Bleomycin-induced flagellate pigmentation.
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Biomedical subjects
Publications and source records attributed to S Hsu.
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Tumor necrosis factor receptor-1 (TNFR-1) death domain (DD) is the intracellular functional domain responsible for the receptor signaling activities. To understand the transduction mechanism of TNFR-1 signaling we performed structural and functional analysis of the TNFR-DD. The secondary structure of the TNFR-DD shows that it consists of six anti-parallel alpha-helices. The determination of the topological fold and an extensive mutagenesis analysis revealed that there are two opposite faces that are involved in self-association and interaction with the TRADD death domain. Interestingly, the same critical residues in TNFR-DD are involved in both interactions. There is a good correlation between the binding activities of the mutant proteins and their cytotoxic activities. These results provide important insight into the molecular interactions mediating TNFR-DD self-association and subsequent recruitment of TRADD in the signaling activity of TNFR-1.
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We describe a 75-year-old patient with pruritic papules on her trunk and extremities, typical of lichen planus, who later experienced subepidermal blisters. These clinical features are consistent with lichen planus pemphigoides. Immunofluorescence of perilesional skin showed linear deposits of C3 along the dermoepidermal junction. Circulating IgG autoantibodies were found to be directed against an epidermal component of the dermoepidermal junction because the patient's serum labeled the epidermal side of 1 mol/L NaCl-split skin. The patient's IgG autoantibodies were directed exclusively against the 180 kd bullous pemphigoid antigen (BPAg2, type XVII collagen) detected in human keratinocyte lysate by Western blot assay. No reactivity was found against the 230 kd bullous pemphigoid antigen, type VII collagen, or the laminin-5 subunits. This study demonstrates that BPAg2 is recognized, not only by bullous pemphigoid sera, but also by lichen planus pemphigoides sera. Our findings attest to the similarity of immunopathology in these two subepidermal blistering skin diseases.
TRADD is a multifunctional signaling adaptor protein that is recruited to TNFR1 upon ligand binding. The C-terminal of TRADD comprises the "death domain" that is responsible for association of TNFR1 and other death domain-containing proteins such as FADD and RIP. The N-terminal domain (N-TRADD) promotes the recruitment of TRAF2 to TNFR1 by binding to the C-terminal of TRAF2, leading to the activation of JNK/AP1 and NF-kappa B. The solution structure of N-TRADD was determined, revealing a novel protein fold. A combination of NMR, BIAcore, and mutagenesis experiments was used to help identify the site of interaction of N-TRADD with C-TRAF2, providing a framework for future attempts to selectively inhibit the TNF signaling pathways.
DNA-based typing of HLA class I alleles of the HLA-A and HLA-B loci using sequence-specific oligonucleotide primers and/or probes has been used for the large-scale typing of individuals for the National Marrow Donor Program unrelated donor registry. Typing was performed by 16 laboratories at a low level of resolution (e.g. A*01, B*07). The results of blinded quality control analysis for the first 12 months of the project show the typing to be highly accurate, specific and reliable. The total error rate based on 11,545 HLA-A and 11,428 HLA-B assignments was 1.1% for HLA-A and 1.9% for HLA-B. This level of accuracy is particularly remarkable because the quality control samples could not be distinguished from 64,180 donor samples tested at the same time by the laboratories.
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We report a case of atrophic skin lesions similar to atrophoderma vermiculatum with unilateral distribution in a patient with an ipsilateral cataract, transient ipsilateral alopecia, and a seizure disorder. Atrophoderma vermiculatum may be a cutaneous marker for various internal abnormalities.
Thyrotropin (TSH), free thyroxine (fT4) and testosterone assays have been used as a probe to evaluate the performances of a new modular chemiluminescence (CL) immunoassay analyser, the Abbott Architect 2000. The evaluation was run in parallel on other systems that use CL as the detection reaction: DPC Immulite, Chiron Diagnostics ACS-180 and ACS Centaur (TSH functional sensitivity only). TSH functional sensitivity was 0.0012, 0.009, 0.033 and 0.039 mU/I for the Architect, Immulite, ACS Centaur and ACS-180, respectively. Testosterone functional sensitivity was 0.38, 3.7 and 2.0 nmol/l for Architect, Immulite and ACS-180, respectively. Good correlation was obtained between the ACS-180 and Architect for all assays. The Immulite correlation did not agree well with the Architect or ACS-180 for fT4 and testosterone but was in good agreement for TSH. Regarding fT4 and testosterone, equilibrium dialysis and isotopic dilution gas-chromatography mass-spectrometry (GC-MS) respectively were used as reference methods. For both within- and between-run precision, the Architect showed the best reproducibility for all three analytes (CV < 6%).
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