tbuckley/cabot-search huggingface dataset:
RETRACTED: Autologous myoblasts and fibroblasts versus collagen for treatment of stress urinary incontinence in women: a randomised controlled trial
Authors: Hannes Strasser, Rainer Marksteiner, Eva Margreiter, Germar Michael Pinggera, Michael Mitterberger, Ferdinand Frauscher, Hanno Ulmer, Martin Fussenegger, Kurt Kofler, Georg Bartsch
Journal: The Lancet (2007)
Regulation of Peripheral Lymph Node Genesis by the Tumor Necrosis Factor Family Member Trance
Authors: Dongku Kim, Reina E. Mebius, John D. MacMicking, Steffen Jung, Tom Cupedo, Yaneth Castellanos, Jaerang Rho, Brian R. Wong, Regis Josien, Nacksung Kim, Paul D. Rennert, Yongwon Choi
Journal: The Journal of Experimental Medicine (2000)

Proper lymph node (LN) development requires tumor necrosis factor-related activation-induced cytokine (TRANCE) expression. Here we demonstrate that the defective LN development in TRANCE(-/)- mice correlates with a significant reduction in lymphotoxin (LT)alphabeta(+)alpha(4)beta(7)(+)CD45(+)CD4(+)CD3(-) cells and their failure to form clusters in rudimentary mesenteric LNs. Transgenic TRANCE overexpression in TRANCE(-/)- mice results in selective restoration of this cell population into clusters, and results in full LN development. Transgenic TRANCE-mediated restoration of LN development requires LTalphabeta expression on CD45(+) CD4(+)CD3(-) cells, as LNs could not be induced in LTalpha(-/)- mice. LTalpha(-/)- mice also showed defects in the fate of CD45(+)CD4(+)CD3(-) cells similar to TRANCE(-/)- mice. Thus, we propose that both TRANCE and LTalphabeta regulate the colonization and cluster formation by CD45(+) CD4(+)CD3(-) cells in developing LNs, the degree of which appears to correlate with the state of LN organogenesis.
Variation in the Pattern of Synonymous and Nonsynonymous Difference Between Two Fungal Genomes
Authors: A. L. Hughes
Journal: Molecular Biology and Evolution (2005)

The proportion of synonymous nucleotide differences per synonymous site (pS) and the proportion of nonsynonymous differences per nonsynonymous site (pN) were computed at 1,993,217 individual codons in 4,133 protein-coding genes between the two yeast species Saccharomyces cerevisiae and Saccharomyces paradoxus. When the modified Nei-Gojobori method was used, significantly more codons with pN > pS were observed than expected, based on random pairing of observed pS and pN values. However, this finding was most likely explained by the presence of a strong negative correlation between the number of synonymous differences and the number of nonsynonymous differences at codons with at least one difference. As a result of this correlation, codons with pN > pS were characterized not only by unusually high pN but also by unusually low pS. On the other hand, the number of codons with \(p_{N}{>}\overline{p_{S}}\) (where pS is the mean \(\overline{p_{S}}\) for all codons) was very similar to the random expectation, and the observed number of 30-codon windows with pN > pS was significantly lower than the random expectation. These results imply that the occurrence of a certain number of codons or codon windows with pN > pS is expected given the nature of nucleotide substitution and need not imply the action of positive Darwinian selection.
Seven year changes in health status and priorities for improvement of health in patients with rheumatoid arthritis
Authors: T Heiberg
Journal: Annals of the Rheumatic Diseases (2005)

To examine possible changes in priorities for improvement in health and health status from 1994 to 2001 within the setting of the Oslo Rheumatoid Arthritis (RA) Register, which provides representative data for the entire RA population in the county.All living patients in the Oslo RA Register area received a postal questionnaire in 1994 and 2001, including the Arthritis Impact Measurement Scales 2 (AIMS2), Short Form-36, the modified Health Assessment Questionnaire, and pain and fatigue visual analogue scales (VAS). Priorities for improvement in health were examined through question 60 in AIMS2, where patients are asked to indicate three of 12 areas of health where they would most like to see improvement.The number of respondents aged 20-79 years in 1994/2001 was 932/830, with similar demographic characteristics (78.8/78.3% were female, mean age 60.6/60.8, and disease duration 12.6/13.9 years). Health status was improved in all dimensions, with statistical improvement for the physical dimension, global health and pain, from 1994 to 2001. The profile of priorities remained mostly unchanged. Improvement in pain had the highest priority in both cohorts. Both symptom modifying and disease modifying drugs were more extensively used in 2001.Health status had improved from 1994 to 2001, probably because of access to better and more aggressive treatments. Pain remained the area of highest priority for improvement among patients with RA-despite an improved level of pain in 2001.
Genome-Wide Search of Gene Conversions in Duplicated Genes of Mouse and Rat
Authors: Kiyoshi Ezawa, Satoshi OOta, Naruya Saitou
Journal: Molecular Biology and Evolution (2006)

Gene conversion is considered to play important roles in the formation of genomic makeup such as homogenization of multigene families and diversification of alleles. We devised two statistical tests on quartets for detecting gene conversion events. Each "quartet" consists of two pairs of orthologous sequences supposed to have been generated by a duplication event and a subsequent speciation of two closely related species. As example data, EnsEMBL mouse and rat cDNA sequences were used to obtain a genome-wide picture of gene conversion events. We extensively sampled 2,641 quartets that appear to have resulted from duplications after the divergence of primates and rodents and before mouse-rat speciation. Combination of our new tests with Sawyer's and Takahata's tests enhanced the detection sensitivity while keeping false positives as few as possible. About 18% (488 quartets) were shown to be highly positive for gene conversion using this combined test. Out of them, 340 (13% of the total) showed signs of gene conversion in mouse sequence pairs. Those gene conversion–positive gene pairs are mostly linked in the same chromosomes, with the proportion of positive pairs in the linked and unlinked categories being 15% and 1%, respectively. Statistical analyses showed that (1) the susceptibility to gene conversion correlates negatively with the physical distance, especially the frequency of 29% was observed for gene pairs whose distances are smaller than 55 kb; (2) the occurrence of gene conversions does not depend on the transcriptional direction; (3) small gene families consisting of between three and six contiguous genes are highly prone to gene conversion; and (4) frequency of gene conversions greatly varies depending on functional categories, and cadherins favor gene conversion, while vomeronasal receptors type 1 and immunoglobulin V–type proteins disfavor it. These findings will be useful to deepen the understanding of the roles of gene conversion.
Alan Theodore Smyth
Authors: R. C. R. S. K. Shinton
Journal: BMJ (2014)

Alan Theodore Smyth was born in Malvern, Worcestershire, the son of a general practitioner. After preparatory school in Malvern he was educated at Rydal School in Colwyn Bay, north Wales. After service with the Coldstream Guards he entered the medical school at the University of Birmingham in 1945. Qualification was followed by house appointments at the Queen Elizabeth Hospital, Birmingham. In 1953 he joined the general practice at Meriden, Warwickshire, as a …
Pharmacokinetics and distribution of heparin-binding growth factor I (endothelial cell growth factor) in the rat.
Authors: T K Rosengart, J P Kuperschmid, T Maciag, R E Clark
Journal: Circulation Research (1989)

Heparin-binding growth factor I (HBGF I), previously designated as endothelial cell growth factor, is a potent mitogen for endothelial cells in vitro, which may prove useful for promoting endothelial regeneration in vivo. Analysis of the pharmacokinetics and organ distribution of HBGF I is necessary before use of HBGF I as a pharmacological agent. Consequently, pharmacological studies were carried out with [125I]HBGF I in the rat. Intravenous injections of HBGF I were given with or without heparin (2.5 units/ng HBGF I). Blood concentrations of HBGF I decreased by one half 17 seconds after HBGF I bolus. This time was prolonged to 60 seconds when HBGF I was injected with heparin. The elimination half-life of HBGF I was 14 minutes in the presence of heparin. The highest concentrations of HBGF I following intravenous bolus were found in kidney, liver, and spleen, and the lowest in fat and brain. Heparin increased HBGF I concentrations in blood and all organs measured except kidney, which was significantly decreased (p less than 0.01). Intact HBGF I was recoverable from blood 5 minutes following intravenous administration. HBGF I underwent near-complete proteolytic digestion after more prolonged ex vivo incubation with rat plasma, but HBGF I was protected from proteolysis when incubations were conducted in the presence of heparin. Thus, it is feasible that HBGF I can be administered as a pharmacological agent in the presence of heparin. Further studies assessing acceleration of in vivo endothelial growth using HBGF I with heparin appear warranted.
MicroRNA-mediated regulation of KRAS in cancer
Authors: Minlee Kim, Frank J Slack
Journal: Journal of Hematology & Oncology (2014)

While microRNAs (miRNAs) and the KRAS oncogene are known to be dysregulated in various cancers, little is known about the role of miRNAs in the regulation of KRAS in cancer. Here we review a selection of studies published in 2014 that have contributed to our understanding of the molecular mechanisms of KRAS regulation by miRNAs and the clinical relevance of sequence variants that may interfere with functional miRNA-mediated KRAS regulation.
Long-term ovarian function in women treated with CHOP or CHOP plus etoposide for aggressive lymphoma
Authors: J. Meissner, D. Tichy, V. Katzke, T. Kühn, S. Dietrich, T. Schmitt, M. Ziepert, E. Kuhnt, T. Rixecker, M. Zorn, M. Witzens-Harig, M. Pfreundschuh, A.D. Ho
Journal: Annals of Oncology (2015)
The role of HBV genotype core promoter and precore mutations in advanced liver disease in renal transplant recipients
Authors: Ming-Chao Tsai, Chien-Hung Chen, Chuan-Mo Lee, Yen-Ta Chen, Yu-Shu Chien, Chao-Hung Hung, Jing-Houng Wang, Sheng-Nan Lu, Yi-Hao Yen, Chi-Sin Changchien, Tsung-Hui Hu
Journal: Journal of Hepatology (2008)
Superactive Gonadotropin-Releasing Hormone Agonists
Authors: R S Swerdloff, D Heber
Journal: Annual Review of Medicine (1983)

Superactive GnRH agonists represent a new class of pharmacologic agents that inhibit reproductive function in both men and women when administered chronically. These hormonal drugs are being tested extensively as both male and female contraceptive agents, as a treatment for prostate cancer, and as a new treatment for idiopathic precocious puberty. Other potential uses include treatment for endometriosis, hirsutism, polycystic ovarian disease, and severe intractable androgen-related acne. This chapter reviews the effects of GnRH agonists on gonadotropin and steroid hormone secretion in both men and women, and assesses the potential of these agents in the varied clinical uses delineated above.
Randomized Phase II Trial of Letrozole and Letrozole Plus Low-Dose Metronomic Oral Cyclophosphamide As Primary Systemic Treatment in Elderly Breast Cancer Patients
Authors: Alberto Bottini, Daniele Generali, Maria Pia Brizzi, Stephen B. Fox, Alessandra Bersiga, Simone Bonardi, Giovanni Allevi, Sergio Aguggini, Giuliana Bodini, Manuela Milani, Rossana Dionisio, Claudio Bernardi, Arianna Montruccoli, Paolo Bruzzi, Adrian L. Harris, Luigi Dogliotti, Alfredo Berruti
Journal: Journal of Clinical Oncology (2006)

To investigate the activity of letrozole plus/minus oral metronomic cyclophosphamide as primary systemic treatment (PST) in elderly breast cancer patients.One hundred fourteen consecutive elderly women with T2-4 N0-1 and estrogen receptor-positive breast cancer were randomly assigned to primary letrozole therapy (2.5 mg daily for 6 months) or a combination of letrozole plus oral cyclophosphamide (50 mg/daily for 6 months) in an open-labeled, randomized phase II trial. Tumor response was assessed clinically, and tumor Ki67 index and vascular endothelial growth factor (VEGF) -A levels were measured before and after treatment.Overall response rate was 71.9% (95% CI, 60.0 to 83.8) in the 57 patients randomly assigned to receive primary letrozole and 87.7% (95% CI, 78.6 to 96.2) in the 57 patients randomly assigned to receive letrozole plus cyclophosphamide. The difference in activity between treatment arms was predominantly confined to patients with ductal histology. There was a significantly greater suppression of Ki67 and VEGF-A expression in the letrozole/cyclophosphamide-treated group than in the letrozole-treated group, leading to lower Ki67 and VEGF expression at post-treatment residual histology (P = .03 and P = .002, respectively).Both letrozole and letrozole plus cyclophosphamide treatments appeared active as PST in elderly breast cancer patients. Metronomic scheduling of cyclophosphamide may have an antiangiogenic effect and the combination of letrozole plus cyclophosphamide warrants testing in a randomized phase III trial.
Achilles tendon rupture: an underrated complication of corticosteroid treatment.
Authors: D M Newnham, J G Douglas, J S Legge, J A Friend
Journal: Thorax (1991)

Ten patients attending outpatient clinics who were taking oral corticosteroids ruptured their Achilles tendon in the course of 12 years. It is suggested that Achilles tendon rupture is a complication of corticosteroid treatment.
EGFR as a potential therapeutic target for a subset of muscle-invasive bladder cancers presenting a basal-like phenotype
Authors: Sandra Rebouissou, Isabelle Bernard-Pierrot, Aurélien de Reyniès, May-Linda Lepage, Clémentine Krucker, Elodie Chapeaublanc, Aurélie Hérault, Aurélie Kamoun, Aurélie Caillault, Eric Letouzé, Nabila Elarouci, Yann Neuzillet, Yves Denoux, Vincent Molinié, Dimitri Vordos, Agnès Laplanche, Pascale Maillé, Pascale Soyeux, Karina Ofualuka, Fabien Reyal, Anne Biton, Mathilde Sibony, Xavier Paoletti, Jennifer Southgate, Simone Benhamou, Thierry Lebret, Yves Allory, François Radvanyi
Journal: Science Translational Medicine (2014)

Muscle-invasive bladder carcinoma (MIBC) constitutes a heterogeneous group of tumors with a poor outcome. Molecular stratification of MIBC may identify clinically relevant tumor subgroups and help to provide effective targeted therapies. From seven series of large-scale transcriptomic data (383 tumors), we identified an MIBC subgroup accounting for 23.5% of MIBC, associated with shorter survival and displaying a basal-like phenotype, as shown by the expression of epithelial basal cell markers. Basal-like tumors presented an activation of the epidermal growth factor receptor (EGFR) pathway linked to frequent EGFR gains and activation of an EGFR autocrine loop. We used a 40-gene expression classifier derived from human tumors to identify human bladder cancer cell lines and a chemically induced mouse model of bladder cancer corresponding to human basal-like bladder cancer. We showed, in both models, that tumor cells were sensitive to anti-EGFR therapy. Our findings provide preclinical proof of concept that anti-EGFR therapy can be used to target a subset of particularly aggressive MIBC tumors expressing basal cell markers and provide diagnostic tools for identifying these tumors.
Immunophenotypic evaluation of the plasma cell compartment in multiple myeloma: a tool for comparing the efficacy of different treatment strategies and predicting outcome
Authors: Jesús F. San Miguel, Julia Almeida, Gema Mateo, Joan Bladé, Consuelo López-Berges, Dolores Caballero, José Hernández, Marı́a Jesús Moro, Javier Fernández-Calvo, Joaquı́n Dı́az-Mediavilla, Luis Palomera, Alberto Orfao
Journal: Blood (2002)
Thalamic Activation During Slightly Subphysiological Glycemia in Humans
Authors: Ana María Arbeláez, Jerrel R. Rutlin, Tamara Hershey, William J. Powers, Tom O. Videen, Philip E. Cryer
Journal: Diabetes Care (2012)

The central nervous system mechanisms of defenses against falling plasma glucose concentrations, and how they go awry and result in iatrogenic hypoglycemia in diabetes, are not known. Hypoglycemic plasma glucose concentrations of 55 mg/dL (3.0 mmol/L) cause symptoms, activate glucose counterregulatory systems, and increase synaptic activity in a network of brain regions including the dorsal midline thalamus in humans. We tested the hypothesis that slightly subphysiological plasma glucose concentrations of 65 mg/dL (3.6 mmol/L), which do not cause symptoms but do activate glucose counterregulatory systems, also activate brain synaptic activities.We measured relative regional cerebral blood flow (rCBF), an index of synaptic activity, in predefined brain regions with [(15)O]water positron emission tomography, symptoms, and plasma epinephrine and glucagon concentrations during a 2-h euglycemic (90 mg/dL) to hypoglycemic (55 mg/dL) clamp (n = 20) or a 2-h euglycemic to slight subphysiological (65 mg/dL) clamp (n = 9) in healthy humans.Clamped plasma glucose concentrations of 65 mg/dL did not cause hypoglycemic symptoms, but raised plasma epinephrine and glucagon concentrations and increased rCBF (P = 0.007) only in the dorsal midline thalamus.Slightly subphysiological plasma glucose concentrations increase synaptic activity in the dorsal midline thalamus in humans.
Isolation of Two Human Tumor Epithelial Cell Lines From Solid Breast Carcinomas&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: E Y Lasfargues, W G Coutinho, E S Redfield
Journal: JNCI Journal of the National Cancer Institute (1978)

Most of the available human breast tumor cell lines have been derived from pleural effusions. The two cell lines herein described, BT-474 and BT-483, were derived from solid, invasive ductal breast carcinomas. Both are epithelial and neoplastic as judged by their general morphology, their fine structure, and their ability to produce growing nodules in nude mice and colonies in soft agar and methocel. BT-474 and BT-483 are human as expressed by chromosome morphology and aneuploid with a modal number of 55 and 72 chromosomes, respectively. Trypsin-Giemsa banding did not reveal the presence of obvious HeLa markers, and the glucose 6-phosphate dehydrogenase electrophoretic migration pattern was of the B-type. Furthermore, the migration of lactic dehydrogenase, malic dehydrogenase, and 6-phosphogluconate dehydrogenase isoenzymes was consistent with a human pattern and different from that of the mouse, rat, or hamster. Quarterly tests to detect the presence of aerobic and anaerobic mycoplasmas were repeatedly negative. A culture medium containing insulin, increased amounts of amino acids, vitamins, and glucose facilitated the isolation of the tumor cells. Cell replication was maintained with 10% fetal calf serum absorbed with activated charcoal and dextran. No production of alpha-lactalbumin was detected by radioimmunoassays, but high levels of progesterone receptors were found in both cell lines.
Effects of dihydroxy bile acids and hydroxy fatty acids on the absorption of oleic acid in the human jejunum.
Authors: R Wanitschke, H V Ammon
Journal: Journal of Clinical Investigation (1978)

Perfusion studies of the normal human jejunum were performed to test whether dihydroxy bile acids and hydroxy fatty acids inhibit the absorption of oleic acid, since previous reports documented their inhibitory effects on the absorption of several other organic solutes. 3 mM deoxycholate and 7 mM glycodeoxycholate inhibited the absorption of 3 mM oleic acid in isotonic micellar solutions while inducing net fluid secretion. Similarly, fractional absorption of oleic acid decreased in the presence of hydroxy fatty acids. However, only the changes induced by 2 mM ricinoleic acid could be distinguished from changes induced by an increase in total fatty acid concentration. Under all experimental conditions, close linear relationships existed between net water movement and fractional absorption of glucose, xylose, and fatty acids, as well as between the absorption rates of these solutes. In contrast, net fluid secretion induced by hypertonic D-mannitol (450 mosmol/liter) had no effect on solute absorption. Our data and observations in the literature do not allow formulation of a hypothesis which would adequately define all effects of dihydroxy bile acids and fatty acids on intestinal transport processes. The observations help explain the malabsorption of fat and other nutrients in patients with the blind loop syndrome.
Protease-Activated Receptors in Cardiovascular Diseases
Authors: Andrew J. Leger, Lidija Covic, Athan Kuliopulos
Journal: Circulation (2006)

Thrombosis associated with the pathophysiological activation of platelets and vascular cells has brought thrombin and its receptors to the forefront of cardiovascular medicine. Thrombin signaling through the protease-activated receptors (PARs) has been shown to influence a wide range of physiological responses including platelet activation, intimal hyperplasia, inflammation, and maintenance of vascular tone and barrier function. The thrombin receptors PAR1 and PAR4 can be effectively targeted in animals in which acute or prolonged exposure to thrombin leads to thrombosis and/or restenosis. In the present study, we describe the molecular and pharmacological basis of small-molecule inhibitors that target PAR1. In addition, we discuss a new class of cell-penetrating inhibitors, termed pepducins, that provide insight into previously unidentified roles of PAR1 and PAR4 in protease signaling.
Redefining the Diagnosis of Diabetes Using Glycated Hemoglobin
Authors: Vivian Fonseca, Silvio E. Inzucchi, Ele Ferrannini
Journal: Diabetes Care (2009)

The worldwide epidemic of type 2 diabetes continues unabated. Despite extensive efforts to educate providers, patients, and even the public at large as to the advantages of early identification and treatment to prevent complications, a large number of patients remain undiagnosed. A serious barrier to an enhanced detection of diabetes has been inadequate screening using tests somewhat inconvenient to patients and clinicians and therefore often not optimally implemented. In this issue of Diabetes Care , a joint American Diabetes Association, International Diabetes Federation, and European Association for the Study of Diabetes International Expert Committee examines diagnostic testing for diabetes, specifically, the role of A1C, and makes significant new recommendations. While this report has not yet been endorsed as a guideline by either of the associations (or other organizations), it does represent a step in that direction and thus deserves attention.

Clearly, no clinical diagnostic test is perfect. However, to be clinically useful, a test must be accurate, specific, standardized (or easily standardizable), handy, and, ideally, inexpensive. While plasma glucose testing meets some of these criteria, its use has been dogged by the need to obtain a sample in the fasting state (most people attend their outpatient visits in the fed state) or under standard carbohydrate challenge conditions, i.e., the oral glucose tolerance test. There also continues to be a degree of uncertainty concerning the diagnostic performance of fasting glucose testing versus that of the oral glucose tolerance test—the latter done rarely in clinical practice for obvious reasons: inconvenience and cost. In addition, considerable variability not only in 2-h postglucose load values but also in fasting glucose has been a problem. Appropriately, clinicians have long wondered why they cannot use another diagnostic index, …