tbuckley/cabot-search huggingface dataset:
Loss of memory B cells during chronic HIV infection is driven by Foxo3a- and TRAIL-mediated apoptosis
Authors: Julien van Grevenynghe, Rafael A. Cubas, Alessandra Noto, Sandrina DaFonseca, Zhong He, Yoav Peretz, Abdelali Filali-Mouhim, Franck P. Dupuy, Francesco A. Procopio, Nicolas Chomont, Robert S. Balderas, Elias A. Said, Mohamed-Rachid Boulassel, Cecile L. Tremblay, Jean-Pierre Routy, Rafick-Pierre Sékaly, Elias K. Haddad
Journal: Journal of Clinical Investigation (2011)

Loss of memory B cells occurs from the onset of HIV-1 infection and persists into the chronic stages of infection. Lack of survival of these cells, even in subjects being treated, could primarily be the consequence of an altered local microenvironment induced by HIV infection. In this study we showed that memory B cell survival was significantly decreased in aviremic successfully treated (ST) subjects compared with subjects who control viral load as a result of natural immunity (elite controller [EC]) or with uninfected control (HIV-) subjects. The lower survival levels observed in memory B cells from ST subjects were the result of disrupted IL-2 signaling that led to increased transcriptional activity of Foxo3a and increased expression of its proapoptotic target TRAIL. Notably, memory B cell survival in ST subjects was significantly enhanced by the addition of exogenous IL-2 in a Foxo3a-dependent manner. We further showed that Foxo3a silencing by siRNA resulted in decreased expression of TRAIL and apoptosis levels in memory B cells from ST subjects. Our results thus establish a direct role for Foxo3a/TRAIL signaling in the persistence of memory B cells and provide a mechanism for the reduced survival of memory B cells during HIV infection. This knowledge could be exploited for the development of therapeutic and preventative HIV vaccines.
What is health?
Authors: F. Godlee
Journal: BMJ (2011)

In a BMJ editorial in December 2008 Alex Jadad and Laura O’Grady called for a “global conversation” about how we define health ( BMJ 2008;337:a2900). This week Jadad and colleagues present the results of that conversation, initiated via a blog on bmj.com to which a good number of you responded (http://bit.ly/r6Usyh), and concluded at a two day meeting in the Netherlands in December 2009 (doi:10.1136/bmj.d4163). They propose a new definition of health as “the ability to adapt and self manage” in the face of social, physical, and emotional challenges.

Why should we be interested in defining health? Because if health is the goal of healthcare and research, we need to know …
Human interferon-inducible protein 10: expression and purification of recombinant protein demonstrate inhibition of early human hematopoietic progenitors.
Authors: A H Sarris, H E Broxmeyer, U Wirthmueller, N Karasavvas, S Cooper, L Lu, J Krueger, J V Ravetch
Journal: The Journal of Experimental Medicine (1993)

Human interferon-inducible protein 10 (IP-10), a member of the family of the small secreted proteins called intercrine cytokines or chemokines, is secreted by interferon gamma-stimulated T cells, monocytes, endothelial cells, and keratinocytes. We have begun to explore the biological properties of IP-10 by cloning and overexpression in baculovirus and in bacterial protein expression systems. A 9.9-kD protein was secreted by infected insect cells, which on sodium dodecyl sulfate-polyacrilamide gel electrophoresis comigrated with keratinocyte IP-10 and with f(22-98), a bacterial recombinant fragment lacking the signal sequence but containing all other residues of IP-10. All three reacted with antibodies recognizing residues 10-98 (alpha IP-10) and 77-98 of IP-10 (alpha 22), demonstrating that it is secreted by keratinocytes and insect cells after removal of the signal sequence but without proteolysis of the COOH-terminal end. Purified rIP-10 suppresses in vitro colony formation by early human bone marrow progenitor cells which need r-steel factor (rSLF) and rGM-CSF or rSLF and r-erythropoeitin (rEPO). The inhibition is dose dependent, is complete at concentrations &amp;gt; or = 50 ng/ml, is prevented by preincubation of rIP-10 with alpha IP-10, but not by alpha 22, and is seen with highly purified CD34+ cells, suggesting direct effect of rIP-10 on the progenitors. Combination of rIP-10 and other chemokines at inactive concentrations inhibited colony formation in a synergistic manner. rIP-10 did not affect colony formation in the absence of any growth factors or in the presence of rEPO or rGM-CSF but in absence of rSLF. The effects of IP-10 may be relevant to normal marrow function and might be harnessed to protect human hematopoietic progenitors from the cytotoxic effects of chemotherapy.
Use of [11C]Choline PET-CT as a Noninvasive Method for Detecting Pelvic Lymph Node Status from Prostate Cancer and Relationship with Choline Kinase Expression
Authors: Kaiyumars Contractor, Amarnath Challapalli, Tara Barwick, Mathias Winkler, Giles Hellawell, Steve Hazell, Giampaolo Tomasi, Adil Al-Nahhas, Paola Mapelli, Laura M. Kenny, Paul Tadrous, R. Charles Coombes, Eric O. Aboagye, Stephen Mangar
Journal: Clinical Cancer Research (2011)

To evaluate the accuracy and biological basis for [(11)C]choline-PET-CT in the nodal staging of high risk localized prostate cancer patients.Twenty-eight patients underwent dynamic [(11)C]choline-PET-CT of the pelvis and lower abdomen prior to extended laparoscopic pelvic lymph node dissection (eLPL). The sensitivity and specificity of [(11)C]choline PET, [(11)C]choline PET-CT, and MRI for nodal detection were calculated. Average and maximal standardized uptake values (SUV(ave), SUV(max)) were compared with choline kinase alpha (CHKα) and Ki67 immunohistochemistry scores.Four hundred and six lymph nodes (LN), in 26 patients, were assessable. Twenty-seven (6.7%) involved pelvic nodes at eLPL were detected in 9 patients. Seventeen of the 27 involved nodes were subcentimeter. The sensitivity and specificity on a per nodal basis were 18.5% and 98.7%, 40.7% and 98.4%, and 51.9% and 98.4% for MRI, [(11)C]choline PET, and [(11)C]choline PET-CT, respectively. Sensitivity was higher for [(11)C]choline PET-CT compared with MRI (P = 0.007). A higher nodal detection rate, including subcentimeter nodes, was seen with [(11)C]choline PET-CT than MRI. Malignant lesions showed CHKα expression in both cytoplasm and nucleus. SUV(ave) and SUV(max) strongly correlated with CHKα staining intensity (r = 0.68, P < 0.0001 and r = 0.63, P = 0.0004, respectively). In contrast, Ki67 expression was generally low in all tumors.This study establishes the relationship between [(11)C]choline PET-CT uptake with choline kinase expression in prostate cancer and allows it to be used as a noninvasive means of staging pelvic LNs, being highly specific and more sensitive than MRI, including the detection of subcentimeter disease.
Systemic Delivery of MicroRNA-181b Inhibits Nuclear Factor-κB Activation, Vascular Inflammation, and Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Xinghui Sun, Shaolin He, A.K.M. Wara, Basak Icli, Eugenia Shvartz, Yevgenia Tesmenitsky, Nathan Belkin, Dazhu Li, Timothy S. Blackwell, Galina K. Sukhova, Kevin Croce, Mark W. Feinberg
Journal: Circulation Research (2013)

Rationale: Activated nuclear factor (NF)-κB signaling in the vascular endothelium promotes the initiation and progression of atherosclerosis. Targeting endothelial NF-κB may provide a novel strategy to limit chronic inflammation. Objective: To examine the role of microRNA-181b (miR-181b) in endothelial NF-κB signaling and effects on atherosclerosis. Methods and Results: MiR-181b expression was reduced in the aortic intima and plasma in apolipoprotein E–deficient mice fed a high-fat diet. Correspondingly, circulating miR-181b in the plasma was markedly reduced in human subjects with coronary artery disease. Systemic delivery of miR-181b resulted in a 2.3-fold overexpression of miR-181b in the aortic intima of apolipoprotein E–deficient mice and suppressed NF-κB signaling revealed by bioluminescence imaging and reduced target gene expression in the aortic arch in apolipoprotein E–deficient/NF-κB-luciferase transgenic mice. MiR-181b significantly inhibited atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4+ T cells in the vessel wall. Mechanistically, miR-181b inhibited the expression of the target gene importin-α3, an effect that reduced NF-κB nuclear translocation specifically in the vascular endothelium of lesions, whereas surprisingly leukocyte NF-κB signaling was unaffected despite a 7-fold overexpression of miR-181b. Our findings uncover that NF-κB nuclear translocation in leukocytes does not involve importin-α3, but rather importin-α5, which miR-181b does not target, highlighting that inhibition of NF-κB signaling in the endothelium is sufficient to mediate miR-181b’s protective effects. Conclusions: Systemic delivery of miR-181b inhibits the activation of NF-κB and atherosclerosis through cell-specific mechanisms in the vascular endothelium. These findings support the rationale that delivery of miR-181b may provide a novel therapeutic approach to treat chronic inflammatory diseases such as atherosclerosis.
Mechanisms by Which Late Coronary Reperfusion Mitigates Postinfarction Cardiac Remodeling
Authors: Munehiro Nakagawa, Genzou Takemura, Hiromitsu Kanamori, Kazuko Goto, Rumi Maruyama, Akiko Tsujimoto, Takamasa Ohno, Hideshi Okada, Atsushi Ogino, Masayasu Esaki, Shusaku Miyata, Longhu Li, Hiroaki Ushikoshi, Takuma Aoyama, Masanori Kawasaki, Kenshi Nagashima, Takako Fujiwara, Shinya Minatoguchi, Hisayoshi Fujiwara
Journal: Circulation Research (2008)

Although recanalization of the infarct-related artery late after myocardial infarction (MI) is known to reduce both cardiac remodeling and mortality, the mechanisms responsible are not yet fully understood. We compared infarcted rat hearts in which the infarct-related coronary artery was opened 24 hours after infarction (late reperfusion [LR] group) with those having a permanently occluded artery. Left ventricular dilatation and dysfunction were significantly mitigated in the LR group 1, 2, and 4 weeks post-MI. Attributable, in large part, to the greater number of cells present, the infarcted wall was significantly thicker in the LR group, which likely reduced wall stress and mitigated cardiac dysfunction. Granulation tissue cell proliferation was increased to a greater degree in the LR group 4 days post-MI, whereas the incidence of apoptosis was significantly lower throughout the subacute stage (4 days, 1 week, and 2 weeks post-MI), further suggesting preservation of granulation tissue cells contributes to the thick, cell-rich scar. Functionally, myocardial debris was more rapidly removed from the infarcted areas in the LR group during subacute stages, and stouter collagen was more rapidly synthesized in those areas. Direct acceleration of Fas-mediated apoptosis by hypoxia was confirmed in vitro using infarct tissue-derived myofibroblasts. In salvaged cardiomyocytes, degenerative changes, but not apoptosis, were mitigated in the LR group, accompanied by restoration of GATA-4 and sarcomeric protein expression. Along with various mechanisms proposed earlier, the present findings appear to provide an additional pathophysiological basis for the benefits of late reperfusion.
Effect of Interleukin-2 on Biodistribution of Monoclonal Antibody in Tumor and Normal Tissues in Mice Bearing SL-2 Thymoma
Authors: K. R. Schultz, C. C. Badger, G. W. Dombi, P. D. Greenberg, I. D. Bernstein
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : Our laboratory demonstrated previously that treatment with a tumor-specific, radiolabeled anti-Thy 1 murine monoclonal antibody (MAb) in mice can eradicate a T-cell lymphoma mass, but the doses required were toxic to normal organs. Approaches to increase MAb concentration in tumor tissue versus normal tissue may overcome this problem. Interleukin-2 (IL-2) has been shown to increase capillary permeability, as indicated by extravasation of albumin. Purpose : The purpose of this study was to determine whether increased extravasation of MAb at the tumor site might result in selective binding to tumor antigen, increasing localization of radiolabeled MAb at the tumor site. Methods : We studied the effect of IL-2 on biodistribution of 1A14 MAb (anti-Thy 1.1) in normal AKR/Cum (Thy 1.2 + ) mice and in AKR/Cum mice bearing SL-2, a spontaneous T-cell lymphoma (Thy 1.1 + ), compared with biodistribution of albumin in normal mice and biodistribution of the nonreactive G3G6 MAb in tumor-bearing mice. IL-2 was given intravenously in the tail vein in doses of 0, 25000, 50000, 100000, or 200000 U twice a day for a total of seven doses over 3.5 days. Mice received injections of a mixture of 1A14 MAb (250 μCi/lOO.μg) and albumin or G3G6 MAb (145 μCi/100.μg) in a total volume of 200 μL at 12 hours after the last IL-2 dose. Results : In normal mice, IL-2 caused a dose-dependent increase of both radiolabeled MAb and albumin in the spleen, liver, lung, and lymph node, but it spared the brain. In tumor- bearing mice, IL-2 resulted in higher levels of MAb in the tumors 72 hours after receiving injections, with 17.5% and 24.3% of the injected dose per gram of tumor present in the mice pretreated with 100 000 or 200 000 U of IL-2 twice a day for 3.5 days, compared with 13.4% in the controls. In IL-2-treated mice, levels of MAb were greater in the tumors than in critical normal organs; the differences were statistically significant for tumors versus lungs at 24 hours after injection and for tumors versus livers at 48 hours and 72 hours after injection. Conclusions : These results suggest that pretreatment with IL-2 may lead to enhanced distribution of tumor-specific MAb to the tumor site, compared with normal tissues, thus increasing therapeutic efficacy of radiolabeled MAb. [J Natl Cancer Inst 84:109-113, 1992].
Urinary Biomarkers of Prenatal Atrazine Exposure and Adverse Birth Outcomes in the PELAGIE Birth Cohort
Authors: Cécile Chevrier, Gwendolina Limon, Christine Monfort, Florence Rouget, Ronan Garlantézec, Claire Petit, Gaël Durand, Sylvaine Cordier
Journal: Environmental Health Perspectives (2011)

Background: Despite evidence of atrazine toxicity in developing organisms from experimental studies, few studies—and fewer epidemiologic investigations—have examined the potential effects of prenatal exposure.Objectives: We assessed the association between adverse birth outcomes and urinary biomarkers of prenatal atrazine exposure, while taking into account exposures to other herbicides used on corn crops (simazine, alachlor, metolachlor, and acetochlor).Methods: This study used a case-cohort design nested in a prospective birth cohort conducted in the Brittany region of France from 2002 through 2006. We collected maternal urine samples to examine pesticide exposure biomarkers before the 19th week of gestation.Results: We found quantifiable levels of atrazine or atrazine mercapturate in urine samples from 5.5% of 579 pregnant women, and dealkylated and identified hydroxylated triazine metabolites in 20% and 40% of samples, respectively. The presence versus absence of quantifiable levels of atrazine or a specific atrazine metabolite was associated with fetal growth restriction [odds ratio (OR) = 1.5; 95% confidence interval (CI), 1.0–2.2] and small head circumference for sex and gestational age (OR = 1.7; 95% CI, 1.0–2.7). Associations with major congenital anomalies were not evident with atrazine or its specific metabolites. Head circumference was inversely associated with the presence of quantifiable urinary metolachlor.Conclusions: This study is the first to assess associations of birth outcomes with multiple urinary biomarkers of exposure to triazine and chloroacetanilide herbicides. Evidence of associations with adverse birth outcomes raises particular concerns for countries where atrazine is still in use.
Tolerance To COX-2 Inhibitors In Children With Multiple Hypersensitivity To Non- Steroidal Anti-Inflammatory Drugs
Authors: Jose Luis Corzo Higueras, Maria Angeles Zambonino, Candelaria Muñoz, Cristobalina Mayorga, Gloria Requena, Antonio Urda, Miguel Blanca, Maria J. Torres
Journal: Journal of Allergy and Clinical Immunology (2014)
Presentation of autoantibody to proliferating cell nuclear antigen in patients with chronic hepatitis B and C virus infection
Authors: B.-S. Tzang, T.-Y. Chen, T.-C. Hsu, Y.-C. Liu, G. J Tsay
Journal: Annals of the Rheumatic Diseases (1999)

To study the association of antibodies to proliferating cell nuclear antigen (PCNA) in patients with chronic hepatitis B (HBV) and C (HCV) virus infection.Sera from 243 patients with chronic HBV infection; 379 patients with chronic HCV infection; 80 patients with systemic lupus erythematosus (SLE); 28 patients with rheumatoid arthritis; 15 patients with Sjogren's syndrome; eight with polymyositis; eight with primary biliary cirrhosis; and 33 healthy control subjects were tested for the presentation of anti-PCNA antibodies by enzyme linked immunosorbent assay (ELISA) and immunoblotting using recombinant PCNA as antigen. The distribution of immunoglobulin isotypes of anti-PCNA antibody was measured by ELISA assay.By ELISA, anti-PCNA antibodies were detected in 30 (12.3%) patients with chronic HBV infection, 71 (18.7%) patients with chronic HCV infection, and five (6.3%) patients with SLE. The inhibition of binding with these sera by purified PCNA was shown to exceed 71%. By immunoblotting, the frequency of anti-PCNA in patients with chronic HBV and HCV infection was 17 of 243 (7%) and 41 of 379 (11%), respectively. Absorption studies on indirect immunofluorescence showed the typical nuclear speckled staining pattern by anti-PCNA sera was abolished by preincubation of sera with PCNA. Anti-PCNA antibody was not detected in sera from patients with autoimmune diseases except SLE. Anti-PCNA antibodies in patients with chronic HBV and HCV infection were predominantly IgG.These data suggest that anti-PCNA antibody are also present in patients with chronic HBV and HCV infection. Anti-PCNA antibody may not be specific for SLE.
A CASE OF ECTODERMAL DEFECT ASSOCIATED WITH HYPERTELORIMS
Authors: G. P. B. WHITWELL
Journal: British Journal of Dermatology (1931)

Journal Article A CASE OF ECTODERMAL DEFECT ASSOCIATED WITH HYPERTELORIMS Get access G. P. B. WHITWELL, M.B. G. P. B. WHITWELL, M.B. Junior Registrar, St. John's Hospital for Diseases of the Skin; Clinical Assistant, Dermatological Department, Guy's Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 43, Issue 12, 1 December 1931, Pages 648–652, https://doi.org/10.1111/j.1365-2133.1931.tb09464.x Published: 01 December 1931
STUDIES ON THE CHEMISTRY OF SEROUS EFFUSIONS
Authors: Albert A. Epstein
Journal: The Journal of Experimental Medicine (1914)

A comparison of the results obtained in the analysis of the different effusions shows that they vary, (1) according to location, and (2) according to the disease in which they are produced. Thus the subcutaneous effusions are totally different in their composition from the abdominal or pleuritic fluids; and again the abdominal fluid of nephritic origin is different from those of cardiac or other origin. The cutaneous effusions are characterized by a very low protein content and a small amount of incoagulable nitrogen. Of the protein present in these fluids, the globulin constitutes the greater portion. In the mixed cardionephritic fluids the ratio of globulin to albumin is lower than that in normal blood serum; but when compared with the blood sera of cardionephritic cases there appears to be a certain parallelism. The chloride content of these fluids is considerably above that found in normal blood serum, but is comparable with those of corresponding cases. The effusions occurring in serous cavities differ from the cutaneous ones by their higher protein content. The highest values are attained in the pleural fluids, in which the protein present is almost the same as that in normal blood serum. The incoagulable nitrogen in these fluids is uniformly low. The chlorides vary in amount according to the nature of the case. In the effusions of inflammatory origin the values are lower than those found in the blood. In the pleural fluids of other than inflammatory origin the chloride content is either the same or higher than that of blood serum. The globulin-albumin ratio in all of these fluids except one (table III, fluid 61) is higher than that of normal blood serum. Otherwise the highest value is presented by a pleural fluid from a case of nephritis (table III, fluid 205) and the lowest by an empyema fluid (table III, fluid 30). The latter case is of especial interest because of the theory, first propounded by Schmidt, that the leucocytes in the purulent fluid are largely responsible for high globulin content. The abdominal fluids in general are less rich in protein than the pleural effusions. Those of cardiac origin give the highest protein values, but the globulin-albumin ratios are lower than in the pleural fluids or in the blood sera of corresponding cases. Only in two fluids does the globulin reach a percentage of 62 and 52.2. In both these cases the chloride content is also high. The incoagulable nitrogen in all of them is rather low. In one fluid of purely nephritic origin the protein content is low and all of it is globulin. This is suggestive, when compared with the values obtained in the analysis of the blood sera from nephritic cases. The results obtained in the analysis of abdominal fluids from cardionephritic cases approach very closely those obtained in purely cardiac cases.
Discussions Regarding Reproductive Health for Young Women With Breast Cancer Undergoing Chemotherapy
Authors: Christine M. Duffy, Susan M. Allen, Melissa A. Clark
Journal: Journal of Clinical Oncology (2005)

Young women who undergo chemotherapy for breast cancer face serious consequences to their reproductive health. Research in this area has previously focused on men, or on childhood cancer survivors. We sought to explore self-report of reproductive health counseling in young women undergoing chemotherapy for breast cancer. A total of 166 premenopausal women aged < or = 50 years were recruited from oncology offices in academic and private practices in four northeastern states, as part of a randomized controlled clinical trial aimed at stress reduction. Women were asked a variety of questions regarding diagnosis and treatment, including whether they received any counseling regarding early menopause and fertility issues. Sixty-eight percent and 34% of women reported recalling a discussion with a physician regarding early menopause or fertility, respectively. In multivariate analysis, hormonal therapy and early stage of disease were associated with significantly increased odds of recall of a discussion regarding menopause. Difficulty communicating with medical team was associated with increased odds of recalling a discussion regarding fertility, whereas older age and anxiety in medical situations were associated with decreased odds. Many women fail to recall discussions regarding the reproductive health impact of chemotherapy. Demographic, psychological, and disease-related variables are related to recalling such discussions. Counseling about premature menopause and fertility changes is an overlooked aspect of preparation for adjuvant chemotherapy in young premenopausal women with breast cancer. Future research should explore this issue further.