tbuckley/cabot-search huggingface dataset:
Bone marrow transplantation versus high-dose cytarabine-based consolidation chemotherapy for acute myelogenous leukemia in first remission.
Authors: G J Schiller, S D Nimer, M C Territo, W G Ho, R E Champlin, J L Gajewski
Journal: Journal of Clinical Oncology (1992)

Despite substantial progress in the treatment of acute myeloid leukemia (AML), fewer than 25% of patients survive free of leukemia for more than 5 years without allogeneic bone marrow transplantation (BMT). In this study we analyzed the results of one or more cycles of high-dose cytarabine-based consolidation chemotherapy as compared with allogeneic BMT in first remission.The results in 28 adult patients, aged 16 to 45 years, who underwent a closely HLA-matched BMT for AML in first remission were compared with those in 54 consecutive, age-matched, adult patients treated with one or more cycles of high-dose, cytarabine-based consolidation chemotherapy.After a median follow-up of 4 years, the actuarial risk of leukemic relapse was considerably lower in the transplant group than in the group treated with consolidation chemotherapy (32% +/- 26% v 60% +/- 14%; P = .05). Treatment-related mortality, however, was much higher in the group treated with BMT (32% v 6%, P = .002). The actuarial disease-free survival at 5 years was not significantly different for the two groups (45% +/- 24% v 38% +/- 14%).Our results show that BMT in first remission AML did not offer a disease-free survival advantage over intensive postremission consolidation chemotherapy. Larger studies are needed to identify patients who might benefit most from BMT.
Linkage of Crohn’s disease to the major histocompatibility complex region is detected by multiple non-parametric analyses
Authors: H Yang, S E Plevy, K Taylor, D Tyan, N Fischel-Ghodsian, C McElree, S R Targan, J I Rotter
Journal: Gut (1999)

BACKGROUND There is evidence for genetic susceptibility to Crohn’s disease, and a tentative association with tumour necrosis factor (TNF) and HLA class II alleles. AIMS To examine the potential of genetic linkage between Crohn’s disease and the MHC region on chromosome 6p. METHODS TNF microsatellite markers and, for some families, additional HLA antigens were typed for 323 individuals from 49 Crohn’s disease multiplex families to generate informative haplotypes. Non-parametric linkage analysis methods, including sib pair and affected relative pair methods, were used. RESULTS Increased sharing of haplotypes was observed in affected sib pairs: 92% (48/52) shared one or two haplotypes versus an expected 75% if linkage did not exist (p=0.004). After other affected relative pairs were included, the significance level reached 0.001. The mean proportion of haplotype sharing was increased for both concordant affected (π=0.60, p=0.002) and unaffected sib pairs (π=0.58, p=0.031) compared with the expected value (π=0.5). In contrast, sharing in discordant sib pairs was significantly decreased (π=0.42, p=0.007). Linear regression analysis using all three types of sib pairs yielded a slope of −0.38 at p=0.00003. It seemed that the HLA effect was stronger in non-Jewish families than in Jewish families. CONCLUSIONS All available analytical methods support linkage of Crohn’s disease to the MHC region in these Crohn’s disease families. This region is estimated to contribute approximately 10–33% of the total genetic risk to Crohn’s disease.
Indoleamine 2,3-dioxygenase–expressing dendritic cells form suppurative granulomas following Listeria monocytogenes infection
Authors: Alexey Popov, Zeinab Abdullah, Claudia Wickenhauser, Tomo Saric, Julia Driesen, Franz-Georg Hanisch, Eugen Domann, Emma Lloyd Raven, Oliver Dehus, Corinna Hermann, Daniela Eggle, Svenja Debey, Trinad Chakraborty, Martin Krönke, Olaf Utermöhlen, Joachim L. Schultze
Journal: Journal of Clinical Investigation (2006)

Control of pathogens by formation of abscesses and granulomas is a major strategy of the innate immune system, especially when effector mechanisms of adaptive immunity are insufficient. We show in human listeriosis that DCs expressing indoleamine 2,3-dioxygenase (IDO), together with macrophages, are major cellular components of suppurative granulomas in vivo. Induction of IDO by DCs is a cell-autonomous response to Listeria monocytogenes infection and was also observed in other granulomatous infections with intracellular bacteria, such as Bartonella henselae. Reporting on our use of the clinically applied anti–TNF-α antibody infliximab, we further demonstrate in vitro that IDO induction is TNF-α dependent. Repression of IDO therefore might result in exacerbation of granulomatous diseases observed during anti–TNF-α therapy. These findings place IDO+ DCs not only at the intersection of innate and adaptive immunity but also at the forefront of bacterial containment in granulomatous infections.
Effect of Kidney Transplantation on Outcomes among Patients with Hepatitis C
Authors: David Roth, Jeffrey J. Gaynor, K. Rajender Reddy, Gaetano Ciancio, Junichiro Sageshima, Warren Kupin, Giselle Guerra, Linda Chen, George W. Burke
Journal: Journal of the American Society of Nephrology (2011)

The long-term outcome of kidney transplantation in patients infected with hepatitis C virus (HCV) and end stage renal disease (ESRD) is not well described. We retrospectively identified 230 HCV-infected patients using enzyme immunoassay and nucleic acid testing obtained during the transplant evaluation. Of 207 patients who had a liver biopsy before transplant, 44 underwent 51 follow-up liver biopsies at approximately 5-year intervals either while on the waitlist for a kidney or after kidney transplantation. Advanced fibrosis was present in 10% of patients biopsied, identifying a population that may warrant consideration for combined liver-kidney transplantation. Kidney transplantation does not seem to accelerate liver injury; 77% of kidney recipients who underwent follow-up biopsies showed stable or improved liver histology. There was a higher risk for death during the first 6 months after transplant, but undergoing transplantation conferred a long-term survival advantage over remaining on the waitlist, which was evident by 6 months after transplant (HR, 0.32; 95% CI, 0.17 to 0.62). Furthermore, the risk for death resulting from infection was significantly higher during the first 6 months after transplant (HR, 26.6; 95% CI, 5.01 to 141.3), whereas there was an early (≤6 months) and sustained decrease in the risk for cardiovascular death (HR, 0.20; 95% CI, 0.08 to 0.47). In summary, these data suggest the importance of liver biopsy before transplant and show that kidney transplantation confers a long-term survival benefit among HCV-infected patients with ESRD compared with remaining on the waitlist. Nevertheless, the higher incidence of early infection-related deaths after transplant calls for further study to determine the optimal immunosuppressive protocol.
Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute–Working Group 1996 guidelines
Authors: Michael Hallek, Bruce D. Cheson, Daniel Catovsky, Federico Caligaris-Cappio, Guillaume Dighiero, Hartmut Döhner, Peter Hillmen, Michael J. Keating, Emili Montserrat, Kanti R. Rai, Thomas J. Kipps
Journal: Blood (2008)
Autonomic modulation of electrical restitution, alternans and ventricular fibrillation initiation in the isolated heart
Authors: G. André Ng, Kieran E. Brack, Vanlata H. Patel, John H. Coote
Journal: Cardiovascular Research (2006)

Objective: Abnormal autonomic nerve activity is a strong prognostic marker for ventricular arrhythmias but the mechanisms underlying the autonomic modulation of ventricular fibrillation (VF) initiation are poorly understood. We examined the effects of direct sympathetic (SS) and vagus (VS) nerve stimulation on electrical restitution, alternans and VF threshold (VFT) in a novel isolated rabbit heart preparation with intact dual autonomic innervation.
Phase I study of weekly oxaliplatin plus irinotecan in previously treated patients with metastatic colorectal cancer
Authors: N. Kemeny, W. Tong, M. Gonen, J. Stockman, C. Di Lauro, J. Teitcher, P. White, C. Price, L. Saltz, S. Sharma, M.A. Graham
Journal: Annals of Oncology (2002)
A Phase I and Pharmacokinetic Study of Weekly Oxaliplatin Followed by Paclitaxel in Patients with Solid Tumors
Authors: Tanios S. Bekaii-Saab, Jing Liu, Kenneth K. Chan, Stanley P. Balcerzak, Percy S. Ivy, Michael R. Grever, Eric H. Kraut
Journal: Clinical Cancer Research (2008)

Oxaliplatin and paclitaxel are widely used in treating solid tumors. We designed a phase I study with the purpose of determining the maximal tolerated dose and pharmacokinetic properties of weekly oxaliplatin followed by paclitaxel based on evidence suggesting that weekly administration of both drugs allows equivalent dose intensity with less neurotoxicity.Twenty-three patients with advanced solid tumors were treated. Starting doses were 35 mg/m2 oxaliplatin followed by 45 mg/m2 paclitaxel weekly for 4 weeks every 6 weeks. Dose was escalated as follows: 45 mg/m2 oxaliplatin and 45 mg/m2 paclitaxel, 60 mg/m2 oxaliplatin and 45 mg/m2 paclitaxel, and 60 mg/m2 oxaliplatin and 60 mg/m2 paclitaxel. Pharmacokinetic studies were evaluated during the first course of therapy for oxaliplatin using population kinetics approach.A total of 49 courses were administered. The dose-limiting toxicity was peripheral neuropathy with oxaliplatin and paclitaxel both at 60 mg/m2. There were three partial responses. There was evidence of pharmacokinetic interaction with a significant amount of total platinum (46.2-49.5%/24 h) eliminated in the urine in this group of patients, consistent with published data from others. The total body clearance values of plasma platinum and ultrafiltrable platinum were higher in this combination compared with corresponding values from our previous study with oxaliplatin only (P < 0.001).The recommended phase II dose of this combination is 60 mg/m2 oxaliplatin followed by 45 mg/m2 paclitaxel. Evidence of antitumor activity and acceptable toxicity with this combination and schedule warrants further investigation. We have obtained more definitive pharmacokinetic properties of oxaliplatin and confirmed its drug interaction with paclitaxel in the current sequence.
Meta-Analysis and Meta-Review of Thyroid Cancer Gene Expression Profiling Studies Identifies Important Diagnostic Biomarkers
Authors: Obi L. Griffith, Adrienne Melck, Steven J.M. Jones, Sam M. Wiseman
Journal: Journal of Clinical Oncology (2006)

Purpose An estimated 4% to 7% of the population will develop a clinically significant thyroid nodule during their lifetime. In many cases, preoperative diagnoses by needle biopsy are inconclusive. Thus, there is a clear need for improved diagnostic tests to distinguish malignant from benign thyroid tumors. The recent development of high-throughput molecular analytic techniques should allow the rapid evaluation of new diagnostic markers. However, researchers are faced with an overwhelming number of potential markers from numerous thyroid cancer expression profiling studies. Materials and Methods To address this challenge, we have carried out a comprehensive meta-review of thyroid cancer biomarkers from 21 published studies. A gene ranking system that considers the number of comparisons in agreement, total number of samples, average fold-change and direction of change was devised. Results We have observed that genes are consistently reported by multiple studies at a highly significant rate (P &lt; .05). Comparison with a meta-analysis of studies reprocessed from raw data showed strong concordance with our method. Conclusion Our approach represents a useful method for identifying consistent gene expression markers when raw data are unavailable. A review of the top 12 candidates revealed well known thyroid cancer markers such as MET, TFF3, SERPINA1, TIMP1, FN1, and TPO as well as relatively novel or uncharacterized genes such as TGFA, QPCT, CRABP1, FCGBP, EPS8 and PROS1. These candidates should help to develop a panel of markers with sufficient sensitivity and specificity for the diagnosis of thyroid tumors in a clinical setting.
Use of aromatic hydroxylation of phenylalanine to measure production of hydroxyl radicals after myocardial ischemia in vivo. Direct evidence for a pathogenetic role of the hydroxyl radical in myocardial stunning.
Authors: J Z Sun, H Kaur, B Halliwell, X Y Li, R Bolli
Journal: Circulation Research (1993)

A pathogenetic role of .OH in myocardial stunning has been inferred from the protective effects of .OH scavengers and iron chelators. However, conclusive demonstration of the .OH radical hypothesis of myocardial stunning requires direct verification of three major, but still unproven, assumptions: (1) .OH is produced in the stunned myocardium in vivo; (2) antioxidant therapy inhibits .OH production; and (3) such inhibition results in enhanced recovery of contractility (ie, .OH is necessary for the development of myocardial stunning). Since phenylalanine (Phe) reacts with .OH to form the hydroxylated products ortho-, meta-, and para-tyrosines (o-, m-, and p-tyr), we used aromatic hydroxylation of Phe to detect .OH formation in the stunned myocardium. Open-chest dogs undergoing a 15-minute coronary occlusion followed by reperfusion received an intravenous infusion of Phe (54.3 mg/kg for 11.5 minutes beginning 90 seconds before reperfusion); these animals were given either no antioxidant therapy (group I, n = 15), N-2-mercaptopropionyl glycine (MPG) (group II, n = 11), or MPG combined with superoxide dismutase, catalase, and desferrioxamine (group III, n = 12). In addition, group IV (nonischemic control group, n = 6) received Phe but did not undergo coronary occlusion, whereas group V (ischemic control group, n = 16) underwent a 15-minute occlusion but did not receive Phe or antioxidants. The plasma concentrations of tyrosines in the local venous effluent and in the arterial blood were measured with high-performance liquid chromatography. In group I, production of o- and m-tyr, which are specific markers of .OH formation, began during coronary occlusion but increased dramatically immediately after reperfusion, peaking at 1 minute and continuing up to 10 minutes of reperfusion. In group II, the production of o- and m-tyr was markedly decreased throughout the first 10 minutes of reperfusion. In group III, the production of m-tyr was decreased to levels similar to those in group II, whereas the production of o-tyr was almost completely abolished. There was no appreciable production of o- or m-tyr in group IV. Recovery of contractile function (assessed as systolic wall thickening) was increased in group I vs group V. Recovery of function was further enhanced in group II, with only a slight additional improvement in group III.(ABSTRACT TRUNCATED AT 400 WORDS)
Recurrent sustained ventricular tachycardia. 2. Endocardial mapping.
Authors: M E Josephson, L N Horowitz, A Farshidi, J F Spear, J A Kastor, E N Moore
Journal: Circulation (1978)

Endocardial ventricular mapping of 21 ventricular tachyardias (VT) in 17 patients was performed using electrode catheters. Activation at multiple left and right ventricular sites was utilized to determine the site of origin of the VT. Eleven VT had a left bundle branch block pattern (VT-LBBB) and 10 VT had right bundle branch block pattern (VT-RBBB). In all VT-RBBB the earliest site of activation was in the LV or septum. In VT-LBBB the earliest site was RV (4/11), LV (5/11) and septum (2/11). All ventricular tachycardias with QRS less than 140 msec arose in the septum. In patients with an aneurysm, the site of origin of ventricular tachycardia was always in the aneursm. All VT-LBBB arising from the left ventricle originated in an aneurysm involving the septum. QRS changes during ventricular tachycardia were associated with alterations in the patterm of ventricular activation without alteration of the site of origin. In three patients the site of origin predicted by endocardial ventricular mapping was confirmed intraoperatively by epi- and/or endocardial mapping. We conclude that endocardial ventricular mapping demonstrates the limitations of the surface electrocardiogram in localizing the site of origin of ventricular tachycardia. The method may provide important data upon which the surgical therapy of ventricular tachycardia is based.
Divergence in Enzymatic Activities in the Soybean GST Supergene Family Provides New Insight into the Evolutionary Dynamics of Whole-Genome Duplicates
Authors: Hai-Jing Liu, Zhen-Xin Tang, Xue-Min Han, Zhi-Ling Yang, Fu-Min Zhang, Hai-Ling Yang, Yan-Jing Liu, Qing-Yin Zeng
Journal: Molecular Biology and Evolution (2015)

Whole-genome duplication (WGD), or polyploidy, is a major force in plant genome evolution. A duplicate of all genes is present in the genome immediately following a WGD event. However, the evolutionary mechanisms responsible for the loss of, or retention and subsequent functional divergence of polyploidy-derived duplicates remain largely unknown. In this study we reconstructed the evolutionary history of the glutathione S-transferase (GST) gene family from the soybean genome, and identified 72 GST duplicated gene pairs formed by a recent Glycine-specific WGD event occurring approximately 13 Ma. We found that 72% of duplicated GST gene pairs experienced gene losses or pseudogenization, whereas 28% of GST gene pairs have been retained in the soybean genome. The GST pseudogenes were under relaxed selective constraints, whereas functional GSTs were subject to strong purifying selection. Plant GST genes play important roles in stress tolerance and detoxification metabolism. By examining the gene expression responses to abiotic stresses and enzymatic properties of the ancestral and current proteins, we found that polyploidy-derived GST duplicates show the divergence in enzymatic activities. Through site-directed mutagenesis of ancestral proteins, this study revealed that nonsynonymous substitutions of key amino acid sites play an important role in the divergence of enzymatic functions of polyploidy-derived GST duplicates. These findings provide new insights into the evolutionary and functional dynamics of polyploidy-derived duplicate genes.
Phase II trial of oral vinorelbine for the treatment of metastatic breast cancer in patients ≥65 years of age: an NCCTG study
Authors: M. Baweja, V.J. Suman, T.R. Fitch, J.A. Mailliard, A. Bernath, K.M. Rowland, S.R. Alberts, J.S. Kaur, E.A. Perez
Journal: Annals of Oncology (2006)
THE RELATION OF THE MENINGES AND CHOROID PLEXUS TO POLIOMYELITIC INFECTION
Authors: Simon Flexner, Harold L. Amoss
Journal: The Journal of Experimental Medicine (1917)

Among the mechanisms which defend the body from infection with the virus of poliomyelitis is the meningeal-choroid plexus complex, which normally is capable of excluding the circulating virus from the central nervous organs. The complex plays a part also in preventing infection from virus present upon the nasal mucosa. Aseptic fluids which irritate, inflame, or even slightly alter the integrity of the meninges and choroid plexus diminish or remove their protective function. Normal monkey or horse serum, isotonic salt solution, and Ringer's and Locke's solutions, when injected into the meninges, promote infection with the virus of poliomyelitis introduced into the blood, the nose, or the subcutaneous tissues. Simple lumbar puncture and the withdrawal and return of the cerebrospinal fluid in normal monkeys, hemorrhage having been absolutely avoided, do not promote infection with virus injected into the blood; while the replacement of the cerebrospinal fluid of one monkey with that of another does in some instances lead to infection. Simple lumbar puncture attended with even very slight hemorrhage opens the way for the passage of the virus from the blood into the central nervous tissues, and thus promotes infection. Hence, changes in the structure or function of the meningealchoroid plexus complex, too slight to be detected by chemical and cellular changes in the cerebrospinal fluid or by morphological alterations, suffice to diminish in an essential manner its protective powers. Of all the irritant fluids tested, immune serum alone injected into the meninges is not succeeded by infection from the virus introduced into the blood. The protective property of the immune serum is capable of overcoming the promoting action of normal monkey and horse serum and the other irritants mentioned. The importance first of the meningeal-choroid plexus complex in preventing infection with the virus of poliomyelitis, and next of immune serum in offsetting the disadvantages and dangers arising from defects in the mechanism is apparent, as is the bearing of the experiments reported on the serum therapy of epidemic poliomyelitis.
A Fluorescence <b> <i>in Situ</i> </b> Hybridization Map of 6q Deletions in Acute Lymphocytic Leukemia
Authors: Paul B. Sinclair, Amani Sorour, Mary Martineau, Christine J. Harrison, Wayne A. Mitchell, Elena O’Neill, Letizia Foroni
Journal: Cancer Research (2004)

Abstract With the objective of identifying candidate tumor suppressor genes, we used fluorescence in situ hybridization to map leukemia-related deletions of the long arm of chromosome 6 (6q). Twenty of 24 deletions overlapped to define a 4.8-Mb region of minimal deletion between markers D6S1510 and D6S1692 within chromosome 6 band q16. Using reverse transcription-PCR, we found evidence of expression in hematopoietic cells for 3 of 15 genes in the region (GRIK2, C6orf111, and CCNC). Comparison between our own and published deletion data singled out GRIK2 as the gene most frequently affected by deletions of 6q in acute lymphocytic leukemia (ALL). Sequence analysis of GRIK2 in 14 ALL cases carrying heterozygous 6q deletions revealed a constitutional and paternally inherited C to G substitution in exon 6 encoding for an amino acid change in one patient. The substitution was absent among 232 normal alleles tested, leaving open the possibility that heterozygous carriers of such mutations may be susceptible to ALL. Although low in all normal hematopoietic tissues, quantitative reverse transcription-PCR showed higher baseline GRIK2 expression in thymus and T cells than other lineages. Among T-cell ALL patients, 6q deletion was associated with a statistically significant reduction in GRIK2 expression (P = 0.0001). By contrast, elevated GRIK2 expression was measured in the myelomonocytic line THP-1 and in one patient with common ALL. Finally, we detected significant levels of GRIK2 expression in prostate, kidney, trachea, and lung, raising the possibility that this gene may be protective against multiple tumor types.