2‐deoxy D‐glucose treatment does not elicit a hair growth response in alopecia areata

2‐deoxy D‐glucose (2DG) was tested for efficacy in treating alopecia areata using the C3H/HeJ skin graft model. 2DG has proven to be efficacious in treatment of various mouse models of autoimmunity with minimal serious side effects noted. This agent has been shown to normalize abnormally activated T‐cell populations while also preventing cell surface expression of NKG2D; key factors defining alopecia areata disease progression. Daily oral ingestion of 2DG via drinking water to mice with patchy or diffuse alopecia areata for 16 weeks failed to prevent expansion of alopecia or cause regrowth of hair in treated mice. Histologically, there were no differences between treated and control groups. These results indicate that, while 2DG is effective for some autoimmune diseases, it was not efficacious for the cell‐mediated autoimmune mouse disease, alopecia areata.     

Novel chondroitin sulfate-modified ligands for L-selectin on lymph node high endothelial venules

The migration of lymphocytes into lymph nodes via high endothelial venules (HEV) is dependent on the expression of L-selectin on the lymphocyte cell surface. HEV express several L-selectin ligands including CD34, GlyCAM-1, MAdCAM-1 and two sulfated glycoproteins (Sgp) of 200 kDa and 170 kDa which remain to be identified. In this investigation, labeling with sodium [35S]sulfate, which is incorporated into and forms part of the functional carbohydrate ligand, has been used to isolate and characterize macromolecular L-selectin ligands. High endothelial cells (HEC) cultured from rat lymph node HEV were shown to express ligands for L-selectin. HEC synthesized two groups of sulfated glycoproteins of 150 kDa and > 200 kDa, which were present in conditioned medium. These coeluted on anion exchange chromatography at 1.0-1.2 M NaCl and supported calcium-dependent L-selectin-mediated cell adhesion. In common with known L-selectin ligands, Sgp 150/> 200 were shown to be O-sialoglycoproteins; however, in contrast to other ligands, Sgp 150/> 200 contained chondroitin sulfate glycosaminoglycan modifications which were required for L-selectin recognition. Chondroitin sulfate-modified ligands for L-selectin were expressed at the HEC surface and by HEV in lymph nodes, suggesting that they may participate in lymphocyte interactions with HEV in vivo.     

Tissue-specific distribution of the Goodpasture antigen demonstrated by 2-D electrophoresis and Western blotting

The target of autoantibodies in Goodpasture's disease, the Goodpastureantigen has recently been characterized as the NC1 domain ofthe 3 chain of type IV collagen. In order to study the Goodpastureantigen in different organs, NC1 domains were isolated frombasement membranes (BM) of human glomeruli (GBM), tubules (TBM),alveoli (ABM), placenta (PBM) and aorta (VBM). NC1 preparationswere separated by 2-D electrophoresis, and silver stained orimmunoblotted to determine the subunit structure and antigenicityof different basement membranes. All basement membranes containedmonomeric components of MW 26 kDa and 24 kDa, and associateddimers, corresponding to the 2-D location of 1(IV) and cc2(IV)chains respectively. However, GBM, ABM, and to a lesser extentTBM possessed an extra set of monomeric components of MW 28kDa and associated dimers corresponding to the proposed locationof 3(IV) and 4(IV) chains. 2-D-separated polypeptides were Westernblotted with autoantibodies from patients with Goodpasture'sdisease, a monoclonal antibody to the Goodpasture antigen (P1)and a monoclonal antibody to the bovine 3(IV) chain. The predominantbinding of all these reagents was to cationic 28 kDa monomersof GBM, ABM and TBM, corresponding to the 3(IV) chain, althoughautoantibodies and P1 also bound to neutral 28 kDa monomers,corresponding to the 4(IV) chain. Autoantibodies bound weaklyto more neutral components of PBM and VBM, but neither monoclonalantibody bound to these basement membranes. This study suggeststhat there are two separate type IV collagen networks: one containingthe l(IV) and 2(IV) chains appears to be present in all basementmembranes, and the other containing the 3(IV) and 4(IV) chainshas a tissue specific distribution. The latter network bearingthe Goodpasture antigen is expressed in the basement membranesof both kidney and lung, the organs involved in Goodpasture'sdisease.     

Correction to: Treatment of adults with intracranial hemorrhage on apixaban or rivaroxaban with prothrombin complex concentrate products

Journal of Thrombosis and Thrombolysis - In the original publication of the article, unfortunately the given name and family name of the author’s in the author group were inadvertently...     

Clinical outcomes and complication profile of total hip arthroplasty after lumbar spine fusion: a meta-analysis and systematic review

European Spine Journal - Hip and spine pathology can alter the biomechanics of spino-pelvic mobility. Lumbar spine fusions can reduce the mobility of the lumbar spine and therefore result in...     

Frequency and histological appearance of adenomas in multiple intestinal neoplasia mice are unaffected by severe combined immunodeficiency (scid) mutation

Well-characterized murine mutations are powerful analytical tools for the genetic analysis of tumorigenesis. We crossed the multiple intestinal neoplasia (Min) allele of adenomatous polyposis coli (Apc), which produces a profound pre-disposition to intestinal neoplasia, with the severe combined immunodeficiency (scid) mutation, which causes defective double-strand DNA repair and severe immunodeficiency, on the common C57BL/6J genetic background to assay for any combined effect on intestinal tumorigenesis. Several phenotypic traits were exacerbated in an apparently additive manner in the double mutant mice, including reduced immunoglobulin levels, reduced body weight and increased morbidity. However, quantitation and histological evaluation of polyp phenotype indicated that these mutations did not interact to affect either polyp frequency or progression. Thus, neither genome instability nor lack of immunosurveillance conferred by scid contributes to intestinal polyps in this model. © 1996 Wiley-Liss, Inc.     

Glycosylphosphatidylinositol-anchored H-2Db molecules are defective in antigen processing and presentation to cytotoxic T lymphocytes

Glycosylphosphatidylinositol-anchored (GPI)-D^b molecules are defective in mediating cytotoxic T lymphocytes (CTL) lysis of transfected lymphoma cells, compared to their transmembrane (TM) counterpart. This defect is manifest when antigenic peptide must be processed and presented through the endogenous pathway. These same transfectants can be lysed by allospecific CTL, or by antigen-specific D^b-restricted CTL when pulsed with appropriate exogenous synthetic peptide, demonstrating that they can bind and present peptide for CTL-mediated lympholysis. The defect apparently results from differences between GPI-D^b and TM-D^b assembly and transport, or from differences in membrane topology that affect CD8⁺ CTL recognition of major histocompatibility complex/peptide complex.