ABSTRACT
HIV-associated neurocognitive disorders prevail in 20-50 percent of infected individuals. Macrophages transmigrate through the blood brain barrier during HIV-1 infection, triggering neuronal dysfunction. HIV-infected macrophages secrete cathepsin B (CATB), and serum amyloid p component (SAPC), inducing neuronal apoptosis by an unknown mechanism. We hypothesized that HIV infection facilitates CATB/SAPC secretion from macrophages followed by neuronal internalization, promoting dysfunction. SK-N-SH neuronal cells were exposed to active recombinant histidine-tagged cathepsin B (His-CATB). His-CATB entry was tracked by intracellular flow cytometry, and neuronal dysfunction was verified by western blot. Macrophage-derived extracellular vesicles (EVs) were tested for the presence of CATB and SAPC. Neurons internalized His-CATB, an effect that was partially decreased by pre-treatment with anti-CATB antibody. Pre-treatment with CATB and SAPC antibodies decreased cleavage of caspase-3 and restored synaptophysin in neurons. Neurons exposed to macrophage-conditioned media differentially internalized His-CATB, dependent on the HIV replication levels. Finally, CATB and SAPC were secreted in EVs. We report for the first time that CATB is secreted from macrophages both free and in EVs, and is internalized by neurons. Moreover, HIV-replication levels modulate the amount of CATB neuronal uptake, and neuronal dysfunction can be decreased with CATB antibodies. In conclusion, the CATB/SAPC complex represents a novel target against HIV-associated neurocognitive disorders.
Subject(s)
AIDS Dementia Complex/genetics , Cathepsin B/genetics , Endoribonucleases/genetics , HIV Infections/metabolism , Neoplasm Proteins/genetics , Neurons/metabolism , AIDS Dementia Complex/metabolism , AIDS Dementia Complex/physiopathology , Apoptosis/drug effects , Apoptosis/genetics , Blood-Brain Barrier/metabolism , Caspase 3/genetics , Cathepsin B/metabolism , Cell Line , Cells, Cultured , Culture Media, Conditioned/metabolism , Culture Media, Conditioned/pharmacology , Deoxyribonucleases, Type II Site-Specific , Endoribonucleases/metabolism , Extracellular Vesicles/metabolism , Extracellular Vesicles/pathology , Flow Cytometry , HIV Infections/complications , HIV Infections/physiopathology , HIV-1/pathogenicity , Hippocampus/metabolism , Hippocampus/pathology , Histidine/metabolism , Humans , Macrophages/metabolism , Macrophages/pathology , Neoplasm Proteins/metabolism , Neurons/pathology , Synaptophysin/geneticsABSTRACT
Atresia of the submandibular duct orifice is a rare developmental anomaly. Early identification and treatment of atresia of the submandibular duct orifice prevent feeding and breathing difficulties, dilatation of the submandibular duct, submandibular gland infection, or pressure atrophy. Imperforate submandibular duct should be distinguished from duplication abnormalities of the duct and other cystic lesions in the floor of the mouth. To date, magnetic resonance imaging findings of the atresia of the submandibular duct orifice have not been reported. The aim of this study was to describe clinical and radiologic evaluation of an infant with atresia of the bilateral submandibular duct orifices.
Subject(s)
Submandibular Gland Diseases/diagnosis , Submandibular Gland/abnormalities , Constriction, Pathologic/diagnosis , Humans , Infant , Magnetic Resonance Imaging , MaleABSTRACT
OBJECTIVE: Three-dimensional imaging can improve the understanding and comprehension of complex anatomy. Recent advances in software development allow the construction of a virtual endoscopic view of anatomic structures. This report applies virtual endoscopic capabilities to imaging of the internal auditory canal. STUDY DESIGN, SETTING, AND PATIENTS: We conducted a retrospective case review at a tertiary referral center of patients with abnormal internal auditory canal anatomy on computed tomography. INTERVENTIONS: Computed tomography images were obtained using conventional clinical algorithms involving multiple, 1-mm-thick slices through the temporal bone. Three-dimensional reconstructions were made using General Electric Advantage Windows Navigator software. The virtual endoscopic image-processing algorithm used selected image intensity threshold levels to visualize internal auditory canal anatomy from an endoscopic perspective. RESULTS: Eleven cases of abnormalities of the internal auditory canal were retrospectively identified. Clinical applications using the virtual endoscopic images are presented. The virtual endoscopic images supported prior clinical decision making in 6 of the 11 cases evaluated. CONCLUSION: This technique shows promise for the diagnosis, surgical planning, and teaching of temporal bone anatomy. Usefulness is dependent on acquisition parameters and clinical indications for examination.
