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1. Age-dependent changes in tolerizability with rabbit gamma-globulin in the Biozzi high and low-responder lines of mice

Author

Katsuji Nakano, Short Papers, Brian H. Sabiston, and Bernhard Cinader

Subjects
Lipopolysaccharides, Aging, medicine.medical_specialty, Lipopolysaccharide, Immunology, Age dependent, Biology, T-Lymphocytes, Regulatory, law.invention, Mice, chemistry.chemical_compound, Immune system, law, Internal medicine, Immune Tolerance, medicine, Animals, Immunology and Allergy, B cell, Gamma globulin, Low responder, Endocrinology, medicine.anatomical_structure, Immunization, chemistry, Suppressor, Female, gamma-Globulins
Abstract

The antibody response to rabbit gamma-globulin (RGG) of high-responder, but not of low-responder Biozzi mice decreased with age. Injection with aggregate-freed RGG reduced the response of high-responder but not of low-responder mice to subsequent injections with aggregated RGG. This reduction in the antibody response, formed by high-responder mice, decreased with increasing age; aggregate-freed RGG appeared to sensitize 6-month-old low-responder mice to a subsequent injection with aggregated RGG. When animals, not pretreated with aggregate-freed RGG, were immunized with RGG and lipopolysaccharide (LPS), the immune response was greatly enhanced. The response of both pretreated low and high responders was substantially smaller than that of corresponding animals which were not given aggregate-freed RGG, prior to immunization. LPS revealed an inhibitory effect on low-responder mice of aggregate-freed RGG, which was not detected upon immunization with heat-aggregated RGG alone. The involvement of nonspecific suppressor cells and of B cell tolerance in low-responder mice is discussed.

Published
1979

2. Composition of the lymphoid cell populations from omental milky spots during the immune response in C57BL/Ka mice

Author

Robert V. Rouse, Bruno Kyewski, Short Paper, and Kazimir Dux

Subjects
B-Lymphocytes, Stromal cell, medicine.drug_class, T-Lymphocytes, Immunology, Cell, Mice, Inbred Strains, T lymphocyte, Biology, Monoclonal antibody, Mice, medicine.anatomical_structure, Lymphatic system, Immune system, Antigen, medicine, Animals, Immunology and Allergy, Cytotoxic T cell, Female, Lymphocytes, Omentum
Abstract

The lymphoid cell composition of milky spots was analyzed in unprimed mice before and after i.p. immunization with sheep red blood cells. Milky spots contained surface immunoglobulin-positive B lymphocytes, and T cells of the helper and cytotoxic phenotype. After secondary antigen challenge (a) the number of lymphocytes increased up to 40-fold, (b) B and T cells were found to segregate into distinct areas in situ, and (c) lymphocytes were found to associate with I-A-negative stromal cells in vivo. These findings qualify milky spots as a peripheral lymphoid organ exhibiting a remarkable change in number and composition of lymphocytes in response to a local antigen stimulus.

Published
1986

3. Anthropometric deficits and the associated risk of death by age and sex in children aged 6–59 months: A meta‐analysis

Author

Susan Thurstans, Stephanie V. Wrottesley, Bridget Fenn, Tanya Khara, Paluku Bahwere, James A. Berkley, Robert E. Black, Erin Boyd, Michel Garenne, Sheila Isanaka, Natasha Lelijveld, Christine M. McDonald, Andrew Mertens, Martha Mwangome, Kieran S. O'Brien, Heather Stobaugh, Sunita Taneja, Keith P. West, Saul Guerrero, Marko Kerac, André Briend, Mark Myatt, London School of Hygiene and Tropical Medicine (LSHTM), SOUtenabilité et RésilienCE (SOURCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut de Recherche pour le Développement (IRD [France-Nord]), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Université Paris Cité (UPCité)-Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Epicentre [Paris] [Médecins Sans Frontières], United States Agency for International Development, USAID, Irish Aid: HQPU/2021/ENN, This paper is made possible by the generous support of the American people through the United States Agency for International Development (USAID), and by funding from Irish Aid (grant number (HQPU/2021/ENN). The contents are entirely the responsibility of its authors and do not necessarily reflect the views of USAID or the United States Government or represent or reflect Irish Aid policy., Tampere University, and Clinical Medicine

Subjects
Male, Adolescent, wasting, Thinness, underweight, 3123 Gynaecology and paediatrics, Clinical Research, Prevalence, Humans, sex, Child, Growth Disorders, Pediatric, Nutrition and Dietetics, Anthropometry, Nutrition & Dietetics, Wasting Syndrome, Prevention, Malnutrition, stunting, Public Health, Environmental and Occupational Health, Infant, Obstetrics and Gynecology, mortality, Good Health and Well Being, age, Pediatrics, Perinatology and Child Health, Female, Zero Hunger, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Risk of death from undernutrition is thought to be higher in younger than in older children, but evidence is mixed. Research also demonstrates sex differences whereby boys have a higher prevalence of undernutrition than girls. This analysis described mortality risk associated with anthropometric deficits (wasting, underweight and stunting) in children 6–59 months by age and sex. We categorised children into younger (6–23 months) and older (24–59 months) age groups. Age and sex variations in near-term (within 6 months) mortality risk, associated with individual anthropometric deficits were assessed in a secondary analysis of multi-country cohort data. A random effects meta-analysis was performed. Data from seven low-or-middle-income-countries collected between 1977 and 2013 were analysed. One thousand twenty deaths were recorded for children with anthropometric deficits. Pooled meta-analysis estimates showed no differences by age in absolute mortality risk for wasting (RR 1.08, p = 0.826 for MUAC < 125 mm; RR 1.35, p = 0.272 for WHZ < −2). For underweight and stunting, absolute risk of death was higher in younger (RR 2.57, p < 0.001) compared with older children (RR 2.83, p < 0.001). For all deficits, there were no differences in mortality risk for girls compared with boys. There were no differences in the risk of mortality between younger and older wasted children, supporting continued inclusion of all children under-five in wasting treatment programmes. The risk of mortality associated with underweight and stunting was higher among younger children, suggesting that prevention programmes might be justified in focusing on younger children where resources are limited. There were no sex differences by age in mortality risk for all deficits.

Published
2022

4. Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study

Author

Eva Ardanaz, Agnetha Linn Rostgaard-Hansen, Alessio Naccarati, Elisabete Weiderpass, Pekka Keski-Rahkonen, Rudolf Kaaks, Tilman Kühn, Anna Winkvist, Jośe Mariá Huerta, H. B. Bueno-De-Mesquita, Guri Skeie, Pietro Ferrari, Krasimira Aleksandrova, Gabriel Perlemuter, Augustin Scalbert, Olatz Mokoroa, Giovanna Tagliabue, Marc J. Gunter, Kim Overvad, José Ramón Quirós, Agneta Kiss, Marie-Christine Boutron-Ruault, Yahya Mahamat-Saleh, Talita Duarte-Salles, Nivonirina Robinot, Anne Tjønneland, Antonia Trichopoulou, Julie A. Schmidt, Christina C. Dahm, Roel Vermeulen, Rosario Tumino, Núria Sala, Joseph A. Rothwell, Sophia Harlid, Magdalena Stepien, Klas Sjöberg, Vivian Viallon, Neil Murphy, Anna Karakatsani, Salvatore Panico, Nicholas J. Wareham, María José Sánchez, Francesca Mancini, Domenico Palli, Mazda Jenab, Elio Riboli, Bodil Ohlsson, Kay-Tee Khaw, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut National Du Cancer, INCa: 2014-1-RT-02-CIRC-1 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Cancer Research UK, CRUK: C570/A16491 Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer German Cancer Research Center, DKFZ Bundesministerium für Bildung und Forschung, BMBF Institut National de la Santé et de la Recherche Médicale, Inserm Kræftens Bekæmpelse, DCS National Research Council, NRC 6236 Hellenic Health Foundation, HHF Fondation Gustave Roussy European Commission, EC Centre International de Recherche sur le Cancer, CIRC Associazione Italiana per la Ricerca sul Cancro, AIRC RD06/0020 Deutsche Krebshilfe World Cancer Research Fund, WCRF Cancerfonden Medical Research Council, MRC: MR/M012190/1, This work was supported by the French National Cancer Institute (L'Institut National du Cancer, INCA) (grant number 2014-1-RT-02-CIRC-1, PI: M. Jenab). The coordination of EPIC is financially supported by the European Commission (DG-SANCO), and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, and Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands), and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) and the Catalan Institute of Oncology (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (14136 for EPIC-Norfolk and C570/A16491 for EPIC-Oxford) and the Medical Research Council (1000143 for EPIC-Norfolk and MR/M012190/1 for EPIC-Oxford) (UK). The funding sources had no influence on the design of the study, the collection, analysis, and interpretation of data, the writing of the report, and or the decision to submit the paper for publication. Disclaimer: Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization.

Subjects
Male, Oncology, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, prospective observational cohort, Glycocholic acid, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mass Spectrometry, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Dehydroepiandrosterone sulfate, Internal medicine, Biomarkers, Tumor, medicine, Humans, Metabolomics, Prospective Studies, Aged, Hepatitis, business.industry, Liver Neoplasms, Cancer, Feeding Behavior, hepatocellular carcinoma, Middle Aged, medicine.disease, 3. Good health, European Prospective Investigation into Cancer and Nutrition, untargeted metabolomics, chemistry, Case-Control Studies, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, Female, business, Metabolic Networks and Pathways, Chromatography, Liquid, Cohort study
Abstract

International audience; Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.

Published
2020

5. Clinical and epidemiological characteristics of 1420 European patients with mild‐to‐moderate coronavirus disease 2019

Author

Lechien, Jerome R., Chiesa‐Estomba, Carlos M., Place, Sammy, Van Laethem, Yves, Cabaraux, Pierre, Mat, Quentin, Huet, Kathy, Plzak, Jan, Horoi, Mihaela, Hans, Stéphane, Rosaria Barillari, Maria, Cammaroto, Giovanni, Fakhry, Nicolas, Martiny, Delphine, Ayad, Tareck, Jouffe, Lionel, Hopkins, Claire, Saussez, Sven, Blecic, Serge, De Siati, Daniele R., Leich, Pierre, Souchay, Christel, Rossi, Camelia, Journe, Fabrice, Hsieh, Julien, Ris, Laurence, El Afia, Fahd, Harmegnies, Bernard, Distinguin, Lea, Chekkoury‐Idrissi, Younes, Circiu, Marta, Lavigne, Philippe, Lopez Delgado, Irene, Calvo‐Henriquez, Christian, Falanga, Chiara, Coppee, Frederique, Le Bon, Serge Daniel, Rodriguez, Alexandra, Dequanter, Didier, Cornelis, Jean‐Philippe, Vergez, Sebastien, Koenen, Lukas, Giuditta, Mannelli, Molteni, Gabriele, Tucciarone, Manuel, Radulesco, Thomas, Khalife, Mohamad, Fourneau, Anne‐Francoise, Cherifi, Soraya, Manto, Mario, Michel, Justin, Mannelli, Giuditta, Cantarella, Giovanna, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance Publique - Hôpitaux de Marseille (APHM), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), We would like to thank Bayesia (BayesiaLab?, Chang?, France) for the Network Analysis, Jean-Louis Vincent and Michel Van Haeverbeek for the review of the paper or their useful comments, the heads of the Hospitals, which have been involved in the study, for their help in the rapid conduction of the study and the agreement of ethics committees, the European Press/Media (i.e. Le Monde, La Libre, Le Soir, MediQuality, MedScape, and Le Specialiste) for their help in the spread of the information about the study, and FRMH & UMONS for the grant and the support., Lechien, J. R., Chiesa-Estomba, C. M., Place, S., Van Laethem, Y., Cabaraux, P., Mat, Q., Huet, K., Plzak, J., Horoi, M., Hans, S., Barillari, M. R., Cammaroto, G., Fakhry, N., Martiny, D., Ayad, T., Jouffe, L., Hopkins, C., Saussez, S., Blecic, S., De Siati, D. R., Leich, P., Souchay, C., Rossi, C., Journe, F., Hsieh, J., Ris, L., El Afia, F., Harmegnies, B., Distinguin, L., Chekkoury-Idrissi, Y., Circiu, M., Lavigne, P., Lopez Delgado, I., Calvo-Henriquez, C., Falanga, C., Coppee, F., Le Bon, S. D., Rodriguez, A., Dequanter, D., Cornelis, J. -P., Vergez, S., Koenen, L., Giuditta, M., Molteni, G., Tucciarone, M., Radulesco, T., Khalife, M., Fourneau, A. -F., Cherifi, S., Manto, M., Michel, J., Mannelli, G., and Cantarella, G.

Subjects
0301 basic medicine, myalgia, Male, medicine, Original, [SDV]Life Sciences [q-bio], coronavirus, symptoms, Disease, epidemiological, 030204 cardiovascular system & hematology, patients, clinical, Olfaction Disorders, Taste Disorders, 0302 clinical medicine, Epidemiology, Sore throat, Prevalence, Nose, Age Factors, Headache, Middle Aged, 3. Good health, Europe, medicine.anatomical_structure, COVID-19, Female, patient, medicine.symptom, Symptom Assessment, Coronavirus Infections, Sex characteristics, Adult, medicine.medical_specialty, Pneumonia, Viral, 03 medical and health sciences, Betacoronavirus, Sex Factors, Throat, Internal medicine, Internal Medicine, Humans, Pandemics, covid‐19, rhinorrhea, business.industry, SARS-CoV-2, Bayes Theorem, Myalgia, coronaviru, 030104 developmental biology, business
Abstract

International audience; Background: The clinical presentation of European patients with mild-to-moderate COVID-19 infection is still unknown. Objective: To study the clinical presentation of COVID-19 in Europe. Methods: Patients with positive diagnosis of COVID-19 were recruited from 18 European hospitals. Epidemiological and clinical data were obtained through a standardized questionnaire. Bayesian analysis was used for analysing the relationship between outcomes. Results: A total of 1,420 patients completed the study (962 females, 30.7% of healthcare workers). The mean age of patients was 39.17 ± 12.09 years. The most common symptoms were headache (70.3%), loss of smell (70.2%), nasal obstruction (67.8%), cough (63.2%), asthenia (63.3%), myalgia (62.5%), rhinorrhea (60.1%), gustatory dysfunction (54.2%) and sore throat (52.9%). Fever was reported by 45.4%. The mean duration of COVID-19 symptoms of mild-to-moderate cured patients was 11.5 ± 5.7 days. The prevalence of symptoms significantly varied according to age and sex. Young patients more frequently had ear, nose and throat complaints, whereas elderly individuals often presented fever, fatigue and loss of appetite. Loss of smell, headache, nasal obstruction and fatigue were more prevalent in female patients. The loss of smell was a key symptom of mild-to-moderate COVID-19 patients and was not associated with nasal obstruction and rhinorrhea. Loss of smell persisted at least 7 days after the disease in 37.5% of cured patients. Conclusion: The clinical presentation of mild-to-moderate COVID-19 substantially varies according to the age and the sex characteristics of patients. Olfactory dysfunction seems to be an important underestimated symptom of mild-to-moderate COVID-19 that needs to be recognized as such by the WHO.

Published
2020
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