tbuckley/cabot-search huggingface dataset:
MicroRNAs and Toll-like Receptor/Interleukin-1 Receptor Signaling
Authors: Anthony Virtue, Hong Wang, Xiao-feng Yang
Journal: Journal of Hematology & Oncology (2012)

Abstract The discovery of miRNAs has revolutionized the way we examine the genome, RNA products, and the regulation of transcription and translation. Their ability to modulate protein expression through mRNA degradation and translation repression resulted in avid scientific interest in miRNAs over the past decade. This research has led to findings that indicate miRNAs can regulate an array of cellular functions such as cellular apoptosis, proliferation, differentiation, and metabolism. Specifically, the capability of miRNAs to finely-tune gene expression naturally lends itself to immune system regulation which requires precise control for proper activity. In fact, abnormal miRNAs expression is often seen with inflammatory disorders like rheumatoid arthritis, systemic lupus erthematosus, experimental autoimmune encephalomyelitis, and inflammatory cancers. As a result, research investigating miRNAs modulation of immune cell proliferation, differentiation, and cellular signaling has yielded fruitful results. Specifically, in this review, we will examine the impact of miRNAs on toll-like receptor (TLRs) and interleukin-1β (IL-1β) signaling, which are integral in the proper functioning of the innate immune system. These signaling pathways share several key downstream signaling adaptors and therefore produce similar downstream effects such as the production of pro-inflammatory cytokines, chemokines, and interferons. This review will examine in depth the specific interactions of miRNAs with receptors, adaptor molecules, and regulator molecules within these cellular pathways. In addition, we will discuss the modulation of miRNAs’ expression by TLR and IL-1R signaling through positive and negative feedback loops.
US study shows that folic acid fortification decreases neural tube defects
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

The incidence of neural tube defects in infants fell by about a third in some ethnic groups when the United States gradually increased enrichment of grain products with folic acid in the 1990s, a study has found ( Pediatrics 2005;116:580-6).

The March of Dimes, a charity active in efforts to prevent birth defects, has called for a doubling of fortification of food with folic acid to further reduce neural tube defects. In 1996 the charity recommended that grain products should be enriched with 350 micrograms for each 100 g of grain. Two paediatricians argue in a commentary to the paper that the concentration of folic acid in grain products in the US should be at least doubled from the current level of 140 micrograms per 100 g of grain and that vitamin B-12 should also be added to flour ( Pediatrics 2005:116:753-5). The paediatricians argued that such fortification was worthwhile, because fears that folic acid supplementation might mask vitamin B-12 deficiency in elderly people were based on a misunderstanding of the biochemistry involved.

The paper's lead author, Sonja Rasmussen, told the BMJ that in the US about 3000 pregnancies a year were affected by neural tube defects such as …
Gastrin response to meals of different composition in normal subjects.
Authors: E L Blair, J R Greenwell, E R Grund, J D Reed, D J Sanders
Journal: Gut (1975)

The serum gastrin responses and the integrated gastrin responses to eating three meals of very different composition were studied in the same normal subjects on different days. Two meals, a milk meal of 500 ml, and a breakfast of eggs, toast, butter, marmalade, fruit juice and coffee, were eaten at breakfast time. The serum gastrin responses to these meals were compared and contrasted with the concentrations observed when the subjects fasted over the same time of day. A steak meal was eaten at lunch time. There were no significant differences between the mean serum gastrin concentrations to the three meals but each meal produced a significant increase in serum gastrin above fasting levels. When the prefeeding gastrin concentration was subtracted from the gastrin responses then the integrated responses to the steak meal were greater than those to either of the breakfast meals. Considerable variability in response to any one meal was observed within the group of subjects, but those subjects who produced high serum gastrin concentrations to one meal did so to the others. Conversely, at low response to one meal was reflected in low responses to the other two meals. Fasting serum gastrin concentration was correlated with the age of the subject. Repeatability of the response to one meal was tested in two subjects who ate the same meal on four separate occasions showing their responses to be repeatable.
A male with a pelvic mass
Authors: K T Kjossev
Journal: Gut (2004)

Background: Anti-Saccharomyces cerevisiae antibodies (ASCA) are a specific but only moderately sensitive diagnostic marker for Crohn's disease.We sought to explore the role of ASCA as a prognostic marker for aggressive disease phenotype in Crohn's disease.Aims: To determine the role of ASCA status as a risk factor for early surgery in Crohn's disease.Subjects: We performed a case control study in a cohort of patients, newly diagnosed with Crohn's disease, between 1991 and 1999.All patients were followed for at least three years.Case subjects (n = 35) included those who had major surgery for Crohn's disease within three years of diagnosis.Controls (n = 35) included patients matched to cases for age, sex, disease location, and smoking status, and who did not undergo major surgery for Crohn's disease within three years of diagnosis.Methods: Blinded assays were performed on serum for ASCA (immunoglobulin (Ig)A and IgG).A paired analysis of cases-controls was performed to test for the association between ASCA status and risk of early surgery.Results: ASCA IgA was strongly associated with early surgery (odds ratio (OR) 8.5 (95% confidence interval (CI) 2.0-75.9);p = 0.0013).ASCA IgG+ and ASCA IgG+/IgA+ patients were also at increased risk for early surgery (OR 5.5 (95% CI 1.2-51.1),p = 0.0265; and OR 5.0 (95% CI 1.1-46.9),p = 0.0433, respectively).The association between ASCA and early surgery was evident in patients requiring surgery for ileal or ileocolonic disease.Conclusions: Patients with Crohn's disease who are positive for ASCA IgA, IgG, or both, may define a subset of patients with Crohn's disease at increased risk for early surgery.
Glucosylceramide Synthase Blockade Down-Regulates P-Glycoprotein and Resensitizes Multidrug-Resistant Breast Cancer Cells to Anticancer Drugs
Authors: Valérie Gouazé, Yong-Yu Liu, Carlton S. Prickett, Jing Y. Yu, Armando E. Giuliano, Myles C. Cabot
Journal: Cancer Research (2005)

Abstract Overexpression of glucosylceramide synthase (GCS), a pivotal enzyme in glycolipid biosynthesis, contributes to cancer cell resistance to chemotherapy. We previously showed that transfection of doxorubicin-resistant MCF-7-AdrR cells with GCS antisense restored cell sensitivity to doxorubicin and greatly enhanced sensitivity to vinblastine and paclitaxel. In that study, doxorubicin promoted generation of ceramide in MCF-7-AdrR/GCS antisense cells; the present study implicates factors in addition to ceramide that augment sensitivity to chemotherapy. Although GCS antisense cells showed enhanced ceramide formation compared with MCF-7-AdrR when challenged with paclitaxel, GCS antisense cells also showed a 10-fold increase in levels of intracellular drug (paclitaxel and vinblastine). In addition, transfected cells had dramatically decreased expression (80%) of P-glycoprotein and a 4-fold decrease in the level of cellular gangliosides. Chemical inhibition of GCS produced the same effects as antisense transfection: exposure of MCF-7-AdrR cells to the GCS inhibitor 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP, 5.0 μmol/L, 4 days) decreased ganglioside levels, restored sensitivity to vinblastine, enhanced vinblastine uptake 3-fold, and diminished expression of MDR1 by 58%, compared with untreated controls. A similar effect was shown in vinblastin-resistant KB-V0.01 cells; after 7 days with PPMP (10 μmol/L), MDR1 expression fell by 84% and P-glycoprotein protein levels decreased by 50%. MCF-7-AdrR cells treated with small interfering RNAs to specifically block GCS also showed a dramatic decrease in MDR1 expression. This work shows that limiting GCS activity down-regulates the expression of MDR1, a phenomenon that may drive the chemosensitization associated with blocking ceramide metabolism. The data suggest that lipids play a role in the expression of multidrug resistance.
Effects of Glucose on Bicarbonate Reabsorption in the Dog Kidney
Authors: Wadi N. Suki, Christy S. Hebert, Bobby J. Stinebaugh, Manuel Martinez-Maldonado, Garabed Eknoyan
Journal: Journal of Clinical Investigation (1974)

The effects of glucose on renal bicarbonate reabsorption were investigated in the dog. The infusion of small amounts of glucose calculated to slightly exceed the renal threshold for glucose absorption increased bicarbonate reabsorption in bicarbonate loaded dogs. Galactose in similar doses also increased the reabsorption of filtered bicarbonate. This effect is not due to insulin secretion since insulin alone did not alter bicarbonate reabsorption and the infusion of glucose into alloxan-diabetic dogs given a steady infusion of insulin also enhanced bicarbonate reabsorption. It is more likely that the increased tubular reabsorption of glucose, secondary to an increased filtered load, resulted in the increase in bicarbonate reabsorption since phlorizin reversibly inhibits the effect of glucose.
Consultation length in general practice: cross sectional study in six European countries
Authors: M. Deveugele
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objectives</b>: To compare determinants of consultation length discussed in the literature with those found in consultations with general practitioners from different European countries; to explore the determinants of consultation length, particularly the effect of doctors9 and patients9 perceptions of psychosocial aspects. <b>Design</b>: Analysis of videotaped consultations of general practitioners from the Eurocommunication study and of questionnaires completed by doctors and by patients. <b>Setting</b>: General practices in six European countries. <b>Participants</b>: 190 general practitioners and 3674 patients. <b>Results</b>: In a multilevel analysis with three levels (country, general practitioner, and patient), country and doctor variables contributed a similar amount to the total variance in consultation length (23% and 22%, respectively) and patient variables accounted for 55% of the variance. The variables used in the multilevel analysis explained 25% of the total variation. The country in which the doctor practised, combined with the doctors9 variables, was as important for the variance in consultation length as the variation between patients. Consultations in which psychosocial problems were considered important by the doctor and the patient lasted longer than consultations about biomedical problems only. The doctor9s perception had more influence in this situation than the patient9s. Consultation length is influenced by the patients9 sex (women got longer consultations), whether the practice was urban or rural, the number of new problems discussed in the consultation (the more problems the longer the consultation), and the patient9s age (the older the patient the longer the consultation). As a doctor9s workload increased, the length of consultations decreased. The general practitioner9s sex or age and patient9s level of education were not related to the length of consultation. <b>Conclusion</b>: Consultation length is determined by variables related to the doctor and the doctor9s country as well as by those related to patients. Women consulting in an urban practice with problems perceived as psychosocial have longer consultations than other patients.
Targeting Regulatory T Cells in Cancer
Authors: William L. Byrne, Kingston H.G. Mills, James A. Lederer, Gerald C. O'Sullivan
Journal: Cancer Research (2011)

Infiltration of tumors by regulatory T cells confers growth and metastatic advantages by inhibiting antitumor immunity and by production of receptor activator of NF-κB (RANK) ligand, which may directly stimulate metastatic propagation of RANK-expressing cancer cells. Modulation of regulatory T cells can enhance the efficacy of cancer immunotherapy. Strategies include depletion, interference with function, inhibition of tumoral migration, and exploitation of T-cell plasticity. Problems with these strategies include a lack of specificity, resulting in depletion of antitumor effector T cells or global interruption of regulatory T cells, which may predispose to autoimmune diseases. Emerging technologies, such as RNA interference and tetramer-based targeting, may have the potential to improve selectivity and efficacy.
MORPHOLOGIC VARIATION IN PNEUMOCOCCUS
Authors: Robert Austrian
Journal: The Journal of Experimental Medicine (1953)

The problem of morphologic variation in pneumococcus has been reviewed and the desirability of studying such variation through an examination of bacterial cells rather than of bacterial colonies has been pointed out. To further this objective, a new terminology to describe the morphologic variants of pneumococcus, potentially applicable to other bacterial species, has been proposed. A hitherto undefined morphologic variant of pneumococcus, the filamentous capsulated (fil+ S+) variant, has been defined and its relationship to the three previously recognized non-filamentous capsulated (fil- S+), nonfilamentous non-capsulated (fil- S-), and filamentous non-capsulated (fil+ S-) variants has been presented.
Re-injury following acute posterior thigh injuries in elite track and field athletes
Authors: T Isinkaye, N Malliaropoulos, K Tsitas, N Maffulli
Journal: British Journal of Sports Medicine (2011)

Introduction Hamstring muscle strains can lead to an increased risk of reinjury. We recently proposed a clinical classification system for acute hamstring strains. We studied the effect of the grade of the initial injury on the subsequent risk of reinjury. We hypothesised that there would be no difference in reinjury rate between acute low grade (grade I and II) and high grade (III and IV) hamstring muscle strains. Methods Between 1994 and 2007, we managed 165 elite Greek track and field athletes with acute, first-time unilateral hamstring muscle strains. Using a validated classification system, strains were classified into four grades (I, II, III and IV) based on objective clinical criteria (knee active range of motion deficit at 48 h). The same rehabilitation protocol was prescribed to all athletes and the rate of reinjury was recorded during the following 24 months. Results At follow-up, 23 of the 165 athletes (13.9%) had experienced a second hamstring muscle strain. Of the 75 athletes presenting with a grade I injury, 7 (9.3%) had experienced a recurrence after 24 months. Of the 58 athletes presenting a grade II injury, 14 (24.1%) experienced a recurrence. Of the 26 athletes presenting a grade III injury, 2 (7.7%) experienced a recurrence and of the 6 athletes presenting a grade IV injury, none had experienced a recurrence after 24 months. Conclusions According to our classification, athletes with acute grade II hamstring muscle strains experience a higher risk of reinjury than athletes with grade I or grade III strains. Low grade hamstring muscle sprains lead to a higher risk of reinjury than high grade hamstring muscle sprains. Objective clinical findings can accurately predict the risk of reinjury following acute hamstring muscle strains.
Diagnostic dilatation and curettage.
Authors: J Giles
Journal: BMJ (1993)

Analysis of obstetric outcome at Coombe Lying-In Hospitalfor 1992.Figures are numbers (percentages) of women Primiparous Multiparous All women women women (n=2457) (n=4029) (n=6486) Prolonged labour 244 (9 9) 83 (2 1) 327 (5 0) Epidural analgesia 1710 (69-6) 1237 (30-7) 2947 (454) Episiotomy 1077 (43 8) 420 (10-4) 1497 (23-1) Forceps delivery
Significance of deeper molecular responses in patients with chronic myeloid leukemia in early chronic phase treated with tyrosine kinase inhibitors
Authors: Lorenzo Falchi, Hagop M. Kantarjian, Xuemei Wang, Dushyant Verma, Alfonso Quintás‐Cardama, Susan O'Brien, Elias J. Jabbour, Farhad Ravandi‐Kashani, Gautam Borthakur, Guillermo Garcia‐Manero, Srdan Verstovsek, Jan A. Burger, Raja Luthra, Jorge E. Cortes
Journal: American Journal of Hematology (2013)

Most patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with tyrosine kinase inhibitors (TKI) achieve complete cytogenetic response (CCyR). An increasing number of patients also achieve deep molecular responses (MR). We determined the frequency and significance of deep MR after TKI therapy for CML in CP. MR included: major molecular response (MMR), MR4, MR4.5, and undetectable transcripts (UND), i.e., BCR-ABL/ABL of ≤0.1, ≤0.01, ≤0.0032%, and undetectable transcripts, respectively. Four hundred eighty-three patients received imatinib 400 mg/day (IM400, 71, July 2000 to April 2001), imatinib 800 mg/day (IM800, 204, June 2001 to July 2005), nilotinib (106, July 2005 to date), or dasatinib (102, November 2005 to date). UND rates at 36 months were 18.1, 30.6, 29.2, and 28.6%, respectively. Patients achieving UND have superior transformation-free survival (TFS) and overall survival (OS) versus those obtaining ≤MMR, but not other MR levels. At the 18- and 24-month landmark analysis, patients achieving UND have no advantage in TFS and OS compared to those achieving a lesser degree of MR. Among patients achieving MR4.5, those who maintain it for ≥2 years (susMR4·5) have no additional benefit in TFS or OS. Most patients with early CP CML receiving TKI achieve MMR. BCR-ABL transcripts become undetectable in a significant fraction of them. Deeper MR at 18 or 24 months are not associated with a benefit in TFS or OS. Furthermore, achieving susMR4·5 does not appear to further reduce the risk of transformation or death.
H-Y Incompatibility Predicts Short-Term Outcomes for Kidney Transplant Recipients
Authors: S. Joseph Kim, John S. Gill
Journal: Journal of the American Society of Nephrology (2009)

A recent report suggested that female recipients of male deceased-donor kidneys are at increased risk for graft failure because of H-Y antigen mismatch. In an attempt to confirm and extend these results, we studied all adult recipients of deceased-donor kidney transplants from 1990 through 2004 in the US Renal Data System. Compared with all other gender combinations, female recipients of male donor kidneys had a 12% increased risk for graft failure at 1 yr (hazard ratio 1.12; 95% confidence interval 1.05 to 1.19) but no excess risk at 10 yr (hazard ratio 1.03; 95% confidence interval 0.98 to 1.07). We observed a similar pattern of short- and long-term risk for both death-censored graft failure and mortality. The main results were consistent across several prespecified patient subgroups and were robust to sensitivity analyses. In conclusion, compared with other recipient-donor gender combinations, female recipients of male donor kidney transplants in the United States have an increased short-term risk but not long-term risk for adverse outcomes.
Survival in Patients With Severe Ischemic Cardiomyopathy Undergoing Revascularization Versus Medical Therapy
Authors: Deborah H. Kwon, Rory Hachamovitch, Zoran B. Popovic, Randall C. Starling, Milind Y. Desai, Scott D. Flamm, Bruce W. Lytle, Thomas H. Marwick
Journal: Circulation (2012)

Background— The value of assessment of viability as a predictor of surgical revascularization benefit in ischemic cardiomyopathy has recently been questioned in a large trial. We sought to determine whether the contribution of viability as myocardial scar burden (SB) to predict revascularization outcomes could be modulated by end-systolic volume index (ESVi). Methods and Results— Delayed hyperenhancement–MRI was obtained in 450 patients with ≥70% stenosis in ≥1 epicardial coronary artery (75% men; median age, 62.8±10.7 years; mean left ventricular ejection fraction, 23±9%; mean ESVi, 115±50 mL) from 2002 to 2006. SB was quantified as scar percentage (infarcted mass/total left ventricular mass). Subsequent surgical revascularization was performed in 245 (54%) patients and subsequent percutaneous coronary interventions were performed in 28 (6%) patients. A propensity score was developed for revascularization. Cox proportional hazards models of all-cause mortality were used for risk adjustment. Over a mean follow-up of 5.8±2.7 years, 186 (41%) deaths occurred. After adjusting for prior revascularization, sex, diabetes, age, use of cardiac resynchronization therapy, implantable cardioverter defibrillator, mitral regurgitation, and mitral valve procedures; an interaction between scar percentage and ESVi ( P =0.016) and an interaction between post-MRI revascularization and ESVi ( P =0.0017) were independently associated with mortality. ESVi demonstrated a significant interaction with revascularization and female sex, such that enhanced survival was associated with ESVi. ESVi also showed an interaction with SB; better survival was associated with lower volumes and less scar. Conclusions— ESVi and SB provide independent, incremental prognostic value in patients with severe ischemic cardiomyopathy. The risk associated with SB should not be assessed in isolation.
Cardiac Sympathetic Dysinnervation in Diabetes
Authors: Martin J. Stevens, David M. Raffel, Kevin C. Allman, Firat Dayanikli, Edward Ficaro, Tracy Sandford, Donald M. Wieland, Michael A. Pfeifer, Markus Schwaiger
Journal: Circulation (1998)

Regional cardiac sympathetic hyperactivity predisposes to malignant arrhythmias in nondiabetic cardiac disease. Conversely, however, cardiac sympathetic denervation predicts increased morbidity and mortality in severe diabetic autonomic neuropathy (DAN). To unite these divergent observations, we propose that in diabetes regional cardiac denervation may elsewhere induce regional sympathetic hyperactivity, which may in turn act as a focus for chemical and electrical instability. Therefore, the aim of this study was to explore regional changes in sympathetic neuronal density and tone in diabetic patients with and without DAN.PET using the sympathetic neurotransmitter analogue 11C-labeled hydroxyephedrine ([11C]-HED) was used to characterize left ventricular sympathetic innervation in diabetic patients by assessing regional disturbances in myocardial tracer retention and washout. The subject groups comprised 10 diabetic subjects without DAN, 10 diabetic subjects with mild DAN, 9 diabetic subjects with severe DAN, and 10 healthy subjects. Abnormalities of cardiac [11C]-HED retention were detected in 40% of DAN-free diabetic subjects. In subjects with mild neuropathy, tracer defects were observed only in the distal inferior wall of the left ventricle, whereas with more severe neuropathy, defects extended to involve the distal and proximal anterolateral and inferior walls. Absolute [11C]-HED retention was found to be increased by 33% (P<0.01) in the proximal segments of the severe DAN subjects compared with the same regions in the DAN-free subjects (30%; P<0.01 greater than the proximal segments of the mild DAN subjects). Despite the increased tracer retention, no appreciable washout of tracer was observed in the proximal segments, consistent with normal regional tone but increased sympathetic innervation. Distally, [11C]-HED retention was decreased in severe DAN by 33% (P<0.01) compared with the DAN-free diabetic subjects (21%; P<0.05 lower than the distal segments of the mild DAN subjects).Diabetes may result in left ventricular sympathetic dysinnervation with proximal hyperinnervation complicating distal denervation. This combination could result in potentially life-threatening myocardial electrical instability and explain the enhanced cardioprotection from beta-blockade in these subjects.