Subject(s)
Coronavirus Infections/prevention & control , Cross Infection/prevention & control , Infection Control/methods , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Betacoronavirus , COVID-19 , Coronavirus Infections/transmission , Hand Disinfection , Health Personnel , Hospitals, University , Humans , Masks , Personal Protective Equipment , Personnel, Hospital , Pneumonia, Viral/transmission , Respiratory Protective Devices , SARS-CoV-2 , SwitzerlandSubject(s)
Latent Tuberculosis/diagnosis , Latent Tuberculosis/epidemiology , Adult , Antitubercular Agents/therapeutic use , Cross-Sectional Studies , Drug Therapy, Combination , Humans , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Interferon-gamma/metabolism , Latent Tuberculosis/drug therapy , Latent Tuberculosis/transmission , Male , Risk Factors , T-Lymphocytes/immunology , Tuberculin TestSubject(s)
Bacterial Infections/diagnosis , Pharyngitis/diagnosis , Pharyngitis/etiology , Tonsillitis/diagnosis , Tonsillitis/etiology , Virus Diseases/diagnosis , Acute Disease , Adult , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/complications , Bacterial Infections/drug therapy , Diagnosis, Differential , Humans , Infectious Mononucleosis/diagnosis , Male , Pharyngitis/complications , Pharyngitis/drug therapy , Tonsillitis/complications , Tonsillitis/drug therapy , Virus Diseases/complications , Virus Diseases/drug therapySubject(s)
Lymphatic Diseases , Biopsy, Fine-Needle , Carcinoma, Adenosquamous/diagnosis , Diagnosis, Differential , Humans , Lymph Node Excision , Lymph Nodes/pathology , Lymphatic Diseases/diagnosis , Lymphatic Diseases/pathology , Lymphatic Metastasis/diagnosis , Male , Middle Aged , Neck/diagnostic imaging , Radiography, Abdominal , Radiography, Thoracic , Tomography, X-Ray Computed , Tongue Neoplasms/diagnosisABSTRACT
Nitric oxide (NO) produced by the inducible form of nitric oxide synthase (iNOS) has bactericidal and virocidal effects. Although NO synthesis and iNOS expression in macrophages affect several aspects of human immunodeficiency virus (HIV) type-1 pathogenesis, their role in HIV disease remains largely unknown. In humans, the expression of iNOS is influenced by a functional CCTTT-repeat polymorphism in the promoter region of the gene. We investigated the association of this polymorphism with HIV pathogenesis in naive HIV-infected patients before the initiation of antiretroviral therapy. The allele frequencies of the iNOS CCTTT-repeat polymorphism were assessed by PCR in 857 patients from the Swiss HIV Cohort Study, including rapid progressors and long-term nonprogressors, and in 240 healthy volunteers. In HIV-infected patients, the initial viral load and the decline in total CD4 cells was calculated to estimate disease progression. Allele frequencies of the iNOS CCTTT-repeat polymorphism were similar between the HIV-infected and noninfected blood donors. In treatment-naive HIV-positive patients, there was no association of the iNOS polymorphism with viral load or with the course of CD4 cells. Regulation of iNOS expression by the functional CCTTT-polymorphism does not modify HIV pathogenesis.
Subject(s)
HIV Infections/etiology , HIV-1/pathogenicity , Nitric Oxide Synthase/genetics , Polymorphism, Genetic , Promoter Regions, Genetic , Adult , CD4-Positive T-Lymphocytes/immunology , Case-Control Studies , Disease Progression , Gene Frequency , HIV Infections/immunology , HIV Infections/metabolism , Humans , Linear Models , Nitric Oxide Synthase Type II , Polymerase Chain Reaction/methods , Viral LoadABSTRACT
Lipoproteins are a subgroup of secreted bacterial proteins characterized by a lipidated N-terminus, processing of which is mediated by the consecutive activity of prolipoprotein diacylglyceryl transferase (Lgt) and lipoprotein signal peptidase (LspA). The study of LspA function has been limited mainly to non-pathogenic microorganisms. To study a potential role for LspA in the pathogenesis of bacterial infections, we have disrupted lspA by allelic replacement in Mycobacterium tuberculosis, one of the world's most devastating pathogens. Despite the presence of an impermeable lipid outer layer, it was found that LspA was dispensable for growth under in vitro culture conditions. In contrast, the mutant was markedly attenuated in virulence models of tuberculosis. Our findings establish lipoprotein metabolism as a major virulence determinant of tuberculosis and define a role for lipoprotein processing in bacterial pathogenesis. In addition, these results hint at a promising new target for therapeutic intervention, as a highly specific inhibitor of bacterial lipoprotein signal peptidases is available.
