tbuckley/cabot-search huggingface dataset:
Evaluation des résultats du traitement endoscopique dans la prise en charge de l'empierrement et des gros calculs cholédocien
Authors: D Gargouri, I Snoussi, N Belhadj, A Ouekaa, H Elloumi, A Kochlef, A Kilani, M Romani, J Kharrat, A Ghorbel
Journal: Endoscopy (2007)

La lithiase résiduelle de la voie biliaire principale (VBP) constitue l'indication de choix de la sphinctérotomie endoscopique (SE). Le traitement endoscopique permet d'obtenir une clairance de la VBP dans plus de 90% des cas. Cependant, la présence d'un empierrement cholédocien ou d'un gros calcul peut en limiter ses résultats. Le but de ce travail est de dégager les résultats de la sphinctérotomie endoscopique (SE) dans la prise en charge des empierrements et/ou gros calculs de la VBP.
A Polymorphism in the P2X<sub>7</sub>Gene Increases Susceptibility to Extrapulmonary Tuberculosis
Authors: Suran L. Fernando, Bernadette M. Saunders, Ronald Sluyter, Kristen K. Skarratt, Hazel Goldberg, Guy B. Marks, James S. Wiley, Warwick J. Britton
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Genetic variation influences susceptibility to clinical tuberculosis (TB). Activation of the P2X(7) receptor on human macrophages induces killing of mycobacteria. We have identified polymorphisms in the P2X(7) gene that markedly reduce this killing.To determine if polymorphisms in P2X7 are associated with increased risk of TB, the prevalence of four polymorphisms was assessed in individuals from Southeast Asia, where the majority of patients with TB in our study originate. The association of these polymorphisms with clinical TB was subsequently investigated in two separate case-control cohorts and the function of P2X(7) was assessed in subjects from one cohort.Genotyping of P2X7 polymorphisms was performed from subjects in a nested case-control study of a longitudinal refugee cohort and a separate case-control study. The functional capacity of P2X(7) was investigated by measuring ATP-mediated mycobacterial killing and apoptosis.Only the 1513A-C polymorphism was present in Southeast Asians and the allele was associated with reduced killing of Mycobacterium tuberculosis. The 1513C allele was strongly associated with extrapulmonary, but not pulmonary, TB in the first (odds ratio, 3.8; 95% confidence interval, 1.6-9.0) and second cohorts (odds ratio, 3.7; 95% confidence interval, 1.7-8.0). ATP-mediated killing of mycobacteria was ablated in macrophages from subjects homozygous for the 1513C allele and significantly impaired in macrophages from heterozygous subjects. There was strong correlation between the degree of mycobacterial killing and ATP-induced apoptosis.The 1513C allele increases susceptibility to extrapulmonary TB, and this defect is associated with the reduction in the capacity of macrophages to kill M. tuberculosis.
Immunological effects and tolerability of a new fast updosed immunologically enhanced subcutaneous immunotherapy formulation with optimized allergen/adjuvant ratio
Authors: O. Pfaar, K. Jung, H. Wolf, E. Decot, J. Kleine‐Tebbe, L. Klimek, E. Wüstenberg
Journal: Allergy (2012)

Abstract Background Subcutaneous immunotherapy ( SCIT ) traditionally includes an updosing phase injecting increasing doses of allergen over a period of several weeks, followed by a maintenance phase. To establish shorter and more convenient updosing schedules, a fast updosed immunologically enhanced SCIT formulation has been developed by optimizing the allergen/adjuvant (aluminium hydroxide) ratio. Methods In a randomized, controlled, parallel‐group trial, patients with grass pollen induced rhinoconjunctivitis with/without asthma were treated with an immunologically enhanced SCIT formulation ( AVANZ , ALK , D enmark). The trial included updosing with five injections (300, 600, 3000, 6000 and 15 000 SQ +) injected either in weekly interval (Group 1) or in 3–4 days interval (Group 2) followed by two maintenance injections (15 000 SQ +), approximately 10 weeks treatment. The immunological effects (primary endpoint) and tolerability (secondary endpoint) of the updosing schedules were evaluated. Results Four hundred patients were treated (Group 1: 201, Group 2: 199). In both groups, an immunological response with statistically significant increases in levels of I g E ‐blocking factor, I g G 4 and I g E ( P &lt; 0.001), was induced from baseline to end of trial. Most frequently reported adverse events were local injection site reactions such as injection site swellings (Group 1: 30% of patients, Group 2: 41% of patients). Other frequently reported adverse events included systemic reactions (Group 1: 21% of patients, Group 2: 33% of patients), primarily mild to moderate allergic rhinitis and urticaria. Conclusions Fast updosed immunologically enhanced SCIT with an optimized allergen/adjuvant ratio induced significant immunological effects and had an acceptable safety profile. Clinical efficacy will be investigated in future clinical trials.
Inhibition of lymphoproliferation by hyperlipoproteinemic plasma.
Authors: C C Waddell, O D Taunton, J J Twomey
Journal: Journal of Clinical Investigation (1976)

Plasma for patients with primary type IV or V hyperlipoproteinemia inhibited [3H]thymidine incorporation by cultured mononuclear leukocytes. This previously unreported abnormality affected mononuclear leukocytes from patients with type IV or V hyperlipoproteinemia and from normal subjects. Patient cells incorporated [3H]thymidine normally when washed and incubated in medium containing normal plasma. Both spontaneous incorporation and stimulated incorporation in response to various mitogens and antigens were inhibited. The inhibitory effect was identified with the chylomicron and very low density lipoprotein fractions isolated from plasma and was concentration-dependent. Lectin used to stimulate cultured cells and [3H]thymidine used to measure responses were not bound to the lipoproteins in appreciable amounts. [3H]-Thymidine incorporation correlated well with morphologic evidence of lymphoproliferation. The mechanism of the inhibitory effect of type IV or V hyperlipoproteinemic plasma upon the response tested was not identified by may be related to interaction between lipoproteins and the cell membranes. We suggest that these lipoproteins may also interfere with the function of other cells.
Export performance of oilseeds and its determinants in Ethiopia
Authors: Hailegiorgis Biramo Allaro
Journal: Journal of Clinical Oncology (2011)

This research examines export performance of oilseeds in Ethiopia using macroeconomic time series data from annual reports of NBE (National Bank of Ethiopia) over the period 1974 to 2009. Analyses of oilseeds export performance through time divulges that the country has not yet diversified the commodity composition and structure of its export, in that its export earnings depend on only a few agricultural products. The findings of the study reveal that the country needs to break away from it’s heavily depends on traditional export commodities for which it is a marginal exporter, thus a price taker. The results also show that the estimated coefficients of real output (Ry) and nominal exchange rate (e) are statistically significant. This discloses that real output and nominal exchange rate have positive brunt on the export performance of oilseeds in Ethiopia.

	 

	Key words: Africa, Ethiopia, export performance, oilseeds.
Abstract 4045: Intragenic ATM methylation in peripheral blood DNA as a biomarker of breast cancer risk
Authors: Kevin Brennan, Montserrat Garcias-Closas, Nicholas Orr, Olivia Fletcher, Michael Jones, Alan Ashworth, Anthony Swerdlow, Elio Riboli, Paolo Vineis, Mirren Dorronsosro, Francoise Clavel, Salvatore Panico, N. Charlotte Onland-Moret, Dimitrios Trichopoulos, Rudolf Kaaks, Kay-Tee Khaw, Robert Brown, James M. Flanagan
Journal: Cancer Research (2012)

Abstract DNA methylation is an important epigenetic modification that could affect cancer risk through direct effects on disease, and/or mediating effects of genetic and environmental factors. Global and gene-specific DNA methylation levels in white blood cells (WBC) have been related to risk of breast and other cancers, however, evidence is generally weak. We analysed WBC DNA methylation of two ATM intragenic loci (ATMmvp2a and ATMmvp2b) and genome-wide DNA methylation in LINE1 repetitive elements in three breast cancer studies with pre-diagnostic blood samples. Studies included a case-control study with cases derived from a prospective cohort of high-risk breast cancer families (KConFab), and nested case-control studies in two prospective cohorts: the Breakthrough Generations Study (BGS) and the European Prospective Investigation into Cancer and Nutrition (EPIC). Total sample size was 640 incident cases of invasive breast cancer and 741 controls. Bisulphite pyrosequencing was used to quantify methylation in WBC DNA. Quintile analyses of the combined data for ATMmvp2a showed an increased risk of breast cancer limited to women in the highest quintile of methylation (OR =1.89 (1.36-2.64), p= 1.64x10-4). We found no significant differences in estimates across studies, however, the largest differences in ATMmvp2a methylation levels were observed for familial cases in KConFab compared to controls. We observed no significant differences in LINE1 or ATMmvp2b methylation levels between cases and controls. These results indicate that WBC DNA methylation levels at ATM could be a marker of breast cancer risk and further support the pursuit of epigenome-wide association studies in peripheral blood DNA methylation. Funding: Breast Cancer Campaign Fellowship and Cancer Research UK Program C536/A6689. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4045. doi:1538-7445.AM2012-4045
Education in Ambulatory Care — Financing is One Piece of the Puzzle
Authors: James D. Bentley, Richard M. Knapp, Robert G. Petersdorf
Journal: New England Journal of Medicine (1989)

Medical education at both the undergraduate and graduate levels is based on the premise that students and residents learn best by participating, under supervision, in the day-to-day care of patients. Historically, most of this clinical education has taken place on the inpatient services of teaching hospitals. Although a few visionary medical educators have argued that inpatient training should be complemented by a meaningful education in ambulatory care, the movement to increase the ambulatory care component of training grew little in the 1960s and 1970s. In fact, some senior faculty members have observed that there was more education in ambulatory care . . .
Esophageal Varices in Adult Patients with Polycystic Kidney and Liver Disease
Authors: Edmund DelGuercio, James Greco, Kwan E. Kim, Joel Chinitz, Charles Swartz
Journal: New England Journal of Medicine (1973)

IN the cases presented below, two middle-aged patients had polycystic kidneys and esophageal varices secondary to polycystic liver disease. One patient died after hemorrhage, which might have been better treated if the index of suspicion for bleeding esophageal varices had been greater.Case ReportsCase 1. A 57-year-old white woman with polycystic kidney and liver disease diagnosed 5 years earlier was admitted to the hospital in shock, vomiting blood, after having become hypertensive during home dialysis. Except for the physical findings of shock and a liver edge palpable at 5 to 6 cm below the right costal margin, physical examination . . .
Abstract C3: Receptor tyrosine kinase(s) modulate androgen receptor signaling in castrate-resistant prostate cancer
Authors: Ankur Sharma, Steven P. Balk
Journal: Cancer Research (2012)

Abstract This study is designed to investigate the mechanisms underlying effects of receptor tyrosine kinase(s) on androgen receptor (AR) in castrate resistant prostate cancer (CRPC). Hormone ablation therapies remain the mainstay of treatment for metastatic prostate cancer, but disease eventually reoccurs as CRPC where AR has been reactivated despite castrate androgen levels. Amongst ways that facilitate restoration of AR activity in CRPC, receptor tyrosine kinases (RTKs) have been reported to activate AR and induce CRPC growth through as of yet unclear mechanisms. Our investigative studies revealed that lapatinib (inhibits Her2/Her3 heterodimer and EGFR) treatment inhibited endogenous AR expression and activity in C4-2 CRPC cells. Lapatinib induced destabilization and proteosomal degradation of the AR with minimal effect on AR mRNA transcript levels. To further investigate if this effect was dependent on Her2/Her3 or EGFR, an EGFR inhibitor erlotinib was used. It produced modest effects on AR, indicating that effects of lapatinib are predominantly through Her2/Her3. As AKT, a serine/threonine kinase, functions downstream of Her2/Her3, we then directly investigated the effects of AKT on AR in CRPC cells. Our studies revealed that inhibition of AKT decreased endogenous AR expression through proteosomal degradation. Moreover AKT inhibition decreased endogenous AR activity and C4-2 cell survival, indicating that AKT positively regulates AR and CRPC growth. As many groups have previously reported conflicting effects of AKT on AR, we are now focused on the molecular basis for this positive effect of AKT on AR expression and function in CRPC. Preliminary studies indicate that AKT inhibition may be decreasing levels of heat shock proteins (Hsp70, Hsp90) that serve as chaperones for cytoplasmic AR, and may by another mechanism be decreasing AR accumulation in the nucleus. We anticipate that these studies will provide a clear mechanistic view of effects of RTKs and AKT on AR in CRPC and highlight molecules that may be targeted for novel therapeutic interventions. Citation Format: Ankur Sharma, Steven P. Balk. Receptor tyrosine kinase(s) modulate androgen receptor signaling in castrate-resistant prostate cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C3.
Hypersensitivity Reactions to Oxaliplatin: Outcomes of Premedication and Desensitization
Authors: Suh-Young Lee, Mi-Yeong Kim, Min-Hye Kim, Woo-Jung Song, Hye-Ryun Kang, Kyung-Up Min, Sang Heon Cho
Journal: Journal of Allergy and Clinical Immunology (2013)
Retrospective correlation of clinical and histologic findings of 189 exchanged kidneys
Authors: Norman Ende, James C. Pierce, Frederic Westervelt, Melville Williams, H.M. Lee, Delford L. Stickel, Duane G. Wombolt, Joseph T. Chandler, Keith H. Johnson, Charles B. Currier, Jimmy A. Light, Agnes M. Barry
Journal: Kidney International (1979)
Points: Sequelae and support after termination of pregnancy for fetal malformation
Authors: N. C Smith, M J Whittle
Journal: BMJ (1985)

During a critical period in the developing mammalian brain, there is a major switch in the nature of GABAergic transmission from depolarizing and excitatory, the pattern of the neonatal brain, to hyperpolarizing and inhibitory, the pattern of the mature brain. This switch is believed to play a major role in determining neuronal connectivity via activity-dependent mechanisms. The GABAergic developmental switch may also be particularly vulnerable to dysfunction leading to seizure disorders. The developmental GABA switch is mediated primarily by KCC2, a neuronal K<sup>+</sup>/Cl<sup>−</sup> cotransporter that determines the intracellular concentration of Cl<sup>−</sup> and, hence, the reversal potential for GABA. Here, we report that <i>kazachoc</i> (<i>kcc</i>) mutations that reduce the level of the sole K<sup>+</sup>/Cl<sup>−</sup> cotransporter in the fruitfly <i>Drosophila melanogaster</i> render flies susceptible to epileptic-like seizures. <i>Drosophila</i> kcc protein is widely expressed in brain neuropil, and its level rises with developmental age. Young <i>kcc</i> mutant flies with low kcc levels display behavioral seizures and demonstrate a reduced threshold for seizures induced by electroconvulsive shock. The <i>kcc</i> mutation enhances a series of other <i>Drosophila</i> epilepsy mutations indicating functional interactions leading to seizure disorder. Both genetic and pharmacological experiments suggest that the increased seizure susceptibility of <i>kcc</i> flies occurs via excitatory GABAergic signaling. The <i>kcc</i> mutants provide an excellent model system in which to investigate how modulation of GABAergic signaling influences neuronal excitability and epileptogenesis.
Abstract 771: Changes in the subcellular pharmacology of cisplatin, in response to treatment of cells with an anti-Gli1 shRNA
Authors: Jason C. Fain, Lauren Amable, Elaine Gavin, Eddie Reed
Journal: Cancer Research (2012)

Abstract We have demonstrated that a specific anti-Gli1 shRNA can ablate Gli1 in A2780-CP70 cells, with no effect on Gli2. Upon ablation of Gli1, platinum-DNA adduct repair is inhibited, along with inhibition of ERCC1, XPD, XRCC1, and c-jun. We therefore asked the question of whether there were other subcellular pharmacologic effects, with respect to cisplatin, in these cells. We assessed total cellular accumulation of cisplatin under three conditions: pretreatment with the anti-Gli1 shRNA; pretreatment with a scrambled shRNA control; and pretreatment with Fugene which was used as the transfection agent. We also assessed platinum-DNA adduct levels, at the same time points that total cellular accumulation was measured. All platinum measurements were performed by AAS with Zeeman background correction. In each independent experiment (n=4), we plated cells on day 1; transfected with shRNA 16-18 hours later; treated with cisplatin for 1 hour at 30 μM (the IC50 under these conditions); and, harvested cells at different time points. Those time points were: zero hours (immediately after the 1 hour cisplatin treatment); 6 hours later; or 12 hours later. At zero hours, measured levels of pt-DNA damage were equivalent between the three conditions. At zero hours, measured levels of total cellular platinum were reduced by 40-45% in anti-Gli1 treated cells; suggesting inhibition of cellular accumulation. At 6 hours, scrambled controls showed reductions in total cellular platinum by ∼40%, demonstrating excretion of cisplatin. This is consistent with previously published work (JCI 1991). Cells treated with anti-Gli1 shRNA showed no reductions in total cellular platinum at 6 hrs, nor at 12 hrs; suggesting inhibition of the processes by which cells may eliminate this drug. Cells treated with anti-Gli1 shRNA showed statistically significant inhibition in platinum-DNA adduct repair, as compared to cells treated with scrambled shRNA. Control cells repaired 67.5% of pt-DNA adducts over 12 hours; as compared to 23.7% repair in cells treated with anti-Gli1 shRNA; p2=0.015. We conclude that ablation of Gli1 in cisplatin-resistant A2780-CP70 human ovarian cancer cells, has at least three effects on the subcellular pharmacology of cisplatin. There is inhibition of processes that determine: cellular uptake of drug; cellular elimination of drug; and platinum-DNA adduct repair. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 771. doi:1538-7445.AM2012-771
Cardiomyopathy of Overload
Authors: Franklin H. Epstein, Arnold M. Katz
Journal: New England Journal of Medicine (1990)

MORE than 80 years ago, Sir James MacKenzie1 noted: "The more I study the symptoms of heart failure, and the more I reflect on the part played by the heart muscle, the more convinced I am that... heart failure is due to the exhaustion of the reserve force of the heart muscle." Except for the cardiac glycosides, however, therapy for congestive heart failure generally has focused on the systemic signs and symptoms that appear when the failing heart becomes unable to meet the hemodynamic demands of the body, rather than on abnormalities in the heart muscle itself, which both cause . . .
CD28-independent Induction of T Helper Cells and Immunoglobulin Class Switches Requires Costimulation by the Heat-stable Antigen
Authors: Yan Wu, Qunmin Zhou, Pan Zheng, Yang Liu
Journal: The Journal of Experimental Medicine (1998)

It is well established that B7-CD28/CTLA4 interactions play an important role in the induction of T helper cells for T-dependent antibody responses. However, targeted mutation of CD28 does not significantly affect production of IgG and activation of CD4 T helper cells in response to infections by some viruses and nematode parasites. To test whether the CD28-independent induction of Ig class switches requires costimulation by the heat-stable antigen (HSA), we compared T helper cell induction and antibody response in mice deficient for either HSA, CD28, or both genes. We found that after immunization with KLH-DNP, mice deficient for both CD28 and HSA lack DNP-specific IgA and all subtypes of IgG. This deficiency corresponds to a reduced number of effector helper T cells that rapidly produce IL-2, IL-4, and IFN-γ after in vitro stimulation with carrier antigen KLH. In contrast, priming of T helper cells and Ig class switch are normal in mice deficient with either HSA or CD28 alone. IgM responses are not affected by any of these targeted mutations. These results demonstrate that CD28-independent induction of T helper cells and Ig class-switches requires costimulation by the HSA.
Beneficial Impact of Ramipril on Left Ventricular Hypertrophy in Normotensive Nonalbummuric NIDDM Patients
Authors: Flemming S Nielsen, Asako Sato, Samir Ali, Lise Tarnow, Ulla M Smidt, Jens Kastrup, Hans-Henrik Parving
Journal: Diabetes Care (1998)

OBJECTIVE To evaluate the effect of the ACE inhibitor ramipril as compared with placebo on left ventricular mass index (LVMl) in normotensive, nonalbuminuric NIDDM patients with left ventricular hypertrophy (LVH). Patients with NIDDM are characterized by excessive cardiovascular morbidity and mortality, and LVH, an independent risk factor for cardiac events, is often present in NIDDM patients. RESEARCH DESIGN AND METHODS A total of 38normotensive, nonalbuminuric (albuminuria &amp;lt;100 mg/24 h) NIDDM patients with LVH (LVMl /131 g/m2in men and &amp;gt;100 g/m2 in women) were enrolled in a 6-month randomized, double-blind parallel group study to compare the effects of ramipril (5 mg/day) with placebo on LVMl (echocardiography, Vingmed CFM725, Diasonics Sonotron), QTC dispersion determined as the interlead variation in QTC interval on standard electrocardiogram (ECG), and 24-h ambulatory blood pressure (A&amp;D TM2420, Tokyo, Japan). A total of 16 ramipril (10 men, 60 ± 9 years [mean ± SD]) and 15 placebo-treated (8 men, 55 ± 10 years) patients completed the study, and their data are presented. RESULTS Ambulatory blood pressure was almost identical at baseline (132/76 ± 3/1 vs. 133/74 ± 5/2 mmHg [mean ± SEM]) and remained stable during follow-up (134/76 ± 3/1 vs. 136/74 ± 6/2 mmHg) in the ramipril and placebo group, respectively. LVMl was comparable at baseline (137.1 ± 7.0 vs. 129.6 ± 3.7 g/m2) in the ramipril and placebo group, respectively, and decreased significantly more in the ramipril group as compared with the placebo group (17.6 ± 3.0 vs. 5.7 ± 4.6 g/m2, respectively, 11.9 [0.7–23.1] g/m2, mean difference [95% CI]; P = 0.037). QTC dispersion was comparable at baseline (60.2 [5.5] vs. 64.1 [6.5] ms) and did not change significantly during follow-up: −2.5 [7.0] vs. −12.2 [9.5] ms; mean difference 9.8 (−14.2 to 33.8 ms) in the ramipril and placebo group, respectively. CONCLUSIONS Ramipril induces regression of LVH in normotensive, nonalbuminuric NIDDM patients, independent of reduction in systemic blood pressure.