsal V fractures (avulsion, Jones and stress fractures, figure 1) and their outcomes in athletes and non-athletes.



Figure 1 
Anatomical locations of the different types of proximal fifth metatarsal fractures. The anatomic locations of the different types of proximal fifth metatarsal fractures are visualised in the grey-coloured areas. 1) Avulsion fracture (fracture of the tuberosity of the fifth metatarsal). 2) Jones fracture (border of metaphysis and diaphysis; fracture involving the intermetatarsal joint). 3) Stress fracture (fracture in the proximal diaphysis, distal from the intermetatarsal joint).



This evaluation is based on a critical overview of the current literature combined with the opinion of a group of international experts.

The hypothesis of this study is that operative treatment is the most effective treatment strategy for all proximal metatarsal V fractures, besides the non-displaced avulsion fracture.

### Literature overview

A literature search was performed covering …
What Is the True Number Needed to Screen and Treat to Save a Life With Prostate-Specific Antigen Testing?
Authors: Stacy Loeb, Edward F. Vonesh, E. Jeffrey Metter, H. Ballentine Carter, Peter H. Gann, William J. Catalona
Journal: Journal of Clinical Oncology (2010)

The European Randomized Study of Screening for Prostate Cancer (ERSPC) reported a 20% mortality reduction with prostate-specific antigen (PSA) screening. However, they estimated a number needed to screen (NNS) of 1,410 and a number needed to treat (NNT) of 48 to prevent one prostate cancer death at 9 years. Although NNS and NNT are useful statistics to assess the benefits and harms of an intervention, in a survival study setting such as the ERSPC, NNS and NNT are time specific, and reporting values at one time point may lead to misinterpretation of results. Our objective was to re-examine the effect of varying follow-up times on NNS and NNT using data extrapolated from the ERSPC report.
Antibiotic prophylaxis in cardiothoracic surgery in the United Kingdom: current practice.
Authors: A P Wilson, T Treasure, M F Sturridge, R N Gruneberg
Journal: Thorax (1986)

A survey was conducted of the current practice of antibiotic prophylaxis in cardiac surgery throughout the United Kingdom. Most surgeons (84%) use a regimen covering a broad spectrum of bacterial species that is continued for two to three days after the operation. The most used regimens are a combination of beta lactamase resistant penicillin with an aminoglycoside (44%) or a single broad spectrum cephalosporin (30%). Just 16% of surgeons preferred a narrow spectrum regimen effective against only the Gram positive organisms commonly responsible for postoperative infection in these patients. Antibiotic prophylaxis has been adopted by all cardiac surgeons in the United Kingdom but is sometimes continued longer than is indicated by the clinical or experimental evidence.
PKCλ in liver mediates insulin-induced SREBP-1c expression and determines both hepatic lipid content and overall insulin sensitivity
Authors: Michihiro Matsumoto, Wataru Ogawa, Kazunori Akimoto, Hiroshi Inoue, Kazuaki Miyake, Kensuke Furukawa, Yoshitake Hayashi, Haruhisa Iguchi, Yasushi Matsuki, Ryuji Hiramatsu, Hitoshi Shimano, Nobuhiro Yamada, Shigeo Ohno, Masato Kasuga, Tetsuo Noda
Journal: Journal of Clinical Investigation (2003)

PKCλ is implicated as a downstream effector of PI3K in insulin action. We show here that mice that lack PKCλ specifically in the liver (L-λKO mice), produced with the use of the Cre-loxP system, exhibit increased insulin sensitivity as well as a decreased triglyceride content and reduced expression of the sterol regulatory element–binding protein-1c (SREBP-1c) gene in the liver. Induction of the hepatic expression of Srebp1c and of its target genes involved in fatty acid/triglyceride synthesis by fasting and refeeding or by hepatic expression of an active form of PI3K was inhibited in L-λKO mice compared with that in control animals. Expression of Srebp1c induced by insulin or by active PI3K in primary cultured rat hepatocytes was inhibited by a dominant-negative form of PKCλ and was mimicked by overexpression of WT PKCλ. Restoration of PKCλ expression in the liver of L-λKO mice with the use of adenovirus-mediated gene transfer corrected the metabolic abnormalities of these animals. Hepatic PKCλ is thus a determinant of hepatic lipid content and whole-body insulin sensitivity.
Acquisition of 16S rRNA methylase gene in Pseudomonas aeruginosa
Authors: Keiko Yokoyama, Yohei Doi, Kunikazu Yamane, Hiroshi Kurokawa, Naohiro Shibata, Keigo Shibayama, Tetsuya Yagi, Haru Kato, Yoshichika Arakawa
Journal: The Lancet (2003)
Effect of 5-lipoxygenase inhibition on bronchoconstriction and airway inflammation in nocturnal asthma.
Authors: S E Wenzel, J B Trudeau, D A Kaminsky, J Cohn, R J Martin, J Y Westcott
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

To investigate the contribution of leukotrienes (LTs) to inflammation and bronchoconstriction in nocturnal asthma, we performed a randomized trial in 12 asthmatic patients and 6 normal control subjects. This study involved pulmonary function testing, methacholine challenge, bronchoscopy for cell counts, LT and thromboxane (TX) levels in bronchoalveolar lavage (BAL) fluid, and collection of urine for LTs at 4:00 P.M. and 4:00 A.M. At 4:00 P.M. BAL fluid LTB4 and sulfidopeptide LT levels in asthmatic and control subjects were not statistically different. At 4:00 A.M. alone, LTB4 and cysteinyl LT levels increased to become significantly greater in asthmatic than in control subjects, LTB4 levels correlating significantly (r = -0.66, p < 0.0001) with nocturnal fall in FEV1. Nocturnal asthmatic urinary LTE4 levels were also significantly higher than those of control subjects. The 4:00 A.M. testing was repeated during treatment with a 5-lipoxygenase inhibitor, zileuton. In asthmatic subjects, zileuton decreased BAL fluid LTB4 (p = 0.01) and urinary LTE4 (p = 0.01) while showing a trend for improving nocturnal FEV1 (p = 0.086). These decreases in LTB4 levels and improvement in FVE1 were associated with significant reductions in 4 A.M. BAL fluid and blood eosinophil percentages on zileuton compared with placebo administration. These findings demonstrate the importance of LTs in both the inflammation and the physiology of nocturnal asthma.
Titin-Based Modulation of Calcium Sensitivity of Active Tension in Mouse Skinned Cardiac Myocytes
Authors: Olivier Cazorla, Yiming Wu, Thomas C. Irving, Henk Granzier
Journal: Circulation Research (2001)

Abstract —We studied the effect of titin-based passive force on the length dependence of activation of cardiac myocytes to explore whether titin may play a role in the generation of systolic force. Force-pCa relations were measured at sarcomere lengths (SLs) of 2.0 and 2.3 μm. Passive tension at 2.3 μm SL was varied from ≈1 to ≈10 mN/mm 2 by adjusting the characteristics of the stretch imposed on the passive cell before activation. Relative to 2.0 μm SL, the force-pCa curve at 2.3 μm SL and low passive tension showed a leftward shift (ΔpCa 50 [change in pCa at half-maximal activation]) of 0.09±0.02 pCa units while at 2.3 μm SL and high passive tension the shift was increased to 0.25±0.03 pCa units. Passive tension also increased ΔpCa 50 at reduced interfilament lattice spacing achieved with dextran. We tested whether titin-based passive tension influences the interfilament lattice spacing by measuring the width of the myocyte and by using small-angle x-ray diffraction of mouse left ventricular wall muscle. Cell width and interfilament lattice spacing varied inversely with passive tension, in the presence and absence of dextran. The passive tension effect on length-dependent activation may therefore result from a radial titin-based force that modulates the interfilament lattice spacing.
Increased injury and intramuscular collagen of the diaphragm in COPD: autopsy observations
Authors: A. Scott, X. Wang, J. D. Road, W. D. Reid
Journal: European Respiratory Journal (2005)

Evidence for diaphragm injury in people with chronic obstructive pulmonary disease (COPD) has been reported, although the extent of injury and collagen accumulation post mortem have not previously been examined. In addition, it is not known whether the amount of injury and collagen are different in key regions of the diaphragm. The cross-sectional area of collagen and the percentage of abnormal myofibres in the post mortem diaphragm and psoas major were determined by computer-assisted image analysis of stained cross-sections of the diaphragm for collagen with picrosirius red and with haematoxylin and eosin for morphology. In the midcostal diaphragm of six subjects with COPD and six subjects with no significant respiratory disease, the COPD diaphragm displayed a greater cross-sectional area of collagen and percentage of abnormal myofibres (collagen: 24.2±1.0 versus 18.6±1.1%; injury: 28.4±7.2 versus 12.0±1.3%). In 18 patients with various respiratory conditions, the midcostal diaphragm displayed more collagen and abnormal myofibres than the crural diaphragm, while both costal and crural diaphragms displaying more collagen and abnormal myofibres than psoas major. This study reveals extensive injury and collagen accumulation in the chronic obstructive pulmonary diseased diaphragm, and reveals a regional pattern of injury and intramuscular collagen which may correspond to variations in diaphragm loading.
ACC/ACP/SCAI/SVMB/SVS clinical competence statement on vascular medicine and catheter-based peripheral vascular interventions11When citing this document, the American College of Cardiology, American College of Physicians, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and the Society for Vascular Surgery would appreciate the following citation format: Creager MA, Goldstone J, Hirshfeld JW, Kazmers A, Kent KC, Lorell BH, Olin JW, Pauly RR, …
Authors: Mark A. Creager, Jerry Goldstone, John W. Hirshfeld, Andris Kazmers, K.Craig Kent, Beverly H. Lorell, Jeffrey W. Olin, Rebecca Rainer Pauly, Kenneth Rosenfield, Gary S. Roubin, Gregorio A. Sicard, Christopher J. White, Mark A. Creager, William L. Winters, John W. Hirshfeld, Beverly H. Lorell, Geno Merli, George P. Rodgers, Cynthia M. Tracy, Howard H. Weitz
Journal: Journal of the American College of Cardiology (2004)
POTENTIATION OF T-CELL-MEDIATED IMMUNITY BY SELECTIVE SUPPRESSION OF ANTIBODY FORMATION WITH CYCLOPHOSPHAMIDE
Authors: P. H. Lagrange, G. B. Mackaness, T. E. Miller
Journal: The Journal of Experimental Medicine (1974)

Delayed-type hypersensitivity (DTH) appears in mice immunized with less than an optimal immunogenic dose of sheep red blood cells (SRBC), but is blocked progressively as antibody production increases in response to larger doses of SRBC. Treatment with cyclophosphamide (CY) was shown to release T cells from this inhibitory influence of the humoral response, and cause enhancement of DTH. The magnitude of this enhancing effect on T-cell activity was markedly dependent on the time of treatment relative to the time of immunization, and on the time chosen for measuring DTH. The reasons for these pronounced effects of timing are threefold: (a) CY given before antigenic stimulation has a long-lasting effect on antibody formation, but no apparent effect on the precursors of activated T cells. (b) After antigenic stimulation, T cells also become susceptible to CY. (c) The production of a nonspecific participant (monocyte) in the DTH reaction is also suppressed by CY, though the supply of circulating monocytes is not immediately affected by the drug. The differential effect of CY on T and B lymphocytes depends on the differing physiological states of the majority of cells that make up these two populations. The former are resting cells that are insensitive to CY until exposed to specific antigen, while the latter are drawn from a rapidly replicating precursor pool and are susceptible to CY at all times.
CUL4A Induces Epithelial–Mesenchymal Transition and Promotes Cancer Metastasis by Regulating ZEB1 Expression
Authors: Yunshan Wang, Mingxin Wen, Yongwon Kwon, Yangyang Xu, Yueyong Liu, Pengju Zhang, Xiuquan He, Qin Wang, Yurong Huang, Kuang-Yu Jen, Mark A. LaBarge, Liang You, Scott C. Kogan, Joe W. Gray, Jian-Hua Mao, Guangwei Wei
Journal: Cancer Research (2013)

The ubiquitin ligase CUL4A has been implicated in tumorigenesis, but its contributions to progression and metastasis have not been evaluated. Here, we show that CUL4A is elevated in breast cancer as well as in ovarian, gastric, and colorectal tumors in which its expression level correlates positively with distant metastasis. CUL4A overexpression in normal or malignant human mammary epithelial cells increased their neoplastic properties in vitro and in vivo, markedly increasing epithelial-mesenchymal transition (EMT) and the metastatic capacity of malignant cells. In contrast, silencing CUL4A in aggressive breast cancer cells inhibited these processes. Mechanistically, we found that CUL4A modulated histone H3K4me3 at the promoter of the EMT regulatory gene ZEB1 in a manner associated with its transcription. ZEB1 silencing blocked CUL4A-driven proliferation, EMT, tumorigenesis, and metastasis. Furthermore, in human breast cancers, ZEB1 expression correlated positively with CUL4A expression and distant metastasis. Taken together, our findings reveal a pivotal role of CUL4A in regulating the metastatic behavior of breast cancer cells.
Unsafe driving behaviour and four wheel drive vehicles: observational study
Authors: Lesley Walker, Jonathan Williams, Konrad Jamrozik
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To assess the level of compliance with the new law in the United Kingdom mandating penalties for using a hand held mobile phone while driving, to compare compliance with this law with the one on the use of seat belts, and to compare compliance with these laws between drivers of four wheel drive vehicles and drivers of normal cars. <b>Design</b> Observational study with two phases—one within the “grace” period, the other starting one week after penalties were imposed on drivers using such telephones. <b>Setting</b> Three busy sites in London. <b>Participants</b> Drivers of 38 182 normal cars and 2944 four wheel drive vehicles. <b>Main outcome measures</b> Proportions of drivers seen to be using hand held mobile phones and not using seat belts. <b>Results</b> Drivers of four wheel drive vehicles were more likely than drivers of other cars to be seen using hand held mobile phones (8.2% <i>v</i> 2.0%) and not complying with the law on seat belts (19.5% <i>v</i> 15.0%). Levels of non-compliance with both laws were slightly higher in the penalty phase of observation, and breaking one law was associated with increased likelihood of breaking the other. <b>Conclusions</b> The level of non-compliance with the law on the use of hand held mobile phones by drivers in London is high, as is non-compliance with the law on seat belts. Drivers of four wheel drive vehicles were four times more likely than drivers of other cars to be seen using hand held mobile phones and slightly more likely not to comply with the law on seat belts.
Topical thrombin and acquired coagulation factor inhibitors: Clinical spectrum and laboratory diagnosis
Authors: Thomas L. Ortel, Linda A. Charles, Frank G. Keller, P. Kelly Marcom, H. Newland Oldham, William H. Kane, B. Gail Macik
Journal: American Journal of Hematology (1994)

Abstract Topical bovine thrombin preparations are used extensively in cardiovascular, neurosurgical, and otolaryngologic procedures. Patients who are treated with these topical thrombin preparations may develop antibodies to bovine coagulation factors that may cross‐react with the endogenous human clotting proteins. We have identified four patients with acquired factor inhibitors following exposure to topical thrombin at Duke University Medical Center and summarize these cases in addition to 13 patients previously reported in the literature. In most cases, the inhibitor developed following a second (or subsequent) exposure to topical thrombin. The clinical course was extremely variable, ranging from totally asymptomatic to life‐threatening hemorrhage. The most consistent laboratory abnormality was a prolonged bovine thrombin clotting time, which corrected, at least partially, when human thrombin was substituted for bovine thrombin. Some of these patients also developed factor V inhibitors with prolonged prothrombin and activated partial thromboplastin times. Although these patients have prolonged clotting times, they should not be considered “autoanticoagulated,” since thromboembolic complications can still occur. Therapeutic intervention is largely empirical and depends on the clinical manifestations of the individual patient. © 1994 Wiley‐Liss, Inc.
Do Older Adults Aged 60–75 Years Benefit From Diabetes Behavioral Interventions?
Authors: Elizabeth A. Beverly, Shane Fitzgerald, Lilya Sitnikov, Om P. Ganda, A. Enrique Caballero, Katie Weinger
Journal: Diabetes Care (2013)

In this secondary analysis, we examined whether older adults with diabetes (aged 60-75 years) could benefit from self-management interventions compared with younger adults. Seventy-one community-dwelling older adults and 151 younger adults were randomized to attend a structured behavioral group, an attention control group, or one-to-one education.We measured A1C, self-care (3-day pedometer readings, blood glucose checks, and frequency of self-care), and psychosocial factors (quality of life, diabetes distress, frustration with self-care, depression, self-efficacy, and coping styles) at baseline and 3, 6, and 12 months postintervention.Both older (age 67 ± 5 years, A1C 8.7 ± 0.8%, duration 20 ± 12 years, 30% type 1 diabetes, 83% white, 41% female) and younger (age 47 ± 9 years, A1C 9.2 ± 1.2%, 18 ± 12 years with diabetes, 59% type 1 diabetes, 82% white, 55% female) adults had improved A1C equally over time. Importantly, older and younger adults in the group conditions improved more and maintained improvements at 12 months (older structured behavioral group change in A1C -0.72 ± 1.4%, older control group -0.65 ± 0.9%, younger behavioral group -0.55 ± 1.2%, younger control group -0.43 ± 1.7%). Furthermore, frequency of self-care, glucose checks, depressive symptoms, quality of life, distress, frustration with self-care, self-efficacy, and emotional coping improved in older and younger participants at follow-up.The findings suggest that, compared with younger adults, older adults receive equal glycemic benefit from participating in self-management interventions. Moreover, older adults showed the greatest glycemic improvement in the two group conditions. Clinicians can safely recommend group diabetes interventions to community-dwelling older adults with poor glycemic control.
Regulatory T-cell Modulation Using Cyclophosphamide in Vaccine Approaches: A Current Perspective
Authors: Dung T. Le, Elizabeth M. Jaffee
Journal: Cancer Research (2012)

Abstract Regulatory T cells (Treg) have become an important player in regulating anticancer immune responses. In fact, published studies describe a correlation between tumor-infiltrating Tregs and poor prognosis. Once called “suppressor T cells,” these T cells evaded isolation because of a lack of known markers that distinguished them from other T cells. However, the biology of these T cells is currently a major focus of immunologic research. Markers have since been discovered that identify these T cells and provide insights into how these T cells are regulated. Despite these advances, much needs to be learned about the subsets of Tregs and their specific roles in regulating immune responses. In addition, specific agents that target Tregs are currently unavailable. Cyclophosphamide has emerged as a clinically feasible agent that can suppress Tregs and allow more effective induction of antitumor immune responses. This review focuses on the use of cyclophosphamide in targeting Tregs to augment cancer vaccine approaches. However, these principles can also be applied to other immunotherapy strategies. Cancer Res; 72(14); 3439–44. ©2012 AACR.
Abnormalities in villin gene expression and canalicular microvillus structure in progressive cholestatic liver disease of childhood
Authors: M James Phillips, Toshifumi Azuma, Sheue-Lim M Meredith, Jeremy A Squire, Cameron A Ackerley, Fred G Pluthero, Eve A Roberts, Riccardo A Superina, Gary A Levy, Philip A Marsden
Journal: The Lancet (2003)