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showing 10 items of 14693 documents

Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein☆

2021

Neurologic complications of symptomatic COVID-19 are common. Brain tissues from 13 autopsies of people who died of COVID-19 were examined. Cultured endothelial and neuronal cells were incubated with and wild type mice were injected IV with different spike subunits. In situ analyses were used to detect SARS-CoV-2 proteins and the host response. In 13/13 brains from fatal COVID-19, pseudovirions (spike, envelope, and membrane proteins without viral RNA) were present in the endothelia of microvessels ranging from 0 to 14 positive cells/200× field (mean 4.3). The pseudovirions strongly co-localized with caspase-3, ACE2, IL6, TNFα, and C5b-9. The surrounding neurons demonstrated increased NMDAR2…

0301 basic medicineAdultMalePathologymedicine.medical_specialtyProtein subunitH&E stainCaspase 3Spike proteinThirstPathology and Forensic Medicine03 medical and health sciencesMice0302 clinical medicineS1 subunitmedicineAnimalsHumansAgedAged 80 and overChemistrySARS-CoV-2COVID-19Endothelial CellsGeneral MedicineOriginal ContributionMiddle AgedMolecular biologyEndothelial stem cellDisease Models AnimalProtein Subunits030104 developmental biologyMembrane protein030220 oncology & carcinogenesisMicrovesselsSpike Glycoprotein CoronavirusImmunohistochemistryRNA ViralTumor necrosis factor alphaFemaleAutopsymedicine.symptomAnnals of Diagnostic Pathology
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Matching for the MICA-129 polymorphism is beneficial in unrelated hematopoietic stem cell transplantation.

2016

Major histocompatibility complex class I polypeptide-related sequence A (MICA) is a highly polymorphic ligand of the activating NKG2D receptor on natural killer (NK) cells, γδ-T cells, and NKT cells. MICA incompatibilities have been associated with an increased graft-versus-host disease (GVHD) incidence, and the MICA-129 (met/val) dimorphism has been shown to influence NKG2D signaling in unrelated hematopoietic stem cell transplantation (uHSCT). We investigated the effect of MICA matching on survival after uHSCT. We sequenced 2172 patients and their respective donors for MICA. All patients and donors were high-resolution HLA-typed and matched for 10/10 (n = 1379), 9/10 (n = 636), or 8/10 (n…

0301 basic medicineAdultMalemedicine.medical_specialtyAdolescentmedicine.medical_treatmentImmunologyHematopoietic stem cell transplantationHuman leukocyte antigenMajor histocompatibility complexBiochemistryGastroenterology03 medical and health sciencesYoung Adult0302 clinical medicineInternal medicinemedicineMinor histocompatibility antigenHumansAgedPolymorphism GeneticbiologyDonor selectionbusiness.industryHistocompatibility TestingHistocompatibility Antigens Class IHematopoietic Stem Cell TransplantationCell BiologyHematologyMiddle AgedNKG2DNatural killer T cellSurvival AnalysisTissue DonorsSurgeryTransplantationstomatognathic diseases030104 developmental biologyGenetic LociMultivariate Analysisbiology.proteinFemalebusiness030215 immunologyBlood
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Effect of gene-gene and gene-environment interactions associated with antituberculosis drug-induced hepatotoxicity.

2017

This study evaluated the association between environmental factors and genetic variations in enzymes that metabolize antituberculosis (anti-TB) drugs [arylamine N-acetyltransferase 2, cytochrome P450 2E1 (CYP2E1), glutathione S-transferase theta 1 (GSTT1), and glutathione S-transferase mu 1] with antituberculosis drug-induced hepatotoxicity (ATDH). We also investigated the potential gene-gene and gene-environment interactions as well as their association with ATDH development in a population of hospitalized TB patients from Buenos Aires.We investigated 364 TB patients who received anti-TB drugs. Physicians collected demographic and clinical data to identify environmental risk factors for AT…

0301 basic medicineAdultMalemedicine.medical_specialtyAntitubercular AgentsBiologyPharmacologyPolymorphism Single Nucleotide03 medical and health scienceschemistry.chemical_compoundYoung Adult0302 clinical medicineMolecular geneticsGenotypeGenetic variationGeneticsmedicineHumansGeneral Pharmacology Toxicology and PharmaceuticsAlleleMolecular BiologyGeneGenetics (clinical)chemistry.chemical_classificationEpistasis GeneticGlutathioneCYP2E1gene antitubercolosis drug drug cytochrome geneticsSettore BIO/18 - Genetica030104 developmental biologyEnzymechemistryLiver030220 oncology & carcinogenesisMolecular MedicineFemalePharmacogenetics and genomics
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Sex Alters the MHC Class I HLA-A Association With Polyglandular Autoimmunity.

2018

Abstract Context The major histocompatibility complex (MHC) strongly contributes to the development of polyglandular autoimmunity (PGA). Objective To evaluate the impact of sex on human leukocyte antigen (HLA) association with PGA for the first time. Design Cross-sectional immunogenetic study. Setting Academic tertiary referral Orphan Disease Center for PGA (ORPHA 282196) and immunogenetics laboratory. Subjects Patients (158) with coexistent type 1 diabetes and autoimmune thyroid disease (adult type 3 PGA, ORPHA 227982) and 479 unrelated healthy controls. Interventions All 637 white subjects were typed for HLA-A, -B, -DRB1, -DQA1, and -DQB1 alleles at a two-field level. Main Outcome Measure…

0301 basic medicineAdultMalemedicine.medical_specialtyEndocrinology Diabetes and MetabolismClinical Biochemistry030209 endocrinology & metabolismContext (language use)Human leukocyte antigenMajor histocompatibility complexmedicine.disease_causeBiochemistryAutoimmunity03 medical and health sciences0302 clinical medicineEndocrinologySex FactorsGene FrequencyInternal medicineMHC class ImedicineHumansGenetic Predisposition to DiseasePolyendocrinopathies AutoimmuneType 1 diabetesMHC class IIbiologyHLA-A Antigensbusiness.industryHistocompatibility TestingBiochemistry (medical)Histocompatibility Antigens Class IMiddle Agedmedicine.diseasePrognosisHLA-A030104 developmental biologyEndocrinologyCross-Sectional StudiesDiabetes Mellitus Type 1HaplotypesCase-Control Studiesbiology.proteinFemalebusinessBiomarkersFollow-Up StudiesThe Journal of clinical endocrinology and metabolism
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Obesity impairs leukocyte‐endothelium cell interactions and oxidative stress in humans

2018

Background:To evaluate the relationship between leukocyte‐endothelial cellinteractions and oxidative stress parameters in non‐diabetic patients with differentgrades of obesity.Material and methods:For this cross‐sectional study, 225 subjects wererecruited from January 1, 2014 to December 31, 2016 and divided into groupsaccording to BMI (40 kg/m²). We determined clin-ical parameters, systemic inflammatory markers, soluble cellular adhesion mole-cules, leukocyte‐endothelium cell interactions—rolling flux, velocity and adhesion—, oxidative stress parameters—total ROS, total superoxide, glutathione—andmitochondrial membrane potential in leukocytes.Results:We verified that HOMA‐IR and hsCRP incr…

0301 basic medicineAdultMalemedicine.medical_specialtyEndotheliumAdolescentClinical BiochemistryCell Communication030204 cardiovascular system & hematologyMitochondrionmedicine.disease_causeBiochemistryProinflammatory cytokineBody Mass Index03 medical and health sciencesYoung Adult0302 clinical medicineInternal medicinemedicineCell AdhesionLeukocytesHumansObesityEndothelial dysfunctionCell adhesionAgedchemistry.chemical_classificationMembrane Potential MitochondrialReactive oxygen speciesChemistryCell adhesion moleculeEndothelial CellsGeneral MedicineMiddle AgedAtherogenesismedicine.diseaseIntercellular Adhesion Molecule-1Oxidative Stress030104 developmental biologyEndocrinologymedicine.anatomical_structureCross-Sectional StudiesCytokinesReactive oxygen specieFemaleMitochondrial membrane potentialReactive Oxygen SpeciesOxidative stress
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Are Mitochondrial Fusion and Fission Impaired in Leukocytes of Type 2 Diabetic Patients?

2016

Mitochondrial fusion/fission alterations have been evaluated in different tissues of type 2 diabetic (T2D) patients. However, it is not known whether mitochondrial dynamics is disturbed in the leukocytes of T2D patients and whether glycemic control affects its regulation. Anthropometric and metabolic parameters in 91 T2D patients (48 with glycated hemoglobin [HbA1c]6.5% and 43 with HbA1c6.5%) were characteristic of the disease when compared with 78 control subjects. We observed increased reactive oxygen species production in leukocytes from diabetic patients, together with a reduced mitochondrial oxygen consumption rate, especially in poorly controlled patients. Mitochondrial fusion was red…

0301 basic medicineAdultMalemedicine.medical_specialtyendocrine system diseasesEndotheliumPhysiologyClinical BiochemistryCell CommunicationBiologymedicine.disease_causeBiochemistryMitochondrial DynamicsMitochondrial Membrane Transport Proteins03 medical and health scienceschemistry.chemical_compound0302 clinical medicineInternal medicineDiabetes mellitusmedicineLeukocytesHumansMolecular BiologyGeneral Environmental ScienceGlycemicAgedCase-control studyIncreased reactive oxygen species productionCell BiologyMiddle Agedmedicine.diseaseMitochondriaOxidative Stress030104 developmental biologyEndocrinologymedicine.anatomical_structuremitochondrial fusionchemistryDiabetes Mellitus Type 2Gene Expression Regulation030220 oncology & carcinogenesisCase-Control StudiesGeneral Earth and Planetary SciencesFemaleGlycated hemoglobinEndothelium VascularReactive Oxygen SpeciesOxidative stressBiomarkersAntioxidantsredox signaling
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Impact of somatic mutations in myelodysplastic patients with isolated partial or total loss of chromosome 7

2020

Monosomy 7 [-7] and/or partial loss of chromosome 7 [del(7q)] are associated with poor and intermediate prognosis, respectively, in myelodysplastic syndromes (MDS), but somatic mutations may also play a key complementary role. We analyzed the impact on the outcomes of deep targeted mutational screening in 280 MDS patients with -7/del(7q) as isolated cytogenetic abnormality (86 with del(7q) and 194 with -7). Patients with del(7q) or -7 had similar demographic and disease-related characteristics. Somatic mutations were detected in 79% (93/117) of patients (82% in -7 and 73% in del(7q) group). Median number of mutations per patient was 2 (range 0-8). There was no difference in mutation frequen…

0301 basic medicineAdultMalemyelodysplastic syndromes chromosome abnormalities prognosisCancer Researchmedicine.medical_specialtyAdolescentSomatic cellTp53 mutationGastroenterology03 medical and health sciences0302 clinical medicinePartial lossCytogenetic AbnormalityInternal medicineAntineoplastic Combined Chemotherapy ProtocolsMedicineHumansMutation frequencyAgedChromosome 7 (human)Aged 80 and overbusiness.industryMyelodysplastic syndromesHematologyMiddle Agedmedicine.diseasePrognosisSurvival AnalysisMutational analysis030104 developmental biologyOncology030220 oncology & carcinogenesisMyelodysplastic SyndromesMutationFemaleChromosome DeletionbusinessChromosomes Human Pair 7
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Human limbal fibroblast-like stem cells induce immune-tolerance in autoreactive T lymphocytes from female patients with Hashimoto’s thyroiditis

2017

Background Due to their “natural immune privilege” and immunoregulatory properties human fibroblast-like limbal stem cells (f-LSCs) have acquired great interest as a potential tool for achieving immunotolerance. Hashimoto’s thyroiditis (HT) is the most common thyroid autoimmune disease and cause of hypothyroidism. To date, conventional hormone replacement therapy and unspecific immunosuppressive regimens cannot provide a definitive cure for HT subjects. We explored the immunosuppressant potential of human f-LSCs on circulating lymphomonocytes (PBMCs) collected from healthy donors and female HT patients. Methods We assessed the immunophenotyping of f-LSCs, both untreated and after 48 h of pr…

0301 basic medicineAdultMedicine (miscellaneous)Hashimoto DiseaseCD8-Positive T-LymphocytesInflammatory diseasesMajor histocompatibility complexBiochemistry Genetics and Molecular Biology (miscellaneous)Settore MED/13 - EndocrinologiaProinflammatory cytokineImmune tolerancelcsh:Biochemistry03 medical and health scienceschemistry.chemical_compoundHuman limbal stem cells Hashimoto’s thyroiditis Immunoregulation Tolerance induction Inflammatory diseasesImmune privilegeImmune ToleranceMedicineHumanslcsh:QD415-436Tolerance inductionCells CulturedAgedlcsh:R5-920biologybusiness.industryResearchStem CellsInterleukinImmunoregulationCarboxyfluorescein succinimidyl esterCell BiologyHashimoto’s thyroiditisFibroblastsMiddle AgedTh1 Cells030104 developmental biologychemistryImmunologybiology.proteinHuman limbal stem cellsMolecular MedicineCytokinesFemaleStem cellbusinesslcsh:Medicine (General)CD8Stem Cell Research & Therapy
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Characterization of endometriosis-associated immune cell infiltrates (EMaICI)

2016

Objective: To identify and characterize endometriosis-associated immune cell infiltrates (EMaICI). Furthermore, to define occurrence and size of EMaICI in various types of endometriosis. Methods: Immune cells were characterized in samples of 60 premenopausal women with histological proven endometriosis. Therefore, immunohistochemical staining with monoclonal antibodies for CD3, CD4, CD8, CD45RO, CD25, CD56, CD68, and CD20 on sections of paraffin-embedded endometriotic tissue was performed. Results: EMaICI were observed in all the types of endometriosis, and characterized as T lymphocytes (CD3+), helper T lymphocytes (CD4+), cytotoxic T lymphocytes (CD8+), antigen-experienced T lymphocytes”m…

0301 basic medicineAdultPathologymedicine.medical_specialtyCellEndometriosisEndometriosisImmune cell defectChronic inflammatory disease03 medical and health sciences0302 clinical medicineImmune systemImmune cell infiltratemedicineHumansLymphocytesOvarian DiseasesEndometriosi030219 obstetrics & reproductive medicinebusiness.industryMacrophagesMedicine (all)Chronic inflammatory diseaseObstetrics and GynecologyGeneral MedicineMiddle Agedmedicine.diseaseImmunohistochemistryHuman genetics030104 developmental biologymedicine.anatomical_structureImmunologyFemalebusiness
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Annulate Lamellae in a Desmoplastic Small Round Cell Tumor

2016

0301 basic medicineAdultPathologymedicine.medical_specialtyOncogene ProteinsDesmoplastic small-round-cell tumorAnnulate lamellaOncogene Proteins FusionBiologyDesmoplastic Small Round Cell TumorPathology and Forensic Medicine03 medical and health sciences0302 clinical medicineNeoplasm RecurrenceMicroscopy Electron TransmissionmedicineBiomarkers TumorHumansRetroperitoneal NeoplasmsReverse Transcriptase Polymerase Chain Reactionmedicine.diseaseImmunohistochemistryRetroperitoneal Neoplasm030104 developmental biology030220 oncology & carcinogenesisImmunohistochemistrySurgeryFemaleAnatomyNeoplasm Recurrence Local
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