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S G Adler

Publications and source records attributed to S G Adler.

31 records · Page 2Linked to original sources
PubMed1992

Laminin B1 is preferentially expressed in the cortex of rat kidney and is not affected by cyclosporine administration.

Cyclosporine has proven beneficial as an immunosuppressive agent for organ rejection in kidney transplants as well as in heart and liver transplants. Cyclosporine administration, however, is associated with certain adverse effects, one of the most important being chronic nephrotoxicity characterized by focal cortical scarring. Recent experimental data show involvement of type I and possibly type IV collagens in this process. Because laminin represents another potential extracellular matrix target, we examined the effects of cyclosporine administration in rats on the expression of laminin at the messenger ribonucleic acid (mRNA) and protein levels. In untreated normal rats, laminin B1 mRNA is preferentially expressed in the renal cortices, as demonstrated by northern blots. Daily administration of cyclosporine leads to focal cortical interstitial fibrosis and tubular atrophy by 4 weeks with, as shown previously, elevated procollagen alpha-1 (type I) mRNA levels at 1 and 4 weeks. In contrast, the amounts of message for laminin B1 remain identical after 1 week and 4 weeks of cyclosporine administration, despite the development of fibrosis at 4 weeks. Similar results were obtained with antilaminin antibody. We conclude that laminin is abundant in renal cortical tissues as compared with its medullary contents and is not altered in the process of renal cortical fibrosis induced by cyclosporine.

Animals↗
PubMed1991

Cyclosporine induces elevated procollagen alpha 1 (I) mRNA levels in the rat renal cortex.

Chronic cyclosporine nephrotoxicity is a poorly understood drug side-effect characterized by renal cortical interstitial scarring. To evaluate procollagen mRNA levels as an early factor in the development of this form of renal fibrosis, we measured renal procollagen alpha 1 (I), alpha 1 (III), alpha 1 (IV) and beta-actin mRNA levels in rats treated with cyclosporine (CsA) or the olive oil vehicle (OO) for one or four weeks. Renal morphology was similar without atrophy or fibrosis in one week CsA and OO and four week OO rats. Four week CsA rats had focal cortical interstitial fibrosis and tubular atrophy. Cortical procollagen alpha 1 (I) mRNA levels were increased in CsA versus OO rats at one week (P less than 0.02) and four weeks (P less than 0.02). One week medullary procollagen alpha 1 (I) and all other one week medullary, and one and four week cortical procollagen and beta-actin mRNA levels were no different in CsA versus OO rats. The early increase in renal cortical procollagen alpha 1 (I) mRNA levels precedes renal morphologic abnormalities, and may represent an important step in the pathogenesis of cyclosporine-induced renal cortical fibrosis.

Actins↗
PubMed1991

Intracellular chloride activity in cultured mesangial cells.

Glomerular mesangial cells require Cl ions for the development of a variety of metabolic and functional properties. In the present study the electrochemical distribution for Cl- was examined in cultured rat mesangial cells with Cl(-)-sensitive intracellular microelectrodes. It was determined that the intracellular Cl activity exceeded the levels predicted for a passively distributed ion. This was further substantiated by exposing mesangial cells to 10(-5) M bumetanide which drove intracellular Cl to a value close to electrochemical equilibrium. We conclude that Cl accumulates in mesangial cells, against its electrochemical gradient, through a transport pathway that is highly sensitive to bumetanide.

Animals↗
PubMed1991

Dimethyl sulfoxide enhances hexose monophosphate shunt activity in cultured glomerular mesangial cells, leukocytes and erythrocytes.

The effect of dimethyl sulfoxide (DMSO) on the rate of glucose oxidation by cultured rat glomerular mesangial cells, human erythrocytes and peritoneal exudate cells was studied. Mesangial cells, erythrocytes and peritoneal exudate cells incubated with DMSO showed enhancement of 14CO2 production from D-[1-14C] glucose but not from D-[6-14C] glucose. The concentration of DMSO required to stimulate respiratory burst activity was lowest for erythrocytes and highest for peritoneal exudate cells. Studies utilizing tritiated deoxyglucose revealed that the increased glucose oxidation associated with DMSO exposure was not due to increased transmembrane glucose movement at low concentrations of DMSO, and only partially responsible at high concentrations of DMSO. This study documents the ability of DMSO to specifically enhance the activity of the hexose monophosphate shunt pathway in all cells studied. The precise mechanism whereby DMSO stimulates shunt activity remains unknown.

Animals↗
PubMed1990

Lupus membranous glomerulonephritis: different prognostic subgroups obscured by imprecise histologic classifications.

Eighteen patients with lupus membranous nephritis were retrospective identified by reviewing the renal biopsy records of an active renal pathology service. Seven had minimally proliferative membranous nephropathy (World Health Organization (WHO) classes Va and b). Eleven had membranous nephropathy with superimposed changes of focal or diffuse proliferative glomerulonephritis (WHO Vc and d). After mean follow-up periods of 73 +/- 6 and 74 +/- 15 mo, respectively, one patient of seven from WHO Va and b and seven of 11 from WHO Vc and d reached end stage renal disease. The latter patients were distinguishable from the former only by the degree of superimposed proliferation on renal biopsy and not by blood pressure, antinuclear antibody, anti-double stranded DNA, or complement levels. These data stand in contrast to the widely held belief that lupus membranous nephropathy is relatively benign. The belatedness of this observation is partially due to imprecision in nosology for patients with lupus who have renal biopsies with "overlap" characteristics.

Biopsy↗
PubMed1989

Cl-/base exchange in rat mesangial cells: regulation of intracellular pH.

The present study was designed to determine whether rat glomerular mesangial cells possess Cl- -dependent intracellular pH (pHi) regulatory processes. Rat glomerular mesangial cells were grown to confluence on glass coverslips. Intracellular pH (pHi) was measured with BCECF. Steady state pHi in HCO3- containing solutions was 7.08 +/- 0.03 (N = 13). When extracellular Cl- was acutely removed, pHi increased at a rate of 0.57 +/- 0.03 pH/min units (N = 8), P less than 0.001. DIDS (0.5 mM) significantly decreased the rate of increase in pHi to 0.34 +/- 0.04 pH/min, P less than 0.01. Na+ removal and amiloride (1 mM) did not alter the increase in pHi induced by Cl- removal. Steady state pHi in the absence of Cl- was significantly increased above control, 7.39 +/- 0.02 (N = 7), P less than 0.001. Following the acute alkalinization of pHi by CO2 removal, pHi recovered at a rate of 0.07 +/- 0.01 pH/min (N = 9). In the absence of Cl-, the pHi recovery rate was significantly decreased to 0.01 +/- 0.008 pH/min (N = 5), P less than 0.01. DIDS (0.5 mM) significantly decreased the rate of pHi recovery to 0.02 +/- 0.01 pH/min (N = 5), P less than 0.01. Na+ removal and amiloride (1 mM) had no effect on the rate of pHi recovery following acute alkaline loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1989

Poor prognosis in end-stage lupus nephritis due to nonautologous vascular access site associated septicemia and lupus flares.

A poor prognosis was observed in patients who had end-stage renal disease (ESRD) as a result of systemic lupus erythematosus (SLE). This was true even in patients in whom SLE disease activity was transiently quiescent during the period of hemodialysis. Six of 9 patients with ESRD and SLE died with active SLE and/or sepsis 1-28 months following the onset of dialysis. In 5 of the 6 patients, acute inflammatory activity of SLE flared within 1 month of the patient's death. Four patients died with superimposed sepsis, but only 2 of the 4 were receiving high-dose concomitant immunosuppressives for more than 1 week prior to death. Infected hemodialysis vascular access sites were implicated as the source of septicemia in 3 of 4 infectious deaths. The 3 surviving patients had minimal lupus activity prior to the development of ESRD, a possible marker for stability in SLE patients who require hemodialysis. Our results suggest that hemodialyzed lupus patients with nonautologous vascular access sites may be at continued increased risk for life-threatening inflammatory and septic complications.

Adult↗
PubMed1989

Clinical utility of kidney biopsies in the diagnosis and management of renal disease.

A prospective study was undertaken to assess the utility of the renal biopsy as a tool in the clinical practice of nephrology. Nephrologists performing this procedure were surveyed concerning prebiopsy diagnosis, plans for therapy and estimation of prognosis, before and after biopsy results were disclosed. On the basis of 108 specimens from both academic centers and community hospitals, clinical and pathological diagnoses differed in 63% and therapeutic approach was altered in 34% of the cases. These results were greatest for nephrotic syndrome and for renal failure of rapid onset. The change in treatment was frequently of major consequence: decisions for the use of corticosteroids, cytotoxic agents and/or plasma exchange were altered based upon biopsy diagnoses. There were no differences either in diagnostic acumen or therapeutic approach between academic and community nephrologists. We conclude that renal biopsies are an important and frequently used part of the nephrologists' approach to patient care.

Acute Kidney Injury↗
PubMed1989

Sex vulnerability in the subtotal nephrectomy model of glomerulosclerosis in the rat.

Unilateral nephrectomy and contralateral ligation of two thirds of the renal arterial circulation were performed on male (N x M, n = 6) and female (N x F, n = 7) Sprague-Dawley rats. Sham nephrectomies were performed in 16 male and female control rats (SN x M, n = 8; SN x F, n = 8). Creatinine clearance corrected for body weight and systolic arterial blood pressure were equal in both nephrectomized groups after 1, 3, and 5 weeks. The appearance of proteinuria was delayed in N x F and was still significantly less than N x M after 5 weeks (79 +/- 22 vs 30 +/- 12 mg per 24 hours, p less than 0.05). Glomerular visceral epithelial cell protein reabsorption droplets and vacuolization were equal in N x M and N x F. N x F exhibited one fifteenth of the glomerulosclerosis seen in N x M (p less than 0.01). In addition, there was one fourth of the mesangial expansion, but this trend did not reach statistical significance (p greater than 0.05). Mean glomerular volume was similar in male and female sham-operated (p greater than 0.05) and nephrectomized rats (p greater than 0.05), and nephrectomy resulted in hypertrophy in both groups (p less than 0.01). Glomerular procollagen alpha 1(IV) mRNA levels were higher in N x M than in all other groups (p less than 0.05) and correlated with mesangial expansion and glomerular sclerosis (p less than 0.01) but not with systemic hypertension, proteinuria, or epithelial cell changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

Hyperglobulinemia may spuriously elevate measured serum inorganic phosphate levels.

Pseudohyperphosphatemia was noted in four patients with hyperglobulinemia when inorganic phosphate levels were measured on the Vickers M-300 discrete automated analyzer (Vickers, Raritan, NJ) used by our clinical laboratory. When the same samples were reanalyzed after protein removal by sulfosalicylic acid precipitation, ultrafiltration, or more extensive dilution, the measured serum inorganic phosphate levels were invariably normal. The addition of human globulin (but not albumin), to pooled normal sera, caused an increase in serum inorganic phosphate levels as measured by the discrete analyzer. The increase correlated with the amount of globulin added (r = 0.72, P less than 0.05), but measured levels did not reach those observed in the hyperphosphatemic, hyperglobulinemic patients. Identification of 13 additional hyperglobulinemia patients revealed that hyperglobulinemia was not invariably associated with hyperphosphatemia. These data suggest that (1) with discrete automated analyzer use, hyperglobulinemia but not hyperalbuminemia may falsely elevate serum inorganic phosphate levels; (2) increased measured serum inorganic phosphate levels appear to be determined by both the concentration and the physicochemical characteristics of the globulin; (3) physicians should avoid prescribing phosphate binders to hyperglobulinemia patients with "hyperphosphatemia" unless they have ascertained that the serum inorganic phosphate level has been measured in a specimen that is free of protein; and (4) the occurrence of "pseudohyperphosphatemia" should suggest the need for an evaluation to rule out the presence of a monoclonal gammopathy.

Blood Chemical Analysis↗
PubMed1988

Antigenic charge as a factor in resistance to immunosuppressive therapy.

This study examines the effects of methylprednisolone (MP) on the glomerular lesions induced by the injection of cationic bovine serum albumin (BSA) in rabbits. Male New Zealand white rabbits (n = 55) were treated with cationic BSA alone (n = 13), cationic BSA plus MP (n = 26), native BSA alone (n = 8), or native BSA plus MP (n = 8). Animals receiving BSA alone developed subepithelial immune complex deposits after injections of cationic BSA or mesangial immune complex deposits after injections of native BSA. Subepithelial deposits were inhibited in only 10 of 26 rabbits receiving MP and cationic BSA. Glomerular lesions occurred rather predictably in this group unless complete ablation of antibody production was achieved. Even minimal amounts of detectable antibody were sufficient to support the development of the full-blown renal lesion. Proteinuria was diminished in all animals receiving cationic BSA and MP in whom a beneficial histologic effect was observed. MP inhibited the development of mesangial deposits in all of the animals given native BSA. This inhibition was associated with almost complete ablation of anti-BSA antibody production in this group. Renal perfusion studies (n = 8) demonstrated that the beneficial effects of MP on the development of immune deposits were related to systemic immunosuppression and not to local structural alterations in the glomerulus. Our findings confirm that the pattern of immune response to native and cationic antigens differ. In addition, they demonstrate that cationic antigens appear to require only small amounts of free circulating antibody in order to produce glomerular immune complexes and cause proteinuria.

Animals↗
PubMed1983

Electrical charge. Its role in the pathogenesis and prevention of experimental membranous nephropathy in the rabbit.

Intravenous cationic bovine serum albumin (BSA, pI > 9.5) induces membranous nephropathy in immunized rabbits. In this study, unimmunized rabbits received intravenous injections of cationic (n = 3) or native (n = 3) or native (n = 3) BSA, followed by ex vivo isolated left renal perfusions with sheep anti-BSA antibody. Capillary wall deposits of IgG and C3 were seen exclusively in the group receiving cationic BSA, confirming an in situ pathogenesis for cationic, BSA-induced membranous nephropathy, and demonstrating the importance of a cationic antigen for its production. We then explored whether membranous nephropathy in this model is prevented by the concomitant injection of protamine sulfate, a filterable, relatively non-immunogenic polycation. An in vitro study demonstrated that protamine sulfate incubated with glomerular basement membrane (GBM) decreased the subsequent binding of radiolabeled cationic BSA (P < 0.05). In vivo, protamine sulfate was shown to bind to anionic sites in the glomerular capillary wall after intravenous injection.Groups of rabbits received 3 wk of daily intravenous injections of cationic BSA alone (n = 15) or cationic BSA and protamine (n = 18). After 2 wk of injection of cationic BSA alone, typical membranous nephropathy developed. Granular deposits of IgG and C3 were present along the GBM associated with subepithelial dense deposits, foot process effacement, and marked albuminuria. Protamine significantly reduced or prevented the formation of deposits (P < 0.001) and in6 of 18 protamine-treated animals, existing deposits decreased or disappeared between 2 and 3 wk of injection. Albuminuria was significantly reduced in protamine-treated animals with a mean of 124+/-55 mg/24 h compared to 632+/-150 mg/24 h in the control group receiving cationic BSA alone. No significant differences between the groups were noted in serum lev9lsof IgG, C3, anti-BSA antibody, or circulating immune complex size. Studies in additional animals (n = 5) given radiolabeled cationic BSA showed that protamine did not alter the clearance of cationic BSA from serum. Control experiments showed that protamine's beneficial effects were not related to its weak anticoagulant property or toits theoretical ability to deplete tissue histamine. The administration of heparin (n = 6) or diphenhydramine (n = 6) had no effect on the development of the epimembranous lesion compared to the group receiving cationic BSA alone. In addition, homogenized whole kidney histamine content was not significantly different in the group receiving cationic BSA alone compared to the group receiving cationic BSA and protamine. This work shows that a cationic BSA-induced glomerular lesion can be produced by a renal perfusion technique involving in situ complex formation and that this process requires a cationic antigen for its development. We believe that the demonstrated beneficial effects of protamine are due to its ability to bind to glomerular anionic sites, and that this electrostatic interaction results in inhibition for the further binding of the cationic antigen, thereby limiting the severity of glomerulonephritis in this model.

Animals↗