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Biomedical subjects

S Hsu

Publications and source records attributed to S Hsu.

At least 19 recordsLinked to original sources
PubMed2001

Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups.

Human narcolepsy-cataplexy, a sleep disorder associated with a centrally mediated hypocretin (orexin) deficiency, is tightly associated with HLA-DQB1*0602. Few studies have investigated the influence that additional HLA class II alleles have on susceptibility to this disease. In this work, 1,087 control subjects and 420 narcoleptic subjects with cataplexy, from three ethnic groups, were HLA typed, and the effects of HLA-DRB1, -DQA1, and -DQB1 were analyzed. As reported elsewhere, almost all narcoleptic subjects were positive for both HLA-DQA1*0102 and -DQB1*0602. A strong predisposing effect was observed in DQB1*0602 homozygotes, across all ethnic groups. Relative risks for narcolepsy were next calculated for heterozygous DQB1*0602/other HLA class II allelic combinations. Nine HLA class II alleles carried in trans with DQB1*0602 were found to influence disease predisposition. Significantly higher relative risks were observed for heterozygote combinations including DQB1*0301, DQA1*06, DRB1*04, DRB1*08, DRB1*11, and DRB1*12. Three alleles-DQB1*0601, DQB1*0501, and DQA1*01 (non-DQA1*0102)-were found to be protective. The genetic contribution of HLA-DQ to narcolepsy susceptibility was also estimated by use of lambda statistics. Results indicate that complex HLA-DR and -DQ interactions contribute to the genetic predisposition to human narcolepsy but that additional susceptibility loci are also most likely involved. Together with the recent hypocretin discoveries, these findings are consistent with an immunologically mediated destruction of hypocretin-containing cells in human narcolepsy-cataplexy.

Black or African American↗
PubMed2001

Multicentric reticulohistiocytosis with neurofibroma-like nodules.

We describe a patient with multicentric reticulohistiocytosis (MR), who presented with 2 different clinical types of lesions. Some were characteristic for MR in that they were deeply set, small, firm papules. Many others were larger, soft, and even sessile, like neurofibromas. Histopathologic features of both types of lesions revealed MR. To our knowledge, this is the first report of lesions of MR mimicking neurofibromas.

Adrenal Cortex Hormones↗
PubMed2000

Mutational analysis and NMR studies of the death domain of the tumor necrosis factor receptor-1.

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.

Amino Acid Sequence↗
PubMed2000

Lichen planus pemphigoides with IgG autoantibodies to the 180 kd bullous pemphigoid antigen (type XVII collagen).

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.

Aged↗
PubMed2000

Solution structure of N-TRADD and characterization of the interaction of N-TRADD and C-TRAF2, a key step in the TNFR1 signaling pathway.

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.

Amino Acid Sequence↗
PubMed2000

Large-scale DNA-based typing of HLA-A and HLA-B at low resolution is highly accurate specific and reliable.

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.

Bone Marrow Transplantation↗