A role for Mac-1 (CDIIb/CD18) in immune complex-stimulated neutrophil function in vivo: Mac-1 deficiency abrogates sustained Fcgamma receptor-dependent neutrophil adhesion and complement-dependent proteinuria in acute glomerulonephritis

Mac-1 (alphambeta2), a leukocyte adhesion receptor, has been shown in vitro to functionally interact with Fcgamma receptors to facilitate immune complex (IC)-stimulated polymorphonuclear neutrophil (PMN) functions. To investigate the relevance of Mac-1-FcgammaR interactions in IC-mediated injury in vivo, we induced a model of Fc-dependent anti-glomerular basement membrane (GBM) nephritis in wild-type and Mac-1-deficient mice by the intravenous injection of anti-GBM antibody. The initial glomerular PMN accumulation was equivalent in Mac-1 null and wild-type mice, but thereafter increased in wild-type and decreased in mutant mice. The absence of Mac-1 interactions with obvious ligands, intercellular adhesion molecule 1 (ICAM-1), and C3 complement, is not responsible for the decrease in neutrophil accumulation in Mac-1- deficient mice since glomerular PMN accumulation in mice deficient in these ligands was comparable to those in wild-type mice. In vitro studies showed that spreading of Mac-1-null PMNs to IC-coated dishes was equivalent to that of wild-type PMNs at 5-12 min but was markedly reduced thereafter, and was associated with an inability of mutant neutrophils to redistribute filamentous actin. This suggests that in vivo, Mac-1 is not required for the initiation of Fc-mediated PMN recruitment but that Mac-1-FcgammaR interactions are required for filamentous actin reorganization leading to sustained PMN adhesion, and this represents the first demonstration of the relevance of Mac-1-FcgammaR interactions in vivo. PMN-dependent proteinuria, maximal in wild-type mice at 8 h, was absent in Mac-1 mutant mice at all time points. Complement C3-deficient mice also had significantly decreased proteinuria compared to wild-type mice. Since Mac-1 on PMNs is the principal ligand for ic3b, an absence of Mac-1 interaction with C3 probably contributed to the abrogation of proteinuria in Mac-1-null mice.     

Preferences as expectation-driven inferences: Effects of affective expectations on affective experience.

Presents a model arguing that affect and emotion are often formed in an expectation-driven fashion. A pilot study and 2 experiments manipulated undergraduate Ss' affective expectations (e.g., how funny they expected a set of cartoons to be) and whether Ss' expectations were confirmed (e.g., whether the cartoons really were funny). When the value of a stimulus was consistent with an affective expectation, people formed evaluations relatively quickly. Even when the value of a stimulus was discrepant from an affective expectation, people sometimes assimilated the value of the stimulus to their expectations. Other times, such as when making a more fine-grained evaluation of the cartoons, people noticed that they were discrepant from their affective expectations. Under these conditions, people appeared to have more difficulty forming preferences. They took longer to evaluate and spent more time thinking about the cartoons. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bronchial carcinoid tumor: demonstration by dynamic inversion recovery turbo-flash MR imaging

A 38-year-old woman was referred to our hospital following the discovery of a right hilar mass on chest radiograph. Retrospectively, a hilar mass could be seen on a chest X-ray which had been obtained 5 years earlier. A coronal dynamic inversion recovery turbo-FLASH gadolinium-enhanced sequence was performed, demonstrating the right lesion which enhanced during the systemic arterial phase indicating an arterial supply from the bronchial arterial circulation. The surgical and pathological findings were a bronchial carcinoid tumor, with foci of bone formation.     

Reconstruction of the distal aspect of the radius with use of an osteoarticular allograft after excision of a skeletal tumor

Twenty-four patients had reconstruction of the distal aspect of the radius with use of an osteoarticular allograft, between 1974 and 1992, after excision of a giant-cell tumor (twenty patients), a desmoplastic fibroma (two patients), a chondrosarcoma (one patient), or an angiosarcoma (one patient). Nine giant-cell tumors were recurrent lesions, and eleven were extracompartmental primary lesions that had extended through the cortex or subchondral bone. The average age of the patients was 31.5 years (range, fifteen to sixty-one years); thirteen patients were female and eleven were male. Seventeen lesions involved the right wrist and seven involved the left wrist. The reconstruction was performed through a dorsoradial incision with use of a size-matched, preserved, fresh-frozen, distal radial allograft. All procedures included internal fixation and reconstruction of the radiocarpal ligaments. All patients were followed for a minimum of two years (average, 10.9 years; range, 2.1 to 22.3 years). At the time of follow-up, two patients -- one who had a giant-cell tumor and one who had a desmoplastic fibroma -- had a local recurrence. Eight patients needed a revision of the osteoarticular allograft, at an average of 8.1 years (range, 0.8 to 17.8 years) after the initial reconstruction. Seven of these patients had an arthrodesis and one had an amputation. The reason for the revision was a fracture of the allograft in four patients, recurrence of the tumor in one, pain in two, and volar dislocation of the carpus in one. There were fourteen other complications, including ulnocarpal impaction necessitating excision of the distal aspect of the ulna (four), painful hardware necessitating removal (four), rupture of the extensor pollicis longus tendon necessitating transfer of the extensor indicis proprius (two), fracture of the allograft necessitating open reduction and internal fixation (two), volar dislocation of the carpus necessitating closed reduction (one), and a ganglion of the dorsal aspect of the wrist necessitating excision (one). Of the sixteen patients in whom the osteoarticular allograft survived, three did not have pain, nine had pain in association with strenuous activities, and four had pain in association with moderate activities. Three patients reported no functional limitation, nine had limitation in the ability to perform strenuous activities, and four had limitation in the ability to perform moderate activities. The average range of motion of the wrist was 36 degrees of dorsiflexion, 21 degrees of volar flexion, 16 degrees of radial deviation, 15 degrees of ulnar deviation, 58 degrees of supination, and 72 degrees of pronation. Reconstruction of the distal aspect of the radius with use of an osteoarticular allograft was associated with a low rate of recurrence of the tumor, a moderately high rate of revision, little pain in association with common activities, good function, and a moderate range of motion. Osteoarticular allografts are an option for reconstruction of the distal aspect of the radius after excision of a malignant tumor or a recurrent or locally invasive benign lesion.     

Comparison of 6-s-cis- and 6-s-trans-locked analogs of 1alpha,25-dihydroxyvitamin D3 indicates that the 6-s-cis conformation is preferred for rapid nongenomic biological responses and that neither 6-s-cis- nor 6-s-trans-locked analogs are preferred for genomic biological responses

The hormone 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] generates biological responses via both genomic and rapid, nongenomic mechanisms. The genomic responses utilize signal transduction pathways linked to a nuclear receptor (VDRnuc) for 1alpha,25(OH)2D3, while the rapid responses are believed to utilize other signal transduction pathways that may be linked to a putative membrane receptor for 1alpha,25(OH)2D3. The natural seco steroid is capable of facile rotation about its 6,7 single carbon bond, which permits generation of a continuum of potential ligand shapes extending from the 6-s-cis (steroid like) to the 6-s-trans (extended). To identify the shape of conformer(s) that can serve as agonists for the genomic and rapid biological responses, we measured multiple known agonist activities of two families of chemically synthesized analogs that were either locked in the 6-s-cis (6C) or 6-s-trans (6T) conformation. We found that 6T locked analogs were inactive or significantly less active than 1alpha,25(OH)2D3 in both rapid responses (transcaltachia in perfused chick intestine, 45Ca2+ influx in ROS 17/2.8 cells) and genomic (osteocalcin induction in MG-63 cells, differentiation of HL-60 cells, growth arrest of MCF-7 cells, promoter transfection in COS-7 cells) assays. In genomic assays, 6C locked analogs bound poorly to the VDRnuc and were significantly less effective than 1alpha,25(OH)2D3 in the same series of assays designed to measure genomic responses. In contrast, the 6C locked analogs were potent agonists of both rapid response pathways and had activities equivalent to the conformationally flexibile 1alpha,25(OH)2D3; this represents the first demonstration that 6-s-cis locked analogs can function as agonists for vitamin D responses.