tbuckley/cabot-search huggingface dataset:
Immunity to the group B streptococci: interaction of serum and macrophages with types Ia, Ib, and Ic.
Authors: B F Anthony
Journal: The Journal of Experimental Medicine (1976)

The opsonization and phagocytosis of group B streptococci of types Ia, Ib, and Ic were studied in vitro by measuring the uptake of radioactivity by coverslip cultures of rabbit alevolar macrophages during incubation with radiolabeled, nonviable bacteria which had been exposed to rabbit serum. The uptake of counts per minute was quantitative, reproducible, and reversibly inhibited by cold, indicating that it was largely a measurement of phagocytic ingestion rather than of attachment of bacteria-immunoglobulin complexes to macrophage membranes. Moreover, suspended macrophages killed approximately 90% of viable streptococci in the presence of specific antiserum. The opsonic activity of immune serum was heat stable, and phagocytosis of streptococci was insignificant after incubation with normal serum and antiserum to some heterologous group B streptococci. By absorption studies, it was possible to identify the effect of antibodies to specific bacterial antigens. Phagocytosis of streptococci containing the corresponding antigens was maximal after opsonization with homologous or heterologous sera containing antibody to IaCHO, IbCHO, or Ibc protein. Phagocytosis of all three serotypes was intermediate when opsonization could be attributed to anti-IabcCHO. The opsonization of a specific group B streptococcus is complex and may involve two or more antigen-antibody systems.
Human granulocyte generation of hydroxyl radical.
Authors: S J Weiss, P K Rustagi, A F LoBuglio
Journal: The Journal of Experimental Medicine (1978)

Human granulocytes were capable of oxidizing 2-keto-4 thiomethylbutyric acid to ethylene during phagocytosis or membrane perturbation. The reaction required hydrogen peroxide and superoxide and in addition was inhibited by various hydroxyl radical (OH) scavengers. These observations represent direct evidence for the generation of OH by human granulocytes. Further, inhibition of ethylene generation by azide and cyanide suggests that OH generation in granulocytes may be linked to myeloperoxidase.
Fibulin-3 as a Blood and Effusion Biomarker for Pleural Mesothelioma
Authors: Harvey I. Pass, Stephen M. Levin, Michael R. Harbut, Jonathan Melamed, Luis Chiriboga, Jessica Donington, Margaret Huflejt, Michele Carbone, David Chia, Lee Goodglick, Gary E. Goodman, Mark D. Thornquist, Geoffrey Liu, Marc de Perrot, Ming-Sound Tsao, Chandra Goparaju
Journal: New England Journal of Medicine (2012)

New biomarkers are needed to detect pleural mesothelioma at an earlier stage and to individualize treatment strategies. We investigated whether fibulin-3 in plasma and pleural effusions could meet sensitivity and specificity criteria for a robust biomarker.
Interferon alfa-2b therapy in children with chronic hepatitis B.
Authors: E M Sokal, S Wirth, P Goyens, A Depreterre, C Cornu
Journal: Gut (1993)

Twenty nine children (mean age 8.3 years, 18 boys, 11 girls) who had biopsy proved chronic hepatitis B virus infection (HBV) with active viral replication were given a 16 week course of interferon alfa-2b treatment (9 million units (MU)/m2, thrice weekly). Fourteen children (48%) showed persistent loss of HBV-DNA 8 months after the end of treatment; 11 (38%) lost hepatitis B e antigen (HBeAg), and two (7%) hepatitis B surface antigen (HBsAg). Alanine aminotransferase activities returned to normal in 12 children. Those who responded had significantly higher initial transaminase activities than those who did not (p &lt; 0.01) but similar serum HBV-DNA. Results were compared with the natural evolution of the disease in a group of 25 children (mean age 8.3 years) with identical initial mean serum HBV-DNA values, followed up during the same period. Two of these (8%) lost HBeAg and one (4%) HBsAg. The 23 remaining control subjects had no decrease in serum HBV-DNA or in transaminase activities compared with values 1 year earlier. It is concluded that treatment with interferon alfa-2b in children may lead to inhibition of HBV replication similar to that described in adults, and may thus shorten disease evolution. Further studies are necessary to establish the best protocols and to identify those patients who are the most likely to respond to treatment.
Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI)
Authors: Birgit Assmus, Volker Schächinger, Claudius Teupe, Martina Britten, Ralf Lehmann, Natascha Döbert, Frank Grünwald, Alexandra Aicher, Carmen Urbich, Hans Martin, Dieter Hoelzer, Stefanie Dimmeler, Andreas M. Zeiher
Journal: Circulation (2002)

Background— Experimental studies suggest that transplantation of blood-derived or bone marrow–derived progenitor cells beneficially affects postinfarction remodeling. The safety and feasibility of autologous progenitor cell transplantation in patients with ischemic heart disease is unknown. Methods and Results— We randomly allocated 20 patients with reperfused acute myocardial infarction (AMI) to receive intracoronary infusion of either bone marrow–derived (n=9) or circulating blood–derived progenitor cells (n=11) into the infarct artery 4.3±1.5 days after AMI. Transplantation of progenitor cells was associated with a significant increase in global left ventricular ejection fraction from 51.6±9.6% to 60.1±8.6% ( P =0.003), improved regional wall motion in the infarct zone (−1.5±0.2 to −0.5±0.7 SD/chord; P &lt;0.001), and profoundly reduced end-systolic left ventricular volumes (56.1±20 mL to 42.2±15.1 mL; P =0.01) at 4-month follow-up. In contrast, in a nonrandomized matched reference group, left ventricular ejection fraction only slightly increased from 51±10% to 53.5±7.9%, and end-systolic volumes remained unchanged. Echocardiography revealed a profound enhancement of regional contractile function (wall motion score index 1.4±0.2 at baseline versus 1.19±0.2 at follow-up; P &lt;0.001). At 4 months, coronary blood flow reserve was significantly ( P &lt;0.001) increased in the infarct artery. Quantitative F-18-fluorodeoxyglucose–positron emission tomography analysis revealed a significant ( P &lt;0.01) increase in myocardial viability in the infarct zone. There were no differences for any measured parameter between blood-derived or bone marrow–derived progenitor cells. No signs of an inflammatory response or malignant arrhythmias were observed. Conclusions— In patients with AMI, intracoronary infusion of autologous progenitor cells appears to be feasible and safe and may beneficially affect postinfarction remodeling processes.
Evaluating the Optimal Timing of Angiography
Authors: Sharon-Lise T. Normand
Journal: Circulation (2007)

study by Tricoci and colleagues 1 in the present issue of Circulation concludes that shortening the time from hospital admission to coronary angiography was associated with fewer ischemic outcomes with no increased bleeding.Although we know that use of an early invasive strategy in patients with non-ST-segment-elevation acute coronary syndromes is associated with improved outcomes, the optimal time to perform coronary angiography in those scheduled to receive an invasive strategy is unknown. Article p 2669The Tricoci et al 1 study capitalized on the clinical data collected as part of the Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial 2 to study this question.Because the goal of the SYNERGY trial was to compare the outcomes of patients treated with enoxaparin versus unfractionated heparin, (1) patients were not randomized to different times to angiography (such as Յ6 hours, 6 to 12 hours, 12 to 18 hours, etc) after hospital arrival, and (2) some patients may have died or experienced an adverse event before receiving angiography.The authors adopted 2 different analytical strategies to address these issues: a landmark analysis 3 and an inverse-probability-weighted approach. 4These 2 approaches differ in their basic assumptions and in the populations to which they apply.
Combining Cognitive Testing and Informant Report to Increase Accuracy in Screening for Dementia
Authors: A Mackinnon, R Mulligan
Journal: American Journal of Psychiatry (1998)

Cognitive testing and an informant report questionnaire were combined to determine whether their use in combination could improve accuracy in screening for the diagnosis of dementia over either test used alone. Methods of combining test scores that can be readily applied in clinical settings were developed and assessed.The subjects were 106 patients admitted to the geriatric hospital or outpatients assessed at the memory clinic of the university hospital system in Geneva, Switzerland. The instruments used were the Mini-Mental State and the short form of the Informant Questionnaire on Cognitive Decline in the Elderly. The diagnosis of dementia was made according to DSM-IV criteria.Logistic regression demonstrated that the combination of the Mini-Mental State and the Informant Questionnaire on Cognitive Decline in the Elderly resulted in more accurate prediction of caseness than either test alone. The performance of logical "or" and "and" combinations of test results and a weighted sum of scores on the two tests as screens for dementia were investigated by using receiver operating characteristic analysis. By using suitable cutoff points, both the "or" rule and the weighted sum were shown to be capable of improving performance over that of either test used alone.This study shows that informant report can be formally incorporated into assessment for dementia in such a way as to increase the accuracy of detection of cases and noncases. A graphical method was developed that enables the most robust approach to be applied to individual cases without any calculation.
Detection of Laryngeal Cancer-The Case for Early Specialist Assessment
Authors: Timothy J Hoare, Hamish G Thomson, David W Proops
Journal: Journal of the Royal Society of Medicine (1993)

The first 300 patients referred from 11 participating general practices (GPs) to the Hoarse Voice Clinic, Queen Elizabeth Hospital, Birmingham, were studied prospectively to estimate the accuracy of GPs' diagnosis of laryngeal symptoms and to assess whether the provision of a direct referral immediate access service for the assessment of persistent laryngeal symptoms is an effective way of ensuring early referral and detection of laryngeal cancer. The GPs' assessment of laryngeal symptoms was inaccurate. Diagnosis after the initial clinic visit was accurate, predicting all histological cases of cancer. Laryngoscopy was possible in all patients at the first clinic visit. Disease requiring admission for direct laryngoscopy and biopsy was found in 39 patients (14%). Ten (3.3%) were found to have laryngeal cancer, of which eight were early lesions. When seen in the clinic 102 (34%) had normal voices and larynxes. A hoarse voice is a symptom requiring specialist assessment. By using the flexible fibreoptic nasendoscope all patients larynxes can be seen in clinic, an accurate diagnosis quickly made and the appropriate management instigated. It is feasible to offer this service without appointments to patients with persistent hoarseness.
Oncostatin M Induces Interleukin-6 and Cyclooxygenase-2 Expression in Human Vascular Smooth Muscle Cells
Authors: Catherine Bernard, Régine Merval, Marilyne Lebret, Philippe Delerive, Isabelle Dusanter-Fourt, Stéphanie Lehoux, Christophe Créminon, Bart Staels, Jacques Maclouf, Alain Tedgui
Journal: Circulation Research (1999)

Abstract —Oncostatin M (OSM), a cytokine first identified from activated monocytes and T lymphocytes, is one of the most potent autocrine growth factor for AIDS and Kaposi’s sarcoma. Little is known about the effects of OSM on normal vascular cells. We thus exposed human aortic smooth muscle cells (hASMCs) to OSM, examined cell proliferation and morphology, and determined interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) expression. OSM had a weak antiproliferative effect. After a 4-day incubation with 100 ng/mL OSM, cell count decreased to 69±3% of control. However, OSM induced striking changes in hASMC morphology, characterized by a polyclonal shape, in contrast to the spindle morphological feature of control hASMCs. OSM stimulated the release of IL-6 by hASMCs in a dose-dependent way; after a 48-hour exposure, values were 8.5±0.7, 29.7±3.5, 50.9±4.4, and 73.8±7.6×10 3 U/mL (n=6) at OSM concentrations of 0, 1, 10, and 100 ng/mL, respectively. OSM induced marked expression of COX-2 protein and mRNA. Leukemia inhibitory factor had no effect on hASMCs, indicating that OSM effects on hASMCs were mediated by the OSM type II receptor and not by the leukemia inhibitory factor receptor. OSM used the JAK/STAT signaling pathway, as demonstrated by rapid phosphorylation of JAK1 and specific activation of STAT1. Interestingly, OSM acted in synergy with IL-1β on IL-6 production and COX-2 expression. In conclusion, OSM is a novel regulator of human smooth muscle cell functions, acting in concert with IL-1β, and OSM may play a role in major vascular diseases such as atherosclerosis.
Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trial and assessment of DCE-MRI as a biomarker of survival
Authors: W.R. Jarnagin, L.H. Schwartz, D.H. Gultekin, M. Gönen, D. Haviland, J. Shia, M. D'Angelica, Y. Fong, R. DeMatteo, A. Tse, L.H. Blumgart, N. Kemeny
Journal: Annals of Oncology (2009)
Detection of Occult Lymph Node Metastases in Locally Advanced Node-Negative Prostate Cancer
Authors: Vincenzo Pagliarulo, Debra Hawes, Frank H. Brands, Susan Groshen, Jie Cai, John P. Stein, Gary Lieskovsky, Donald G. Skinner, Richard J. Cote
Journal: Journal of Clinical Oncology (2006)

The purpose of this study was to determine the incidence and clinical significance of occult metastases in the lymph nodes of patients with prostate cancer originally considered node negative by routine histologic evaluation.Two hundred seventy four patients with pT3 prostate carcinoma treated by radical prostatectomy and bilateral lymph node dissection were included in this study. One hundred eighty patients were staged node negative (N0), while 94 patients were lymph node positive (N+), based on routine histologic evaluation. All lymph nodes from the 180 N0 patients were evaluated for occult metastases by immunohistochemistry using antibodies to cytokeratins and, if positive, prostate-specific antigen. Recurrence and overall survival were compared among patients with occult tumor cells (OLN+), with patients whose lymph nodes remained negative (OLN-), and with the 94 N+ patients.A total of 3,914 lymph nodes were evaluated from 180 N0 patients (average, 21.7 lymph nodes per patient). Occult tumor cells were found in 24 of 180 patients (13.3%). The presence of OLN+ was significantly associated with increased recurrence and decreased survival compared with OLN- patients (P < .001 and P = .019, respectively; relative risk of recurrence, 2.27; relative risk of death 2.07, respectively). The presence of occult lymph node metastases was an independent predictor of recurrence and death in a multivariable analysis. The outcome for patients with OLN+ disease was similar to that for patients with N+ disease.The detection of occult lymph node metastases in patients with pT3N0 prostate cancer identifies those with significantly increased risk of prostate cancer recurrence and death.
Probiotics in pregnant women to prevent allergic disease: a randomized, double-blind trial
Authors: C.K. Dotterud, O. Storrø, R. Johnsen, T. Øien
Journal: British Journal of Dermatology (2010)

Previous reports have suggested that certain probiotics given to mothers and children at risk of atopy halves the incidence of atopic dermatitis (AD) at 2 years of age.To examine if probiotics given to pregnant women in a nonselected population could prevent atopic sensitization or allergic diseases during the child's first 2 years.In a randomized, double-blind trial of children from a nonselected maternal population (ClinicalTrials.gov identifier: NCT00159523), women received probiotic milk or placebo from 36 weeks of gestation to 3 months postnatally during breastfeeding. The probiotic milk contained Lactobacillus rhamnosus GG, L. acidophilus La-5 and Bifidobacterium animalis subsp. lactis Bb-12. Children with an itchy rash for more than 4 weeks were assessed for AD. At 2 years of age, all children were assessed for atopic sensitization, AD, asthma and allergic rhinoconjunctivitis. The intention-to-treat (ITT) analysis was enabled by multiple imputations.Four hundred and fifteen pregnant women were computer randomized. At 2 years, 138 and 140 children in the probiotic and the placebo groups, respectively, were assessed. In the ITT analysis, the odds ratio (OR) for the cumulative incidence of AD was 0·51 in the probiotic group compared with the placebo [95% confidence interval (CI) 0·30-0·87; P=0·013]. There were no significant effects on asthma (OR 0·68, 95% CI 0·26-1·80; P=0·437) or atopic sensitization (OR 1·52, 95% CI 0·74-3·14; P=0·254). Probiotics given to nonselected mothers reduced the cumulative incidence of AD, but had no effect on atopic sensitization.
Risk of Lactic Acidosis or Elevated Lactate Concentrations in Metformin Users With Renal Impairment: A Population-Based Cohort Study
Authors: Willemijn L. Eppenga, Arief Lalmohamed, Arjen F. Geerts, Hieronymus J. Derijks, Michel Wensing, Antoine Egberts, Peter A.G.M. De Smet, Frank de Vries
Journal: Diabetes Care (2014)

OBJECTIVE The objective of this study was to determine whether treatment with metformin in patients with renal impairment is associated with a higher risk of lactic acidosis or elevated lactate concentrations compared with users of a noninsulin antidiabetic drug (NIAD) who had never used metformin. RESEARCH DESIGN AND METHODS A cohort of 223,968 metformin users and 34,571 diabetic patients who had never used metformin were identified from the Clinical Practice Research Datalink (CPRD).The primary outcome was defined as either a CPRD READ code lactic acidosis or a record of a plasma lactate concentration &amp;gt;5 mmol/L. The associations between renal impairment, dose of metformin, and the risk of lactic acidosis or elevated lactate concentrations were determined with time-dependent Cox models and expressed as hazard ratios (HRs). RESULTS The crude incidence of lactic acidosis or elevated lactate concentrations in current metformin users was 7.4 per 100,000 person-years (vs. 2.2 per 100,000 person-years in nonusers). Compared with nonusers, risk of lactic acidosis or elevated lactate concentrations in current metformin users was significantly associated with a renal function &amp;lt;60 mL/min/1.73 m2 (adjusted HR 6.37 [95% CI 1.48–27.5]). The increased risk among patients with impaired renal function was further increased in users of ≥730 g of metformin in the preceding year (adjusted HR 11.8 [95% CI 2.27–61.5]) and in users of a recent high daily dose (&amp;gt;2 g) of metformin (adjusted HR 13.0 [95% CI 2.36–72.0]). CONCLUSIONS Our study is consistent with current recommendations that the renal function of metformin users should be adequately monitored and that the dose of metformin should be adjusted, if necessary, if renal function falls below 60 mL/min/1.73 m2.
PML-RARα/RXR Alters the Epigenetic Landscape in Acute Promyelocytic Leukemia
Authors: Joost H.A. Martens, Arie B. Brinkman, Femke Simmer, Kees-Jan Francoijs, Angela Nebbioso, Felicetto Ferrara, Lucia Altucci, Hendrik G. Stunnenberg
Journal: Cancer Cell (2010)
Phosphodiesterase inhibitors: new opportunities for the treatment of asthma.
Authors: T J Torphy, B J Undem
Journal: Thorax (1991)

<h3>Background</h3> Central blood flow measurements can provide detailed information on the hemodynamic condition of the preterm infant. However, reference values for right and left ventricular output (RVO and LVO) and superior vena cava flow (SVC flow) are only available for infants in the transitional period. The aim of this study was to determine RVO, LVO and SVC after the transitional period in stable preterm infants. <h3>Methods</h3> RVO, LVO and SVC flow were measured with functional echocardiography on days 7 and 14 of life in stable preterm infants less than 32 weeks gestation, with minimal respiratory support and no cardiovascular support. Infants with a clinical suspicion of an infection within 48 h after data collection or a ductal diameter &gt;1.4 mm were excluded from analysis. <h3>Results</h3> We performed 111 measurements in 62 preterm infants with a median (range) gestational age of 28 (25–31) weeks and birth weight of 1105 (650–2370) g. 57 measurements were analysed on day 7 and 47 on day 14. The mean (SD) RVO, LVO and SVC flow were 429 (116), 296 (74) and 89 (33) ml/kg/min on day 7 and 433 (81), 300 (79) and 86 (26) ml/kg/min on day 14. There were no significant differences in flows between days 7 and 14 in the paired measurements. <h3>Conclusion</h3> This study provides central blood flow values in stable preterm infants after the transitional period. The flow variables were shown to remain stable between days 7 and 14.
PKD1 Haploinsufficiency Causes a Syndrome of Inappropriate Antidiuresis in Mice
Authors: Ali K. Ahrabi, Sara Terryn, Giovanna Valenti, Nathalie Caron, Claudine Serradeil-Le Gal, Danielle Raufaste, Soren Nielsen, Shigeo Horie, Jean-Marc Verbavatz, Olivier Devuyst
Journal: Journal of the American Society of Nephrology (2007)

Mutations in PKD1 are associated with autosomal dominant polycystic kidney disease. Studies in mouse models suggest that the vasopressin (AVP) V2 receptor (V2R) pathway is involved in renal cyst progression, but potential changes before cystogenesis are unknown. This study used a noncystic mouse model to investigate the effect of Pkd1 haploinsufficiency on water handling and AVP signaling in the collecting duct (CD). In comparison with wild-type littermates, Pkd1(+/-) mice showed inappropriate antidiuresis with higher urine osmolality and lower plasma osmolality at baseline, despite similar renal function and water intake. The Pkd1(+/-) mice had a decreased aquaretic response to both a water load and a selective V2R antagonist, despite similar V2R distribution and affinity. They showed an inappropriate expression of AVP in brain, irrespective of the hypo-osmolality. The cAMP levels in kidney and urine were unchanged, as were the mRNA levels of aquaporin-2 (AQP2), V2R, and cAMP-dependent mediators in kidney. However, the (Ser256) phosphorylated AQP2 was upregulated in Pkd1(+/-) kidneys, with AQP2 recruitment to the apical plasma membrane of CD principal cells. The basal intracellular Ca(2+) concentration was significantly lower in isolated Pkd1(+/-) CD, with downregulated phosphorylated extracellular signal-regulated kinase 1/2 and decreased RhoA activity. Thus, in absence of cystic changes, reduced Pkd1 gene dosage is associated with a syndrome of inappropriate antidiuresis (positive water balance) reflecting decreased intracellular Ca(2+) concentration, decreased activity of RhoA, recruitment of AQP2 in the CD, and inappropriate expression of AVP in the brain. These data give new insights in the potential roles of polycystin-1 in the AVP and Ca(2+) signaling and the trafficking of AQP2 in the CD.
Adjuvant polyarthritis. V. Induction by N-acetylmuramyl-L-alanyl-D-isoglutamine, the smallest peptide subunit of bacterial peptidoglycan.
Authors: Y H Chang, C M Pearson, L Chedid
Journal: The Journal of Experimental Medicine (1981)

N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), an apparently nonimmunogenic bacterial peptidoglycan-derived small peptide, was found to induce a polyarthritis the rat similar to that induced by Freund's complete adjuvant when injected in the form of an oil emulsion. An oil emulsion of its isomer, N-acetylmuramyl-L-alanyl-L-isoglutamine, which unlike MDP has no immunostimulatory activity, failed to induce the disease.