tbuckley/cabot-search huggingface dataset:
Influence of Polymorphic OATP1B-Type Carriers on the Disposition of Docetaxel
Authors: Anne-Joy M. de Graan, Cynthia S. Lancaster, Amanda Obaidat, Bruno Hagenbuch, Laure Elens, Lena E. Friberg, Peter de Bruijn, Shuiying Hu, Alice A. Gibson, Gitte H. Bruun, Thomas J. Corydon, Torben S. Mikkelsen, Aisha L. Walker, Guoqing Du, Walter J. Loos, Ron H. N. van Schaik, Sharyn D. Baker, Ron H. J. Mathijssen, Alex Sparreboom
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Docetaxel is extensively metabolized by CYP3A4 in the liver but mechanisms by which the drug is taken up into hepatocytes remain poorly understood. We hypothesized that (i) liver uptake of docetaxel is mediated by the polymorphic solute carriers OATP1B1 and OATP1B3 and (ii) inherited genetic defects in this process may impair systemic drug elimination. Experimental Design: Transport of docetaxel was studied in vitro using various cell lines stably transfected with OATP1B1*1A (wild-type), OATP1B1*5 [c.521T&amp;gt;C (V174A); rs4149056], OATP1B3, or the mouse transporter Oatp1b2. Docetaxel clearance was evaluated in wild-type and Oatp1b2-knockout mice as well as in two cohorts of patients with multiple variant transporter genotypes (n = 213). Results: Docetaxel was found to be a substrate for OATP1B1, OATP1B3, and Oatp1b2 but was not transported by OATP1B1*5. Deficiency of Oatp1b2 in mice was associated with an 18-fold decrease in docetaxel clearance (P = 0.0099), which was unrelated to changes in intrinsic metabolic capacity in mouse liver microsomes. In patients, however, none of the studied common reduced function variants in OATP1B1 or OATP1B3 were associated with docetaxel clearance (P &amp;gt; 0.05). Conclusions: The existence of at least two potentially redundant uptake transporters in the human liver with similar affinity for docetaxel supports the possibility that functional defects in both of these proteins may be required to confer substantially altered disposition phenotypes. In view of the established exposure–toxicity relationships for docetaxel, we suggest that caution is warranted if docetaxel has to be administered together with agents that potently inhibit both OATP1B1 and OATP1B3. Clin Cancer Res; 18(16); 4433–40. ©2012 AACR.
Histopathological evaluation of colonic mucosal biopsy specimens in chronic inflammatory bowel disease: diagnostic implications.
Authors: C A Seldenrijk, B C Morson, S G Meuwissen, N W Schipper, J Lindeman, C J Meijer
Journal: Gut (1991)

In a prospective blind evaluation of multiple colonic mucosal biopsy specimens, 45 clinically well defined patients with chronic inflammatory bowel disease (21 Crohn9s disease and 24 ulcerative colitis) and 16 control subjects (seven normal subjects and nine patients with diverticular disease) were studied to identify reproducible histopathological features which could distinguish chronic inflammatory bowel disease (CIBD) from non-CIBD and Crohn9s disease from ulcerative colitis. Using kappa statistics 16 of 41 histological features were sufficiently reproducible for further stepwise discriminant analysis to differentiate between CIBD and non-CIBD, and between Crohn9s disease and ulcerative colitis. Using the combination of three features (an increase of lymphocytes and plasma cells in the lamina propria, the presence of branching of crypts, and neutrophils in the crypt epithelium) we were able to distinguish CIBD from non-CIBD in 89% of the cases with high probability (p greater than 0.85). To separate Crohn9s disease from ulcerative colitis three features (an excess of histiocytes in combination with a villous or irregular aspect of the mucosal surface and granulomas) had a high predictive value. Using these features 70% of Crohn9s disease patients and 75% of ulcerative colitis patients were correctly classified with a high probability (p greater than 0.85). These findings indicate that the pathologist is dependent on the presence of only a few histological features for a reliable classification of Crohn9s disease and ulcerative colitis.
Impact of tumor Epstein-Barr virus status on presenting features and outcome in age-defined subgroups of patients with classic Hodgkin lymphoma: a population-based study
Authors: Ruth F. Jarrett, Gail L. Stark, Jo White, Brian Angus, Freda E. Alexander, Andrew S. Krajewski, June Freeland, G. Malcolm Taylor, Penelope R. A. Taylor
Journal: Blood (2005)
Increased Prevalence of Impaired Glucose Tolerance in Patients With Painful Sensory Neuropathy
Authors: J. Robinson Singleton, A. Gordon Smith, Mark B. Bromberg
Journal: Diabetes Care (2001)

To characterize a cohort of patients with neuropathy and impaired glucose tolerance (IGT) but no other identifiable cause of neuropathy. Of patients with diabetes, 10% have peripheral neuropathy at the time of their diagnosis, suggesting that axonal injury may occur early in the course of glucose intolerance. The American Diabetes Association (ADA) revised diagnostic criteria to recognize IGT (a serum glucose between 140 and 200 mg/dl in a 2-h oral glucose tolerance test [OGTT]) as a risk factor for cardiovascular disease independent of development of diabetes.Using revised ADA criteria for diabetes and IGT, we prospectively evaluated 107 sequential patients with idiopathic neuropathy.A total of 13 of the 107 patients had diabetes, whereas 36 (34%) had IGT, nearly three times the prevalence in age-matched control subjects (P < 0.01). OGTT was often elevated, whereas both fasting plasma glucose and HbA(1c) were normal. Comparing patients with diabetes, IGT, or normal OGTT, age and BMI were similar. However, painful sensory symptoms were more common in patients with IGT and diabetes, and family history of neuropathy was significantly more common in normoglycemic patients. Electrodiagnostic findings of axonal injury were less severe in patients with IGT and were more likely to be confined to sensory fibers than in patients with diabetes.Our results suggest that IGT may cause or contribute to small-fiber neuropathy, which is similar in phenotype to the painful sensory neuropathy commonly encountered in diabetes. Two-hour OGTT is more sensitive than other measures of glucose handling in screening these patients.
Nonallergic respiratory morbidity improved along with a decline of traditional air pollution levels: a review
Authors: J. Heinrich
Journal: European Respiratory Journal (2003)

The tremendous decline of combustion-derived emissions of traditional air pollutants such as sulphur dioxide (SO 2 ) and total suspended particles (TSP) in Eastern Germany shortly after German reunification in 1990 provided the unique opportunity to study trends of prevalence of respiratory illness along with the improvement of air quality. The present review focused on the results of two repeated surveys of nonallergic respiratory illness in children living in East Germany. The crude prevalence of respiratory illness such as lifetime bronchitis, otitis media, tonsillitis, frequent colds, and frequent cough decreased during the 1990s in East German children. For two surveys the effect estimates showed consistently statistically significant association of TSP with bronchitis. For SO 2 statistically significant associations with frequent colds were also consistently found, whereas at least one survey reported higher statistically significant effect estimates for tonsillitis, otitis media, frequent cough and reduced forced vital capacity. The present study concludes that the prevalence of nonallergic respiratory illness in East German children is associated with sulphur dioxide and total suspended particles and that the improvement of air quality has beneficial effects on respiratory health.
Intestinal Pseudo-obstruction with Steatorrhoea
Authors: J. M. Naish, W. M. Capper, N. J. Brown
Journal: Gut (1960)

A hitherto undescribed syndrome is recorded. Its features are gross overactivity of the small intestine with episodes of obstruction, but without any mechanical factor being found, and steatorrhoea. In one patient the inner circular coat showed gross hypertrophy.
Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I–II feasibility study
Authors: D. Schrijvers, C. Van Herpen, J. Kerger, E. Joosens, C. Van Laer, A. Awada, D. Van den Weyngaert, H. Nguyen, C. Le Bouder, J.A. Castelijns, J. Kaanders, P. De Mulder, J.B. Vermorken
Journal: Annals of Oncology (2004)
Staphylococcus aureus sensitivity changes to antibiotics under the influence of dissolved ozone
Authors: Igor Belyanin, Lubov Selina, Evgenii Shmelev, Alla Plotnikova
Journal: European Respiratory Journal (2011)

Aim:  To study the sensitivity change of the clinical strains of staphylococcus aureus to antibiotics under the influence of dissolved ozone. (pO3).   Methods:  We investigated 20 S.aureus strains from sputum culture resistant antibiotics. A suspension was prepared from a day portion of the agar culture of each strain (1-2×10 8 /ml), which was treated with dissolved ozone (pO3 3mcg/ml) or with air (control) during 5-10-15 min. Then, the strains treated with pO3 were cultured on Muller-Hinton agar containing strains resistant antibiotics and incubated by 370C. In a day of incubation we recorded the results of antibiotic resistance change according the diameter zone of the growth inhibition round the antibiotic discs.   Results:  The growth inhibition zone increased from 3.8 to 25.7±2.1 mm in all cases of cultured S.aureus strains treated with pO3. And in cases with control strains the growth inhibition zone was not change.   Conclusion:  Staphylococcus aureus sensitivity to antibiotics restores after dissolved ozone treatment.
Hepatic and glucagon-like peptide-1–mediated reversal of diabetes by glucagon receptor antisense oligonucleotide inhibitors
Authors: Kyle W. Sloop, Julia Xiao-Chun Cao, Angela M. Siesky, Hong Yan Zhang, Diane M. Bodenmiller, Amy L. Cox, Steven J. Jacobs, Julie S. Moyers, Rebecca A. Owens, Aaron D. Showalter, Martin B. Brenner, Achim Raap, Jesper Gromada, Brian R. Berridge, David K. B. Monteith, Niels Porksen, Robert A. McKay, Brett P. Monia, Sanjay Bhanot, Lynnetta M. Watts, M. Dodson Michael
Journal: Journal of Clinical Investigation (2004)

Uncontrolled hepatic glucose production contributes significantly to hyperglycemia in patients with type 2 diabetes. Hyperglucagonemia is implicated in the etiology of this condition; however, effective therapies to block glucagon signaling and thereby regulate glucose metabolism do not exist. To determine the extent to which blocking glucagon action would reverse hyperglycemia, we targeted the glucagon receptor (GCGR) in rodent models of type 2 diabetes using 2′-methoxyethyl–modified phosphorothioate-antisense oligonucleotide (ASO) inhibitors. Treatment with GCGR ASOs decreased GCGR expression, normalized blood glucose, improved glucose tolerance, and preserved insulin secretion. Importantly, in addition to decreasing expression of cAMP-regulated genes in liver and preventing glucagon-mediated hepatic glucose production, GCGR inhibition increased serum concentrations of active glucagon-like peptide-1 (GLP-1) and insulin levels in pancreatic islets. Together, these studies identify a novel mechanism whereby GCGR inhibitors reverse the diabetes phenotype by the dual action of decreasing hepatic glucose production and improving pancreatic β cell function.
Factors predicting future ACS episodes in children with sickle cell anemia
Authors: Michael R. DeBaun, Mark Rodeghier, Robyn Cohen, Fenella J. Kirkham, Carol L. Rosen, Irene Roberts, Ben Cooper, Janet Stocks, Olu Wilkey, Baba Inusa, John O. Warner, Robert C. Strunk
Journal: American Journal of Hematology (2014)

While a doctor-diagnosis of asthma is associated with an increased risk of pain and acute chest syndrome (ACS) in children with sickle cell anemia (SCA), little is known about the relationship between specific asthma characteristics and clinical factors and future morbidity in children with SCA. We evaluated the relationship between (i) asthma risk factors at the time of a clinical visit (respiratory symptoms, maternal history of asthma, allergy skin tests, spirometry results) and (ii) the known risk factor of ACS early in life, on prospective pain and ACS episodes in a cohort of 159 children with SCA followed from birth to a median of 14.7 years. An ACS episode prior to 4 years of age, (incidence rate ratio [IRR] = 2.84; P < 0.001], female gender (IRR = 1.80; P = 0.009), and wheezing causing shortness of breath (IRR = 1.68; P = 0.042) were associated with future ACS rates. We subsequently added spirometry results (obstruction defined as FEV1 /FVC less than the lower limits of normal; and bronchodilator response, FEV1 ≥ 12%) and prick skin test responses to the model. Only ≥ 2 positive skin tests had a significant effect (IRR 1.87; P = 0.01). Thus, early in life ACS events, wheezing causing shortness of breath, and ≥ 2 positive skin tests predict future ACS events.
Echocardiographic evaluation of pericardial effusion in myxedema. Incidence and biochemical and clinical correlations.
Authors: R E Kerber, B Sherman
Journal: Circulation (1975)

Pericardial effusion is a recognized consequences of myxedema. Its incidence is unknown, primarily because of past difficulties in establishing the diagnosis. We studied 33 hypothyroid patients by echocardiography. Ten of the 33 patients (30%) had positive echoes for pericardial effusion. Seven of these ten patients had enlarged hearts on chest X-ray. Five patients had cardiac enlargement but no echo evidence of pericardial effusion. Serum concentrations of thyroxine, 1.8+/-0.3 vs 1.5+/-0.1 mcg/dl and of thyroid stimulating hormone, 34+/-4 vs 38+/-5 muU/ml did not differ in the groups with and without pericardial effusion, respectively. However, the pericardial effusion group had significantly slower heart rates on ECG than those without pericardial effusion: 53+/-8 vs 68+/-2 beats/min, P less than 0.05. Low voltage was present in five of the ten patients with pericardial effusion and five of the 23 nonpericardial effusion patients. None of the patients with pericardial effusion developed tamponade. Seven patients with pericardial effusion were restudied after periods of thyroxine replacement therapy ranging from six months to two years. All were euthyroid and had negative echoes on follow-up, but two still showed cardiomegaly on chest X-ray (both had associated coronary artery disease). We conclude that pericardial effusion occurs frequently in patients with myxedema. Tamponade is uncommon and the effusions disappear with thyroid replacement therapy. Cardiomegaly on chest X-ray and low voltage on ECG are not reliable indicators of pericardial effusion.
Impact of anti-interleukin-6 receptor blockade on circulating T and B cell subsets in patients with systemic lupus erythematosus
Authors: Yuko Shirota, Cheryl Yarboro, Randy Fischer, Tuyet-Hang Pham, Peter Lipsky, Gabor G Illei
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Circulating plasmablasts/plasma cells and activated B and T cells are increased in systemic lupus erythematosus (SLE). Interleukin (IL)-6 induces differentiation of B cells into antibody-forming cells and of T cells into effector cells. <h3>Objective</h3> To examine the hypothesis that blocking IL-6 would reverse some of the immune abnormalities present in SLE. <h3>Methods</h3> Fifteen patients with SLE with mild-to moderate disease activity were treated with biweekly infusions of tocilizumab, a humanised anti-IL-6 receptor monoclonal antibody for 12 weeks. Lymphocyte subsets (analysed by flow cytometry) and serum immunoglobulin levels were compared at baseline and at weeks 6 and 12. <h3>Results</h3> Tocilizumab decreased activated T and B cells, the frequency of CD27<sup>high</sup>CD38<sup>high</sup>IgD− plasmablasts/plasma cells and IgD−CD27+ post-switched memory B cells as well as IgG+ memory B cell, whereas it increased the frequency of IgD+CD27− antigen-inexperienced B cells. Among antigen-inexperienced IgD+CD27− B cells, CD38<sup>low</sup> mature naïve B cells increased significantly and CD38<sup>Intermediate</sup>CD5+ pre-naïve B cells showed a decreasing trend, whereas CD38<sup>high</sup>CD5+ transitional type 1 B cells did not change. Most of the changes occurred in patients who had abnormal values at baseline. IgG, IgA, IgG1 and IgG3 serum levels decreased albeit within the normal range. The frequency of CD4+CD45RA+CCR7+ naïve T cells increased. <h3>Conclusions</h3> In vivo blockade of the IL-6 receptor decreases lymphocyte activation and restores B and T cell homoeostasis by either blocking differentiation and/or trafficking in patients with SLE and leads to normalisation of the abnormal B and T cell subsets seen at baseline.
Acetylcholinesterase Plays a Pivotal Role in Apoptosome Formation
Authors: Sang Eun Park, Nam Deuk Kim, Young Hyun Yoo
Journal: Cancer Research (2004)

Abstract Although a recent study (Zhang et al. Cell Death Differ 2002; 9; 790–800) presented that acetylcholinesterase (AChE) might be an important common component in leading to various types of apoptosis, the molecular mechanism, by which AChE functions, had remained elusive before that study. We explored the role of AChE in apoptosis by silencing the AChE gene. Silencing of the AChE gene abolished the expression of AChE and prevented caspase-9 activation, decrease of cell viability, nuclear condensation and poly(adenosine diphosphate-ribose) polymerase cleavage but not mitochondrial events. Importantly, silencing of the AChE gene blocked the interaction between apoptotic protease-activating factor-1 and cytochrome c. Here we propose that AChE plays a pivotal role in the formation of apoptosome.
Inhaled corticosteroid beliefs, complementary and alternative medicine, and uncontrolled asthma in urban minority adults
Authors: Maureen George, Maxim Topaz, Cynthia Rand, Marilyn (Lynn) Sawyer Sommers, Karen Glanz, Michael V. Pantalon, Jun J. Mao, Judy A. Shea
Journal: Journal of Allergy and Clinical Immunology (2014)
Infertility and the provision of infertility medical services in developing countries
Authors: W. Ombelet, I. Cooke, S. Dyer, G. Serour, P. Devroey
Journal: Human Reproduction Update (2008)

Worldwide more than 70 million couples suffer from infertility, the majority being residents of developing countries. Negative consequences of childlessness are experienced to a greater degree in developing countries when compared with Western societies. Bilateral tubal occlusion due to sexually transmitted diseases and pregnancy-related infections is the most common cause of infertility in developing countries, a condition that is potentially treatable with assisted reproductive technologies (ART). New reproductive technologies are either unavailable or very costly in developing countries. This review provides a comprehensive survey of all important papers on the issue of infertility in developing countries. Medline, PubMed, Excerpta Medica and EMBASE searches identified relevant papers published between 1978 and 2007 and the keywords used were the combinations of ‘affordable, assisted reproduction, ART, developing countries, health services, infertility, IVF, simplified methods, traditional health care'. The exact prevalence of infertility in developing countries is unknown due to a lack of registration and well-performed studies. On the other hand, the implementation of appropriate infertility treatment is currently not a main goal for most international non-profit organizations. Keystones in the successful implementation of infertility care in low-resource settings include simplification of diagnostic and ART procedures, minimizing the complication rate of interventions, providing training-courses for health-care workers and incorporating infertility treatment into sexual and reproductive health-care programmes. Although recognizing the importance of education and prevention, we believe that for the reasons of social justice, infertility treatment in developing countries requires greater attention at National and International levels.
Diseases caused by reactions of T lymphocytes towards incompatible structures of the major histocompatibility complex. VI. Autoantibodies characteristic of systemic lupus erythematosus induced by abnormal T-B cell cooperation across I-E.
Authors: F M van Rappard-van der Veen, A G Rolink, E Gleichmann
Journal: The Journal of Experimental Medicine (1982)

By induction of a suitable graft-vs-host reaction (GVHR) in H-2-different F1 mice, one can induce the production of autoantibodies characteristic of systemic lupus erythematosus (SLE). The purpose of the present study was to define the intra-H-2 differences in the F1 recipients that are capable of triggering this process. A GVHR was induced in [B10.A(2R) x B10.A(4R)]F1 mice by injecting 10(8) lymphocytes from either parental strain. Whereas the donor B10.A(4R) induced a massive formation of autoantibodies to thymocytes, erythrocytes, nuclear antigens, and double-stranded DNA, the donor B10.A(2R) failed to do so. The intra-H-2 genetics of these two parent leads to F1 combinations are such that the observed autoantibody formation after the injection of B10.A(4R) T cells must have been triggered exclusively by the incompatible I-Ek subregion of the [B10.A(2R) x B10.A(4R)]F1 recipients. Because I-E appears to be the murine analogue of HLA-D/DR, this finding is of interest with respect to the increased frequency of certain HLA-DR alleles in SLE patients, as discussed.
Improvement of Postnatal Neovascularization by Human Embryonic Stem Cell–Derived Endothelial-Like Cell Transplantation in a Mouse Model of Hindlimb Ischemia
Authors: Seung-Woo Cho, Sung-Hwan Moon, Soo-Hong Lee, Sun-Woong Kang, Jumi Kim, Jae Min Lim, Hyo-Soo Kim, Byung-Soo Kim, Hyung- Min Chung
Journal: Circulation (2007)

We established an efficient preparation method to obtain endothelial-like cells (ECs) from human embryonic stem cells (hESCs) and tested whether these hESC-ECs would show therapeutic potential for treatment of hindlimb ischemia.ECs differentiated from hESCs were obtained by mechanical isolation and cell sorting for von Willebrand factor. The isolated hESC-ECs maintained endothelial cell-specific characteristics such as endothelial marker expression and capillary formation. One day after surgical induction of hindlimb ischemia in athymic mice, hESC-ECs were injected intramuscularly into ischemic limbs. Four weeks after treatment, hESC-EC treatment significantly increased limb salvage (36%) compared with treatment with medium (0%). In addition, laser Doppler imaging showed that the ratio of blood perfusion (ischemic to normal limb) was increased significantly (P<0.01) by hESC-EC treatment (0.511+/-0.167) compared with medium injection (0.073+/-0.061). Capillary and arteriole densities were 658+/-190/mm2 and 30+/-11/mm2 in the hESC-EC group, respectively, whereas those in the medium group were 392+/-118/mm2 and 16+/-8/mm2, respectively (P<0.01). Reverse-transcription polymerase chain reaction with human-specific primers revealed mRNA expression of human endothelial markers and human angiogenic factors in ischemic mouse tissues. The transplanted hESC-ECs were localized as capillaries near muscle tissues in ischemic regions or incorporated in the vessels between muscle tissues, as confirmed by human nuclear antigen staining with platelet/endothelial cell adhesion molecule or von Willebrand factor.This study demonstrates that hESC-EC transplantation improves blood perfusion and limb salvage by facilitating postnatal neovascularization in a mouse model of hindlimb ischemia. Thus, hESC-ECs might be useful as an alternative cell source for angiogenic therapy.