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S Adler

Publications and source records attributed to S Adler.

At least 181 records · Page 10Linked to original sources
PubMed1986

Charge selective properties of the glomerular capillary wall influence antibody binding in rat membranous nephropathy.

IgG antibodies, eluted from kidneys of rats with Heymann nephritis were separated into cationic and anionic fractions, labeled with 125I and 131I, respectively, mixed in equal amounts, and then injected in incremental doses into 10 rats. Glomerular antibody binding was highly correlated with blood concentration of antibody at 24 hr, however, significantly more cationic antibody bound to glomeruli than did anionic antibody at all blood levels studied. The differences were not due to greater antibody content and/or avidity of the cationic preparation, as measured by binding to isolated glomeruli in vitro. These studies demonstrate the influence of glomerular permselectivity and antibody charge on subepithelial antibody deposition.

Animals↗
PubMed1986

Advances in single-chamber pacemaker diagnostic data.

Diagnostic data, which is Holter-type information documenting the pulse generators' interaction with the patient over time, are now available in single chamber pulse generators from at least six manufacturers. Diagnostic data are available in bradycardia, tachycardia, and rate-responsive pulse generators. Six hypothetical examples discuss the clinical utility of advanced diagnostic data. Three examples examine the use of diagnostic data with bradycardia pulse generators. These use rate histograms or high-rate counters to solve programming and patient problems. Two examples involve antitachycardia pulse generators and the uses for diagnostic data in both chronic and acute cases. One example deals with the use of maximum and minimum temperature diagnostics in proper programming of a temperature rate-responsive device.

Arrhythmias, Cardiac↗
PubMed1986

Genital edema in patients on continuous ambulatory peritoneal dialysis. Report of 3 cases and review of the literature.

Severe genital edema is a well-described complication of continuous ambulatory peritoneal dialysis (CAPD). Leakage of dialysate fluid from defects in the peritoneum may occur from clinically detectable and undetectable inguinal hernias, defects at the catheter insertion site, or other defects in the peritoneal membrane. We describe 3 patients (who underwent five surgical procedures), illustrating the complexity of the problem. In 2 patients, unsuccessful surgical repairs (1 catheter replacement, 1 hernia repair) were performed based on misleading radiologic findings using intraperitoneal contrast without computerized tomography (CT) scanning. The use of CT scanning with intraperitoneal contrast led to the correct diagnosis and prompt surgical correction in both patients so studied. One patient had leakage from a clinically undetectable inguinal hernia, and the other had a peritoneal defect at the Tenckhoff insertion site which was only demonstrated following a period of upright posture with a 3-liter exchange. Our experience and a review of the literature convinces us that a CT scan of the abdomen utilizing radiocontrast material added to the dialysate accurately identifies the site of leakage in CAPD patients who develop genital edema. Thus, the CT scan can help avoid unnecessary surgery and prolonged hospitalization in CAPD patients who develop genital edema.

Adult↗
PubMed1986

Complement membrane attack complex stimulates production of reactive oxygen metabolites by cultured rat mesangial cells.

To explore possible mechanisms by which complement membrane attack complexes (MAC) that are deposited in the glomerular mesangium might be pathogenic, we stimulated rat glomerular mesangial cells grown in vitro with nascent MACs formed from the purified human complement components C5b6 and normal human serum and measured production of superoxide ion (O2-) and hydrogen peroxide (H2O2). Mesangial cells incubated with C5b6 + serum, which results in cell membrane interaction with the MAC, produce 0.9 +/- 0.15 nmol O2-/10(5) cells per 30 min, which was significantly greater than the amount produced by cells incubated with C5b6 alone, serum alone, or decayed MACs that can no longer interact with the cell membrane (0.3 +/- 0.2, 0.4 +/- 0.1, 0.3 +/- 0.2 nmol O2-/10(5) cells per 30 min, respectively; P less than 0.02). Production of O2- after stimulation with MACs increased during the first 20 min of incubation but then plateaued. Cells exposed to decayed MACs produced small amounts of O2-, which did not increase from 20 to 60 min. Production of H2O2 was also observed after stimulation with MACs, and continued to increase during 60 min of incubation (1.22 +/- 0.16 nmol H2O2/10(5) cells per 60 min), whereas H2O2 production could not be detected after exposure to decayed MACs. Cell viability was not adversely affected by exposure to nascent MACs as determined by trypan blue exclusion or chromium-51 release. These results demonstrate that glomerular mesangial cell membrane interaction with the MAC stimulates the production of the toxic oxygen metabolites O- and H2O2. Activation of the terminal complement pathway by mesangial immune deposits in vivo might lead to tissue injury by stimulation of local production of toxic oxygen-free radicals.

Animals↗
PubMed1986

Studies of progressive glomerular sclerosis in the rat.

To obtain a better understanding of the sequential development of sclerosis in immune glomerular disease, the authors induced experimental membranous nephropathy in unilaterally nephrectomized rats and evaluated the lesions that developed over a 35-week period. Serial renal biopsies were examined by light and immunofluorescence microscopy for IgG, C3, neoantigens of the membrane attack complex (MAC), and interstitial (Type III) and basement membrane (Type IV) collagen. Urinary protein excretion increased from 208 +/- 19 mg/day to 308 +/- 36 mg/day during the period of observation. Progressive mesangial sclerosis, crescent formation, and interstitial fibrosis developed in association with deposition of Type IV but not Type III collagen in the glomeruli. Capillary wall deposits of IgG, C3, and MAC gradually decreased, whereas coarse granular deposits of C3 and MAC were visible in sclerotic areas beginning at 8 weeks. The appearance of complement components in early sclerotic lesions raises the possibility that they are of pathogenetic importance. The absence of interstitial collagen in sclerotic glomeruli suggests that the components of the lesion are produced solely by glomerular cells.

Animals↗
PubMed1986

Repair of etheno DNA adducts by N-glycosylases.

After incubation of chloroacetaldehyde-treated DNA with cell-free homogenates, the excision of N2,3-ethenoguanine and 1,N6-ethenoadenine was observed with a rat brain tumour cell line. The repair mechanism was that of an N-glycosylase. The high specificity of all known DNA N-glycosylases and some unique properties of the enzymatic reaction indicate the existence of N-glycosylases specific for the repair of etheno, or similar, adducts.

Acetaldehyde↗
PubMed1985

Autosomal dominant polycystic kidney disease: presentation, complications, and prognosis.

Fifty-three symptomatic adults with autosomal dominant polycystic kidney disease were studied retrospectively for a mean follow-up of 12 years (range 10 months to 33 years). Diagnosis was confirmed by either x-ray, ultrasound, laparotomy, or autopsy. Commonest presenting clinical findings were flank pain (30%), hypertension (21%), symptomatic urinary tract infection (UTI) (19%), gross hematuria (19%), and palpable masses (15%). A total of nine patients (17%) progressed to end-stage renal disease. Change in renal function measured using the reciprocal of plasma creatinine plotted against time was linear for each individual patient with a maximum functional decline of 0.7 mg/dL/yr (slope = -0.07). Past the age of sixty renal failure was uncommon. Easily controlled hypertension developed in 64% attended by mild retinopathy. UTIs were common (53%), often recurrent (61%), precipitated by instrumentation in 6 of 14 patients (43%), leading to death in two (33%). Renal calculi were extremely common (34%) and had no defined metabolic cause. The presence of hematuria (64%), gross or microscopic, bore no relationship to the decline in renal function. Pregnancy was normal in these patients with no increase in fetal or maternal morbidity or mortality. We conclude the following: Renal functional deterioration is linear, less than previously reported, and bears no relationship to hematuria. Hypertension is common, easily treated, and causes minor end-organ damage. Renal calculi are frequent. Urinary tract instrumentation often induces infection with considerable morbidity and mortality and must be avoided. Pregnancy is not contraindicated if renal function is normal. The prognosis for survival in this disease is better than previously reported.

Adolescent↗
PubMed1985

Influence of antigen distribution on the mediation of immunological glomerular injury.

To determine if the site of immune reaction could influence the mediation and morphological expression of glomerular injury in experimental anti-glomerular basement membrane (anti-GBM) nephritis and membranous nephropathy, we studied the events that followed the in situ reaction of rat antibody with antigen planted in either the GBM (especially the lamina rara interna) or in the subepithelial space (SE). Non-nephritogenic amounts of noncomplement-fixing sheep anti-GBM or anti-tubular brushborder antibody were injected into separate groups of rats to plant sheep IgG in the GBM and SE, respectively. Kidneys containing sheep IgG were then transplanted into naive recipients that were passively immunized with rat anti-sheep IgG. There was marked proteinuria after 2 days (antigen in GBM: 226 +/- 50.7; antigen in SE: 69 +/- 50.7 mg/24 hr) that was abrogated by prior depletion of complement in both groups (antigen in GBM: 10.2 +/- 1.7; antigen in SE: 14.3 +/- 8.7 mg/24 hr). When antigen was planted in SE, inflammatory-cell depletion with either anti-neutrophil (PMN) serum or lethal irradiation had no effect on proteinuria. In contrast, anti-PMN abolished proteinuria (12.0 +/- 5.6 mg/24 hr) and irradiation reduced it by 60% when antigen was in GBM. Glomeruli of kidneys with antigen in GBM were significantly larger and more hypercellular than those with antigen in SE after transplantation into immunized recipients. Endothelial cell injury and adherence of inflammatory cells to denuded GBM were prominent in the former (antigen in GBM), while glomeruli with antigen in SE showed only subepithelial deposits, adjacent slit-diaphragm displacement, and epithelial cell foot-process effacement. Thus, the reaction of antigen and antibody in glomeruli produced complement-mediated injury which was cell-independent when complex formation occurred on the outer aspect of the GBM but was cell-dependent when the same reagents reacted more proximally to the circulation. We therefore conclude that antigen distribution can critically influence the mediation and morphologic expression of immune glomerular injury and may, in part, account for variations in the clinical and histological manifestations of antibody-induced glomerular disease in humans.

Animals↗
PubMed1985

Immunologic mechanisms of renal disease.

Most immune renal diseases are caused by the formation of immune complexes of antibody with either fixed glomerular antigens or exogenous non-renal antigens. Much progress has been made recently in understanding the ways by which these immune deposits form in glomeruli. Immune complex deposits of exogenous antigens may involve prior antigen localization in the glomerulus to initiate immune complex formation locally, or in situ. The type of glomerular lesion produced depends in large part on the site at which deposit formation occurs, which in turn determines what mediators of tissue injury are activated. The nature and quantity of immune reactants are also important. Subepithelial deposits may result from antibody binding to fixed epithelial cell-derived antigens or to exogenous antigens localized by direct interaction with glomerular anionic sites (cationic antigens) or with nonimmune cationic proteins bound to glomerular anionic sites (anionic antigens). Cationic antibody may also localize first, and deposits can form from subendothelial immune complex deposits dissociating to cross the GBM and re-form in a subepithelial distribution. Proteinuria induced by subepithelial immune deposit formation appears to be due to a direct effect of complement, probably involving membrane attack complexes, and independent of inflammatory cells. Intramembranous deposits form from anti-GBM antibody reacting with intrinsic GBM antigens. Subendothelial and mesangial deposits appear not to involve fixed antigens. Rather, they represent immune complexes containing exogenous antigens and antibody to the antigens. These complexes may result from the passive trapping of pre-formed immune complexes from the circulation or may form in situ by several different mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Antibody Complex↗
PubMed1985

Anti-GBM antibody-induced proteinuria in isolated perfused rat kidney.

The effect of anti-GBM antibody on protein excretion was studied in isolated rat kidneys perfused with 20 mg of sheep anti-rat GBM (experimental) or nonantibody sheep IgG (control). Six control kidneys excreted 176 +/- 31 micrograms/min of BSA initially, rising to 296 +/- 111 micrograms/min at 2 h. Fractional clearance of BSA rose from 0.51 to 1.70%. Eight experimental kidneys excreted 211 +/- 56 micrograms/min of BSA, increasing to 1,924 +/- 804 micrograms/min at 2 h. Fractional BSA clearance increased from 0.56 to 11.49%. After 60 min, BSA excretion in anti-GBM-perfused kidneys exceeded controls by a factor of 6.5-7.9 (P less than 0.05) and fractional BSA clearance exceeded controls by a factor of 5.8-7.1 (P less than 0.05). Studies with fluorescent markers indicated proteinuria to be of glomerular origin in antibody-perfused kidneys. There were no significant differences between anti-GBM-perfused and control kidneys in perfusion pressures, perfusate flow rates, urine flow rates, inulin clearance, or sodium reabsorption. Antibody to GBM can induce a marked increase in glomerular permeability to BSA and IgG without participation of other systemic humoral or cellular mediation systems.

Animals↗
PubMed1985

Membrane attack complex deposition in experimental glomerular injury.

The complement (C) system is an important mediator of glomerular injury both through its attraction of inflammatory cells and by a cell-independent effect on glomerular capillary wall permeability. We have postulated that the latter effect may be mediated by the terminal components of the C system, the membrane attack complex (MAC). We examined several models of immunologic renal injury in the rat by immunofluorescence for the presence of neoantigens of the MAC. Rats with experimental membranous nephropathy induced by antibody binding to a fixed glomerular antigen (passive Heymann nephritis, PHN) or a planted antigen (autologous phase of PHN) had moderate proteinuria and 1-2+ capillary wall deposits of IgG, rat C3, and MAC. C depletion with cobra venom factor (CVF) significantly decreased proteinuria and prevented deposition of C3 and MAC. Rats with active Heymann nephritis had similar capillary wall deposits of MAC. Rats with anti-glomerular basement membrane nephritis developed severe proteinuria which was not affected by CVF treatment and had no glomerular deposits of MAC. Rats with nonimmunologic proteinuria induced by aminonucleoside of puromycin also had no glomerular deposits of MAC. In rats unilaterally nephrectomized before the induction of PHN segmental glomerular sclerosis developed after 6 months with deposits of MAC in the sclerotic areas. The presence or absence of glomerular deposits of MAC in experimental renal disease correlates well with the pathogenetic role of C in the production of injury. These results support a role for the MAC in the mediation of several types of glomerular injury.

Animals↗
PubMed1985

Late effects of chemotherapy on hematopoietic progenitor cells.

Residual damage to marrow function has been observed in cyclophosphamide-treated or irradiated mice following recovery of marrow hematopoietic stem cells (CFU-S) and peripheral blood counts to pretreatment levels. Residual damage is evidenced by less rapid recovery of marrow CFU-S and blood counts following subsequent exposure to sublethal irradiation. Mice treated with busulfan also demonstrate residual marrow damage as evidenced by incomplete recovery of marrow CFU-S to pretreatment levels. We report here on studies to determine whether the residual marrow damage after radiation, cyclophosphamide, or busulfan therapy is exerted on the hematopoietic stroma's ability to support CFU-S proliferation (HS-P) or on the repopulating potential of the CFU-S per se. HS-P function is determined by measuring the ability of femora implanted subcutaneously into syngeneic mice to support the growth of host CFU-S. Evidence is presented to show that this function depends on fixed (nonmigrating) cells in the marrow environment. The repopulating potential of CFU-S is determined by measuring the rate of regeneration of marrow CFU-S after transplantation into lethally irradiated mice. The results of these studies indicate that exposure to 950 rad, busulfan, or cyclophosphamide all cause damage to the HS-P that persists for at least six weeks after therapy. After cyclophosphamide therapy, but not after exposure to the other two agents, HS-P function continues to improve six weeks after therapy and eventually reaches pretreatment levels. Only in busulfan-treated mice was the residual damage to the CFU-S repopulating capacity significantly more marked than damage to HS-P function.

Animals↗
PubMed1985

Effect of alterations in glomerular charge on deposition of cationic and anionic antibodies to fixed glomerular antigens in the rat.

Reduction of the negative charge of the glomerular capillary wall alters its charge- and size-selective properties. To investigate the effect of alteration in glomerular charge properties on antibody localization, we prepared cationic and anionic fractions of antibodies to subepithelial and glomerular basement membrane (GBM) antigens, and compared their deposition in normal rats and rats treated with protamine sulfate or aminonucleoside of puromycin to reduce capillary wall charge. IgG antibodies were eluted from kidneys of rats with active Heymann's nephritis (AICN), passive Heymann's nephritis (PHN), or anti-GBM nephritis (NTN), separated into cationic and anionic fractions, and radiolabeled with iodine 125 or iodine 131. Relative antibody content of each fraction was determined by incubation with an excess of glomerular antigen. Varying amounts of cationic and anionic IgG eluted from kidneys of rats with AICN or PHN were injected into 24 normal or protamine sulfate-treated rats. Glomerular binding of all antibodies was highly correlated with IgG delivery to the kidney. The ratio of cationic to anionic antibody deposited in the glomeruli of normal rats after 4 hours was 1.08 +/- 0.07 for AICN eluate and 0.37 +/- 0.04 for PHN eluate. The ratios were not significantly different in animals pretreated with protamine sulfate (1.15 +/- 0.06 and 0.44 +/- 0.06, respectively; P greater than 0.05). Varying amounts of cationic and anionic IgG eluted from kidneys of rats with NTN were injected into 10 normal rats and four rats treated with aminonucleoside of puromycin. Glomerular binding of antibody was again highly correlated with IgG delivery to the kidney. The ratio of cationic to anionic antibody deposited in the glomeruli of normal rats after 1 hour was 1.03 +/- 0.06, and was not significantly altered in rats treated with aminonucleoside of puromycin (1.05 +/- 0.03, P greater than 0.5). Proteinuria in PHN rats was also unaffected by treatment with protamine sulfate for 5 days (controls: 68 +/- 21 mg/day; protamine sulfate-treated: 65 +/- 14 mg/day; n = 25, P greater than 0.08). These results demonstrate that treatment to reduce glomerular polyanion does not significantly alter the ratio of cationic to anionic antibodies to fixed glomerular antigens that deposit in the glomerulus, or reduce proteinuria caused by deposition of antibody to a fixed subepithelial antigen.

Animals↗
PubMed1985

Relationship of phosphate-dependent glutaminase activity to ammonia excretion in potassium deficiency and acidosis.

Ammonia production and excretion are elevated in potassium depletion alkalosis, although normally they are reduced in alkalosis and elevated in acidosis. Studies were conducted with or without acute acid loading in normokalemic rats or rats made chronically hypokalemic with deoxycorticosterone acetate and a potassium-deficient diet to examine the role of phosphate-dependent glutaminase (PDG) in regulating ammonia excretion. Renal cortical PDG rose fourfold, and urinary ammonia excretion (UAE) doubled in potassium depletion compared to potassium-repleted controls. Following acid challenge PDG and urinary ammonia increased four- to sevenfold in both normokalemic and hypokalemic animals, but the rise in UAE did not correspond to the increase in PDG. Thus, PDG levels in acidotic normokalemic rats were one half those seen in potassium-depleted rats, but UAE in the acidotic rats was six times greater. These results could not be explained solely by changes in blood pH. The poor correlation between PDG and UAE also could not be explained by limited substrate availability, since blood glutamine levels were unaffected by potassium depletion. The disparity between UAE and PDG in potassium depletion was studied further during 9 days of potassium repletion of depleted rats. UAE was again increased by depletion but, after only 3 days of potassium repletion, UAE fell to levels found in normokalemic rats. The renal PDG activity, however, remained three times normal. Indeed, PDG remained significantly elevated even after 9 days of potassium replacement. Other enzymes involved in renal ammoniagenesis, including delta glutamyl transferase, glutamine transferase and omega deamidase, were assayed, and alterations in their activities could not account for the changes in UAE.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1984

The use of streptokinase to treat renal artery thromboembolism.

The effects of streptokinase are difficult to determine. Furthermore, it has toxic side effects, and renal function may not recover from its use. However, because of favorable experiences with this drug in the early treatment of venous thromboembolism and following myocardial infarction, as well as the favorable findings with early perfusion in the dog model, the use of local streptokinase may be justified if the infusion is begun early, preferably within four to six hours.

Aged↗
PubMed1984

Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane.

Fixed anionic sites within the glomerular capillary wall influence the permeation of serum proteins, the localization of various antigens, and the deposition of antibody in the subepithelial space. In anti-GBM nephritis antibody deposition occurs very rapidly to antigenic sites located relatively proximal in the glomerular capillary wall. We examined the influence of the glomerular charge barrier on anti-GBM antibody deposition by comparing the rate of deposition of antibodies with cationic and anionic isoelectric points. Purified sheep anti-rat GBM IgG was isolated from acid eluates of kidneys obtained 24 hr after rats were injected with sheep antiserum to rat GBM. Anti-GBM IgG was separated into cationic (pI 6.4-8.5) and anionic (pI 4.2-6.8) fractions, which were radiolabelled with 131I and 125I, respectively, shown to have equal antibody contents measured by in vitro binding to normal glomeruli, mixed in equal amounts, and injected in incremental doses to ten rats. At 1 hr the glomerular antibody binding of each fraction was directly related to the blood level (r = 0.95, r = 0.97) and delivery of antibody (r = 0.98, r = 0.98). Glomerular binding of cationic antibody was four times greater than anionic antibody over the entire range of deliveries studied (P less than 0.001). We conclude that glomerular deposition of anti-GBM antibody is directly related to blood concentration and delivery of antibody. Furthermore, the deposition of cationic antibodies to GBM antigens was significantly greater than the deposition of anionic antibodies. The charge-selective glomerular filtration barrier may be an important determinant of the quantity and subclass composition of anti-GBM IgG deposits in glomeruli, and therefore of the severity of tissue injury produced.

Animals↗