ABSTRACT
Major histocompatibility complex class I-bound antigenic peptides generated in the cytosol are translocated into the ER by TAP. In the present study, the physical association of HSC73 with TAP in human lymphoblastoid T1 cells was demonstrated. The dissociation was induced in the presence of 10 mM ATP, indicating that the ADP-binding form of HSC73 might be associated with TAP. We found that HSC73-binding immunosuppressant, MeDSG disrupted the HSC73-TAP association, whereas it did not affect the binding of HSC73 to a substrate protein. MHC class I expression on the cell surface was also downregulated. Then, the effect of MeDSG on the TAP-mediated ER translocation was examined using two homologous model peptides, NGT-Bw4 and NGT-Bw6, which had distinct binding affinity to HSC73. Although high-affinity peptide NGT-Bw4 was translocated by TAP, low-affinity peptide NGT-Bw6 was not. The TAP-dependent translocation of NGT-Bw4 was abolished in the presence of MeDSG. Decreased presentation on the cell surface was shown for the human leukocyte antigen (HLA)-A31-restricted natural antigenic peptide F4.2, which had high affinity to HSC73, in the presence of MeDSG. It was indicated that disruption of the HSC73-TAP association resulted in inhibition of TAP-dependent translocation of HSC73-bound peptides. Our findings highlighted an important role of HSC73 for feeding antigenic peptides to TAP, and suggested a possibility that a synthetic polyamine might inhibit the function of HSC73, thereby suppressing MHC class I-restricted presentation of HSC73-bound antigenic peptides.
Subject(s)
ATP-Binding Cassette Transporters/metabolism , Antigen Presentation , Antigens/metabolism , Endoplasmic Reticulum/metabolism , HSC70 Heat-Shock Proteins/metabolism , Peptides/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 2 , Cell Line , Down-Regulation , Guanidines/pharmacology , HSC70 Heat-Shock Proteins/genetics , Histocompatibility Antigens Class I/biosynthesis , Humans , Immunosuppressive Agents/pharmacology , Protein BindingSubject(s)
Acyclovir/therapeutic use , Bone Marrow Transplantation , Herpes Zoster Ophthalmicus/etiology , Panuveitis/etiology , Adult , Antibodies, Viral/analysis , DNA, Viral/analysis , Female , Fluorescein Angiography , Follow-Up Studies , Fundus Oculi , Herpes Zoster Ophthalmicus/diagnosis , Herpes Zoster Ophthalmicus/drug therapy , Herpesvirus 3, Human/genetics , Herpesvirus 3, Human/immunology , Humans , Immunoglobulin G/immunology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/surgery , Panuveitis/diagnosis , Panuveitis/drug therapyABSTRACT
Acute annular outer retinopathy is an uncommon disorder of uncertain aetiology characterized by a unilateral visual field defect with an irregular annular band of grey-white, deep retinal opacification in a peripapillary location. Acute annular outer retinopathy is considered to be a variant of acute zonal occult outer retinopathy. The case is reported of acute annular outer retinopathy with spontaneous good visual recovery and no ophthalmoscopic sequelae.
Subject(s)
Retinal Diseases/complications , Vision Disorders/complications , Visual Fields , Acute Disease , Adult , Electroretinography , Female , Fluorescein Angiography , Humans , Remission, Spontaneous , Retinal Diseases/physiopathology , Vision Disorders/physiopathology , Visual Acuity/physiology , Visual Field TestsABSTRACT
PURPOSE: To evaluate the clinical features of nosocomial epidemic keratoconjunctivitis(EKC) occurring in the ophthalmology ward of Sapporo Medical University Hospital and to devise preventive measures for it. MATERIALS AND METHODS: We studied the symptoms and clinical course of 2 patients who had EKC and 16 patients who had EKC caused by nosocomial infections in our hospital. We attempted to detect adenovirus antigen and viral DNA from conjunctival swabs and also to isolate the virus. RESULTS: The clinical symptoms of EKC were conjunctival hyperemia in 18 patients(100%), conjunctival follicles in 11 patients (61.1%), discharge in 8 patients(44.4%), superficial punctate keratopathy in 7 patients(38.9%), swelling of the eyelids in 3 patients(16.7%), and fever in 3 patients(16.7%). 72% were positive for Adeno-check. Adenovirus type 4 was isolated from the conjunctival swabs. We considered that the route of hospital infection was infection from the doctor's hands, from eye drops, and from contact lenses. We disclosed that nosocomical EKC had occurred in our hospital. The hospital infection was eliminated by closing the ophthalmology ward and sterilizing instruments and washing hands. CONCLUSIONS: The delay of proper measures increased the risk of nosocomical infection. We recognized the importance of careful observation of patients and immediate preventive efforts in nosocomical infection.
Subject(s)
Adenovirus Infections, Human/transmission , Cross Infection/transmission , Keratoconjunctivitis/etiology , Adenovirus Infections, Human/prevention & control , Cross Infection/prevention & control , Female , Humans , Keratoconjunctivitis/prevention & control , MaleABSTRACT
A 60-year-old man was admitted for progressive visual loss in both eyes. He was diagnosed with retinopathy and chest computed tomography revealed an invasive thymoma. In western blot analysis, serum autoantibodies against recoverin, photoreceptor-specific calcium-binding protein, and heat shock cognate protein 70 which were identified as the cause of cancer-associated retinopathy (CAR). Immunofluorescence staining showed that thymoma cells also expressed recoverin. These observations strongly suggested that similar pathogenesis of CAR was involved in the presented case.
