University of Alabama at Birmingham

About: University of Alabama at Birmingham is a education organization based out in Birmingham, Alabama, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 38523 authors who have published 86775 publications receiving 3930642 citations. The organization is also known as: UAB & The University of Alabama at Birmingham.

Synovial fibroblasts of patients with rheumatoid arthritis attach to and invade normal human cartilage when engrafted into SCID mice

Abstract: Rheumatoid arthritis (RA) has been thought to be largely a T-cell-mediated disease. To evaluate the role of T-cell-independent pathways in RA, we examined the interaction between isolated RA synovial fibroblasts and normal human cartilage engrafted into SCID mice in the absence of T cells and other human cells. The expression of cartilage-de grading enzymes and adhesion molecules was examined by immunohistochemistry and in situ hybridization techniques. The RA synovial fibroblasts invaded the cartilage and kept their transformed appearing cellular shape. They expressed VCAM-1 and produced the cathepsins L and B at the site of invasion. We conclude that RA synovial fibroblasts maintain their invasive and destructive behavior over longer periods of time in the absence of human T cells, indicating that T-cell-independent pathways play a significant role in rheumatoid joint destruction.

Drusen complement components C3a and C5a promote choroidal neovascularization

Abstract: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrialized nations, affecting 30-50 million people worldwide. The earliest clinical hallmark of AMD is the presence of drusen, extracellular deposits that accumulate beneath the retinal pigmented epithelium. Although drusen nearly always precede and increase the risk of choroidal neovascularization (CNV), the late vision-threatening stage of AMD, it is unknown whether drusen contribute to the development of CNV. Both in patients with AMD and in a recently described mouse model of AMD, early subretinal pigmented epithelium deposition of complement components C3 and C5 occurs, suggesting a contributing role for these inflammatory proteins in the development of AMD. Here we provide evidence that bioactive fragments of these complement components (C3a and C5a) are present in drusen of patients with AMD, and that C3a and C5a induce VEGF expression in vitro and in vivo. Further, we demonstrate that C3a and C5a are generated early in the course of laser-induced CNV, an accelerated model of neovascular AMD driven by VEGF and recruitment of leukocytes into the choroid. We also show that genetic ablation of receptors for C3a or C5a reduces VEGF expression, leukocyte recruitment, and CNV formation after laser injury, and that antibody-mediated neutralization of C3a or C5a or pharmacological blockade of their receptors also reduces CNV. Collectively, these findings establish a mechanistic basis for the clinical observation that drusen predispose to CNV, revealing a role for immunological phenomena in angiogenesis and providing therapeutic targets for AMD.

Petrogenesis of slab-derived trondhjemite–tonalite-dacite/adakite magmas

Abstract: The prospect of partial melting of the subducted oceanic crust to produce arc magmatism has been debated for over 30 years. Debate has centred on the physical conditions of slab melting and the lack of a definitive, unambiguous geochemical signature and petrogenetic process. Experimental partial melting data for basalt over a wide range of pressures (1–32 kbar) and temperatures (700–1150°C) have shown that melt compositions are primarily trondhjemite–tonalite–dacite (TTD). High-Al (> 15% Al 2 O 3 at the 70% SiO 2 level) TTD melts are produced by high-pressure (≥ 5 kbar) partial melting of basalt, leaving a restite assemblage of garnet + clinopyroxene ± hornblende. A specific Cenozoic high-Al TTD (adakite) contains lower Y, Yb and Sc and higher Sr, Sr/Y, La/Yb and.Zr/Sm relative to other TTD types and is interpreted to represent a slab melt under garnet amphibolite to eclogite conditions. High-Al TTD with an adakite-like geochemical character is prevalent in the Archean as the result of a higher geotherm that facilitated slab melting. Cenozoic adakite localities are commonly associated with the subduction of young ( −1 ) conducive for slab dehydration melting. Viable alternative or supporting tectonic effects that may enhance slab melting include highly oblique convergence and resultant high shear stresses and incipient subduction into a pristine hot mantle wedge. The minimum P–T conditions for slab melting are interpreted to be 22–26 kbar (75–85 km depth) and 750–800°C. This P–T regime is framed by the hornblende dehydration, 10°C/km, and wet basalt melting curves and coincides with numerous potential slab dehydration reactions, such as tremolite, biotite + quartz, serpentine, talc, Mg-chloritoid, paragonite, clinohumite and talc + phengite. Involvement of overthickened (>50 km) lower continental crust either via direct partial melting or as a contaminant in typical mantle wedge-derived arc magmas has been presented as an alternative to slab melting. However, the intermediate to felsic volcanic and plutonic rocks that involve the lower crust are more highly potassic, enriched in large ion lithophile elements and elevated in Sr isotopic values relative to Cenozoic adakites. Slab-derived adakites, on the other hand, ascend into and react with the mantle wedge and become progressively enriched in MgO, Cr and Ni while retaining their slab melt geochemical signature. Our studies in northern Kamchatka, Russia provide an excellent case example for adakite-mantle interaction and a rare glimpse of trapped slab melt veinlets in Na-metasomatised mantle xenoliths.