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Z Laszik

Publications and source records attributed to Z Laszik.

25 records · Page 2Linked to original sources
PubMed1994

Renal interleukin-1 expression during endotoxemia and gram-negative septicemia in conscious rats.

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.

Animals↗
PubMed1994

Lack of suppressed renal thrombomodulin expression in a septic rat model with glomerular thrombotic microangiopathy.

BACKGROUND: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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. CONCLUSIONS: These results indicate that suppressed TM expression does not contribute to the development of the glomerular capillary thrombosis in this septic rat model.

Animals↗
PubMed1994

Absence of association between cytomegalovirus infection and obliterative transplant arteriopathy in renal allograft rejection.

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.

Adult↗
PubMed1993

Immunohistochemical and lectin dissection of the human nephron in health and disease.

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.

Humans↗
PubMed1989

The role of the complement system in the pathogenesis of multiple organ failure in shock.

The results of our experiments suggest that the development of MOF is the result of a concerted autodestructive inflammatory process affecting the endothelium which is probably triggered off by the complement system. The combination of two noxious events (application of a low dose of endotoxin during hemorrhagic shock) leads to an enormous intravasal activation of complement including formation of C5a and the deposition of active split products of C3 (C3a, C3b) in the tissue of lung, liver, small intestine and kidney. Histological examination revealed ARDS-like pulmonary changes with inflammatory microvascular lesions and granulocytic infiltration primarily in the liver and to a lesser degree in the intestines and the kidney. The severity of organic lesion closely correlated with the extent of complement deposited. This corroborates the clinical observation that pulmonary and hepatic lesions are always the first signs of MOF, no matter what kind of noxious influence (trauma or peritonitis) gave rise to its development (Mc Menamy, 1980). Which mechanisms are involved in the processes by which active split products of C3 cause damage to tissue? C3a possesses strong chemotactic forces which can bring about aggregation of granulocytes in the tissue. Deposition of C3b on the contrary may lead to the formation of the cytolytically active membrane-attack-complex with the result of direct cell damage. We did not find any severe organic lesion or deposition of complement in our controls (endotoxin only, hemorrhage only). Our results suggest that MOF is a sequel of a generalized, autodestructive, inflammatory process which results from a hyperintensive and uncontrolled humoral immunoresponse to noxious events.(ABSTRACT TRUNCATED AT 250 WORDS)

Anaphylatoxins↗
PubMedDate not supplied

Cell proliferation in the developing human kidney.

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.

Cell Division↗