PubMed · 8347189
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
D Munro. 1993-03-27. Thyroid eye disease.. https://doi.org/10.1136/bmj.306.6881.805
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Brain-derived neurotrophic factor (BDNF) has potent effects on neuronal survival and plasticity during development and after injury. In the nervous system, neurons are considered the major cellular source of BDNF. We demonstrate here that in addition, activated human T cells, B cells, and monocytes secrete bioactive BDNF in vitro. Notably, in T helper (Th)1- and Th2-type CD4(+) T cell lines specific for myelin autoantigens such as myelin basic protein or myelin oligodendrocyte glycoprotein, BDNF production is increased upon antigen stimulation. The BDNF secreted by immune cells is bioactive, as it supports neuronal survival in vitro. Using anti-BDNF monoclonal antibody and polyclonal antiserum, BDNF immunoreactivity is demonstrable in inflammatory infiltrates in the brain of patients with acute disseminated encephalitis and multiple sclerosis. The results raise the possibility that in the nervous system, inflammatory infiltrates have a neuroprotective effect, which may limit the success of nonselective immunotherapies.
A RARE DISEASE: Paraneoplastic pemphigus is an rare autoimmune bullous skin disease recently recognized. About 50 cases have been reported since its first description in 1990. CLINICAL MANIFESTATIONS: Clinical signs are polymorphous resembling the cutaneomucosal manifestations of pemphigus vulgar (skin and mucosa erosions, fragile interdermal bullae), pemphigoid (urticaria, distended subepidermal bullae), and polymorphous erythema (plaque lesions). Mucosal erosions predominate however. ASSOCIATED CANCERS: Most cancers associated with paraneoplastic pemphigus are hematologic diseases (non-Hodgkin's lymphomas, chronic lymphoid leukemia). SEVERE PROGNOSIS: No standard treatment has been defined. General corticosteroids and treatment of the causal disease are indicated. The clinical course of paraneoplastic pemphigus does not always follow the course of the associated neoplasm. POSITIVE DIAGNOSIS: Pathology criteria (keratinocyte necrosis, suprabasal keratinocyte vacuolization, intraepidermal acantholysis) and immunohistological findings (antibody and complement deposits at the dermo-epidermal junction and within the keratinocytes on different epithelial substrates) are insufficient for positive diagnosis. Autoantibodies must be identified by immunoprecipitation or immunoblotting to identify the target antigen complex plakin components (desmoplakin I and II, periplakin, envoplakin), the major pemphigoid antigen, desmoglein 3, and certain yet unidentified antigens with a molecular weight of 170 kD. PATHOGENESIS: Paraneoplastic pemphigus appears as a model autoimmune paraneoplastic disease. Its origin remains elusive. It has been hypothesized that tumor-induced inhibition of tolerance to certain antigens implicated in the keratinocyte junctional systems could be involved.
Core snRNP proteins bind snRNA through the conserved Sm site, PuA(U)n>/=3GPu. While yeast U1 snRNA has three matches to the Sm consensus, the U1 3'-terminal Sm site was found to be both necessary and sufficient for U1 function. Mutation of this site inhibited pre-mRNA splicing, blocked cell division and resulted in the accumulation of two 3'-extended forms of the U1 snRNA. Cells which harbor the Sm site mutation lack mature U1 RNA (U1alpha) but have a minor polyadenylated species, U1gamma, and a prominent, non-polyadenylated species, U1beta. Metabolic depletion of the essential Sm core protein, Smd1p, also resulted in the increased accumulation of U1beta and U1gamma. In vitro, synthetic U1 precursors were cleaved by Rnt1p (RNase III) very near the U1beta 3'-end observed in vivo. We propose that U1beta is an Rnt1p-cleaved intermediate and that U1 maturation to the U1alpha form occurs through an Sm-sensitive step. Interestingly, both U1alpha and a second, much longer RNA, U1straightepsilon, were produced in an rnt1 mutant strain. These results suggest that yeast U1 snRNA processing may progress through Rnt1p-dependent and Rnt1p-independent pathways, both of which require a fun-ctional Sm site for final snRNA maturation.