Fundus abnormalities in a patient with type I Gaucher's disease with 12-year follow-up

PURPOSE: To report a case of type I Gaucher's disease with rare presentation of fundus abnormalities in long-term observation. DESIGN: Observational case report. METHODS: This 53-year-old Taiwanese woman suffered from type I Gaucher's disease for 12 years, with initial presentation of hepatoslpenomegaly in 1992. RESULTS: At that time, poor vision with unusual macular change and peripheral retinal vessel leakage was also noted. She received a complete ophthalmic examination at the initial visit and again 12 years later in 2003. She was treated with imiglucerase injection during the last 4 years. However, her visual acuity was 10/200 in both eyes. The macular and peripheral retinal degenerative change progressed after 12 years. CONCLUSIONS: Fundus changes associated with Gaucher's disease are uncommon. We should not neglect the possibility of retinal involvement and progression in these patients.     

Hypothalamic obesity syndrome: Rare presentation of CNS+ B-cell lymphoblastic lymphoma

Hypothalamic obesity syndrome can affect brain tumor patients following surgical intervention and irradiation. This syndrome is rare at diagnosis in childhood cancer, but has been reported with relapse of acute lymphoblastic leukemia. Here we present a case of hypothalamic obesity syndrome as the primary presentation of a toddler found to have CNS+ B‐cell lymphoblastic lymphoma. Cytogenetic studies on diagnostic cerebrospinal fluid revealed MLL gene rearrangement (11q23). Hyperphagia and obesity dramatically improved following induction and consolidation chemotherapy. We describe a novel presentation of hypothalamic obesity syndrome in CNS B‐cell lymphoblastic lymphoma, responsive to chemotherapy. Pediatr Blood Cancer 2012; 59: 930–933. © 2011 Wiley Periodicals, Inc.     

Gene expression profiling suggests a pathological role of human bone marrow-derived mesenchymal stem cells in aging-related skeletal diseases

Aging is associated with bone loss and degenerative joint diseases, in which the aging of bone marrow-derived mesenchymal stem cell (bmMSC)[1] may play an important role. In this study, we analyzed the gene expression profiles of bmMSC from 14 donors between 36 and 74 years old, and obtained age-associated genes (in the background of osteoarthritis) and osteoarthritis-associated genes (in the background of old age). Pathway analysis of these genes suggests that alterations in glycobiology might play an important role in the aging of human bmMSC. On the other hand, antigen presentation and signaling of immune cells were the top pathways enriched by osteoarthritis-associated genes, suggesting that alteration in immunology of bmMSC might be involved in the pathogenesis of osteoarthritis. Most intriguingly, we found significant age-associated differential expression of HEXA, HEXB, CTSK, SULF1, ADAMTS5, SPP1, COL8A2, GPNMB, TNFAIP6, and RPL29; those genes have been implicated in the bone loss and the pathology of osteoporosis and osteoarthritis in aging. Collectively, our results suggest a pathological role of bmMSC in aging-related skeletal diseases, and suggest the possibility that alteration in the immunology of bmMSC might also play an important role in the etiology of adult-onset osteoarthritis.     

Motivations and decision-making dilemmas of overseas liver transplantation: Taiwan recipients' perspectives

Purpose

This study sought to explore the motivation and dilemmas in the decision-making process encountered by Taiwan overseas orthotopic liver transplant (OLT) recipients.

Patients and methods

We used an exploratory qualitative research method on a sample of transplant recipients. Face-to-face in-depth interviews were performed with a semistructured interview guide. Data were evaluated by qualitative content analysis.

Results

We interviewed 15 patients including 11 males and 4 females aged between 41 and 68 years (mean = 57.3) including 14 who received OLT in China and one in the United States. The most important motivations were saving lives from end-stage liver disease and avoiding a hopeless sense of their residual lives with the psychological torture of a waiting death. Their decision-making process leading to overseas OLT could be divided into several phases among which the phase of transplant data evaluation and decision was the most critical one. Nevertheless, every stage and phase had its unique contents, factors, and dilemmas.

Conclusion

This study demonstrated that patients encountered various dilemmas at different phases in the decision-making process of considering overseas OLT. This information is important for care providers and policy makers in dealing with patients who consider overseas OLT.     

Mechanistic characterization of GS-9190 (Tegobuvir), a novel nonnucleoside inhibitor of hepatitis C virus NS5B polymerase

GS-9190 (Tegobuvir) is a novel imidazopyridine inhibitor of hepatitis C virus (HCV) RNA replication in vitro and has demonstrated potent antiviral activity in patients chronically infected with genotype 1 (GT1) HCV. GS-9190 exhibits reduced activity against GT2a (JFH1) subgenomic replicons and GT2a (J6/JFH1) infectious virus, suggesting that the compound's mechanism of action involves a genotype-specific viral component. To further investigate the GS-9190 mechanism of action, we utilized the susceptibility differences between GT1b and GT2a by constructing a series of replicon chimeras where combinations of 1b and 2a nonstructural proteins were encoded within the same replicon. The antiviral activities of GS-9190 against the chimeric replicons were reduced to levels comparable to that of the wild-type GT2a replicon in chimeras expressing GT2a NS5B. GT1b replicons in which the β-hairpin region (amino acids 435 to 455) was replaced by the corresponding sequence of GT2a were markedly less susceptible to GS-9190, indicating the importance of the thumb subdomain of the polymerase in this effect. Resistance selection in GT1b replicon cells identified several mutations in NS5B (C316Y, Y448H, Y452H, and C445F) that contributed to the drug resistance phenotype. Reintroduction of these mutations into wild-type replicons conferred resistance to GS-9190, with the number of NS5B mutations correlating with the degree of resistance. Analysis of GS-9190 cross-resistance against previously reported NS5B drug-selected mutations showed that the resistance pattern of GS-9190 is different from other nonnucleoside inhibitors. Collectively, these data demonstrate that GS-9190 represents a novel class of nonnucleoside polymerase inhibitors that interact with NS5B likely through involvement of the β-hairpin in the thumb subdomain.