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S Adler

Publications and source records attributed to S Adler.

At least 199 records · Page 11Linked to original sources
PubMed1984

Detection of terminal complement components in experimental immune glomerular injury.

Complement mediates glomerulonephritis by inflammatory cell-dependent and non-inflammatory cell-independent effects on glomerular permeability. The latter may involve terminal components of the complement system. We examined several models of immunologic renal injury in the rat by immunofluorescence (IF) for terminal complement components C5, C6, C7, and C8 in glomeruli using antisera to human C5-8, which cross-react with the analogous rat complement components. Rats with the heterologous and autologous phases of passive Heymann nephritis (PHN) had proteinuria and 1 to 2+ capillary wall deposits of heterologous or rat IgG, rat C3, and C5-8. Complement depletion with cobra venom factor (CVF) significantly decreased proteinuria in both models and prevented deposition of all complement components. Rats with active Heymann nephritis had similar deposits of rat IgG and C5-8. Rats with anti-GBM nephritis and aminonucleoside nephrosis had severe proteinuria which was not affected by CVF treatment and deposits of C5-8 were absent. The presence of terminal complement components in immune deposits in experimental glomerular disease correlates with a functional role for complement in mediating glomerular injury. These data support the hypothesis that the terminal complement pathway may be a major mediator of some types of immune glomerular injury.

Animals↗
PubMed1984

Estimation of cellular pH gradients with 31P-NMR in intact rabbit renal tubular cells.

To determine intracellular pH gradients rabbit renal cortical tubular cells were prepared by collagenase separation, suspended in a Krebs-Ringer buffer solution, and gassed with 95% O2-5% CO2 in a special nuclear magnetic resonance (NMR) probe. Renal tubular cellular pH was determined simultaneously from the distribution of 14C-dimethadione (DMO) (pHDMO) or the chemical shift of inorganic phosphate (pHNMR). Experiments were performed at different external pH values (pHe) ranging between 6.52 and 7.20. pHNMR, a measure of cytoplasmic pH, changed by an amount equal to the change in pHe. pHDMO, however, a measure of cytoplasmic plus mitochondrial pH, changed less than pHe as the latter increased. pHDMO, higher than pHNMR at low pHe, became equal to pHNMR at higher pHe values. By use of assumed mitochondrial volumes of 30-40% mitochondrial pH was calculated from pHDMO and pHNMR. Mitochondrial pH remained relatively constant over the entire pHe range studied. Since cytoplasmic pH fell as pHe was lowered, the transmitochondrial pH gradient increased at low pHE values. These findings suggest that the transmitochondrial pH gradient may be important in regulating metabolism.

Animals↗
PubMed1984

Complement activation by heat-killed human kidney cells: formation, activity, and stabilization of cell-bound C3 convertases.

Heat-killed kidney cells (HKKC) incubated with serum or purified C3 and factors B and D stain intensely for C3 by immunofluorescence. Binding of complement (C) did not occur if ethylenediaminetetraacetic acid (EDTA) was added to the C source or if factor B or D was omitted from the mixture of alternative pathway components. When the C-treated cells were washed, then incubated in purified C3 containing 10 mM EDTA, C3 conversion ensued, confirming the presence of a cell-bound C3 convertase. C3-reactive cells were not generated if EDTA was present during formation of the convertase. The addition of C3 nephritic factor (C3NeF) during formation of the C3 convertase from alternative pathway components greatly enhanced subsequent C3 cleavage, presumably by stabilizing labile C3bBb sites; however, binding of C3NeF did not appear to extend the half-life of the convertase, which was 35 min at 37 degrees C in each case. In contrast, little or no effect on C3 conversion could be detected after the addition of equivalent C3NeF to serum and HKKC. Thus, C activation by HKKC involves formation and activity of a cell-bound C3 convertase, which under certain circumstances can be stabilized by C3NeF.

Cells, Cultured↗
PubMed1983

T7-induced DNA polymerase. Requirement for thioredoxin sulfhydryl groups.

Bacteriophage T7-induced DNA polymerase is composed of a 1:1 complex of phage-induced gene 5 protein and Escherichia coli thioredoxin. Preparation of active subunits in the absence of sulfhydryl reagents indicates the reduced form of thioredoxin is sufficient for formation of the active holoenzyme. The oxidized form of thioredoxin, thioredoxin modified at one active site sulfhydryl by iodoacetate or methyl iodide, or thioredoxin modified at both active site sulfhydryls by N-ethylmaleimide, are all inactive, being defective in complex formation with gene 5 protein. Thioredoxin sulfhydryl groups present in native T7 DNA polymerase do not appear to be involved in an intersubunit disulfide bond; one and probably both sulfhydryls are available in the native holoenzyme for modification by N-ethylmaleimide. Furthermore, DNA substrates alter the reactivity of thioredoxin cysteines within the holoenzyme with respect to this reagent. Substrates for the single strand exonuclease enhance the reactivity of thioredoxin sulfhydryl groups while those for the polymerase or double strand exonuclease functions afford protection. It, therefore, seems likely that thioredoxin sulfhydryl groups are present in the reduced state within the native polymerase.

Bacterial Proteins↗
PubMed1983

Neuroleptic malignant syndrome: successful treatment with dantrolene and bromocriptine.

A patient with chronic schizophrenia treated with fluphenazine developed neuroleptic malignant syndrome, characterized by fever, obtundation, rigidity, and tremulousness. Hyperthermia and elevated serum creatine kinase were successfully corrected by parenteral treatment with dantrolene. Obtundation, rigidity, and tremulousness responded to high doses of bromocriptine.

Adult↗
PubMed1983

Role of the terminal complement pathway in experimental membranous nephropathy in the rabbit.

Our recent observations of a complement-mediated, cell-independent mechanism of altered glomerular permeability in rat membranous nephropathy suggested a possible role for the terminal complement pathway in the mediation of proteinuria in certain forms of glomerular disease. To directly determine whether the membranolytic terminal complement components (C5b-C9) are involved in glomerular injury, we studied the development of proteinuria in normal and C6-deficient (C6D) rabbits, in both of which a membranous nephropathy-like lesion develops early in the course of immunization with cationized bovine serum albumin (cBSA) (pI 8.9-9.2). C6 hemolytic activity of C6D was 0.01% that of control rabbits. After 1 wk of daily intravenous injections of cBSA, proteinuria developed in 71% of controls (median 154, range 1-3,010 mg/24 h, n = 24), whereas none of C6D were proteinuric (median 6, range 2-12 mg/24 h, n = 12, P less than 0.01). After 1 wk of cBSA, both groups had qualitatively identical glomerular deposits of BSA, rabbit IgG, and C3 on immunofluorescence microscopy, predominantly subepithelial electron-dense deposits on electron microscopy, and minimal glomerular inflammatory cell infiltration of glomeruli. Glomeruli were isolated from individual animals after 1 wk of cBSA and deposits of rabbit IgG antibody were quantitated by a standardized in vitro assay using anti-rabbit IgG-125I. Rabbit IgG deposits were found to be similar in control (29.8 +/- 13.2, range 12.7-48.6 micrograms anti-IgG/2,000 glomeruli, n = 6) and C6D rabbits (32.6 +/- 13.8, range 16.8-48.8 micrograms anti-IgG/2,000 glomeruli, n = 5, P greater than 0.05). After 2 wk, coincident with a prominent influx of mononuclear cells and neutrophils, proteinuria developed in C6D rabbits. These results document, for the first time, a requirement for a terminal complement component in the development of immunologic glomerular injury. Since the only known action of C6 is in the assembly of the membrane attack complex, these observations suggest that the membranolytic properties of complement may contribute to glomerular damage.

Animals↗
PubMed1982

Stereochemical course of nucleotidyl transfer catalyzed by bacteriophage T7 induced DNA polymerase.

The bacteriophage T7 induced DNA polymerase, consisting of the phage specified gene 5 protein associated with Escherichia coli thioredoxin, catalyzes the copolymerization of SP-dATP alpha S with dTTP, producing the alternating of polymer poly[dTs-A)] by a mechanism involving inversion of configuration at P alpha. Degradation of poly[d(5s-A)] by the nucleolytic action of E. coli DNA polymerase produced the dinucleotide pdTps-dA, whose configuration at the phosphorothioate diester was assigned as R by comparison of the phosphorus-31 nuclear magnetic resonance chemical shift (55.0 ppm downfield from H3PO4) with that of an authentic sample. Further degradation by alkaline phosphatase to Rp-dTps-dA (55.6 ppm downfield from H3PO4) confirmed the configuration. The stereochemistry provides no evidence of a double displacement mechanism.

DNA-Directed DNA Polymerase↗
PubMed1982

Altered glomerular permeability induced by F(ab')2 and Fab' antibodies to rat renal tubular epithelial antigen.

Rats injected with F(ab')2 and Fab' antibody fragments directed against an antigen in the rat proximal tubular epithelial brushborder (Fx1A) developed immediate proteinuria [F(ab')2 43.2 +/- 6.7, N=6; Fab' 9.5 +/- 2.8, N=5; normal 1.6 +/- 0.9 mg/day, N=20]), that subsided after 3 to 5 days' duration. This reaction is in contrast to one exhibited by rats given intact IgG anti-Fx1A; the rats that did not develop immediate proteinuria (2.2 +/- 0.3 mg/day, N=5), and the glomerular binding of 125I-antibody fragments was significantly less than that of intact IgG [F(ab')2 0.11 +/- 0.01; Fab' 0.03 +/- 0.01; IgG 0.17 +/- 0.01% administered equimolar dose] at 24 hr. No proteinuria resulted from equimolar doses of nonantibody F(ab')2 and Fab'. Less than 8% of the proteinuria induced by antibody fragments represented injected material, and 30 to 38% was albumin. Immunofluorescence revealed faint and diffuse glomerular capillary wall deposits of F(ab')2 and Fab' and tubular brushborder staining. Subepithelial, electron-dense deposits and focal, podocyte effacement were seen by electron microscopy in rats given the F(ab')2 antibody. Light microscopy and colloidal iron-staining were normal. In our study antibody fragments appear to interact directly with components of the outer, glomerular capillary wall to alter permeability in the absence of recognized mediators such as complement and inflammatory cells.

Animals↗
PubMed1981

Mechanism of volume expansion on citrate, ammonia, and acid excretion in the rat.

Potassium-depleted rats receiving sodium chloride or i.v. mannitol decrease their blood bicarbonate concentration isohydrically, reduce urinary citrate, and increase urinary ammonia excretion per milligram of urinary creatinine. To determine the mechanisms of these renal changes, we volume expanded normal rats with mannitol, normal saline, or saline bicarbonate solutions. Blood pH in each group remained constant, but blood bicarbonate fell significantly in the mannitol and saline-infused rats. In these two groups, urinary citrate per unit GFR decreased 27% and 25% (P less than 0.01) but urinary ammonia excretion per unit GFR increased 120% and 90% (P less than 0.01). By contrast, in saline bicarbonate rats, citrate excretion increased 27% and urinary ammonia excretion rose 29% (P greater than 0.2). Rats with metabolic acidosis given saline did not alter blood pH or bicarbonate. Citrate excretion per unit GFR increased 150% (P less than 0.02) but urinary ammonia excretion rose insignificantly by 11%. Calculated net tubular reabsorption of citrate increased in the mannitol and saline-infused rats. The rise in urinary pH in these two groups during expansion suggest that renal ammonia production was also increased. We conclude that volume expansion changes renal citrate and ammonia metabolism by isohydrically reducing blood bicarbonate concentration, thereby demonstrating another effect of bicarbonate, independent of pH, on renal metabolism.

Acid-Base Equilibrium↗
PubMed1981

Rapid progressive glomerulonephritis: relapse after prolonged remission.

Three patients with epithelial cell crescents and rapid progressive glomerulonephritis (RPGN) had prolonged remission, presumably induced by treatment with maintenance oral prednisone and cyclophosphamide plus plasmapheresis. Patient 1 had anti-glomerular basement membrane-mediated RPGN, patient 2 had an immune complex disease, and patient 3 did not show any immune deposits. After a two-year remission in two patients and a greater than one-year remission in the third patient, renal function deteriorated. Epithelial cell crescents were again demonstratable on repeated renal biopsy specimens in each patient. One patient again received triple therapy, while the other two patients received megadoses of intravenous prednisolone sodium succinate in place of plasmapheresis. Each patient again entered a stable remission. These three cases demonstrate that RPGN may recur after prolonged remission in all three varieties of this syndrome. If the exacerbation is treated promptly, a second remission may be induced.

Aged↗