tbuckley/cabot-search huggingface dataset:
Cationic Amino Acids Involved in Dicarboxylate Binding of the Flounder Renal Organic Anion Transporter
Authors: NATASCHA A. WOLFF, BETTINA GRÜNWALD, BJÖRN FRIEDRICH, FLORIAN LANG, STEFAN GODEHARDT, GERHARD BURCKHARDT
Journal: Journal of the American Society of Nephrology (2001)

Three conserved cationic amino acids in predicted transmembrane domains 1, 8, and 11, respectively, of the flounder renal organic anion transporter, fROAT, were changed by site-directed mutagenesis and the resulting mutants functionally characterized in Xenopus laevis oocytes. Uptake of p-aminohippurate (PAH) in oocytes that expressed mutant H34I, K394A, or R478D was markedly reduced compared with oocytes that expressed wild-type fROAT, but was still several-fold higher than that in water-injected control oocytes. Immunocytochemically, no decrease in cell surface expression of the mutants could be detected. Only mutant R478D appeared to have a lower PAH affinity than the wild type. Similar to wild-type—dependent PAH transport, uptake induced by mutant H34I was sensitive to glutarate (GA) cis-inhibition. In contrast, mutants K394A and R478D could not be significantly affected by up to 10 mM GA, although the cRNA-dependent PAH uptake could still be almost completely suppressed by probenecid. Moreover, again in contrast to the wild type, neither PAH influx nor PAH efflux mediated by these two mutants could be trans-stimulated by GA, nor did they induce GA transport. These data suggest that amino acids K394 and R478 in fROAT are required for dicarboxylate binding and PAH/dicarboxylate exchange.
Effects of Sho-saiko-to on hepatocarcinogenesis and 8-hydroxy-2'-deoxyguanosine formation
Authors: Goshi Shiota, Yoshiko Maeta, Tomoyuki Mukoyama, Atsushi Yanagidani, Akihide Udagawa, Kenji Oyama, Kazuo Yashima, Yosuke Kishimoto, Yoichiro Nakai, Tetsuo Miura, Hisao Ito, Yoshikazu Murawaki, Hironaka Kawasaki
Journal: Hepatology (2002)

Oxidative stress plays an important role in hepatocarcinogenesis. Although Sho-saiko-to (TJ-9), a Japanese herbal medicine which has been recently administered to patients with chronic liver disease in Japan, prevents hepatocarcinogenesis, the mechanism by which TJ-9 protects against cancer development is not fully understood. 8-Hydroxy-2'-deoxyguanosine (8-OHdG), a DNA adduct by reactive oxygen species, is known as a parameter of genetic risk for hepatocarcinogenesis. To clarify whether the preventive effect on hepatocarcinogenesis by TJ-9 is dependent on 8-OHdG, the effect on 8-OHdG levels by TJ-9 was examined by using high-performance liquid chromatography-mass spectrometry (LC-MS) in a diethylnitrosamine (DEN)-induced hepatocarcinogenesis model of male Fisher rats. TJ-9 reduced the number of preneoplastic cells, detected as the glutathione S transferase P (GST-P)-positive hepatocytes, and inhibited the development of liver tumors. TJ-9 also significantly decreased the formation of 8-OHdG, as indicated by LC-MS and immunohistochemical analysis. In addition, ornithine decarboxylase (ODC) activity and the number of proliferating cell nuclear antigen (PCNA)-positive cells were not altered. An electron paramagnetic resonance spin-trapping technique showed that TJ-9 scavenges hydroxyl radicals in a dose-dependent manner. In conclusion, the results of the present study suggest that TJ-9 prevents hepatocarcinogenesis in association with inhibition of 8-OHdG formation.
Alternative Methods of Insulin Sensitivity Assessment in Obese Children and Adolescents
Authors: Sophia M. Rössner, Martin Neovius, Scott M. Montgomery, Claude Marcus, Svante Norgren
Journal: Diabetes Care (2008)

To validate fasting indexes against minimal model analysis (MMOD) of the frequently sampled intravenous glucose tolerance test (FSIVGTT) in an obese pediatric population.FSIVGTT-MMOD results were compared with homeostasis model assessment of insulin resistance (HOMA-IR) and fasting insulin with the sample stratified by sex, puberty, and sensitivity index (S(i)) median in 191 children (82 males and 109 females, 13.9 +/- 2.9 years of age, BMI 36.9 +/- 6.2 kg/m(2), BMI SD score 6.1 +/- 1.6).Across pubertal groups, correlation coefficients between S(i) and HOMA-IR ranged from -0.43 to -0.78 in males and from -0.53 to -0.57 in females (age and BMI adjusted, P < 0.05 in all instances). Similar results were seen for fasting insulin. In females, the relationship was significantly weaker in more-insulin-resistant subjects.The validity of fasting indexes in explaining S(i) was sex dependent, varied with pubertal stage, and in females was influenced by degree of insulin sensitivity. In obese pediatric populations, we generally discourage the use of fasting indexes, although the validity varies within subgroups.
Dual Tyrosine Kinase Inhibitor for Focal Adhesion Kinase and Insulin-like Growth Factor-I Receptor Exhibits Anticancer Effect in Esophageal Adenocarcinoma <i>In vitro</i> and <i>In vivo</i>
Authors: Nobuyuki Watanabe, Munenori Takaoka, Kazufumi Sakurama, Yasuko Tomono, Shinji Hatakeyama, Osamu Ohmori, Takayuki Motoki, Yasuhiro Shirakawa, Tomoki Yamatsuji, Minoru Haisa, Junji Matsuoka, David G. Beer, Hitoshi Nagatsuka, Noriaki Tanaka, Yoshio Naomoto
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Focal adhesion kinase (FAK) regulates integrin and growth factor–mediated signaling pathways to enhance cell migration, proliferation, and survival, and its up-regulation correlates malignant grade and poor outcome in several types of cancer. In this study, we aimed to raise a potential therapeutic strategy using a FAK inhibitor for Barrett's esophageal adenocarcinoma. Experimental Design: The expression status of FAK in clinical Barrett's esophageal adenocarcinoma tissues was determined by immunohistochemistry. Cultured esophageal adenocarcinoma cells were treated with TAE226, a specific FAK inhibitor with an additional effect of inhibiting insulin-like growth factor-I receptor (IGF-IR), to assess its anticancer effect in vitro. Western blot was carried out to explore a participating signaling pathway for TAE226-induced cell death. Furthermore, TAE226 was orally administered to s.c. xenograft animals to investigate its anticancer effect in vivo. Results: Strong expression of FAK was found in 94.0% of Barrett's esophageal adenocarcinoma compared with 17.9% of Barrett's epithelia, suggesting that FAK might play a critical role in the progression of Barrett's esophageal adenocarcinoma. When esophageal adenocarcinoma cells were treated with TAE226, cell proliferation and migration were greatly inhibited with an apparent structural change of actin fiber and a loss of cell adhesion. The activities of FAK, IGF-IR, and AKT were suppressed by TAE226 and subsequent dephosphorylation of BAD at Ser136 occurred, resulting in caspase-mediated apoptosis. In vivo tumor volume was significantly reduced by oral administration of TAE226. Conclusions: These results suggest that TAE226, a dual tyrosine kinase inhibitor for FAK and IGF-IR, could become a new remedy for Barrett's esophageal adenocarcinoma.
Abnormal thymic development, impaired immune function and gamma delta T cell lymphomas in a TL transgenic mouse strain.
Authors: Y Obata, O Taguchi, Y Matsudaira, H Hasegawa, N Hamasima, T Takahashi
Journal: The Journal of Experimental Medicine (1991)

During derivation of transgenic mouse strains with various TL and TL/H-2 chimeric genes, one strain, Tg.Tlaa-3-1, introduced with a TL gene (Tlaa-3), was found to have an abnormal thymic T cell population and to develop a high incidence of T cell lymphomas. To investigate the etiology of the thymic abnormalities and of the lymphomas, the development of lymphoid organs in transgenic mice was studied. The thymus of these mice goes through three unusual successive events: perturbation of thymic development during embryogenesis, disappearance of thymocytes between day 14 and day 21 after birth, and subsequent proliferation of large blast-like cells. These events are associated with the abolishment of T cell receptor (TCR) alpha beta lineage of the T cell differentiation, leading to preponderance of cells belonging to the TCR gamma delta L3T4-Lyt-2- double negative (DN) lineage. Bone marrow transplantation and thymic graft experiments demonstrate that the abnormality resides in the bone marrow stem cells rather than in the thymic environment. The expression of TL antigen in the transgenic mice is greatly increased and TL is expressed in a wide range of T cells, including normally TL- DN cells and L3T4+ Lyt-2- and L3T4-Lyt-2+ single positive cells. These quantitative and qualitative abnormalities in TL expression most likely cause the abnormal T cell differentiation. The gamma delta DN cells migrate into peripheral lymphoid organs and constitute nearly 50% of peripheral T cells. Immune function of the transgenic mice is severely impaired, as T cell function is defective in antibody production to sheep red blood cells, in mixed lymphocyte culture reaction to allogenic spleen cells and also in stimulation with concanavalin A. These results indicate that the gamma delta cells are incapable of participating in these reactions. Molecular and serological analysis of T cell lymphomas reveal that they belong to the gamma delta lineage, suggesting that the gamma delta DN cells in this strain are susceptible to leukemic transformation. Based on cell surface phenotype and TCR expression of the DN thymocytes and T cell lymphomas, a map of the sequential steps involved in the differentiation of gamma delta DN cells is proposed.(ABSTRACT TRUNCATED AT 400 WORDS)
Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial
Authors: José Baselga, Ian Bradbury, Holger Eidtmann, Serena Di Cosimo, Evandro de Azambuja, Claudia Aura, Henry Gómez, Phuong Dinh, Karine Fauria, Veerle Van Dooren, Gursel Aktan, Aron Goldhirsch, Tsai-Wang Chang, Zsolt Horváth, Maria Coccia-Portugal, Julien Domont, Ling-Min Tseng, Georg Kunz, Joo Hyuk Sohn, Vladimir Semiglazov, Guillermo Lerzo, Marketa Palacova, Volodymyr Probachai, Lajos Pusztai, Michael Untch, Richard D Gelber, Martine Piccart-Gebhart
Journal: The Lancet (2012)
A Multiple Myeloma Classification System That Associates Normal Bone Marrow B-Cell Subset Phenotypes with Disease Stage and Prognosis
Authors: Hans Erik Johnsen, Julie Støve Bødker, Alexander Schmitz, Malene Krag Kjeldsen, Kim Steve Bergkvist, Steffen Falgreen, Anders Ellern Bilgrau, Tarec Christoffer El-Galaly, Karen Dybkær, Martin Bøgsted
Journal: Blood (2014)
Visualizing Length of Survival in Time-to-Event Studies: A Complement to Kaplan Meier Plots
Authors: P. Royston, M. K. B. Parmar, D. G. Altman
Journal: JNCI Journal of the National Cancer Institute (2008)

Because of censoring, standard methods of plotting individual survival times are invalid. Therefore, graphic display of time-to-event data usually takes the form of a Kaplan–Meier survival plot. Kaplan–Meier plots, however, make differences between groups seem larger than they really are. To overcome these limitations, we developed a technique for producing scatter plots with survival data and applied it to data from a randomized trial of patients with renal cancer. As of June 21, 2001, 25 of the 347 patients with kidney cancer in the Medical Research Council RE01 randomized treatment trial for whom data were available had been censored, and the remainder had died. Values of the censored survival times were imputed by assuming a log-normal distribution in survival times and by drawing a random sample given that that each patient with censored data survived at least to the point of censoring. The combined original and imputed data were then examined by use of dot plots and scatter plots. In the RE01 trial, median survival of patients treated with interferon was 3.0 months (95% confidence interval = 0.3 to 5.5 months) longer than that in patients treated with medroxyprogesterone acetate. The Kaplan–Meier analysis showed clear separation between treatment groups and between prognostic groups. In contrast, comparisons of individual observed and imputed survival times between groups of patients showed considerable overlap and gave a more realistic idea of the modest between-group differences than Kaplan–Meier comparisons. These graphs of the distribution of survival times for individuals in each study group, which are simple to produce, may usefully complement Kaplan–Meier plots.
Effect of antiviral treatment in patients with chronic HCV infection and t(14;18) translocation
Authors: Francesca Giannelli, Stefania Moscarella, Carlo Giannini, Patrizio Caini, Monica Monti, Laura Gragnani, Roberto Giulio Romanelli, Vera Solazzo, Giacomo Laffi, Giorgio La Villa, Paolo Gentilini, Anna Linda Zignego
Journal: Blood (2003)
Combination therapy with adapalene-benzoyl peroxide and oral lymecycline in the treatment of moderate to severe acne vulgaris: a multicentre, randomized, double-blind controlled study
Authors: B. Dréno, R. Kaufmann, S. Talarico, V. Torres Lozada, M.A. Rodríguez-Castellanos, M. Gómez-Flores, J. De Maubeuge, M. Berg, P. Foley, A. Sysa-Jedrzejowska, N. Kerrouche, F. Paliargues, V. Bettoli
Journal: British Journal of Dermatology (2011)

Background Oral antibiotics in association with a topical retinoid with or without benzoyl peroxide (BPO) are the recommended first‐line option in the treatment of moderate to severe acne vulgaris. Objectives To evaluate the efficacy and safety of oral lymecycline 300 mg with adapalene 0·1%–BPO 2·5% (A/BPO) fixed‐dose gel in comparison with oral lymecycline 300 mg with a vehicle gel in subjects with moderate to severe acne vulgaris. Methods A total of 378 subjects were randomized in a double‐blind, controlled trial to receive once‐daily lymecycline with either A/BPO or vehicle for 12 weeks. Evaluations included percentage changes from baseline in lesion counts, success rate (subjects ‘clear’ or ‘almost clear’), skin tolerability, adverse events and patients’ satisfaction. Results The median percentage reduction from baseline in total lesion counts at week 12 was significantly higher (P < 0·001) in the lymecycline with A/BPO group (−74·1%) than in the lymecycline with vehicle group (−56·8%). The success rate was significantly higher (47·6% vs. 33·7%, P = 0·002) in subjects treated with lymecycline and A/BPO. Both inflammatory and noninflammatory lesions were significantly reduced at week 12 (both P <0·001) with a rapid onset of action from week 2 for noninflammatory lesions (P < 0·001) and week 4 for inflammatory lesions (P = 0·005). The A/BPO and lymecycline combination was well tolerated. The proportion of satisfied and very satisfied subjects was similar in both groups, but the number in the A/BPO group who were ‘very satisfied’ was significantly greater (P = 0·031). Conclusion These results demonstrate the clinical benefit of combining A/BPO with lymecycline in the treatment of moderate to severe acne vulgaris.
Clinical Features and Outcome of Patients With Non–Small-Cell Lung Cancer Harboring <i>BRAF</i> Mutations
Authors: Antonio Marchetti, Lara Felicioni, Sara Malatesta, Maria Grazia Sciarrotta, Luigi Guetti, Antonio Chella, Patrizia Viola, Carmela Pullara, Felice Mucilli, Fiamma Buttitta
Journal: Journal of Clinical Oncology (2011)

Purpose To investigate the prevalence, distribution, and prognostic role of BRAF mutations in a large cohort of white patients with non–small-cell lung cancer (NSCLC). Patients and Methods A retrospective series of 1,046 NSCLCs—comprising 739 adenocarcinomas (ADCs) and 307 squamous cell carcinomas (SCCs)—was investigated for BRAF mutations. High-resolution melting analysis followed by sequencing and strip hybridization assay were used. All patients were also analyzed for KRAS and EGFR mutations. Results BRAF mutations were present in 36 ADCs (4.9%) and one SCC (0.3%; P = .001). Twenty-one of the mutations (56.8%) were V600E, and 16 (43.2%) were non-V600E. V600E mutations were significantly more prevalent in females (16 of 187 patients; 8.6%) than in males (five of 552 patients; 0.9%), as indicated by multivariate logistic regression analysis (hazard ratio [HR], 11.29; P &lt; .001). V600E-mutated tumors showed an aggressive histotype characterized by micropapillary features in 80% of patients and were significantly associated with shorter disease-free and overall survival rates on both univariate (HR, 2.67; P &lt; .001 and HR, 2.97; P &lt; .001, respectively) and multivariate analyses (HR, 2.19; P = .011 and HR, 2.18; P = .014, respectively). All non-V600E mutations were found in smokers (P = .015) and were associated with neither clinicopathologic parameters nor prognosis. BRAF and EGFR were concomitantly mutated in two tumors. Conclusion We report for the first time to our knowledge that V600E and non-V600E BRAF mutations affect different patients with NSCLC. V600E mutations are significantly associated with female sex and represent a negative prognostic factor. In addition, we identified a number of other clinicopathologic parameters potentially useful for the selection of patients carrying BRAF mutations.
Estimation of potential effects of improved community-based drug provision, to augment health-facility strengthening, on maternal mortality due to post-partum haemorrhage and sepsis in sub-Saharan Africa: an equity-effectiveness model
Authors: Christina Pagel, Sonia Lewycka, Tim Colbourn, Charles Mwansambo, Tarek Meguid, Grace Chiudzu, Martin Utley, Anthony ML Costello
Journal: The Lancet (2009)
Mesangial cell proliferation inhibitors for the treatment of proliferative glomerular disease
Authors: Yasuhisa Kurogi
Journal: Medicinal Research Reviews (2002)

Mesangial cells (MC) serve a number of functions in the renal glomerular capillary including structural support of the capillary tuft, modulation of glomerular hemodynamics, and a phagocytic function allowing removal of macromolecules and immune complexes. The proliferation of MC is a prominent feature of glomerular disease including IgA nephropathy, membranoproliferative glomerulonephritis, lupus nephritis, and diabetic nephropathy. In experimental animal models of nephritis, MC proliferation frequently precedes and is linked to the increase of extracellular matrix in the mesangium and glomerulosclerosis. Reduction of MC proliferation in glomerular disease models by treatment with heparin, low-protein diet, or antibodies to platelet-derived growth factor (PDGF), have been shown to reduce extracellular matrix expansion and glomerulosclerotic changes. Therefore, MC proliferation inhibitors may offer therapeutic opportunities for the treatment of proliferative glomerular disease. It is also known that the MC proliferation is inhibited by many kinds of pharmacological drugs, for example, angiotensin converting enzyme (ACE) inhibitors, leukotriene D(4) (LTD(4)) antagonists, PDGF inhibitors, matrix metalloproteinases (MMP) inhibitors, 3-hydroxy-3 methyl glutaryl-coenzymeA (HMG-CoA) inhibitors, cyclin-dependent kinases (CDK) inhibitors, and others. This review summarizes the recently reported MC proliferation inhibitors with their pharmacological properties on the basis of their chemical structures.
A 2-month cisplatin–epirubicin–paclitaxel (PET) weekly combination as primary systemic therapy for large operable breast cancer: a phase II study
Authors: G. Frasci, G. D'Aiuto, P. Comella, R. Thomas, G. Botti, M. Di Bonito, M. D'Aiuto, G. Romano, M.R. Rubulotta, G. Comella
Journal: Annals of Oncology (2005)
Blinded, multicenter quality control study for the quantification of human immunodeficiency virus type 1 RNA in plasma by the Belgian AIDS reference laboratories
Authors: G. Muyldermans, L. Debaisieux, K. Fransen, D. Marissens, K. Miller, D. Vaira, A.-M. Vandamme, A.-T. Vandenbroucke, C. Verhofstede, R. Schuurman, G. Zissis, S. Lauwers
Journal: Clinical Microbiology and Infection (2000)
How Many Patients Are Necessary to Assess Test Performance?
Authors: R. E. Fried, L. J. Appel
Journal: JAMA (1990)

<h3>To the Editor.—</h3> We would like to point out an important oversight in the recent article by Arkin and Wachtel.<sup>1</sup>At the heart of the matter is the choice of an appropriate study design for the comparison of two laboratory tests. Ideally, a paired study design would be used, in which both tests are applied to all specimens. It would be inefficient to use an unpaired design, in which one test is applied to only a portion of the available specimens and the other test to the remainingspecimens. In the authors' first example, an investigator plans to compare the sensitivities of serum levels of complement and a-fetoprotein in the detection of hepatocellular carcinoma. One would naturally expect the investigator to apply both tests to serum samples obtained from patients with hepatocellular carcinoma, ie, two aliquots of serum from each patient are tested. Perhaps unintentionally, the authors suggest
Sequence analysis of cDNA coding for a major house dust mite allergen, Der p 1. Homology with cysteine proteases.
Authors: K Y Chua, G A Stewart, W R Thomas, R J Simpson, R J Dilworth, T M Plozza, K J Turner
Journal: The Journal of Experimental Medicine (1988)

A cDNA clone coding for Der p 1, a major allergen from the house dust mite Dermatophagoides pteronyssinus, has been sequenced. It codes for a 222 residue mature protein with a derived molecular weight of 25,371 and contains 1 potential N-glycosylation site. In addition, the cDNA appears to code for a 13 residue proregion, and an incomplete signal peptide. The deduced sequence shows a high degree of homology with animal and plant cysteine proteases, particularly in the region of the contact residues making up the active site. Southern analysis of genomic DNA indicates that the allergen is coded by a noncontiguous gene. These data will now facilitate epitope mapping studies.
Detect, manage, inform: a paradigm shift in the care of athletes with cardiac disorders?
Authors: Jonathan A Drezner
Journal: British Journal of Sports Medicine (2012)

Every once in a while you read an article that you know is truly a ‘landmark’. An article that presents new, original and impactful data to better the care of patients, and simultaneously serves to validate a practice model applied by many but with limited scientific data.

Johnson and Ackerman1 present their findings on athletes with congenital long QT syndrome (LQTS) and the outcomes of continued sports participation contrary to the 2005 guidelines of the 36th Bethesda Conference and the European Society of Cardiology.2 ,3 (link to article by Johnson) In over 650 athlete-years of follow-up after returning to sport with LQTS, there were no deaths and only one athlete with sport-related cardiac events involving appropriate VF-terminating implantable cardioverter defibrillator (ICD) shocks in a very-high-risk child (QTc>550 ms and history of resuscitated cardiac arrest).

Everybody supports screening—AHA, ACC, ESC, IOC, FIFA, AMSSM, AAP, AAFP, NCAA… you name it. Major medical and sport governing organisations universally endorse cardiovascular screening …