tbuckley/cabot-search huggingface dataset:
Thioredoxin expression in primary T-cell acute lymphoblastic leukemia and its therapeutic implication.
Authors: Li-en Shao, Mitchell B. Diccianni, Tetsuya Tanaka, Ruby Gribi, Alice L. Yu, Jeanette D. Pullen, Bruce M. Camitta, John Yu
Journal: Cancer Research (2001)

Increased expression of intracellular thioredoxin has been implicated in the inhibition of apoptosis and in a decrease in the sensitivity of the malignancies to drug-induced apoptosis. In the present studies, we analyzed expression of thioredoxin in samples from 28 children with T-cell acute lymphoblastic leukemia and analyzed their sensitivity toward inhibition of thioredoxin expression. Thioredoxin was expressed in variable amounts. Higher expression was associated with higher WBC counts. Exogenously added thioredoxin stimulated proliferation of clonogenic cells among the T-cell acute lymphoblastic leukemia samples expressing relatively lower levels of intracellular thioredoxin, whereas there was no effect on the clonogenic cells expressing high levels of thioredoxin. In addition, there was differential sensitivity of the leukemia clonogenic cells toward 1-methylpropyl 2-imidazolyl disulfide, an inhibitor of thioredoxin expression, as compared with normal hematopoietic progenitors. This suggests the possibility of using this approach for treatment. Because overexpression of thioredoxin is associated with resistance to many anticancer drugs, the inhibition of thioredoxin expression may overcome this drug resistance and probably sensitize leukemia cells to other chemotherapeutic agents.
Targets and self monitoring in hypertension: randomised controlled trial and cost effectiveness analysis
Authors: R J McManus, J Mant, A Roalfe, R A Oakes, S Bryan, H M Pattison, F D R Hobbs
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To assess whether blood pressure control in primary care could be improved with the use of patient held targets and self monitoring in a practice setting, and to assess the impact of these on health behaviours, anxiety, prescribed antihypertensive drugs, patients9 preferences, and costs. <b>Design</b> Randomised controlled trial. <b>Setting</b> Eight general practices in south Birmingham. <b>Participants</b> 441 people receiving treatment in primary care for hypertension but not controlled below the target of &lt; 140/85 mm Hg. <b>Interventions</b> Patients in the intervention group received treatment targets along with facilities to measure their own blood pressure at their general practice; they were also asked to visit their general practitioner or practice nurse if their blood pressure was repeatedly above the target level. Patients in the control group received usual care (blood pressure monitoring by their practice). <b>Main outcome measures</b> Primary outcome: change in systolic blood pressure at six months and one year in both intervention and control groups. Secondary outcomes: change in health behaviours, anxiety, prescribed antihypertensive drugs, patients9 preferences of method of blood pressure monitoring, and costs. <b>Results</b> 400 (91%) patients attended follow up at one year. Systolic blood pressure in the intervention group had significantly reduced after six months (mean difference 4.3 mm Hg (95% confidence interval 0.8 mm Hg to 7.9 mm Hg)) but not after one year (mean difference 2.7 mm Hg (– 1.2 mm Hg to 6.6 mm Hg)). No overall difference was found in diastolic blood pressure, anxiety, health behaviours, or number of prescribed drugs. Patients who self monitored lost more weight than controls (as evidenced by a drop in body mass index), rated self monitoring above monitoring by a doctor or nurse, and consulted less often. Overall, self monitoring did not cost significantly more than usual care (£251 ($437; 364 euros) (95% confidence interval £233 to £275) versus £240 (£217 to £263). <b>Conclusions</b> Practice based self monitoring resulted in small but significant improvements of blood pressure at six months, which were not sustained after a year. Self monitoring was well received by patients, anxiety did not increase, and there was no appreciable additional cost. Practice based self monitoring is feasible and results in blood pressure control that is similar to that in usual care.
Heterogeneity of Nucleotide Frequencies Among Evolutionary Lineages and Phylogenetic Inference
Authors: M. S. Rosenberg
Journal: Molecular Biology and Evolution (2003)

A major assumption of many molecular phylogenetic methods is the homogeneity of nucleotide frequencies among taxa, which refers to the equality of the nucleotide frequency bias among species. Changes in nucleotide frequency among different lineages in a data set are thought to lead to erroneous phylogenetic inference because unrelated clades may appear similar because of evolutionarily unrelated similarities in nucleotide frequencies. We tested the effects of the heterogeneity of nucleotide frequency bias on phylogenetic inference, along with the interaction between this heterogeneity and stratified taxon sampling, by means of computer simulations using evolutionary parameters derived from genomic databases. We found that the phylogenetic trees inferred from data sets simulated under realistic, observed levels of heterogeneity for mammalian genes were reconstructed with accuracy comparable to those simulated with homogeneous nucleotide frequencies; the results hold for Neighbor-Joining, minimum evolution, maximum parsimony, and maximum-likelihood methods. The LogDet distance method, specifically designed to deal with heterogeneous nucleotide frequencies, does not perform better than distance methods that assume substitution pattern homogeneity among sequences. In these specific simulation conditions, we did not find a significant interaction between phylogenetic accuracy and substitution pattern heterogeneity among lineages, even when the taxon sampling is increased.
Survey of Health Care–Associated Infections
Authors: Shelley S Magill, Jonathan R Edwards, Scott K Fridkin
Journal: New England Journal of Medicine (2014)

report a 4% prevalence of health care-associated infections among 11,282 patients from 183 U.S. hospitals.In our view, an important limitation of the study is the ascertainment of patients.By exclusively including patients who were receiving antimicrobial agents, the authors may have missed a substantial proportion of patients with health care-associated infections, despite their assumption that the use of antimicrobial therapy is a highly sensitive indicator for these infections. 2 An established national prevalence surveillance system from the Netherlands reported that only 71.9% of the patients with a health care-associated infection received antimicrobial drugs at the moment of inclusion. 3 The extent of this underestimation probably depends on the type of infection and local treatment guidelines, but it may be as high as one third of all cases and will, moreover, lead to a flawed distribution of types of health care-associated infections and their causative microorganisms.Depending on the exact methods used, the distribution of types of health care-associated infections may furthermore be influenced by the fact that Magill and colleagues chose a cross-sectional approach (limiting the number of patients included per hospital).
Study of cardiac and hemodynamic changes with airway pressure release ventilation and pressure control ventilation in children with acute respiratory distress syndrome
Authors: Hamdy Hamed Abo-Hagar, Rania Gaber, Gehan H. Abo El-Magd
Journal: European Respiratory Journal (2012)

Background :  Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality. Airway pressure release ventilation (APRV) was suggested to be a suitable mode for ventilating such patients with less liability of lung injury.    Aim:  to compare the effect of APRV and pressure control ventilation (PCV) on cardiac and hemodynamic functions in children with ARDS.    Patients and Methods:   Twenty children aged 1-14 years fulfilling ARDS criteria were included. The following parameters were recorded after ventilating the patients on PCV and APRV: ventilation parameters [peak inspiratory pressure (PIP) and mean airway pressure (MAP)], oxygenation parameters PaO 2 /FiO 2  ratio and oxygen delivery, hemodynamic parameters and urine output.   Results:  PIP significantly decreased from 29±7 with PCV to 24±4 cmH 2 O with APRV, while MAP was significantly higher during APRV(17±5) than during PCV (13±3(cmH 2 O. PaO 2 /FiO 2  ratio increased significantly from 265±25 during PCV to 295±33 during APRV. Oxygen delivery increased significantly from 865±98 during PCV to 1196±127 ml/min during APRV. Cardiac index increased significantly from 3.2±0.2 during PCV to 4.1±0.3 l/min/m 2  during APRV. Urine output increased significantly from 0.78±0.1 during PCV to 0.97±0.2 ml/kg/h during APRV. The use of sedatives and inotropics were decreased significantly during APRV compared to PCV.   Conclusions:  APRV may be a suitable mode for ventilating ARDS patients providing better lung recruitment and oxygenation, avoiding more lung injury and cardiac compromise compared with pressure control ventilation.
Severity of post-ERCP pancreatitis directly proportional to the invasiveness of endoscopic intervention: a pilot study in a canine model
Authors: J. Buscaglia, B. Simons, B. Prosser, D. Ruben, S. Giday, P. Magno, J. Clarke, E. Shin, A. Kalloo, S. Kantsevoy, K. Gabrielson, S. Jagannath
Journal: Endoscopy (2008)

See also: Commentaire de travail de J. M. Buscaglia et al., pp. 506Endoscopy 2008; 40(06): 546-546DOI: 10.1055/s-0032-1306846
B.C.G. and Vole Bacillus Vaccines
Authors: H. G. Calwell
Journal: BMJ (1956)

<h3>ABSTRACT</h3> Nanobodies offer several potential advantages over mAbs for the control of SARS-CoV-2. Their ability to access cryptic epitopes conserved across SARS-CoV-2 variants of concern (VoCs) and feasibility to engineer modular, multimeric designs, make these antibody fragments ideal candidates for developing broad-spectrum therapeutics against current and continually emerging SARS-CoV-2 VoCs. Here we describe a diverse collection of 37 anti-SARS-CoV-2 spike glycoprotein nanobodies extensively characterized as both monovalent and IgG Fc-fused bivalent modalities. The panel of nanobodies were shown to have high intrinsic affinity; high thermal, thermodynamic and aerosolization stability; broad subunit/domain specificity and cross-reactivity across many VoCs; wide-ranging epitopic and mechanistic diversity; high and broad <i>in vitro</i> neutralization potencies; and high neutralization efficacies in hamster models of SARS-CoV-2 infection, reducing viral burden by up to six orders of magnitude to below detectable levels. <i>In vivo</i> protection was demonstrated with anti-RBD and previously unreported anti-NTD and anti-S2 nanobodies. This collection of nanobodies provides a therapeutic toolbox from which various cocktails or multi-paratopic formats could be built to tackle current and future SARS-CoV-2 variants and SARS-related viruses. Furthermore, the high aerosol-ability of nanobodies provides the option for effective needle-free delivery through inhalation.
A polymorphism that delays fibrosis in hepatitis C promotes alternative splicing of AZIN1, reducing fibrogenesis
Authors: Andrew J. Paris, Zohar Snapir, Cindy D. Christopherson, Shirley Y. Kwok, Ursula E. Lee, Zahra Ghiassi-Nejad, Peri Kocabayoglu, John J. Sninsky, Josep M. Llovet, Chaim Kahana, Scott L. Friedman
Journal: Hepatology (2010)

Abstract Among several single-nucleotide polymorphisms (SNPs) that correlate with fibrosis progression in chronic HCV, an SNP in the antizyme inhibitor (AzI) gene is most strongly associated with slow fibrosis progression. Our aim was to identify the mechanism(s) underlying this observation by exploring the impact of the AzI SNP on hepatic stellate cell (HSC) activity. Seven novel AZIN1 splice variants (“SV2-8”) were cloned by polymerase chain reaction from the LX2 human HSC line. Expression of a minigene in LX2 containing the AZIN1 slow-fibrosis SNP yielded a 1.67-fold increase in AZIN1 splice variant 2 (AZIN1 SV2) messenger RNA (mRNA) ( P = 0.05). In healthy human leukocytes, the SNP variant also correlated with significantly increased SV2 mRNA. Cells (293T) transfected with short hairpin RNA (shRNA) complementary to the exonic splicing chaperone SRp40 expressed 30% less SRp40 ( P = 0.044) and 43% more AzI SV2 ( P = 0.021) than control shRNA-expressing cells, mimicking the effect of the sequence variant. LX2 cells transfected with AZIN1 full-length complementary DNA expressed 35% less collagen I mRNA ( P = 0.09) and 18% less α-smooth muscle actin mRNA ( P = 0.09). Transient transfection of AZIN1 SV2 complementary DNA into LX2 cells reduced collagen I gene expression by 64% ( P = 0.001) and α-smooth muscle actin by 43% ( P = 0.005) compared to vector-transfected controls, paralleling changes in protein expression. Both AZIN1 and AZIN-SV2 mRNAs are detectable in normal human liver and reduced in HCV cirrhotic livers. The AZIN1-SV2 acts via a polyamine-independent pathway, as it neither interacts with antizyme nor affects the ability of AZIN1 lacking this variant to neutralize antizyme. Conclusion: An SNP variant in the AZIN1 gene leads to enhanced generation of a novel alternative splice form that modifies the fibrogenic potential of HSCs. (Hepatology 2011)
Combined Treatment With Buserelin and Tamoxifen in Premenopausal Metastatic Breast Cancer: a Randomized Study
Authors: Jan G. M. Klijn, Louk V. A. M. Beex, Louis Mauriac, Jacobus A. van Zijl, Corinne Veyret, Johan Wildiers, Jacek Jassem, Martine Piccart, Jos Burghouts, Dominique Becquart, Carolien Seynaeve, Françoise Mignolet, Luc Duchateau
Journal: JNCI Journal of the National Cancer Institute (2000)

Surgical or medical castration and antiestrogenic treatment with tamoxifen are common endocrine treatments for premenopausal women with breast cancer. However, tamoxifen therapy induces high levels of plasma estradiol, with unknown long-term effects. In this study, we investigated the effect of combining estrogen suppression with the luteinizing hormone-releasing hormone agonist buserelin and estradiol receptor blockade with tamoxifen to determine whether the high estradiol levels induced by tamoxifen could be reduced and whether the antitumor effects would be better.In a three-arm, randomized, prospective trial, from 1988 through 1995, a total of 161 premenopausal patients with advanced breast cancer were randomly assigned to treatment with buserelin, tamoxifen, or both. Patients with steroid receptor-negative tumors or with tumors of unknown receptor status who had a disease-free interval of less than 2 years were excluded. The median follow-up was 7.3 years, during which 76% of the patients died, all of breast cancer. Patient and tumor characteristics were well balanced among treatment groups. All P values are from two-sided tests.Combined treatment with buserelin and tamoxifen was superior to treatment with buserelin or tamoxifen alone by objective response rate (48%, 34%, and 28% of patients who could be evaluated, respectively; P =.11 [chi(2) test]), median progression-free survival (9.7 months, 6.3 months, and 5.6 months; P =.03), and overall survival (3.7 years, 2.5 years, and 2.9 years; P =.01). Actuarial 5-year survival percentages were 34.2% (95% confidence interval [CI] = 20.4%-48.0%), 14.9% (95% CI = 3.9%-25.9%), and 18.4% (95% CI = 7.0%-29.8%), respectively. No differences in antitumor effects were observed between single-agent treatment groups. During combined treatment or treatment with buserelin alone, plasma estradiol levels were suppressed equally; in contrast, during treatment with tamoxifen alone, plasma estradiol levels increased threefold to fourfold over pretreatment levels.Combined treatment with buserelin and tamoxifen was more effective and resulted in longer overall survival than treatment with either drug alone.
A Genetically Engineered Oncolytic Adenovirus Decoys and Lethally Traps Quiescent Cancer Stem–like Cells in S/G2/M Phases
Authors: Shuya Yano, Hiroshi Tazawa, Yuuri Hashimoto, Yasuhiro Shirakawa, Shinji Kuroda, Masahiko Nishizaki, Hiroyuki Kishimoto, Futoshi Uno, Takeshi Nagasaka, Yasuo Urata, Shunsuke Kagawa, Robert M. Hoffman, Toshiyoshi Fujiwara
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Because chemoradiotherapy selectively targets proliferating cancer cells, quiescent cancer stem–like cells are resistant. Mobilization of the cell cycle in quiescent leukemia stem cells sensitizes them to cell death signals. However, it is unclear that mobilization of the cell cycle can eliminate quiescent cancer stem–like cells in solid cancers. Thus, we explored the use of a genetically-engineered telomerase-specific oncolytic adenovirus, OBP-301, to mobilize the cell cycle and kill quiescent cancer stem–like cells. Experimental Design: We established CD133+ cancer stem–like cells from human gastric cancer MKN45 and MKN7 cells. We investigated the efficacy of OBP-301 against quiescent cancer stem–like cells. We visualized the treatment dynamics of OBP-301 killing of quiescent cancer stem–like cells in dormant tumor spheres and xenografts using a fluorescent ubiquitination cell-cycle indicator (FUCCI). Results: CD133+ gastric cancer cells had stemness properties. OBP-301 efficiently killed CD133+ cancer stem–like cells resistant to chemoradiotherapy. OBP-301 induced cell-cycle mobilization from G0–G1 to S/G2/M phases and subsequent cell death in quiescent CD133+ cancer stem–like cells by mobilizing cell-cycle–related proteins. FUCCI enabled visualization of quiescent CD133+ cancer stem–like cells and proliferating CD133− non–cancer stem–like cells. Three-dimensional visualization of the cell-cycle behavior in tumor spheres showed that CD133+ cancer stem–like cells maintained stemness by remaining in G0–G1 phase. We showed that OBP-301 mobilized quiescent cancer stem–like cells in tumor spheres and xenografts into S/G2/M phases where they lost viability and cancer stem–like cell properties and became chemosensitive. Conclusion: Oncolytic adenoviral infection is an effective mechanism of cancer cell killing in solid cancer and can be a new therapeutic paradigm to eliminate quiescent cancer stem–like cells. Clin Cancer Res; 19(23); 6495–505. ©2013 AACR.
The MRP4/ABCC4 Gene Encodes a Novel Apical Organic Anion Transporter in Human Kidney Proximal Tubules
Authors: Rémon A. M. H. van Aubel, Pascal H. E. Smeets, Janny G. P. Peters, René J. M. Bindels, Frans G. M. Russel
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The cyclic nucleotides cAMP and cGMP play key roles in cellular signaling and the extracellular regulation of fluid balance. In the kidney, cAMP is excreted across the apical proximal tubular membrane into urine, where it reduces phosphate reabsorption through a dipyridamole-sensitive mechanism that is not fully understood. It has long been known that this cAMP efflux pathway is dependent on ATP and is inhibited by probenecid. However, its identity and whether cGMP shares the same transporter have not been established. Here the expression, localization, and functional properties of human multidrug resistance protein 4 (MRP4) are reported. MRP4 is localized to the proximal tubule apical membrane of human kidney, and membrane vesicles from Sf9 cells expressing human MRP4 exhibit ATP-dependent transport of [ 3 H]cAMP and [ 3 H]cGMP. Both probenecid and dipyridamole are potent MRP4 inhibitors. ATP-dependent [ 3 H]methotrexate and [ 3 H]estradiol-17β- d -glucuronide transport by MRP4 and interactions with the anionic conjugates S -(2,4-dinitrophenyl)-glutathione, N -acetyl-(2,4-dinitrophenyl)-cysteine, α-naphthyl-β- d -glucuronide, and p -nitrophenyl-β- d -glucuronide are also demonstrated. In kidneys of rats deficient in the apical anionic conjugate efflux pump Mrp2, Mrp4 expression is maintained at the same level. It is concluded that MRP4 is a novel apical organic anion transporter and the putative efflux pump for cAMP and cGMP in human kidney proximal tubules.
REMARKS ON THE ESTIMATION OF THE CALCIUM METABOLISM: With a Description of a Clinical Method of Estimating the Amount of Calcium in the Urine and Other Physiological Fluids
Authors: W. B. Bell
Journal: BMJ (1912)

3. The resuilts are much better when glands are removed, recurrence being greatly delayed or altogetlier prevented in many cases.4. Partial remiiovals of the tongue were followed by local recurrence in 6 out of 29 cases.
Targeting Melanoma Growth and Metastasis with Systemic Delivery of Liposome-Incorporated Protease-Activated Receptor-1 Small Interfering RNA
Authors: Gabriel J. Villares, Maya Zigler, Hua Wang, Vladislava O. Melnikova, Hong Wu, Ran Friedman, Michael C. Leslie, Pablo E. Vivas-Mejia, Gabriel Lopez-Berestein, Anil K. Sood, Menashe Bar-Eli
Journal: Cancer Research (2008)

Abstract The thrombin receptor [protease-activated receptor-1 (PAR-1)] is overexpressed in highly metastatic melanoma cell lines and in patients with metastatic lesions. Activation of PAR-1 leads to cell signaling and up-regulation of genes involved in adhesion, invasion, and angiogenesis. Herein, we stably silence PAR-1 through the use of lentiviral short hairpin RNA and found significant decreases in both tumor growth (P &amp;lt; 0.01) and metastasis (P &amp;lt; 0.001) of highly metastatic melanoma cell lines in vivo. The use of viruses for therapy is not ideal as it can induce toxic immune responses and possible gene alterations following viral integration. Therefore, we also used systemic delivery of PAR-1 small interfering RNA (siRNA) incorporated into neutral liposomes [1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC)] to decrease melanoma growth and metastasis in vivo. Significant decreases in tumor growth, weight, and metastatic lung colonies (P &amp;lt; 0.001 for all) were found in mice treated with PAR-1 siRNA-DOPC. The in vivo effects of PAR-1 on invasion and angiogenesis were analyzed via immunohistochemistry. Concomitant decreases in vascular endothelial growth factor, interleukin-8, and matrix metalloproteinase-2 expression levels, as well as decreased blood vessel density (CD31), were found in tumor samples from PAR-1 siRNA-treated mice, suggesting that PAR-1 is a regulator of melanoma cell growth and metastasis by affecting angiogenic and invasive factors. We propose that siRNA incorporated into DOPC nanoparticles could be delivered systemically and used as a new modality for melanoma treatment. [Cancer Res 2008;68(21):9078–86]
(2) Ichthyosis hystrix
Authors: B.R. Allen
Journal: British Journal of Dermatology (1978)

Journal Article (2) Ichthyosis hystrix Get access B.R. Allen B.R. Allen General Hospital, Newark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 99, Issue s16, 1 December 1978, Page 26, https://doi.org/10.1111/j.1365-2133.1978.tb15224.x Published: 01 December 1978