RESUMO
We report two cases of middle-aged men who presented with clinical features that satisfied the diagnostic criteria for multisystem inflammatory syndrome in adults (MIS-A). Both patients were treated for toxic shock syndrome and MIS-A and have recovered. The purpose of this article is to communicate our experience and challenges of assessing and treating this condition and to raise awareness of the condition.
Assuntos
COVID-19 , Choque Séptico , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Choque Séptico/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/terapiaRESUMO
Parenteral ivermectin treatment of disseminated strongyloidiasis and hyperinfection is increasing, although not licensed in humans and with limited pharmacokinetic data available. Plasma and postmortem tissue analysis in an human immunodeficiency virus (HIV)/hepatitis C virus-positive man with disseminated strongyloidiasis suggests loading subcutaneous ivermectin doses are required, from which the central nervous system is protected.
Assuntos
Antiparasitários/farmacocinética , Diarreia/diagnóstico , Infecções por HIV/diagnóstico , Hepatite C/diagnóstico , Pseudo-Obstrução Intestinal/diagnóstico , Ivermectina/farmacocinética , Estrongiloidíase/diagnóstico , Adulto , Animais , Autopsia , Diarreia/complicações , Diarreia/tratamento farmacológico , Diarreia/patologia , Evolução Fatal , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/patologia , Humanos , Injeções Subcutâneas , Pseudo-Obstrução Intestinal/complicações , Pseudo-Obstrução Intestinal/tratamento farmacológico , Pseudo-Obstrução Intestinal/patologia , Masculino , Strongyloides/patogenicidade , Strongyloides/fisiologia , Estrongiloidíase/complicações , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/patologiaRESUMO
Ras guanine nucleotide-releasing protein-4 (RasGRP4) is an evolutionarily conserved calcium-regulated, guanine nucleotide exchange factor and diacylglycerol/phorbol ester receptor. While an important intracellular signaling protein for CD117+ mast cells (MCs), its roles in other immune cells is less clear. In this study, we identified a subset of in vivo-differentiated splenic CD117+ dendritic cells (DCs) in wild-type (WT) C57BL/6 mice that unexpectedly contained RasGRP4 mRNA and protein. In regard to the biologic significance of these data to innate immunity, LPS-treated splenic CD117+ DCs from WT mice induced natural killer (NK) cells to produce much more interferon-γ (IFN-γ) than comparable DCs from RasGRP4-null mice. The ability of LPS-responsive MCs to cause NK cells to increase their expression of IFN-γ was also dependent on this intracellular signaling protein. The discovery that RasGRP4 is required for CD117+ MCs and DCs to optimally induce acute NK cell-dependent immune responses to LPS helps explain why this signaling protein has been conserved in evolution.
Assuntos
Células Dendríticas/imunologia , Células Matadoras Naturais/imunologia , Lipopolissacarídeos/farmacologia , Mastócitos/imunologia , Proteínas Proto-Oncogênicas c-kit/imunologia , Fatores ras de Troca de Nucleotídeo Guanina/fisiologia , Animais , Técnicas de Cocultura , Interferon gama/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ligante OX40 , Transdução de Sinais , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Fatores de Necrose Tumoral/metabolismoRESUMO
The interleukin (IL)-7 receptor (IL-7R) is expressed on human pre-B but not mature B-cells. We hypothesised that aberrant expression of IL-7R contributes to B-cell oncogenesis. Surface expression of IL-7R components CD127 and CD132, and intracellular Ki-67 and Bcl-2 were examined by flow cytometry on peripheral blood or bone marrow mononuclear cells (PBMC; BMMC) from patients with B-cell derived neoplasms, chronic human immunodeficiency virus type-1 (HIV-1) infection alone, or healthy volunteers. Plasma IL-7, IL-2, IL-4, IL-6, IL-10, IL-21, TNF-alpha, IFN-gamma and BAFF were measured by enzyme-linked immuno-sorbent assay or bead array. The effects of exogenous IL-7 on PBMC and BMMC were examined. CD127 expression was elevated in pre-B-cell acute lymphoblastic leukemia (pre-B-ALL) and in some cases of Non-Hodgkin's Lymphoma (B-NHL). Plasma IL-7 levels were higher in pre-B-ALL, B-cell chronic lymphocytic leukemia (B-CLL) and HIV-1 associated B-NHL (HIV-B-NHL) compared with control groups. CD127+ pre-B-ALL cells had higher expression of Ki-67, Bcl-2 and CD132 than CD127- counterparts. Unlike T-lineage cells, CD127+ pre-B-ALL cells did not down-regulate CD127 in response to exogenous IL-7. Patients with B-cell derived neoplasms had elevated circulating IL-10 and decreased BAFF. These findings support a role for the IL-7/IL-7R system in B-cell oncogenesis.