Cellular receptors for matrix proteins in normal human kidney and human mesangial cells

In the present study we evaluated the distribution of cell adhesion molecules, referred as very late antigens (VLA), in the normal human kidney and in mesangial cells in culture (MC). In addition, we assessed the functional properties of VLA proteins on MC. Normal human kidney and MC were stained by immunoperoxidase with mouse monoclonal antibodies to VLA proteins. We demonstrated that VLA-3, a protein that binds FN, laminin and collagen, is the predominant VLA protein in the human glomerulus and on MC. VLA-3 is located in the mesangium and on the glomerular visceral epithelial cell and endothelial cell surfaces in contact with the glomerular basement membrane. VLA-1 was demonstrated in the glomerular mesangium and VLA-5, an FN specific receptor, was present in the mesangium on glomerular endothelial cells and on MC. VLA-2 and VLA-4 were not present in the normal glomerulus nor on MC. In functional studies we evaluated the binding of MC to FN coated surfaces and the binding and phagocytosis of FN coated fluorescent beads by MC. We showed that MC bind to FN coated surfaces and that the binding is inhibited by anti-FN antibodies, EDTA and peptides containing the amino acid sequence Arg-Gly-Asp (RGD). In addition, anti-VLA-5 but not anti-VLA-3 antibodies inhibited significantly the binding of MC to FN, MC demonstrated binding and phagocytosis of FN coated beads and, purified FN inhibited both phenomena. By affinity chromatography and immunoprecipitation we demonstrated that MC FN binding proteins and MC VLA proteins are composed of two distinct protein chains that have Mr characteristics similar to those of normal human fibroblasts VLA proteins. In conclusion, the glomerular distribution of VLA-3 suggests that this protein is primarily involved on the adhesion of glomerular cells to basement membranes and matrix. MC FN receptors (VLA-5) mediate the binding of MC to FN and could mediate the phagocytosis of FN coated antigen or immune complexes by mesangial cells.     

Interpreting Post-Transplant Proteinuria in Patients with Proteinuria Pre-Transplant

Increasing numbers of patients receive kidney transplants before initiation of dialysis or shortly thereafter. Some of these patients have significant proteinuria pre-transplant making the interpretation of post-transplant proteinuria problematic. In this study, we evaluated post-transplant proteinuria in 115 patients who had urine protein measured within 3 months of transplant and assessed the association of proteinuria with allograft pathology. Proteinuria declined rapidly from 3650 +/- 3702 mg/day pre-transplant to 550 + 918 at 3 weeks (p < 0.0001) and continued to decline until 1 year post-transplant (472 +/- 1116, p < 0.0001 vs. 3 weeks). Proteinuria greater than 3000 mg/day was present in 48 patients (42%) pre-transplant, in 1 patient (1%) at 3 weeks and in 4 patients (4%) at 1 year. Surveillance graft biopsies were done at 1 year in 93% of patients. Proteinuria > or = 1500 mg/day and/or an absolute increase in proteinuria > 500 mg/day after 3 weeks post-transplant was associated with allograft glomerular pathology. In conclusion, pre-transplant proteinuria, even when high grade, declines rapidly after transplantation. Failure to decline or persistence of proteinuria greater than 1500 mg/day is indicative of allograft pathology.     

Soda pop vending machine injuries: an update.

Soda pop vending machine tipping continues to be a dangerous behavior that can result in lethal or crippling injuries. This study analyzes 64 cases of injuries secondary to crushing by a soda machine. All were male victims except one. The average age was 19.8 years with a range of 5-39 years. Thirteen victims sustained multiple trauma. Fifteen victims were killed. Increased public awareness coupled with support by the government and private industry has contributed to a sharp reduction in incidence of accidents and improved public safety.     

Histologic Findings One Year After Positive Crossmatch or ABO Blood Group Incompatible Living Donor Kidney Transplantation

Recent protocols have allowed successful positive crossmatch (+XM) and ABO incompatible (ABOI) kidney transplantation, although their long-term outcome is not clear. To begin to assess this issue we compared protocol biopsies performed 12 months posttransplant in 37 +XM, 24 ABOI and 198 conventional allografts. Although the majority in all three groups had only minimal histologic changes, transplant glomerulopathy (TG) was significantly increased in +XM (22% vs. 13% ABOI vs. 8% conventional, p = 0.015), and correlated with prior humoral rejection (HR) by multivariate analysis (odds ratio 17.5, p < or = 0.0001). Patients with a prior history of HR also had a significant increase in interstitial fibrosis (No HR 54% vs. HR 86%, p = 0.045). In the absence of HR no difference in histologic changes was seen between groups, although all three groups had a demonstrable mild increase in interstitial fibrosis from biopsies performed at the time of transplant. Thus, although HR is associated with an increase in TG, in its absence allograft histology is similar in +XM, ABOI and conventional allografts 1 year posttransplant.     

Role of precipitating and nonprecipitating antibodies in glomerular immune complex formation

The present study compared directly the ability of precipitating and nonprecipitating antibodies to form and sustain glomerular immune deposits. The antigen phenylated gelatin (DNP-GL) was injected i.v. into rats. DNP-GL is cleared from the circulation rapidly and becomes localized in glomeruli. Two hours later, rats received either precipitating or nonprecipitating mouse monoclonal anti-DNP antibodies. These antibodies were comparable with respect to size, affinity, number of antigen combining sites and isoelectric point. However, in vitro, nonprecipitating antibodies demonstrated a faster dissociation rate from antigen than precipitating antibodies. Control rats received DNP-GL alone or antibody alone. Antibody deposition in glomeruli was quantitated by Computerized Image Analysis (CIA) of immunoperoxidase stained tissue sections and by glomerular radioactive counts in experiments using 125I labelled antibodies. We demonstrated that glomerular uptake of anti-DNP antibody was similar two hours after injection of precipitating and nonprecipitating antibodies. However, six or more hours after injection, significantly less antibody was present in the glomeruli of rats injected with nonprecipitating antibodies. These differences could not be explained by a greater rate of antigen removal from kidney in rats injected with nonprecipitating antibodies. To assess whether nonprecipitating antibodies modify the glomerular binding and retention of precipitating antibody, in a separate series of experiments rats were injected with equal amounts of precipitating and nonprecipitating antibodies. Both types of antibody bound to glomeruli. However, with time glomerular antibody levels paralleled those found in rats injected with nonprecipitating antibody alone. We conclude that the precipitating characteristics of antibodies do not affect their ability to deposit in kidney.(ABSTRACT TRUNCATED AT 250 WORDS)     

Patellofemoral joint: kinematic MR imaging to assess tracking abnormalities

The patellofemoral joint was imaged with magnetic resonance (MR) in the axial plane while the knee was positioned from 0 degrees to 32 degrees of flexion (nine positions). These multiple sequential images obtained within the early phases of flexion of the knee were viewed in a "cine-loop" format, producing a kinematic study that clearly demonstrated the relationship of the patella to the trochlear groove. Four healthy subjects and one patient with known bilateral subluxing patellae were studied. The preliminary results suggest that kinematic MR imaging of the patellofemoral joint is potentially useful for the evaluation of patellar tracking abnormalities.