Search PubMed⌕ Search

Biomedical subjects

R J Falk

Publications and source records attributed to R J Falk.

At least 145 records · Page 8Linked to original sources
PubMed1985

Membrane attack complex of complement in dermatitis herpetiformis.

The assembly of membrane attack complex (MAC) of complement implies activation of complement to the attachment of C9 and the presence of MAC on tissue suggests a possible pathogenic role for complement in disease since MAC is able to damage membranes. We examined normal skin of five patients with dermatitis herpetiformis for the presence of MAC using a monoclonal antibody (poly C9-MA) that recognizes a neoantigen of C9 that is not present on monomeric C9 but is common to both isolated MAC and to polymerized C9. Granular deposits of polymerized C9 were found at the sites of IgA deposition in the dermal papillae of normal skin from all patients. The pathologic importance of this finding is uncertain.

Antibodies, Monoclonal↗
PubMed1984

Complement channels in membranes: inhibition with a monoclonal antibody to a neoantigen of polymerized C9.

The channels produced by complement in red cell membranes are heterogeneous, with diameters of approximately 0.5 to approximately 12.0 nm. We investigated the relationship of the components of the membrane attack complex, C5b through C9, to the functional transmembrane channels greater than 3 nm in diameter. Radiolabelled macromolecules were incorporated into resealed red cell membrane ghosts which were then treated with complement. A monoclonal antibody to a neoantigen in polymerized C9 inhibited macromolecule diffusion through the complement channels. There was also inhibition with polyclonal antisera to C9 but not with antisera to any of the other components of the membrane attack complex. The results demonstrate a functional correlation of the larger complement lesions with the previously described poly C9 tubular structures.

Animals↗
PubMed1984

Cell populations and membrane attack complex in glomeruli of patients with post-streptococcal glomerulonephritis: identification using monoclonal antibodies by indirect immunofluorescence.

Poststreptococcal glomerulonephritis (PSGN) had been thought to arise from renal deposition of immune complexes and as such is analogous to acute serum sickness. Recent studies of acute serum sickness in animals and PSGN in humans, however, have suggested a pathogenetic role for cellular immunity. To enlarge on these observations, cellular components of glomeruli were characterized by indirect immunofluorescence in 11 tissues from individuals with PSGN using monoclonal antibodies. These studies demonstrate infiltration of glomeruli by monocytes, granulocytes, and lymphoid cells. Focal accumulations of T lymphocytes were also observed adjacent to Bowman's capsule. Analysis of glomerular T-cell subpopulations revealed a predominance of cells reactive with OKT4 early and with OKT8 later in the course of disease. Proliferation of parietal and visceral epithelial cells was associated with increased binding of BA-1 and J5, respectively. The presence of the membrane attack complex of complement was demonstrated by glomerular reactivity with a monoclonal antibody (poly-C9 MA) which recognizes a neoantigen present in poly-C9. Fluorescence was present along the glomerular basement membrane early and within the mesangium late in the course of disease, a distribution similar to that observed for C3 and C5. These observations suggest that immune cells as well as terminal components of complement either provoke or mark tissue injury in PSGN.

Adolescent↗
PubMed1984

Deposition of the membrane attack complex of complement in bullous pemphigoid.

Bullous pemphigoid is associated with deposition of IgG and C3 at the dermal-epidermal junction. In order to see whether complement activation in bullous pemphigoid resulted in deposition of membrane attack complex (MAC) at the basement membrane zone, skin biopsies from patients with bullous pemphigoid were examined using a direct immunofluorescence technique. By employing a monoclonal antibody to a neoantigen of C9, the MAC was demonstrated in linear pattern at the basement membrane zone. These deposits were seen in both involved and uninvolved skin but the amount of MAC was greater in involved skin as judged by intensity of staining. Stippled deposits of MAC were also present in or around epidermal basal cells. The MAC could be generated in vitro by reaction of normal plasma with antibasement membrane antibody bound to sections of monkey esophagus. The IgG antibody activated complement and this complement activation proceeded all the way to the terminal step.

Basement Membrane↗
PubMed1983

Neoantigen of the polymerized ninth component of complement. Characterization of a monoclonal antibody and immunohistochemical localization in renal disease.

A monoclonal antibody to a neoantigen of the C9 portion of the membrane attack complex (MAC) of human complement has been developed and characterized. The distribution of this neoantigen was assessed by indirect immunofluorescence microscopy in nephritic and nonnephritic renal diseases. The antibody (Poly C9-MA) reacted on enzyme-linked immunosorbent assay (ELISA) with a determinant in complement-activated serum that was undetectable in normal human serum (NHS). Zymosan particles incubated in NHS had positive immunofluorescent staining with Poly C9-MA; however, binding of Poly C9-MA was not observed with zymosan particles incubated in sera deficient in individual complement components C3, C5, C6, C7, C8, or C9. Reconstitution of C9-deficient sera with purified C9 restored the fluorescence with Poly C9-MA. Poly C9-MA reacted positively by ELISA in a dose-dependent manner with purified MC5b-9 solubilized from membranes of antibody-coated sheep erythrocytes treated with NHS but not with intermediate complement complexes. Poly C9-MA also reacted in a dose-dependent manner on ELISA and in a radioimmunoassay with polymerized C9 (37 degrees C, 64 h) (poly C9) but not with monomeric C9. Increasing amounts of either unlabeled poly C9 or purified MC5b-9 inhibited the 125I-poly C9 RIA in an identical manner. These studies demonstrate that Poly C9-MA recognizes a neoantigen of C9 common to both the MAC and to poly C9. By immunofluorescence, Poly C9-MA reacted minimally with normal kidney tissue in juxtaglomerular loci, the mesangial stalk, and vessel walls. Poly C9-MA stained kidney tissue from patients with glomerulonephritis in a pattern similar to that seen with polyclonal anti-human C3. In tissue from patients with nonnephritic renal disease--diabetes, hypertension, and obstructive uropathy--Poly C9-MA was strongly reactive in the mesangial stalk and juxtaglomerular regions, tubular basement membranes, and vascular walls. Poly C9-MA binding was especially prominent in areas of advanced tissue injury. Poly C9-MA frequently stained loci where C3 was either minimally present or absent. These studies provide strong evidence for complement activation not only in nephritic but also in nonnephritic renal diseases.

Adult↗
PubMed1983

Polyantigenic expansion of basement membrane constituents in diabetic nephropathy.

The immunohistopathology of the intrinsic basement membrane-associated antigens were examined in diabetic nephropathy. In early and moderate stages of disease there was polyantigenic expansion of all the intrinsic components of mesangium, glomerular basement membrane (GBM), and tubular basement membrane (TBM) assessed by polyclonal antisera to collagen types IV and V, laminin, and by monoclonal antibodies to type IV collagen and fibronectin and to four other intrinsic components of normal renal extracellular matrices (MBM10, 11, 12, and 15). In the mesangium the first intrinsic antigens to increase were fibronectin and type V collagen. In late stages of disease, there was a diminution in the mesangium of all of these antigens with the exception of type V collagen, which persisted. Additionally, antigens appeared in the mesangium, recognized by MBM11 and MBM15, which are normally present in fetal but not adult mesangial regions. Similarly, in the GBM in late stages of disease, there was a decrease in all of the antigens, except for a persistence of the antigen recognized by MBM15. However, in TBM all of the antigens assessed increased in early, moderate, and severe disease. These studies document the complexity of polyantigenic alterations in the development of diabetic nephropathy.

Animals↗
PubMed1983

Infections associated with subclavian Uldall catheters.

During a 12-month period, the use of a subclavian vein Uldall catheter (UC) for hemodialysis or plasmapheresis in 27 patients was studied prospectively. Ten patients had ten UC site infections. Organisms associated with these infections included Staphylococcus epidermidis (five), Staphylococcus aureus (four), Proteus mirabilis (two), and Enterococcus (one). The four S aureus infections occurred 1, 2, 4, and 9 days after UC insertion, whereas the five S epidermidis infections occurred 6, 17, 17, 26, and 97 days after insertion. Five patients had associated bacteremias; in one of these patients, the bacteremia was the major cause of death. The incidence of UC site infection and bacteremia based was higher than the incidence of infection reported with any other type of vascular access for hemodialysis. Further studies are necessary to define whether the UC should be routinely employed for temporary vascular access.

Bacterial Infections↗