T Nadasdy

Johns Hopkins University, Baltimore, MD, United States

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Publications (36)101.08 Total impact

  • M Samaniego · G M Nadasdy · Z Laszik · T Nadasdy
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    ABSTRACT: Fibrillary glomerulonephritis (FGN) is a rare but progressive glomerular disease usually with end-stage renal disease (ESRD) developing within months or few years following the diagnosis. Little is known about the outcome of renal transplantation in patients with ESRD due to FGN. We report four patients with FGN who received renal allografts. Two patients developed recurrent FGN in their grafts. One patient was diagnosed to have recurrent FGN 9 years post-transplant, and lost his graft 4 years thereafter. Another patient had recurrent disease 2 years post-transplant but has stable graft function after 7 years. One patient died with normal renal allograft function 7 years following transplantation. The fourth patient has chronic transplant nephropathy 34 months post-transplant without evidence of recurrent FGN. A literature review revealed 10 additional patients who received 11 renal allografts due to ESRD caused by FGN. Four of these 10 patients had biopsy-proven recurrence (one patient in two subsequent grafts), but this caused graft loss only in 2 patients 56 months and 7 years post-transplant, respectively. The earliest recurrence was diagnosed 2 years post-transplant. We conclude that although the recurrence rate of FGN in renal transplants is high (around 50%), the recurrent disease has a relatively benign course and prolonged graft survival is possible.
    Clinical nephrology 03/2001; 55(2):159-66. · 1.23 Impact Factor
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    ABSTRACT: In a previous study, utilizing antibodies to proliferating cell nuclear antigen (PCNA), we determined the proliferation index (PI) (percentage of PCNA-positive cells) of intrinsic renal cell populations in the normal adult and pediatric kidney. We have found that the PI in both adult and pediatric kidneys was very low (below 0.5 in all examined cell populations). In our present study, we investigated cell proliferation in the developing human kidney with an antibody to PCNA. Histologically normal kidneys were collected from 25 fetuses (spontaneous abortions and stillborns) ranging from 10 wk of gestation to term. Immature mesenchyme (blastema), immature early tubules, ampulla of ureteric bud, proximal tubules, Tamm-Horsfall protein (THP)-positive tubules, distal tubules, collecting ducts, and glomeruli were evaluated separately. The PI for each cell population was calculated. The PI of immature early tubules remains high (33-43) throughout embryonic life. The PI of blastemal cells is initially similarly high, but gradually decreases starting from the second trimester. The PI of THP-positive tubules, distal tubules, collecting ducts, and glomeruli starts out relatively high (5.9, 8.6, 6.0, and 12.4, respectively) and decreases gradually as term approaches (1.8, 1.3, 1.2, and 1.4, respectively). Interestingly, as soon as proximal tubules become differentiated (appearance of light microscopic features of proximal tubular epithelium with TP lectin positive brush border), their PI becomes very low (below 1) irrespective of the age of the kidney. This is the first quantitative study to show changes of the PI in various renal cell populations during human nephrogenesis. These changes in the PI relate to the stage of differentiation of the developing nephron segments.
    Pediatric and Developmental Pathology 01/1998; 1(1):49-55. DOI:10.1007/s100249900006 · 0.86 Impact Factor
  • G Lajoie · T Nadasdy · Z Laszik · K E Blick · F G Silva
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    ABSTRACT: Mast cells (MCs), few in the normal kidney, are found in increased number in the renal parenchyma in diseases associated with persistent chronic inflammation. MCs are not easily identified in routinely processed archival tissue sections with histochemical stains. A more reliable method of detection was provided with the introduction of MC tryptase-specific monoclonal antibodies. To determine the possible role of MCs in renal allograft rejection, we studied 28 biopsy specimens from renal allografts that had been in place for various lengths of time (from 3 days to 40 months) in patients whose primary diagnosis was acute interstitial rejection; the specimens were associated with varying degrees of interstitial fibrosis, edema, and hemorrhage. The specimens were graded on a semiquantitative scale (from 0 to 3+) for the severity of rejection, the degree of interstitial fibrosis, interstitial edema, and interstitial hemorrhage. Eosinophils, plasma cells, and MCs were quantitatively evaluated in these biopsy specimens. MCs were detected by use of a commercially available anti-MC tryptase monoclonal antibody, which proved to be an excellent tool to detect MCs in routinely processed paraffin sections. A positive correlation was found between the number of MCs and the time since transplantation (R = 0.841, P < 0.005) and between the number of MCs and the severity of interstitial fibrosis (R = 0.489, P < 0.005), as well as with interstitial edema (R = 0.517, P < 0.005). MCs were increased in number in patients with moderate (n = 18; mean, 18.00 MCs per 10 high power fields [HPFs]) and severe (n = 5; mean, 12.20 MCs per 10 HPFs) acute rejection compared with patients with mild (n = 5; mean, 2.44 MCs per 10 HPFs) acute rejection and normal kidneys (n = 6; mean, 1.75 MCs per 10 HPFs). These results suggested that MCs might play a role in the process of acute rejection of renal allografts and in the development of interstitial fibrosis.
    Modern Pathology 01/1997; 9(12):1118-25. · 6.36 Impact Factor
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    ABSTRACT: To determine the nephron segment distribution of tubular epithelial damage and regeneration and the proliferative activity of various nephron segments in human acute tubular necrosis (ATN) with an antibody to proliferating cell nuclear antigen (PCNA) and to compare the findings in native kidneys with ATN with those in transplant kidneys with ATN, archival tissues from 12 native and 21 transplant kidney biopsy specimens and nine transplant nephrectomy specimens were collected that all showed obvious morphological signs of ATN. Nineteen patients with transplant kidneys with ATN were immunosuppressed with cyclosporine and 11 were immunosuppressed with prednisone and azathioprine. There was a predominance of "regenerating" tubules (tubules with thin epithelium) in the distal nephron in native kidneys with ATN; in the transplant kidneys this was less conspicuous. The number of Tamm-Horsfall protein (THP)-positive tubules was decreased in all kidneys with ATN compared with normal human kidneys. In contrast, the number of THP-positive casts was much higher in all kidneys with ATN than in the normal kidneys. In transplant kidneys with ATN the number of THP-positive casts was substantially lower than in native kidneys with ATN. The macula densa appears to maintain its morphological integrity in kidneys with ATN. Both regenerating and normal appearing tubules expressed vimentin and HLA-DR. The proliferation index (PI; ie, percentage of PCNA-positive nuclei) of the renal tubular epithelium in normal control kidneys varied between 0.22 and 0.33, depending on the tubule segment. The highest PI was noted in the transplant kidneys with ATN not treated with cyclosporine (8.0), followed by the native kidneys with ATN (4.4) and the transplant kidneys with ATN treated with cyclosporine (4.3). We did not find any significant difference in the PI between the regenerating (5.0) and normal appearing (5.6) tubules. Proximal tubules (8.7) showed significantly higher PI values than distal tubules (3.5) in transplant kidneys with ATN. Our results show substantial differences between native kidneys and transplant kidneys with ATN. Tubular epithelial cell proliferation in human ATN is prominent and appears to correlate with the severity of ATN. Light microscopically normal appearing tubules and regenerating tubules participate equally in the regeneration of injured tubules. Cyclosporine may have an inhibitory effect on cell regeneration (proliferation) in human transplant kidneys with ATN.
    Human Pathlogy 03/1995; 26(2):230-9. DOI:10.1016/0046-8177(95)90042-X · 2.81 Impact Factor
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    T Nadasdy · Z Laszik · G Lajoie · K E Blick · D E Wheeler · F G Silva
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    ABSTRACT: Increased proliferative activity of the renal tubular epithelium is thought to be a prerequisite for renal cyst formation by many investigators. However, in humans, the exact in vivo proliferation rate of epithelial cells lining these cysts is not known. In this study, which used immunohistochemical methods with an antibody to proliferating cell nuclear antigen (PCNA), the proliferation index (PI) (percentage of PCNA positive cell nuclei among epithelial cells lining the renal cysts) was determined in 10 cases of autosomal dominant polycystic kidney disease (ADPKD), 8 cases of autosomal recessive polycystic kidney disease (ARPKD), and 8 cases of acquired cystic kidney disease (ACKD). Cysts with proximal and distal nephron phenotype and cysts with markedly thickened basement membranes, as well as cysts lined by atrophic (flattened), "regular" (cuboidal or cylindrical), and hyperplastic epithelium, were evaluated separately. The overall PI of cyst epithelium (excluding hyperplastic cysts) was 2.58 in ADPKD, was 10.5 in ARPKD, and was 3.61 in ACKD. Overall, there were only minor differences in the PI between the various types of cysts. Cysts with hyperplastic epithelium in ACKD (unlike in ADPKD) showed a high PI (9.1). For comparison, the PI of two renal cell carcinomas occurring in two ACKD cases was also determined (13.70 and 8.67%). The PI of tubular epithelium in normal kidneys was only 0.22 to 0.33%, depending on the tubule segment. In contrast, in polycystic kidneys, those noncystic segments of the nephron from which the cysts are thought to originate (distal nephron (specifically collecting duct)) in ARPKD, primarily distal in ADPKD, proximal and distal in ACKD, had PI values similar to those of the cyst epithelium.(ABSTRACT TRUNCATED AT 400 WORDS)
    Journal of the American Society of Nephrology 02/1995; 5(7):1462-8. · 9.47 Impact Factor
  • G Lajoie · Z Laszik · T Nadasdy · F G Silva
    Seminars in Nephrology 10/1994; 14(5):441-63. · 2.94 Impact Factor
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    ABSTRACT: Endotoxin-induced cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) are thought to contribute to the proinflammatory effects of endotoxin in gram-negative infections. Using a conscious rat model of sepsis, induced by intravenous challenge with LD95 doses of endotoxin (n = 24) or live Escherichia coli (E. coli) (n = 24), we examined frozen sections of kidney at various intervals for evidence of IL-1 alpha and TNF alpha expression. A transient glomerular endothelial IL-1 alpha expression was demonstrated at 30 and 90 min after initiation of the sepsis in both endotoxin and E. coli-treated animals using immunohistochemistry. The endothelial IL-1 alpha expression as determined by immunohistochemistry occurred at the same time as IL-1 alpha mRNA expression, as determined by Northern blot analysis. The glomerular endothelial IL-1 alpha expression coincided with a slight but significant increase in the number of the glomerular polymorphonuclear leukocytes as identified by naphthol AS-D chloroacetate esterase enzyme histochemical reaction. Glomerular endothelial IL-1 alpha expression was virtually absent by 180 and 360 min. No TNF alpha expression was detected in the renal tissues at any time interval. Neither alpha-naphthyl acetate esterase-positive nor acid phosphatase-positive monocytes/macrophages were identified in the glomeruli. Our findings provide direct in vivo evidence that the IL-1 alpha gene product is expressed locally in the kidney by glomerular endothelial cells in this septic rat model.
    Circulatory shock 08/1994; 43(3):115-21.
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    T Nadasdy · Z Laszik · K E Blick · L D Johnson · F G Silva
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    ABSTRACT: The proliferative activity of various normal human renal cell populations is unknown. Recently, antibodies to cell proliferation-associated nuclear proteins, such as proliferating cell nuclear antigen (PCNA) and KI-67, which are applicable to archival paraffin sections, became available. With antibodies to PCNA and Ki-67 after microwave pretreatment of the paraffin sections, the proliferation indexes (ratio of positive nuclei with PCNA and Ki-67 antibodies/all nuclei counted x 100, i.e. percentage of positive cells) of 12 different intrinsic renal cell populations in 20 normal human kidneys have been determined. The following proliferation indexes (percentages of positive cells) were found with the PCNA and the Ki-67 antibodies, respectively: proximal tubular epithelium, 0.22, 0.24; thin limb of Henle, 0.29, 0.30; thick ascending limb of Henle, 0.32, 0.29; distal tubular epithelium (distal convoluted tubules and cortical collecting ducts, 0.33, 0.44; medullary collecting ducts, 0.32, 0.3; glomerular mesangial cells, 0.07, 0.12; glomerular visceral epithelial cells, 0.04, 0.08; glomerular parietal epithelial cells, 0.07, 0.1; glomerular capillary endothelium, 0.42, 0.47; peritubular capillary endothelial cells, 0.38, 0.43; endothelium of large intrarenal vessels (arteries and veins), 0.09, 0.12. Thus, normally capillary endothelium (glomerular and peritubular) appears to have the highest proliferation index in the human kidney by these techniques. These results indicate major variation in the proliferative activity of normal human renal cell populations, along with a significant correlation between PCNA and Ki-67 staining. Furthermore, this study provides normal values for the proliferative activity of different human renal cell populations.(ABSTRACT TRUNCATED AT 250 WORDS)
    Journal of the American Society of Nephrology 07/1994; 4(12):2032-9. · 9.47 Impact Factor
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    ABSTRACT: The thrombomodulin-dependent protein C anticoagulant pathway plays a major physiologic role in the down-regulation of the coagulation process. In cell culture, inflammatory cytokines or endotoxin can down-regulate endothelial thrombomodulin (TM) suggesting that suppressed TM expression may contribute to thrombotic complications noted in Gram-negative sepsis. In the present study, we have examined TM expression in the kidneys of septic rats utilizing indirect immunofluorescence and have quantified TM antigen and TM activity in extracts of the same kidneys by enzyme-linked immunosorbent assays and protein C activation assays, respectively. Conscious Sprague-Dawley rats were injected intravenously with LD95 doses of live E. coli (N = 30), or endotoxin (N = 30). Control animals (N = 30) were injected with equivalent volumes of saline. The rats were killed 30, 90, 180, 360, and 720 minutes after the initiation of sepsis. Glomerular capillary thrombosis developed by 180 minutes in approximately half of the animals after the initiation of sepsis. We failed to demonstrate suppressed TM expression in the kidneys of septic animals using immunofluorescence. Neither enzyme-linked immunosorbent assays, nor protein C activation assays showed decreased levels in TM antigen expression or activity at different time points during the sepsis. These results indicate that suppressed TM expression does not contribute to the development of the glomerular capillary thrombosis in this septic rat model.
    Laboratory Investigation 07/1994; 70(6):862-7. · 3.83 Impact Factor
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    ABSTRACT: We report the case of a 50 year old woman with metastatic breast carcinoma refractory to chemotherapy who died of candidal septicemia after autologous bone marrow transplantation. Although there was no apparent active cytomegalovirus (CMV) infection (negative cultures and serology for active infection), autopsy revealed histologic evidence of CMV inclusions limited to both ovaries. DNA in situ hybridization was performed on multiple organs, and additional foci of infection in one fallopian tube and the adrenal glands were detected. Previous reports of isolated CMV oophoritis may represent sampling error. An ascending route of infection is suggested. Tubo-ovarian changes due to CMV infection may occur more frequently than suspected; they are difficult to diagnose because even actively CMV infected cells may not be detected by routine histology alone, and because, after the active infection 'heals', no evidence of the virus can be found on histologic examination.
    Acta Obstetricia Et Gynecologica Scandinavica 06/1994; 73(5):429-31. DOI:10.3109/00016349409006258 · 1.99 Impact Factor
  • T Nadasdy · J Smith · Z Laszik · J L Waner · L D Johnson · F G Silva
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    ABSTRACT: Cytomegalovirus (CMV) was recently identified, using in situ hybridization, in the coronary arteries of patients with cardiac transplant rejection, suggesting a role of CMV in the development of obliterative transplant arteriopathy in cardiac allografts. We sought to verify this observation by examining arteries in kidney transplants with intimal thickening due to chronic rejection. Eleven renal biopsies and 13 nephrectomies from 24 patients, all showing obliterative transplant arteriopathy, were collected for this study. Of these patients, six were seropositive for CMV before transplantation, three were identified as seropositive following renal transplantation, nine had no evidence of CMV infection, and clinical data were not available for an additional six patients. Paraffin-embedded renal sections were examined for the presence of CMV by immunohistochemistry in situ hybridization and polymerase chain reaction. By these methods, only one case (1/24) was demonstrated to have CMV infected cells in the renal interstitium, tubules, and glomeruli, but none (0/24) showed CMV to be located in any of the renal arteries or arterioles. Thus, our results suggest that obliterative transplant arteriopathy can occur in the absence of demonstrable CMV and is probably unrelated to direct CMV infection of the graft.
    Modern Pathology 05/1994; 7(3):289-94. · 6.36 Impact Factor
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    ABSTRACT: Atrophic tubules in end-stage renal disease (ESRD) may have various morphologic appearances: some show microscopic features of "classic" atrophic tubules (thick, wrinkled tubular basement membrane and simplified epithelium), others show "thyroidization" (round tubules with simplified epithelium and casts), and many have the appearance of "endocrine" tubules (small tubules with narrow lumina, clear cells, and relatively thin basement membranes). Other tubules in ESRD may be enlarged and dilated with hypertrophic cells ("super" tubules). The exact segment of the nephron from which these tubules arise in ESRD has not been well studied. We examined paraffin sections of 28 end-stage kidneys with a panel of nephron-segment-specific renal epithelial markers (proximal nephron markers: Tetragonolobus purpureas and Phaseolus vulgaris erythroagglutinin lectins; distal nephron markers: antibodies to epithelial membrane antigen, low molecular weight cytokeratin [AE1/AE3], the lectin Arachis hypogaea, and an antibody to Tamm-Horsfall protein labeling the thick ascending limb of Henle). In addition, an antibody to proliferating cell nuclear antigen was applied to determine the proliferation index (proliferating cell nuclear antigen-positive nuclei/all counted nuclei x 100, ie, the percentage of proliferating cell nuclear antigen-positive nuclei) of the various atrophic and "super" tubules in ESRD. Classic atrophic tubules and the "super" tubules showed primarily a proximal phenotype. Tubules showing thyroidization were consistently positive with markers of the distal tubular epithelium. "Endocrine" tubules stained primarily with distal tubular markers; however, some proximal staining also was noted. The widened renal interstitium contained single cells or loosely organized small cell clusters positive with both the AE1/AE3 and the epithelial membrane antigen antibodies. Serial sectioning showed that the majority of these single cells were not forming tubules. The proliferation index of the "classic" atrophic tubules was the highest (3.08%), followed by the "super" tubules (2.39%), the "endocrine" tubules (1.58%), and the "thyroid" tubules (1.09%). These indexes are all considerably higher than the proliferation index of the normal renal tubular epithelium. Our findings suggest that different types of tubular atrophy may arise from different segments of the nephron, and that the renal interstitium in ESRD may harbor isolated cells with epithelial characteristics. Furthermore, the end-stage kidney is not a resting organ; on the contrary, it shows a high proliferative activity, particularly in the epithelium of the "classic" atrophic and the "super" tubules.
    Human Pathlogy 02/1994; 25(1):22-8. DOI:10.1016/0046-8177(94)90166-X · 2.81 Impact Factor
  • T Nadasdy
    Nephrology Dialysis Transplantation 02/1994; 9(11):1699-700. · 3.49 Impact Factor
  • F G Silva · T Nadasdy · Z Laszik
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    ABSTRACT: Many renal diseases involving the tubular epithelium appear to preferentially affect certain nephron segments. While major portions of the nephron, such as proximal and distal convoluted tubules and collecting ducts, can be identified in the normal kidney, the distinction of diseased nephron segments can be difficult in tissue sections. Thus, to identify which nephron segments are involved in pathologic changes is usually impossible by routine histologic examination alone. Recently antibody and lectin probes that react with specific nephron segment-specific epitopes and carbohydrates, respectively, have become available. Some of these antibodies and lectins can be used on formalin-fixed, paraffin-embedded, archival tissues. Because renal tubules appear to retain their nephron segment-specific epitopes and glycoprotein moieties under most pathologic conditions, these nephron segment-specific tubular epithelial markers provide a method to study renal diseases involving the tubular system also in archival material. Such nephron segment-specific tubular epithelial markers are: the lectins, Tetragonolobus purpuras and Phaseolus vulgaris erythroagglutinin (proximal tubular markers); antibodies to low-molecular-weight cytokeratin (AE1/AE3); epithelial membrane antigen and the lectin Arachis hypogaea (distal nephron [distal convoluted tubule and collecting duct] markers); and antibodies to Tamm-Horsfall protein (labeling the thick ascending limb of Henle). We review the application of these and other renal tubular epithelial markers in the normal kidney and in various renal diseases including cystic disease of the kidney, interstitial nephritis, tubular atrophy, acute tubular necrosis, myeloma cast nephropathy, and renal tumors.
    Archives of pathology & laboratory medicine 01/1994; 117(12):1233-9. · 2.88 Impact Factor
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    ABSTRACT: Eight cases of congenital mesoblastic nephroma (CMN) were examined. Three CMNs were of the classical (typical) variant, two were cellular (atypical), and three showed a mixed pattern. A panel of nephron segment-specific tubular epithelial markers (the lectins Tetragonolobus purpureas, Phaseolus vulgaris erythroagglutinin, and Arachis hypogaea and antibodies to epithelial membrane antigen, cytokeratin, and Tamm-Horsfall protein) were used to differentiate epithelial structures within the tumor. Antibodies against vimentin, desmin, and muscle-specific actin were used as mesenchymal markers. A monoclonal antibody to the long (embryonic) form of polysialic acid (PSA) on the neural cell adhesion molecule was used as a putative renal oncodevelopmental marker. An antibody to proliferating cell nuclear antigen also was applied, which revealed increased proliferative rate in cellular CMNs. In addition to clearly entrapped native renal tubules, CMNs contain tubular structures with immature, dysplastic epithelium and occasional epithelial cell clusters embedded deep within the tumor. These immature tubules and clusters express distal nephron, including collecting duct markers and, occasionally, vimentin and PSA. We propose that these primitive tubules and epithelial structures may originate from the ureteric bud. An epithelial differentiation of the tumor cells also is possible. In one pure cellular CMN and two mixed CMNs the cellular component showed diffuse staining for PSA. The PSA (neural cell adhesion molecule) expression of the cellular component suggests that CMN may originate from the uninduced nephrogenic mesenchyme.
    Human Pathlogy 05/1993; 24(4):413-9. DOI:10.1016/0046-8177(93)90090-4 · 2.81 Impact Factor
  • M D Hughson · T Nadasdy · G A McCarty · C Sholer · K W Min · F Silva
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    ABSTRACT: Current studies indicate that a thrombotic microangiopathy (TMA) identifies patients with systemic lupus erythematosus (SLE) who are at high risk of progressing to end-stage renal disease. We have observed two patients with SLE and one patient with a primary antiphospholipid syndrome (APS) who developed acute renal insufficiency with thrombocytopenia. Renal biopsies showed a TMA characterized by thrombi or by cellular and mucoid intimal hyperplasia of small arteries and arterioles. No arterial or arteriolar immune-complex deposits were detected by immunofluorescent or electron microscopy. Biopsies from one SLE patient and the APS patient showed no immune-complex glomerular disease. Both had serum antiphospholipid antibodies (aPL). aPL were not detected in the serum of the other SLE patient who had an active lupus nephritis. Acute renal failure and thrombocytopenia resolved in each case following treatment by plasmapheresis or prednisone and heparin. None of the patients were initially treated with cytotoxic drugs. As more knowledge is gained, the accurate identification of renal vascular lesions in SLE or related diseases could influence renal prognosis and choice of therapy. The cases reported here provide further evidence that a TMA can cause acute renal failure independent of lupus nephritis. TMA should be distinguished from other forms of renal vascular disease, particularly a noninflammatory lupus microangiopathy, which is probably mediated by subendothelial immune-complex deposits. The absence of immunoglobulin deposits in vessels involved by a TMA indicates that microvascular thrombosis is promoted by mechanisms other than those usually attributed to immune-complex disease. Phospholipid reactive antibodies may be pathogenetic in some cases.
    American Journal of Kidney Diseases 09/1992; 20(2):150-8. DOI:10.1016/S0272-6386(12)80543-9 · 5.76 Impact Factor
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    T Nadasdy · C S Park · S C Peiper · J E Wenzl · J Oates · F G Silva
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    ABSTRACT: There are only a few reports of renal disease associated with Epstein-Barr virus (EBV) infection. The diagnosis of EBV infection in these previously reported patients was based primarily on positive serology. Two patients with renal disease who, despite repeatedly negative serologies, were shown by molecular hybridization techniques--in situ hybridization (ISH) and polymerase chain reaction (PCR)--to have EBV infection are reported here. Site-specific molecular probes directed against specific, tandemly repeated EBV genomic regions were used. A synthetic 23-mer terminally biotin-labeled oligonucleotide probe selected from the EBV NotI region was used for ISH. For PCR, oligonucleotide primers were designed from sequences of the highly conserved, long internal direct repeat region of EBV to specifically amplify a 110-base-pair segment. The first patient, a 3-yr-old girl with a 1-yr history of fatigue, fever, splenomegaly, and lymphadenopathy developed hematuria. A renal biopsy revealed widespread glomerular mesangiolysis admixed with segmental mesangial sclerosis; no immune deposits were noted by electron microscopy or immunofluorescence. ISH on paraffin sections of the resected spleen and lymph nodes was positive for EBV. The second patient, a 28-yr-old male renal allograft recipient, received a double dose of OKT3. Seven weeks after transplantation, a renal biopsy revealed a lymphoproliferative disorder. Paraffin sections of the nephrectomy specimen were positive for EBV by both ISH and PCR. It was concluded that (1) EBV cannot be excluded on the basis of multiple negative serologies in some patients, and (2) ISH and PCR may lead to the detection of viral genomic information in renal and nonrenal tissues.
    Journal of the American Society of Nephrology 07/1992; 2(12):1734-42. · 9.47 Impact Factor
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    ABSTRACT: A number of studies have suggested that HIV infection can be detected in a variety of routinely fixed archival tissues using antibodies to various viral proteins. In order to study this immunocytochemical approach, paraffin sections were examined with a large panel of commercially available monoclonal antibodies against the various HIV proteins (5 antibodies to p24, 1 to p17, 1 to gp41, and 1 to gp120) using a streptavidin-biotin method. A polyclonal antibody against p24 was also tested. Formalin-fixed, paraffin-embedded HIV infected CEM E5 T cells were used as positive controls. Tissues from AIDS patients included 31 kidneys, 8 lymph nodes, 2 spleens and 3 brains. Non-AIDS tissues examined were 6 renal biopsies with focal segmental glomerulosclerosis, 5 with interstitial nephritis, 6 reactive lymph nodes, and a brain with encephalitis, all from patients not known to be at high risk for HIV infection. Additional negative controls included: 1) replacement of primary antibody with a hybridoma derived mouse monoclonal IgG1 standard, 2) omission of the primary antibody, and 3) sections of formalin-fixed paraffin-embedded CEM E5 T cells cultures not infected with HIV. Competition experiments with excess recombinant p24 protein were also performed. False positive staining with the IgG1 standard or with the antibodies to HIV proteins was frequently seen in tissues with pathologic findings (inflammation, hyalin degeneration), particularly following protein digestion. Protein digestion also had a major impact on specific staining. Digestion with proteinase K abolished specific staining for the core proteins of the virus (p17, p24) on the positive control sections.(ABSTRACT TRUNCATED AT 250 WORDS)
    Modern Pathology 06/1992; 5(3):283-91. · 6.36 Impact Factor
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    ABSTRACT: Although it has been suggested that cytomegalovirus (CMV) infection of the kidney might facilitate the development of human immunodeficiency virus-associated nephropathy (HIVAN) or other morphologic renal changes in patients with AIDS, no systematic study has been performed on kidneys from AIDS patients. We examined 75 autopsy kidneys, two renal biopsy specimens, and a nephrectomy specimen from 78 HIV-infected patients (five with HIVAN) for the presence of CMV. Immunocytochemistry (ICC) utilizing a monoclonal antibody against the late antigen of CMV and in situ hybridization (ISH) with a biotinylated DNA probe for CMV sequences were used. The detection system for both ICC and ISH was streptavidin-conjugated alkaline phosphatase with Fast Red TR chromogen. CMV was detected in only 10 of the 78 kidneys examined (12.8%): eight by both methods, one by ISH only, and another by ICC only. All 10 positive kidneys were obtained from autopsies of patients with AIDS. The average number of positive cells (in approximately 15 x 10 mm sections) was 22 with ICC and 10 with ISH. Glomerular intracapillary cells (possibly endothelial cells) were the most commonly stained, followed by positive cells in the interstitium and peritubular capillaries. Relatively few tubular epithelial cells were stained. The majority of positive cells by either ICC or ISH did not show nuclear or cytoplasmic inclusions; however, only two of the 10 positive kidneys did not contain cells with typical Cowdry type-A intranuclear CMV inclusions. The most frequent pathologic finding in the kidneys positive for CMV by either ICC or ISH was acute tubular necrosis (in six of 10, 60%).(ABSTRACT TRUNCATED AT 250 WORDS)
    Modern Pathology 06/1992; 5(3):277-82. · 6.36 Impact Factor
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    ABSTRACT: Acquired renal cysts derive from terminally differentiated tubular epithelium in adults as a consequence of increased epithelial cell proliferation, fluid accumulation and extracellular matrix remodelling. To understand better how human epithelial cysts may be initiated and progressively expand, cells from primary cultures of normal human adult renal cortex were dispersed in polymerized type I collagen. The transparent matrix permitted repeated observation by light microscopy of cyst formation from individual renal cells. The cyst cells reacted strongly with distal nephron histochemical markers (cytokeratin antibodies AE1/AE3, epithelial membrane antigen, and Arachis hypogaea lectin) but inconsistently or not at all to markers of proximal tubules (Tetragonolobus purpureas lectin and Phaseolus vulgaris erthroagglutinin lectin). The number of spherical, fluid-filled epithelial cysts that developed in a standardized microscope field quantified cyst initiation. Cyst progression was determined from the increase in the diameter (surface area) of cysts and represents a hyperplastic event. EGF or TGF alpha, were required in serum-free defined medium to cause cysts to develop from individual epithelial cells dispersed in the matrix; insulin was required as a co-factor. The EC50 for EGF was approximately 0.1 ng/ml, and for insulin 1 microgram/ml. Early cultures of normal cortex formed cysts more efficiently when dispersed in collagen matrix than cells passaged several times before suspension in the gel. Agonists of adenylate cyclase (PGE1, AVP, VIP, PTH, forskolin, cholera toxin), methylisobutylxanthine, and 8-Br-cAMP, though incapable of causing cyst formation alone in defined medium, enhanced cyst initiation and progression in the presence of EGF and insulin. Angiotensin II, TNF alpha, beta-estradiol, and pertussis toxin had no effect in the absence or presence of EGF and insulin. Pertussis toxin inhibited cyst initiation and expansion caused by EGF and forskolin but potentiated cyst initiation and expansion caused by EGF and PGE1. Cyst formation and expansion were inhibited by TGF beta 1 and 2-chloroadenosine. Polarized monolayers of human renal cortical cells grown on permeable membranes were used to independently quantify the effects of agonists on the net secretion of solute and water from the basolateral to the apical surface of the cells. PGE1, forskolin, and 8-Br-cAMP stimulated net fluid secretion that was sustained for several days; EGF enhanced forskolin-stimulated fluid secretion. We conclude that the formation and expansion of in vitro cysts derived from solitary human cortex cells depends on the coordinated interplay between cellular proliferation and fluid secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
    Kidney International 06/1992; 41(5):1222-36. DOI:10.1038/ki.1992.184 · 8.52 Impact Factor

Publication Stats

640 Citations
101.08 Total Impact Points

Institutions

  • 2001
    • Johns Hopkins University
      • Department of Pathology
      Baltimore, MD, United States
  • 1998
    • University of Oklahoma
      Norman, Oklahoma, United States
  • 1994–1997
    • University of Oklahoma Health Sciences Center
      • Department of Pathology
      Oklahoma City, OK, United States
  • 1992–1995
    • Oklahoma City University
      Oklahoma City, Oklahoma, United States
  • 1993
    • University of Zurich
      Zürich, Zurich, Switzerland
  • 1988–1991
    • University of Szeged
      • Department of Pathology
      Algyő, Csongrád, Hungary