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J Markovic-Lipkovski

Publications and source records attributed to J Markovic-Lipkovski.

18 recordsLinked to original sources
PubMed2005

Correlation of high-molecular cytokeratin in tissue of prostatic cancer with Gleason score and PSA.

The absence of basal cell layer of prostatic acini containing high-molecular cytokeratin, which is immunohistochemically detected by monoclonal antibody 34betaE12, is an essential diagnostic characteristic of prostatic cancer. The absence of immunohistochemical reaction in 3 or more pseudoglandular structures of prostatic tissue indicates malignant process. The percentage of immunohistochemically completely negative glandular structures was determined by semiquantitative measurement in tissue specimens obtained by TRUS biopsy of the prostate, and it was correlated with serum PSA concentration and Gleason score. The increase of percentage of glandular prostatic formations completely negative to high-molecular cytokeratin detected by 34betaE12 led to simultaneous rise of mean value of Gleason prostatic cancer score (p < 0.001) as well as the average serum PSA concentration in subjects (p < 0.05).

Adenocarcinoma↗
PubMed2000

Regional hemodynamics after chronic nitric oxide inhibition in spontaneously hypertensive rats.

BACKGROUND: Inhibition of nitric oxide (NO) synthase by L-arginine analogs is associated with elevation of blood pressure in rats. Because endothelium-dependent vasomotion in different vascular beds is not homogenous, the aim of this study was to characterize and compare regional hemodynamic responses in carotid, femoral, and renal vascular beds after chronic NO inhibition in spontaneously hypertensive rats. The possible role of circulating endothelin and renin angiotensin systems in mediating the effects of chronic NO inhibition was also studied. METHODS: Systemic and regional hemodynamics, left ventricular mass, plasma renin activity, and plasma endothelin-1 were determined in control and Nomega-nitro-Larginine methyl ester (L-NAME)-treated (10 mg/kg/day, 4 weeks) spontaneously hypertensive rats. RESULTS: L-NAME treatment increased arterial pressure and total peripheral and regional vascular resistance and decreased cardiac output, stroke volume, and regional blood flow. An increase in blood flow ratio and a decrease in vascular resistance ratio between carotid and renal as well as femoral and renal vascular beds in rats treated with L-NAME was found. Blood flow and vascular resistance ratios between femoral and carotid vascular beds remained unchanged. L-NAME increased plasma renin activity and left ventricular weight/body weight ratio, whereas plasma endothelin-1 was not modified. CONCLUSIONS: The results of this study showed that the renal circulation seemed to be more sensitive to the effects of chronic NO inhibition than carotid and femoral vascular beds. Simultaneous activation of the renin angiotensin system may further potentiate cardiovascular effects of chronic NO inhibition. No evidence that circulating endothelin-1 plays a role in this model of hypertension was found.

Angiotensins↗
PubMed1999

HLA class I antigens expression in renal cell carcinoma: histopathological and clinical correlation.

Immunohistochemical analysis of HLA class I antigens expression in 26 renal cell carcinomas (RCCs)--18 clear cell, 6 granular and 2 chromophobe--was performed with indirect immunoperoxidase method. Results were correlated with extent and immunophenotype of tumor infiltrating mononuclear cells, histopathological (histology, cytology, grade, presence of necrosis) and clinical (tumor diameter, TNM classification) characteristics of RCC. 4 (15%) RCCs showed reduced HLA class I presence and this was associated with greater tumor diameter and more frequent T3, T4 and M1 stage. All tumors with altered HLA class I antigens expression were grade 2 or 3 and strong correlation with presence of necrosis (p=0.006) was noticed, while mononuclear cell infiltrates (especially CD8+ T lymphocytes) were less extensive compared to tumors with normal HLA class I level. Our results suggest more aggressive clinical behavior of RCCs with reduced HLA class I antigens expression, probably due to impaired cellular antitumor immune response.

Aged↗
PubMed1996

Adhesion molecules in renal diseases.

Different adhesion molecules are implicated in the pathogenesis in glomerulonephritis. Leukocyte adhesion molecules play a critical role in causing renal damage in a variety of glomerulonephritic conditions. In order to understand the mechanisms by which distinct adhesion molecules are involved in human glomerulonephritis, it is necessary to have an overview of their function in maintenance of tissue architecture, morphogenesis, immunosurveillance, inflammation, tumor growth, etc. Thus, this review addresses the role of cadherins, selectins, integrins, and members of the immunoglobulin supergene family in developing, normal, and diseased kidney with special attention to glomerulonephritis and possible new therapeutic approaches.

Animals↗
PubMed1996

[Histogenesis of renal cell carcinoma].

Immunomorphological characteristics of 27 renal cell carcinomas--18 clear cell, 6 granular, 2 chromophobic, 1 sarcomatoid--as well as 1 oncocytoma were analyzed. The investigation was performed on cryostat sections with indirect immunoperoxidase technique using monoclonal antibodies to intermediate filaments-cytokeratin and vimentin--and renal differentiation antigens--CD10 and CD24. All carcinomas, with the exception of chromophobic type, showed cytokeratin/vimentin coexpression together with strong CD24 and weak (or absent) CD10 staining indicating at primitive cells with initial differentiation toward proximal tubule epithelium as most probable site of origin. In chromophobic cells only cytokeratin and CD24 antigen presence was observed, pattern similar to that seen in oncocytoma. It could be supposed that those two tumors have closely related histogenesis, originating from more differentiated cells with tendency to develop toward distal tubule epithelium.

Carcinoma, Renal Cell↗
PubMed1995

Immunomorphological characteristics of renal cell carcinoma.

Immunomorphological characteristics of 27 renal cell carcinoma (RCC): 18 clear cell, 6 granular (chromophilic), 2 chromophobe, 1 spindle cell (sarcomatoid) as well as of 1 oncocytoma, were analyzed. The investigation was performed on cryostat sections by immunoperoxidase technique applying a panel of monoclonal antibodies which defined: proximal (TNE3, TN5, 5D9) and distal (TN8, TN9, 7C2) tubular antigens; intercellular adhesion molecule 1 (ICAM1); HLA class II (-DQ, -DR and -DP) antigens, intermediary filaments (cytokeratin and vimentin); and antigens on tumour infiltrating mononuclear leucocytes (TT1, TT2 and LeuM3 for CD4, CD8 and CD14 antigens, respectively). All RCC with exception of chromophobe co-expressed cytokeratin and vimentin. In addition, they were usually positive for all proximal and two distal tubular markers (TN8, TN9) indicating primitive cells which could differentiate into the epithelium of both parts of tubule system as the most probable originators of in RCC. Almost all RCC but the chromophobe aberrantly expressed HLA class II antigens which great variability from case to case. The presence of HLA-DR antigens was more intensive and widespread than of HLA-DQ and -DP antigens. Expression of ICAM1 mostly correlated with presence of HLA class II antigens, particularly with -DR on tumour cells of RCC. HLA-DR antigen expression was always more prominent than mononuclear cell infiltrate (among which macrophages prevailed over T cells) which could suggest that increased histocompatibility antigen expression precedes mononuclear cell influx. In contrast to all other RCC, chromophobe tumours had quite distinct features revealing the most intense reaction with 7C2 (MAb that produced the weakest reaction with other tumour types), absence of vimentin and very weak reaction with antibodies for HLA class II Ag and ICAM1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Oxyphilic↗
PubMed1992

Human cytomegalovirus in immunoglobulin A nephropathy: detection by polymerase chain reaction.

Human cytomegalovirus (HCMV) has been suspected to participate in the pathogenesis of IgA nephropathy (IgAN). However, with regard to the presence of HCMV in the renal tissue of IgAN, conflicting results have been reported using a variety of different techniques. Renal biopsies of 29 patients with IgAN, of 7 with focal segmental glomerulosclerosis (FSGS) and of 11 normal kidneys were analyzed for the presence of HCMV-DNA using the polymerase chain reaction. HCMV-DNA was detected by hybridization with digoxigenin-labelled probes in 14 of 19 analyzed frozen renal biopsies from patients with IgAN. However, only 1 of 17 renal biopsies of IgAN embedded in paraffin was positive for HCMV-DNA. Furthermore, HCMV-DNA was detected in 4 of 18 frozen normal kidneys but in none of the tissues from patients with FSGS. The present results provide further evidence of an association between the presence of HCMV in renal tissue and IgAN.

Adult↗
PubMed1992

The role of interstitial cells in the progression of renal diseases.

Renal interstitial fibrosis (RIF) is frequently associated with distinct inflammatory and noninflammatory glomerular diseases. RIF is mainly responsible for a decline of excretory renal function and therefore influences the prognosis of several renal diseases. The resident interstitial cells of the kidney, which play a major role in causing RIF, are different renal fibroblasts, which respond to a variety of cytokines released by various cell types. Immunohistochemical analysis of human renal biopsies with different glomerulopathies revealed that CD2+ T lymphocytes are the major cells infiltrating the renal interstitium. In most forms of glomerulonephritis accompanied by interstitial inflammation, an abnormal expression of HLA-DQ/HLA-DP antigens, often associated with an aberrant expression of the intercellular adhesion molecule 1, was observed on proximal tubular epithelial cells, indicating that these cells may play an important role in local immune responses and probably function as antigen-presenting cells. Furthermore, it has been shown by Northern blot analysis that renal epithelial cells in culture express interleukin 6, platelet-derived growth factor and granulocyte-macrophage colony stimulating factor. Cell cultures established from renal biopsies revealed the presence of the three mitotic fibroblast types (MF I through MF III) and the three postmitotic types (PMF IV through PMF VI). The frequencies of the various progenitor fibroblasts MF I, MF II, and MF III differed significantly in cultures established from kidneys with (FKIF cells) and without RIF (NKF cells). In comparison to NKF cells, FKIF cells are characterized by the expression of a "new" protein, called "FIBROSIN," which seems to be specific for FKIF cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗
PubMed1992

Human cytomegalovirus in rejected kidney grafts; detection by polymerase chain reaction.

Human cytomegalovirus (CMV) infections are frequently associated with graft rejection in the immunosuppressed patients following organ transplantation. Thirty-four tissue samples from rejected kidneys and 18 samples from normal adult kidneys obtained from autopsies were investigated for the presence of CMV-DNA by the polymerase chain reaction (PCR) and by immunohistochemistry. DNA extracted from renal tissues after proteinase K digestion was specifically amplified in 32 cycles using primers which flank a 147 bp DNA fragment of the immediate early CMV gene and analysed by slot-blot hybridization with digoxigenin-labelled detection oligonucleotides. CMV-DNA was detected by PCR in a range from 0.1 fg up to 100 fg in 14 (41%) rejected kidney transplants. Comparative immunohistological analysis revealed presence of CMV in only three biopsies of these rejected kidneys. Furthermore, CMV-DNA was also found in four of 18 (22%) normal donor kidneys. These results reveal that CMV is often present in rejected kidneys and that the infection can be transferred from the donor to the recipient, since the normal adult kidney appears to be a frequent site of latency for CMV. No differences in local immunological changes, characterized by interstitial mononuclear leukocyte infiltration as well as by aberrant expression of HLA-class II antigens and of ICAM1 on proximal tubular epithelial cells, could be detected by further immunohistological analysis between grafted kidneys at late stage of rejection with and without CMV infection.

Adolescent↗
PubMed1991

The progression of renal diseases: on the pathogenesis of renal interstitial fibrosis.

Renal interstitial fibrosis (RIF) frequently occurs in inflammatory and non-inflammatory kidney diseases and is associated with a decline in renal excretory function. Fibroblasts which occupy the renal interstitium are involved mainly in the formation of RIF not only by the production of extracellular matrix, but also by regulatory processes. They respond to a variety of cytokines released by different cell types. To investigate mechanisms leading to RIF, immunohistochemical analysis and cell cultures of renal biopsies in various renal diseases have been performed. T lymphocytes are the major cells infiltrating the renal interstitium, and their number correlates with the impairment of renal function. In most forms of glomerulonephritis accompanied by interstitial inflammation, an abnormal expression of HLA-DQ/-DP molecules, frequently associated with an aberrant expression of the intercellular adhesion molecule 1 (ICAM-1), was observed on proximal tubular epithelial cells, indicating that these cells may play a role in antigen presentation. The cell biological experiments revealed the presence of the three mitotic fibroblast types (MFI-MFIII) and the three postmitotic types (PMFIV-PMFVI) in the cell culture. The number of fibroblasts in primary and passage-1 culture was increased seven-fold in cultures derived from kidneys with RIF (FKIF cells) in comparison to normal kidneys (NKF cells). FKIF cells show hyperproliferative growth and synthesize an increased amount of total collagen, especially types III and V. These cells express a protein, named "FIBROSIN", which seems to be specific for FKIF cells. Further extended cell biological analyses are currently being performed to investigate interactions of tubular cells, lymphocytes, macrophages, and fibroblasts in order to shed more light on the pathomechanisms involved in fibrogenesis leading to renal interstitial fibrosis.

Collagen↗
PubMed1991

Mononuclear leukocytes, expression of HLA class II antigens and intercellular adhesion molecule 1 in focal segmental glomerulosclerosis.

Immunophenotyping of infiltrating glomerular and interstitial mononuclear leukocytes performed in renal tissues of 15 patients with focal segmental glomerulosclerosis (FSGS) was compared to 15 normal kidneys in order to investigate a possible role for cell-mediated immunity (CMI) in FSGS. In addition, distribution of HLA class II (-DQ, -DR, -DP and -DY) antigens and of the intercellular adhesion molecule 1 (ICAM-1) as well as the expression of well-defined renal antigens along the human nephron was analyzed. In comparison to normal kidneys, a reduction in HLA class II antigens of ICAM-1 and of renal antigens defined by the monoclonal antibodies TN8-TN10 was observed in sclerotic glomeruli. Furthermore, an increased number of T lymphocytes was found in glomeruli of FSGS with slight predominance of the CD8+ subset. Interstitial inflammation was present in all FSGS cases except 1 with T lymphocytes and monocytes/macrophages constituting the predominant infiltrating cell types. In contrast to the glomerular T cells, the number of interstitial CD4+ cells was greater than the number of CD8+ cells in almost all cases. As a sign of activation, most interstitial inflammatory cells carried HLA class II antigens and some of them also expressed ICAM-1. Proximal tubular epithelial cells often presented an abnormal expression of HLA-DQ and HLA-DP antigens associated with aberrant expression of ICAM-1 and TN8. The number of interstitial mononuclear leukocytes was correlated to serum creatinine levels at the time of renal biopsy. The present results provide further support for the involvement of CMI in the pathogenesis of FSGS.

Adult↗
PubMed1991

Intercellular adhesion molecule-1 expression in human kidneys with glomerulonephritis.

Intercellular adhesion molecule-1 (ICAM-1) plays an important role in immune responses. Expression of this molecule was examined on cryostat sections of 15 normal human and 112 glomerulonephritic kidneys using a specific monoclonal antibody and the indirect immunoperoxidase staining technique. The expression of ICAM-1 on renal structures was compared to that of HLA-DQ, -DR, -DR/DP and -DP antigens. On normal kidneys ICAM-1 was observed on some Bowman's capsular cells and on single glomerular cells which probably represent endothelial and mesangial cells. ICAM-1 was present on peritubular capillaries and on vascular endothelium of large vessels as well as on fibroblasts, whereas no expression of ICAM-1 on proximal tubular epithelial cells (PTECs) was detected. In normal renal tissues the distribution of ICAM-1 was similar to that of HLA-DQ and -DP antigens. In kidneys with different forms of glomerulonephritis especially in association with interstitial inflammation, an abnormal expression of ICAM-1 on PTECs was frequently correlated with aberrant expression of HLA-DQ and -DP antigens. These results further support the hypothesis that PTECs may participate in cell-mediated immune reactions in glomerulonephritis.

Antibodies, Monoclonal↗
PubMed1990

Association of glomerular and interstitial mononuclear leukocytes with different forms of glomerulonephritis.

Immunophenotyping of mononuclear leukocytes was performed in renal tissue obtained from 69 patients with different forms of glomerulonephritis (GN) and from ten donors' kidneys for transplantation used as controls. A panel of monoclonal antibodies was used in the immunoperoxidase technique on frozen sections to define B- and T-lymphocyte subpopulations, NK cells and monocytes/macrophages, as well as the expression of HLA class II antigens-DQ, -DR and -DP. Quantification of labelled leukocytes revealed a significant increase of CD4+ and CD8+ T-cells in glomeruli of rapidly progressive glomerulonephritis, membranoproliferative glomerulonephritis and even of focal gomerulosclerosis. The number of glomerular monocytes/macrophages was significantly increased only in rapidly progressive glomerulonephritis, whereas in membranoproliferative glomerulonephritis it was decreased. No differences to normal tissue were detected in glomeruli for all other types of inflammatory cells. Interstitial cells were mostly T-lymphocytes in all forms of glomerulonephritis. In all groups the CD4+/CD8+ ratio was somewhat greater than 1 and even about 2 in rapidly progressive glomerulonephritis. Only in particular case was this ratio inversed. High expression of HLA class II antigens was observed on interstitial mononuclear leukocytes, as a sign of their activation. The excess of HLA-DQ-positive cells over the sum of CD14+ and CD20+ cells provides evidence not only for presence of activated T-lymphocytes but perhaps also for accumulation of renal dendritic cells in the interstitium in glomerulonephritis associated with interstitial infiltration.

Antibodies, Monoclonal↗
PubMed1989

Expression of HLA-DQ, -DR, and -DP antigens in normal kidney and glomerulonephritis.

Expression of the defined subtypes of HLA-class II antigens DQ, DR, DP, as well as of a putatively new HLA-class II determinant DY was evaluated with specific monoclonal antibodies on frozen sections of 15 normal kidneys, as well as of renal tissue of 65 patients with different forms of glomerulonephritis (GN). In normal kidney HLA-DR and/or -DY versus DQ or DP antigens were shown to be differentially expressed on subpopulations of glomerular and interstitial cells, as well as vascular endothelia. Normal proximal tubular epithelia lacked HLA-DQ and -DP antigens, but carried -DY and variably -DR products constitutively. In comparison, aberrant presence of HLA-DQ and/or -DP antigens was found on proximal tubular cells in the majority of patients with rapidly progressive (RPGN), membranoproliferative GN (MPGN), or focal glomerular sclerosis (FGS), but more rarely observed in other forms of proliferative or non-proliferative GN. In addition all cases with RPGN revealed reduction of HLA-DQ, -DR, -DP or -DY+ glomerular cells. Decline of HLA-DP and/or -DR+ glomerular cells was variably seen in mesangioproliferative glomerulonephritis (MesPGN) and MPGN, whereas in FGS HLA-DQ antigens appeared to be increased in glomeruli. HLA-DQ, -DR, -DY+ interstitial cellular infiltrates were present in RPGN, FGS and MPGN and only occasionally occurred in other forms of GN. Altered renal expression of HLA-class II antigens may indicate specific sites of immunologically-mediated kidney injuries in GN.

Antibodies, Monoclonal↗
PubMed1988

Renal, major histocompatibility complex antigens and cellular components in rapidly progressive glomerulonephritis identified by monoclonal antibodies.

Identification of crescent-forming cells in rapidly progressive glomerulonephritis (RPGN) is very difficult, and controversial results on the participation of different epithelia as well as of monocytes have been reported. In the present study different monoclonal antibodies were used to analyze cellular infiltrates of crescents and the interstitium as well as the distribution of well-defined renal antigens and major histocompatibility complex (MHC) encoded antigens along the human nephron in cryostat sections of renal biopsies from patients with RPGN. The results demonstrate that monocytes/macrophages infiltrate Bowman's space and that cellular components of crescents present with phenotypes of parietal glomerular and proximal tubular cells. T lymphocytes are significantly found in glomeruli and also in interstitium with predominance for CD4+ lymphocytes. Reduction of MHC class-II antigens within diseased glomeruli correlates with changes in renal antigen expression. Tubular cells, however, often presented an abnormal expression of MHC class-II antigens. Differences of renal and MHC-encoded antigen expression may be due to rapid regeneration episodes of renal parenchymal cells in RPGN.

Adult↗
PubMed1987

[Phenotypic heterogeneity of cardiac myxomas].

Histogenesis of cardiac myxoma is still unclear. Beside endothelial cells a variety of different cell types were detected in this benign cardiac tumor. Cryostat sections of four myxomas were analysed in the indirect immunoperoxidase technique using monoclonal antibodies (MoABs) directed against MHC class I and II antigens, as well as different surface determinants specific for endothelial cells or monocytes/macrophages. Tumor cells forming cell clusters and blood vessel like structures differed in their expression of endothelial antigens suggesting cellular heterogeneity within single and different myxomas. Like in fetal cardiac tissue vascular channels rarely carried HLA-class II antigens. Tumor cells carrying antigens of monocytes/macrophages, as well as intracellular alkaline phosphatase of endothelial cells could represent subpopulations of an early differentiation stage. This analysis further supports previous hypothesis of an endothelial origin of myxomas.

Adult↗
PubMedDate not supplied

Cadherins and integrins in renal cell carcinoma: an immunohistochemical study.

AIMS AND BACKGROUND: The aim of this study was to determine the expression of cadherins and integrins in renal cell carcinoma (RCC) and their relationship with tumor morphology and TNM status. METHODS: Cadherin and integrin expression was investigated using an indirect immunoperoxidase technique, applying antibodies to E-, N-, P- and VE-cadherin and to alpha1, alpha2, alpha3, alpha4, alpha5, alpha6, and alpha(v) integrin subunits. Correlation of semiquantitatively scored adhesion molecule levels with histopathological parameters (cytology, growth pattern, nuclear grade) and TNM status was performed for 24 RCCs (17 clear cell, 3 granular, 3 spindle cell and 1 chromophobe cell type according to the WHO classification). RESULTS: E-cadherin and N-cadherin were present in most cases (88% and 67%, respectively) and were usually coexpressed. T3 RCCs displayed higher E-cadherin and N-cadherin levels than T1/T2 tumors regardless of tumor grade, suggesting that impairment of their function might exist without actual loss from tumor cells. P-cadherin was found focally in two RCCs only, while VE-cadherin was present on stromal vessel endothelium in five tumors, showing no differences with regard to cell type, growth pattern, tumor grade or TNM status. All integrins were present in the studied RCCs (ranging from 12% for alpha5 to 79% for alpha3), including those that are normally absent from adult kidney tissue (alpha4 and alpha5). Tumors of higher grade showed increased alpha(v) and decreased alpha6 levels, while RCCs with metastases less often showed diffuse alpha3 presence and never expressed alpha5 integrin. CONCLUSIONS: Our results suggest that the level of expression of N-cadherin and some integrins (most notably alpha3, alpha6 and alpha5) is associated with the capacity of RCC for local and distant spread, regardless of tumor grade.

Antigens, CD↗