tbuckley/cabot-search huggingface dataset:
Immediate Gene Expression Changes After the First Course of Neoadjuvant Chemotherapy in Patients with Primary Breast Cancer Disease
Authors: Olga Modlich, Hans-Bernd Prisack, Marc Munnes, Werner Audretsch, Hans Bojar
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Our goal was to identify genes undergoing expressional changes shortly after the beginning of neoadjuvant chemotherapy for primary breast cancer. Experimental Design: The biopsies were taken from patients with primary breast cancer prior to any treatment and 24 hours after the beginning of the neoadjuvant chemotherapy. Expression analyses from matched pair samples representing 25 patients were carried out with Clontech filter arrays. A subcohort of those 25 paired samples were additionally analyzed with the Affymetrix GeneChip platform. All of the transcripts from both platforms were queried for expressional changes. Results: Performing hierarchical cluster analysis, we clustered pre- and posttreatment samples from individual patients more closely to each other than the samples taken from different patients. This reflects the rather low number of transcripts responding directly to the drugs used. Although transcriptional drug response occurring during therapy differed between individual patients, two genes (p21WAF1/CIP1 and MIC-1) were up-regulated in posttreatment samples. This could be validated by semiquantitative and real-time reverse transcription-PCR. Partial least- discriminant analysis based on approximately 25 genes independently identified by either Clontech or Affymetrix platforms could clearly discriminate pre- and posttreatment samples. However, correlation of certain gene expression levels as well as of differential patterns and clusters as determined by a different platform was not always satisfying. Conclusions: This study has demonstrated the potential of monitoring posttreatment changes in gene expression as a measure of the pharmacodynamics of drugs. As a clinical laboratory model, it can be useful to identify patients with sensitive and reactive tumors and to help for optimized choice for sequential therapy and obviously improve relapse- free and overall survival.
Expression of Nephrin in Pediatric Kidney Diseases
Authors: JAAKKO PATRAKKA, VESA RUOTSALAINEN, ILKKA KETOLA, CHRISTER HOLMBERG, MARKKU HEIKINHEIMO, KARL TRYGGVASON, HANNU JALANKO
Journal: Journal of the American Society of Nephrology (2001)

Nephrin is a podocyte cell adhesion protein located at the slit diaphragm area of the kidney glomerulus. Mutations in the nephrin gene (NPHS1) lead to congenital nephrosis, suggesting that nephrin is essential for the glomerular filtration barrier. This prompted this study of the expression of nephrin in acquired pediatric kidney diseases using in situ hybridization and immunohistochemistry. In situ hybridization for nephrin mRNA was performed in biopsy samples from patients with proteinuria caused by minimal change nephrosis, focal segmental glomerulosclerosis, and membranous nephropathy. The expression of nephrin mRNA was evaluated by grading the signal intensity visually and by counting the number of grains in separate glomeruli. No significant difference was observed in these samples as compared with controls. Immunostaining for nephrin was performed using antibodies directed against extra- and intracellular parts of the molecule. Nephrin staining gave a linear pattern along the glomerular capillary loops. In minimal change nephrosis, focal segmental glomerulosclerosis, and membranous nephropathy, the distribution of nephrin was similar to that in controls. In proliferative forms of glomerulonephritides (Henoch-Schönlein nephritis, IgA nephropathy, postinfectious and membranoproliferative glomerulonephritis), crescents and sclerotic lesions were negative for nephrin, and mesangial proliferation led to a scattered and sparse staining pattern. The staining pattern of nephrin was compared to that of ZO-1, a component of the cytoplasmic face of the slit diaphragm. The distributions of these two proteins in capillary tufts were similar in all disease entities studied. In conclusion, immunohistochemistry and in situ hybridization did not reveal major alterations in the expression of nephrin in proteinuric kidney diseases in children. Further studies are needed for more precise evaluation of the role of nephrin in these diseases.
B-cell tolerance. III. Effect of papain-mediated cleavage of cell surface IgD on tolerance susceptibility of murine B cells.
Authors: J C Cambier, E S Vitetta, J R Kettman, G M Wetzel, J W Uhr
Journal: The Journal of Experimental Medicine (1977)

Under defined conditions, papain removes IgD from cells while leaving IgM, H-2, Ia, Lyb-2, and complement receptor intact. The effect of such treatment with papain on the induction of tolerance in murine splenic B cells was determined in an in vitro system. Treatment of the cells with papain has no effect on subsequent antibody responsiveness presumably because surface receptors regenerate before and during incubation with immunogen. Removal of increasing amounts of IgD results in increasing susceptibility of thymus-dependent responsive cells to tolerance induction. The tolerance susceptibility of thymus-independent responsive cells, which we have previously suggested are immature cells that bear only IgM, is unaffected by cleavage of IgD. If cells are incubated for 24 h after treatment with papain, cell surface IgD and tolerance resistance return. These results indicate that a surface molecule affects susceptibility of B cells to induction of tolerance and suggest that this molecule may be IgD.
Comparison of Fluticasone Propionate–Salmeterol Combination Therapy and Montelukast in Patients Who Are Symptomatic on Short-acting β<sub>2</sub>-Agonists Alone
Authors: WILLIAM J. CALHOUN, HAROLD S. NELSON, ROBERT A. NATHAN, PAMELA J. PEPSIN, CHRIS KALBERG, AMANDA EMMETT, KATHLEEN A. RICKARD, PAUL DORINSKY
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The objective of this study was to determine whether initial maintenance therapy for the treatment of inflammation and bronchoconstriction associated with persistent asthma is more effective with a combination product (100 μ g of fluticasone propionate and 50 μ g of salmeterol [FSC]) administered twice daily through the Diskus device (GlaxoWellcome, Research Triangle Park, NC) or with montelukast at 10 mg once daily. A 12-wk, randomized, double-blind, double-dummy, multicenter study was conducted with 423 patients 15 yr of age and older with asthma and who were symptomatic while receiving short-acting β2-agonists alone. At end point, FSC resulted in significantly greater increases in morning predose FEV1 (0.54 ± 0.03 vs. 0.27 ± 0.03 L), morning peak expiratory flow (PEF) (89.9 ± 6.7 vs. 34.2 ± 4.7 L/min), evening PEF (69.9 ± 5.8 vs. 31.1 ± 4.5 L/min), the percentage of symptom-free days (48.9 ± 2.9 vs. 21.7 ± 2.5%), the percentage of rescue-free days (53.0 ± 2.8 vs. 26.2 ± 2.5%), and the percentage of nights with no awakenings (23.0 ± 2.5 vs. 15.5 ± 2.4%) compared with montelukast (p ⩽ 0.001, all comparisons). FSC significantly reduced asthma symptom scores ( − 1.0 ± 0.1 vs. − 0.6 ± 0.1), rescue albuterol use ( − 3.3 ± 0.2 vs. − 1.9 ± 0.2 puffs/d), and the number of exacerbations (0 vs. 11) compared with montelukast (p < 0.001). Both treatments were well tolerated. In summary, treatment of the two main components of asthma (inflammation and bronchoconstriction) with fluticasone propionate and salmeterol in a combination product was a more effective initial maintenance treatment strategy than treatment with montelukast, a single-mediator antagonist.Keywords: adrenal cortex hormones; antiasthmatic agents; asthma; fluticasone propionate; leukotriene antagonists; long-acting β2-agonists; montelukast
Clinical and Biological Effects of Valproic Acid as a Histone Deacetylase Inhibitor on Tumor and Surrogate Tissues: Phase I/II Trial of Valproic acid and Epirubicin/FEC
Authors: Pamela Munster, Douglas Marchion, Elona Bicaku, Mira Lacevic, Jongphil Kim, Barbara Centeno, Adil Daud, Anthony Neuger, Susan Minton, Daniel Sullivan
Journal: Clinical Cancer Research (2009)

The aim was to study the biological and molecular effects of the histone deacetylase (HDAC) inhibitor, valproic acid, in patients with solid tumor malignancies.A phase I dose escalation of valproic acid given on days 1 to 3 followed by epirubicin (day 3) was followed by a dose expansion of valproic acid combined with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC100). Pharmacodynamic and pharmacokinetic studies entailed valproic acid and epirubicin plasma levels and their interaction, the effects of valproic acid on histone acetylation in peripheral blood mononuclear cells (PBMC) and tumor cells at baseline and day 3, and baseline expression of HDAC2 and HDAC6 as therapeutic targets.Forty-four patients were enrolled in the phase I part, with a disease-specific cohort expansion of 15 breast cancer patients (median age, 55 years; range, 28-66 years) receiving 120 mg/kg/day valproic acid followed by FEC100. Partial responses were seen in 9 of 41 (22%) patients during the phase I part. Objective responses were seen in 9 of 14 (64%) evaluable patients at the dose expansion with a median number of 6 administered cycles. Predominant toxicities were valproic acid-associated somnolence and epirubicin-induced myelosuppression. Valproic acid plasma levels were associated with short-term, reversible depletion of WBC and neutrophils within 48 hours. Histone acetylation in tumor samples and in PBMCs correlated with valproic acid levels and was further linked to baseline HDAC2 but not to HDAC6 expression.Valproic acid is a clinically relevant HDAC inhibitor, and PBMCs may serve as a surrogate for tumor histone acetylation in solid tumor malignancies. HDAC2 should be further considered as a relevant therapeutic target.
MOLES AND MALFORMATIONS OF THE SKIN IN THEIR RELATIONSHIP TO INHERITANCE AND PHYLOGENESIS.
Authors: E. MEIROWSKY
Journal: British Journal of Dermatology (1942)

Journal Article MOLES AND MALFORMATIONS OF THE SKIN IN THEIR RELATIONSHIP TO INHERITANCE AND PHYLOGENESIS: (NEW AND OLD INVESTIGATIONS.) Get access E. MEIROWSKY E. MEIROWSKY London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 54, Issue 5, 1 May 1942, Pages 129–153, https://doi.org/10.1111/j.1365-2133.1942.tb10635.x Published: 01 May 1942
Is bronchodilation required routinely before diagnostic sputum induction? Evidence from studies with tuberculosis
Authors: A Dunleavy, R A M Breen, F Perrin, M C I Lipman
Journal: Thorax (2008)

Sputum induction (SI) by inhalation of nebulised hypertonic saline is an efficient and non-invasive way of obtaining samples to assess airway inflammation and diagnose pulmonary infections such as tuberculosis (TB).1 2 Data published on the safety of SI are largely derived from subjects with obstructive lung disease. Yet on this basis a Working Group of the European Respiratory Society (ERS) recommended that all patients undergoing SI should receive pre-procedure bronchodilation with monitoring throughout by either serial forced expiratory volume in 1 s or peak expiratory flow rate (PEFR) measurements.3 Subjects with other respiratory conditions may not be at the …
Gabapentin in patients with the pruritus of cholestasis: A double-blind, randomized, placebo-controlled trial
Authors: Nora V. Bergasa, Monnie McGee, Iona H. Ginsburg, Danielle Engler
Journal: Hepatology (2006)

Pruritus is defined as the second order of nociception, the first being pain; thus, there is a rationale to study gabapentin, a drug that increases the threshold to experience nociception. The aim of this double-blind, randomized, placebo-controlled trial was to study the effect of gabapentin on the perception of pruritus and its behavioral manifestation, scratching, in cholestasis. The participants were 16 women with chronic liver disease and chronic pruritus. Hourly scratching activity (HSA) was continuously recorded for up to 48 hours at baseline and on treatment for at least 4 weeks in an inpatient setting. The perception of pruritus was assessed by interviews and by a visual analog score (VAS) of pruritus recorded every hour while patients were awake. Patients were randomized to the study drug (gabapentin or placebo) at a starting dose of 300 mg orally per day in divided doses to a maximum of 2,400 mg or until relief from pruritus. Gabapentin was associated with an increase in mean HSA, in contrast to the placebo, which was associated with a decrease. The mean VAS decreased significantly among those taking the placebo and in some patients on gabapentin. In conclusion , gabapentin did not provide a significant therapeutic advantage over the placebo; in fact, it was associated with an increase in the perception of pruritus and in HSA in some patients.
Prospective Multi-Institutional Study Evaluating the Performance of Prostate Cancer Risk Calculators
Authors: Robert K. Nam, Michael W. Kattan, Joseph L. Chin, John Trachtenberg, Rajiv Singal, Ricardo Rendon, Laurence H. Klotz, Linda Sugar, Christopher Sherman, Jonathan Izawa, David Bell, Aleksandra Stanimirovic, Vasundara Venkateswaran, Eleftherios P. Diamandis, Changhong Yu, D. Andrew Loblaw, Steven A. Narod
Journal: Journal of Clinical Oncology (2011)

Prostate cancer risk calculators incorporate many factors to evaluate an individual's risk for prostate cancer. We validated two common North American-based, prostate cancer risk calculators.We conducted a prospective, multi-institutional study of 2,130 patients who underwent a prostate biopsy for prostate cancer detection from five centers. We evaluated the performance of the Sunnybrook nomogram-based prostate cancer risk calculator (SRC) and the Prostate Cancer Prevention Trial (PCPT) -based risk calculator (PRC) to predict the presence of any cancer and high-grade cancer. We examined discrimination, calibration, and decision curve analysis techniques to evaluate the prediction models.Of the 2,130 patients, 867 men (40.7%) were found to have cancer, and 1,263 (59.3%) did not have cancer. Of the patients with cancer, 403 (46.5%) had a Gleason score of 7 or more. The area under the [concentration-time] curve (AUC) for the SRC was 0.67 (95% CI, 0.65 to 0.69); the AUC for the PRC was 0.61 (95% CI, 0.59 to 0.64). The AUC was higher for predicting aggressive disease from the SRC (0.72; 95% CI, 0.70 to 0.75) compared with that from the PRC (0.67; 95% CI, 0.64 to 0.70). Decision curve analyses showed that the SRC performed better than the PRC for risk thresholds of more than 30% for any cancer and more than 15% for aggressive cancer.The SRC performed better than the PRC, but neither one added clinical benefit for risk thresholds of less than 30%. Further research is needed to improve the AUCs of the risk calculators, particularly for higher-grade cancer.
Human Body Composition: Advances in Models and Methods
Authors: Steven B. Heymsfield, ZiMian Wang, Richard N. Baumgartner, Robert Ross
Journal: Annual Review of Nutrition (1997)

▪ Abstract The field of human body composition research is reaching a mature stage in its development: The three interconnected areas that define body composition research—models and their rules, methodology, and biological effects—are well-defined and are actively investigated by scientists in diverse disciplines from many different nations; and methods are available for measuring all major atomic, molecular, cellular, and tissue-system level body composition components in research, clinical, and epidemiological settings. This review summarizes main body composition research concepts, examines new component-measurement methodologies, and identifies potential areas of future research.
Microalbuminuria and Risk for Cardiovascular Disease
Authors: Coen D.A. Stehouwer, Yvo M. Smulders
Journal: Journal of the American Society of Nephrology (2006)

Microalbuminuria is a strong and independent indicator of increased cardiovascular risk among individuals with and without diabetes. Therefore, microalbuminuria can be used for stratification of risk for cardiovascular disease. Once microalbuminuria is present, cardiovascular risk factor reduction should be more "aggressive." The nature of the link between microalbuminuria and cardiovascular risk, however, remains poorly understood. There is no strong evidence that microalbuminuria causes atherothrombosis or that atherothrombosis causes microalbuminuria. Many studies have tested the hypothesis that a common risk factor underlies the association between microalbuminuria and cardiovascular disease but, again, have found no strong evidence in favor of this contention. At present, the most likely possibility is that a common pathophysiologic process, such as endothelial dysfunction, chronic low-grade inflammation, or increased transvascular leakage of macromolecules, underlies the association between microalbuminuria and cardiovascular disease, but more and prospective studies of these hypotheses are needed.
MRI: the new reference standard in quantifying hepatic steatosis?
Authors: Dimitri Aristotle Raptis, Michael Alexander Fischer, Rolf Graf, Daniel Nanz, Achim Weber, Wolfgang Moritz, Yinghua Tian, Christian Eugen Oberkofler, Pierre-Alain Clavien
Journal: Gut (2011)

<h3>Objective</h3> The purpose of this study was to assess non-invasive imaging modalities including MRI and CT and compare the quantitative amount of fat with data provided by the pathologist and a chemical lipid assay in leptin-deficient mouse livers. <h3>Methods</h3> A liver/fat phantom was first used to assess the accuracy of small-animal MRI and human MRI and CT, followed by correlation analysis with ob/ob mouse liver fat quantified by an accurate chemical lipid assay. Similarly, the authors compared the pathologist9s quantification and the automated software quantification of fat with the lipid assay. The authors then investigated whether hepatic steatosis assessed by MRI correlates with the degree of liver injury in a model of ischaemia/reperfusion in leptin-deficient mice as well as with serious postoperative complications in patients undergoing major liver resection (NCT01234714). <h3>Results</h3> The authors designed lipid/liver mixtures at various ratios to mimic a wide range of fat liver contents. Small-animal and human MRI detected this fat with a high correlation to the actual fat contents. Mouse livers assessed by human MRI correlated best with total intrahepatic fat by chemical lipid analysis (r=0.975). Human CT, the pathologist9s assessment and the automated software were less reliable (r=−0.873, 0.512 and 0.873, respectively). There was a significant correlation of the MRI fat quantification with several parameters of liver injury, and MRI data could predict mouse survival after ischaemia/reperfusion injury. In patients undergoing major liver resection, higher liver fat content was associated with more serious postoperative complications, such as liver or multiorgan failure and sepsis, necessitating admission to the intensive care unit. <h3>Conclusions</h3> With the use of a well-defined set of biological standards, MRI can predict intrahepatic fat with high accuracy. In contrast to biopsies, this method is non-invasive, giving a representative assessment of the whole liver.
The Updated EAU Guidelines on Muscle-Invasive and Metastatic Bladder Cancer
Authors: Arnulf Stenzl, Nigel C. Cowan, Maria De Santis, Gerhard Jakse, Marcus A. Kuczyk, Axel S. Merseburger, Maria José Ribal, Amir Sherif, J. Alfred Witjes
Journal: European Urology (2009)
Diagnosis and Prognosis in Acute Myeloid Leukemia — The Art of Distinction
Authors: Bob Löwenberg
Journal: New England Journal of Medicine (2008)

The days when the microscope was the principal tool for classifying the various forms of acute myeloid leukemia (AML) and predicting the outcome of affected patients seem long past. The discovery, during the past 15 years, of acquired mutations and alterations in gene expression in the leukemic cells in all varieties of AML has not only changed the role of the microscope in diagnosing leukemia but also influenced the management of these diseases and how we think about their causes. Genomic alterations in AML affect the function of signaling molecules, transcription factors, and growth-factor receptors and also determine the phenotype . . .
Can semi-automated image cytometry on induced sputum become a screening tool for lung cancer?: Evaluation of quantitative semi-automated sputum cytometry on radon- and uranium-exposed workers
Authors: W. Marek, N. Kotschy-Lang, A. Muti, Ch. Köhler, L. Nielsen, Th. Topalidis, Z. Atay, J.A. Nakhosteen
Journal: European Respiratory Journal (2001)

The correlations between semi-automated sputum cytometry (ASC), conventional cytology and the final diagnosis was investigated in industrially-exposed workers. Slides of sputum samples from 201 former uranium miners with silicosis, 100 patients with asbestosis, 103 workers resected for lung cancer, and 200 controls (50% smokers), were stained using the Papanicolaou (Pap) method and the Feulgen reaction with thionin. Cytometry was performed using the Cyto-Savant automated system. Atypical nuclei were found in 72 of 404 patient samples, 327 samples were normal and five were inadequate for ASC analysis. Thirteen tumours (Pap IV, Pap V) and 11 cases of severe dysplasia were identified by cytology. Lung cancer was confirmed in 20 patients. Compared to the final diagnosis of lung cancer, the sensitivity of ASC was 75% (15 out of 20) and specificity 89.8% (520 out of 579). The results represent a diagnostic efficiency of 89.3%. The combination of ASC with cytology increased sensitivity to 80% (16 out of 20) without significant loss of specificity (89.7% or 523 out of 581). In this investigation of a limited number of patients with occupational radon or asbestos exposure, semi-automated sputum cytometry appears to be sensitive and reliable for the detection of malignant changes in the tracheobronchial mucosa. Together with conventional cytology, it would be reasonable to test the validity of the combined methods in a large-scale feasibility study of early lung cancer detection.