J Grond

Laboratories of Pathology Eastern-Netherlands, Enschede, Overijssel, Netherlands

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Publications (70)227.11 Total impact

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    ABSTRACT: We present the case of a 29-year-old female patient with an isolated peritoneal metastatic mass in the Douglas pouch, following ileocecal resection for a Dukes C2 colon cancer of the caecum. As initial treatment, four courses of continuous infusion with epiadriamycin were administered. The effect on the tumour size was marginal. Palliative radiotherapy (33 Gy) resulted in a reduction of the tumour size and subsequently a wide posterior exenteration could be performed. Five years after the initial diagnosis the patient is still in good health with no evidence of tumour recurrence. We sincerely believe that a maximum effort aiming for cure is warranted in selected patients with localized residual or metastatic peritoneal colon cancer, even if the initial prospects seem less favourable.
    European Journal of Surgical Oncology 01/1995; 20(6):698-700. · 2.89 Impact Factor
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    ABSTRACT: In this multimodel overview, we have provided the seminal experimental evidence for the crucial contribution of macrophages in the progression of glomerular and interstitial fibrosis. Although all the experimental data provided in this review definitely increase our understanding of the progress of renal disease, we have been mindful to use caution in extrapolating data from animal experiments to the clinical setting (109). In addition, uncertainty still exists as to whether macrophages activation entails a generalized mechanism in which the cells release growth factors and other mediators such as bioactive lipids and nitric oxide simultaneously, or a selective mechanism in which the cells release some but not all macrophage products (110). However, we anticipate that further substantial clinical and experimental observations are on the horizon. Novel therapeutic strategies in these models must be concerned with the prevention of renal macrophage recruitment and/or the suppression of the fibrogenic ability of this pluripotential inflammatory cell.
    Laboratory Investigation 11/1994; 71(4):456-64. · 3.83 Impact Factor
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    ABSTRACT: To determine if bacterial translocation and endotoxin absorption occur in organ donors with an anatomically intact gastrointestinal tract. Case series. Intensive care units in general and university hospitals. Twenty-one (multiple) organ donors. None. Occurrence of factors that may promote bacterial translocation and/or endotoxin absorption. Bacterial concentration in mesenteric lymph nodes, abdominal fluid, blood, liver, lung, and spleen. Endotoxin level in abdominal fluid, peripheral blood, and portal blood. Anatomical integrity of the bowel wall. Factors that may promote bacterial translocation and/or endotoxin absorption were present in all organ donors. Culture specimens revealed bacteria in 14 organ donors (67%). In 210 (81%) of 260 culture specimens, the bacteria isolated were identical to those isolated from the bowel content, demonstrating bacterial translocation. Endotoxin was found in nine (53%) of 17 abdominal fluid samples, in four (19%) of 21 peripheral blood samples, and in two (10%) of 21 portal blood samples. Light- and electron-microscopic examination of the bowel wall showed no anatomical abnormalities. Bacterial translocation and endotoxin absorption are frequent among organ donors and may adversely influence organ function in transplant recipients and other critically ill patients.
    Archives of Surgery 11/1994; 129(10):1063-6. · 4.30 Impact Factor
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    ABSTRACT: Generalized peritonitis causes a reduction in abdominal fibrinolytic activity, resulting in persistence of intraabdominal fibrin with subsequent adhesion and abscess formation. The activities of tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI) were measured in the peritoneal fluid of rats with faecal peritonitis and correlated with the extent of peritoneal damage to determine the cause of decreased fibrinolysis. Activity of tPA was low during the study period of 8 days, but higher in rats with peritonitis than in controls. The activity of PAI in rats with peritonitis was significantly increased compared with that of controls during the whole study period (P < 0.001). Histological signs of damage to the peritoneum were similar in rats with peritonitis and controls. There was no correlation between the extent of peritoneal damage and tPA or PAI activity. The increased activity of PAI in the peritoneal fluid of rats with faecal peritonitis may be the main cause of reduced fibrinolysis in the abdominal cavity. Activities of tPA and PAI may originate not only from the mesothelium but from other sources.
    British Journal of Surgery 07/1994; 81(7):1046-9. DOI:10.1002/bjs.1800810740 · 5.21 Impact Factor
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    ABSTRACT: Multiple injections of D-galactosamine induce liver fibrosis and cirrhosis in rats. The purpose of this immunopathological study was to correlate inflammation and hepatic extracellular matrix remodeling after repeated administration of galactosamine. Rats were given 10, 20, 30, 40, 60, 80, 100 and 140 intraperitoneal injections of D-galactosamine (500 mg/kg body wt, three times weekly). Controls received injections of saline solution. Cryostat sections of liver tissue obtained on biopsy or autopsy were immunostained with a panel of monoclonal and polyclonal monospecific antibodies reactive with macrophages, T and B lymphocytes, desmin, the extracellular matrix components fibronectin; laminin; collagen types I, III and IV; and the fibronectin receptor alpha 5 beta 1. Total RNA was extracted and Northern-blot analysis was performed with a specific cDNA probe for rat collagen type III. Spotty liver cell necrosis and mild portal and parenchymal inflammation was seen after 10 injections of galactosamine. After 20 to 40 injections, expansion of protal tracts, prominent bile ductular proliferation and gradual formation of fibrous septa were encountered with the development of cirrhosis at later intervals. These progressive histological changes were paralleled by a gradual increase of desmin-positive cells in developing septa with deposition of fibronectin; collagen types I, III, and IV; and laminin. Northern-blot analysis showed that this accumulation of extracellular matrix was not accompanied by increase of mRNA for collagen type III. In conclusion, repetitive administration of galactosamine causes progressive liver disease with prominent bile ductule proliferation and development of fibrous septa. These pathological alterations bear some resemblance to the morphological changes in chronic biliary disease in human beings.
    Hepatology 03/1994; 19(3):775-81. DOI:10.1002/hep.1840190334 · 11.19 Impact Factor
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    ABSTRACT: Heparins blunt the development of glomerulosclerosis in several disease models in the rat and this protective effect may be related to suppression of glomerular cell proliferation. In this study the direct effect of heparins on another key event in glomerulosclerosis, extracellular matrix (ECM) deposition, was examined. Standard heparin (hep) and non-anticoagulant N-desulfated acetylated heparin (DSA-hep) significantly reduced the fibronectin content in the conditioned media of subconfluent, confluent, and supraconfluent rat glomerular mesangial cells (MCs) in culture, as assessed by a sandwich ELISA technique. Both heparins significantly increased the amount of cell-associated fibronectin in sparse and subconfluent MCs. DSA-hep, but not hep, increased the fibronectin content of ECM formed by confluent and supraconfluent MCs. Using3H-proline pulse-labeling, Hep and DSA-hep were found to significantly decrease cell-associated collagen in subconfluent but not in confluent MCs. No effects were seen on newly synthesized collagen secreted into the culture medium. Neither hep nor DSA-hep affected total protein synthesis, studied by metabolic labeling with35S-methionine. High resolution 2-D electrophoresis (molecular weight range, 120 to 10 Kd; isoelectric interval, 5.0 to 7.0) revealed one particular intracellular protein (molecular weight 54 Kd, pI 5.91) which was consistently overexpressed by MCs exposed to DSA-hep but underexpressed in hep. Both heparins affected an identical set of another 19 different intracellular MC proteins (over-/ underexpression or shift to higher molecular weights). In conclusion, the present data demonstrate the profound direct metabolic effects of hep and DSA-hep. In addition to their antiproliferative activity, heparins may also affect the course of glomerular disease in-vivo by direct modulation of ECM and protein synthesis of MCs.
    Virchows Archiv B Cell Pathology 11/1993; 63(1):181-189. DOI:10.1007/BF02899259
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    ABSTRACT: To find out if fish oil given intraperitoneally would cause a reduction in the release of tumour necrosis factor and interleukin-6 in abdominal exudate and blood (experiment A), and if it reduces the incidence of organ failure in rats with peritonitis (experiment B). Laboratory experiment. University animal laboratory. Thirty-six selectively decontaminated rats in each experiment. All rats were pretreated with 2 ml fish oil, lecithin, or saline, intraperitoneally for one or six weeks before intraperitoneal injection of zymosan. Experiment A: Samples of abdominal exudate and plasma were taken regularly for 24 hours after the zymosan had been given. Experiment B: Clinical, biochemical, and histological variables were measured over a 12-day period after the zymosan had been given. Experiment A: Concentrations of tumour necrosis factor and interleukin-6 in abdominal exudate and plasma. Experiment B: Incidence of multiple organ failure. Experiment A: Concentrations of tumour necrosis factor and interleukin-6 in abdominal exudate and plasma were significantly higher in rats pretreated with fish oil, compared with control rats. This effect was more pronounced after six weeks of pretreatment. Experiment B: There were no significant differences between the groups for any variable. Fish oil given intraperitoneally increased rather than reduced local and systemic release of tumour necrosis factor and interleukin-6, and did not reduce the incidence of organ failure in rats with sterile peritonitis.
    The European Journal of Surgery 11/1993; 159(10):563-70.
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    A Wolthuis, A Boes, J Grond
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    ABSTRACT: Mesangial cell (MC) hyperplasia and accumulation of extracellular matrix are hallmarks of chronic glomerular disease. The present in vitro study examined the effects of cell density on growth, extracellular matrix formation, and protein synthesis of cultured rat MCs. A negative linear relationship was found between initial plating density and DNA synthesis per cell after 24 hours incubation in medium with 10% fetal calf serum (range: 1 x 10(3) to 7 x 10(5) MCs/2cm2, r = 0.996, P < 0.001). Enzyme-linked immunosorbent assay of the amount of fibronectin in the conditioned medium after 72 hours showed a negative relationship with increasing cell density. In contrast, the amount of cell-associated fibronectin increased to maximal values in confluent cultures, and no further increase was seen at supraconfluency. The relative collagen synthesis in the conditioned medium and cell layer--assessed by collagenase digestion after 5 hours [3H]proline pulse labeling--showed a similar pattern. Secreted collagen decreased with increasing cell density from 3.4% to 0.2% of total protein synthesis. In contrast, cell-associated collagen increased from 1.1% to 11.8% of newly synthesized protein until confluency followed by a decrease to 4.2% at supraconfluency. Specific immunoprecipitation of collagen types I, III, and IV revealed a significant (twofold) increase in collagen I synthesis per cell at confluency. Collagen III and IV synthesis was not affected by cell density. Specific protein expression in both the medium and cell layer were analyzed by two-dimensional polyacrylamide gel electrophoresis (150 to 20 kd, pI 5.0 to 7.0) after 20 hours steady-state metabolic labeling with [35S]methionine. Supraconfluent MCs displayed overexpression of 10, underexpression of four, new expression of five, and changed mobility of three different intracellular proteins. Of interest was the overexpression of two proteins (89 kd, pI 5.31 and 72 kd, pI 5.32) that were identified by immunoblotting as the stress proteins heat-shock protein 90 and glucose-related protein 78, respectively. The progressive increase of cell-associated fibronectin and collagens, particularly collagen type I, in confluent MCs resembles extracellular matrix accumulation in glomerular disease. The increased expression of stress proteins in supraconfluent MCs is of interest in view of the analogy between glomerulosclerosis and atherosclerosis in which stress proteins are expressed in high concentrations.
    American Journal Of Pathology 10/1993; 143(4):1209-19. · 4.60 Impact Factor
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    ABSTRACT: Recent experimental data suggest a role for lipids in the pathogenesis of glomerulosclerosis. In this study, we examined the main apolipoproteins (apo) of high density lipoproteins (A-I, A-IV, E), low density lipoproteins (B), and very low density lipoproteins (B,E) in plasma and kidney tissue of rats with puromycin aminonucleoside or adriamycin nephrosis. In full-blown nephrosis, plasma concentrations of apo A-I and apo B were significantly elevated, apo A-IV and apo E levels did not change. Immunohistological studies in plastic sections revealed increased apo A-I, apo A-IV, and apo E immunoreactivity in glomerular visceral epithelial cells both in puromycin aminonucleoside and adriamycin nephrosis. This was confirmed by immunoelectronmicroscopy. In addition, apo B and apo E were encountered in increased amounts in the mesangium and colocalized with Oil Red O-positive lipid deposits, particularly in puromycin aminonucleoside nephrosis rats. Double-staining showed a preferential localization of apo B and apo E at sites of increased mesangial matrix in close proximity to ED1-positive foam cells, i.e., the mesangial macrophages. The close topographic association between apo B and apo E, lipid deposits, and macrophages in the mesangium lend further support to the concept of lipid-mediated glomerular injury in nephrosis.
    American Journal Of Pathology 07/1993; 142(6):1804-12. · 4.60 Impact Factor
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    ABSTRACT: This paper briefly reviews recent experimental data derived from work in animals and cell cultures that have increased our understanding of the pathobiologic pathways leading to focal sclerosis. These pathways include glomerular visceral epithelial cell damage, leukocyte infiltration, hyperplasia and matrix accumulation in the mesangium, and endothelial injury.
    Current Opinion in Nephrology and Hypertension 06/1993; 2(3):458-64. DOI:10.1097/00041552-199305000-00014 · 4.24 Impact Factor
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    ABSTRACT: The relation between plasma lipoprotein composition and renal apolipoprotein deposition was studied in nephrotic rats in which stable renal function had been monitored for 7 months after a single low dose of adriamycin (ADR, 3 mg/kg). Proteinuria was observed 3 weeks after ADR and increased progressively up to about 0.5 g/day (versus 0.07 g/day in controls; P < 0.001), while the creatinine clearance remained stable at about 80% of control values. Hypercholesterolaemia was observed 6 weeks after ADR, and increased progressively up to 7.0 +/- 1.0 mmol/l (versus 2.3 +/- 0.1 mmol/l in controls; P < 0.001). Cholesterol was primarily located in LDL2 and HDL2 lipoproteins. Plasma apolipoprotein (apo) A-I increased by more than 400% in the nephrotic rats (P < 0.001). Apo B and apo E increased by about 60% (P < 0.01), whereas apo A-IV remained unchanged. Focal sclerotic lesions in glomeruli had an incidence of 50 +/- 10% in ADR rats versus 2 +/- 1% in controls (P < 0.001). Immunohistochemistry revealed apo A-I and apo A-IV in the visceral epithelium. Apo E immunoreactivity and lipid deposits were observed in focal glomerular sclerotic lesions of ADR rats. Neither apolipoproteins nor lipids were detected in glomeruli of controls. Proximal tubular localization of apolipoproteins was extensive for apo A-I, apo A-IV and apo E, but no differences were observed in tubular deposition of apolipoproteins between ADR and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
    Nephrology Dialysis Transplantation 01/1993; 8(9):831-8. · 3.49 Impact Factor
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    ABSTRACT: A sensitive and reproducible microassay is described for quantification of adhesion of cells to matrix-coated 96-wells plates under different experimental conditions. For this purpose glomerular visceral epithelial cells (GVEC) were used. Attached GVEC were fixed with methanol and incubated with a monoclonal anti-DNA antibody. Following standard procedures, the amount of bound antibody was quantified by ELISA. A positive linear relationship in the range of 800-5000 cells per well was found between OD values and cell numbers obtained by hand-counting (r = 0.94, p less than 0.001). The assay is 10 to 100 times more sensitive than most other adhesion assays. The applicability of the ELISA assay was demonstrated by manipulation of the temperature during adhesion and by using different concentrations of the matrix-molecules fibronectin, EHS-laminin and collagen type I. The ELISA assay was found to be unaffected by non-specific interaction of anti-DNA antibodies with the matrix molecules used for coating. The assay was neither affected by potential release of DNA from the GVEC under these different experimental conditions. In conclusion, this cell adhesion microassay is simple, reliable, sensitive, and cost-effective, since it requires small amounts of GVEC and reagents.
    Hybridoma 09/1992; 11(4):529-37. DOI:10.1089/hyb.1992.11.529
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    ABSTRACT: Recent studies have provided evidence for the involvement of macrophages (m phi) in various types of human and experimental glomerular disease. The aim of the present study was to examine the effect of m phi depletion on glomerular injury after 3/4 renal ablation in the rat. This "remnant kidney" model is a widely used experimental model of focal and segmental glomerulosclerosis. Sustained glomerular m phi depletion was induced in remnant kidney rats by a regimen of sublethal triple systemic X-irradiation with shielding of the kidney remnants. Groups of 8 X-irradiated and 8 non-irradiated rats were studied at 5, 9, and 13 weeks after renal ablation. X-irradiated rats showed severe peripheral blood leukopenia at 5 and 9 weeks which had normalized at 13 weeks. The number of remnant glomerular m phi (immunohistochemistry with the monoclonal antibody ED1) in X-irradiated rats at 5 weeks was significantly lower when compared to non-irradiated remnant kidney rats. A rebound effect occurred at 9 and 13 weeks with increased m phi in remnant glomeruli of X-irradiated rats. Light microscopic examination disclosed significantly lower semiquantitative scores for mesangial cellularity and mesangial matrix expansion in remnant glomeruli of X-irradiated rats at 5 weeks when compared to non-irradiated remnant kidney rats. Mesangial matrix expansion had increased in X-irradiated rats at 9 and 13 weeks after ablation coincident with elevated glomerular m phi at these intervals. Multiple linear regression analysis indicated a highly significant contribution of m phi to the best fitting regression model predicting mesangial matrix expansion (multiple r2 = 0.81). In conclusion, these data provide evidence for a contributory role of m phi in the evolution of glomerular injury in the rat after renal ablation.
    Laboratory Investigation 06/1992; 66(5):564-71. · 3.83 Impact Factor
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    ABSTRACT: A case of primary squamous cell carcinoma in a pre-existing hepatic cyst is presented. A review of the literature suggests that this rare type of liver tumor tends to arise from solitary, nonparasitic cysts, lined with squamous epithelium. Effective therapy is not available, the prognosis is grave.
    HPB Surgery 05/1992; 5(3):203-8. DOI:10.1155/1992/32474
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    ABSTRACT: A single injection of D-galactosamine hydrochloride induces acute self-limiting liver disease in rats that morphologically resembles drug-induced hepatitis in human beings. In this immunohistochemical study we examined the localization and expression of the hepatic extracellular matrix components fibronectin, laminin, collagen type I, collagen type III and collagen type IV and of the cell surface receptors (integrins) for fibronectin and laminin. Sections of liver tissue obtained at intervals of 6, 12, 18, 24, 30, 36, 48 and 72 hr and 7 and 21 days after galactosamine administration were immunostained with a panel of polyclonal monospecific antibodies and studied independently by two of us. Fibronectin was the first extracellular matrix component found to be increased, 12 hr after galactosamine injection, followed by collagen type III, and, in a later phase, collagen type IV, type I and laminin. Increased deposition of extracellular matrix was found in areas with liver cell necrosis and along sinusoids. Extracellular matrix immunoreactivity reached a maximum at 36 to 48 hr and decreased thereafter to preinjury levels 3 wk after galactosamine. Immunostaining for the fibronectin and laminin receptors revealed tissue localization identical to that of their ligands. However, the intensity of staining was opposite of that for the extracellular matrix, with a decrease of immunoreactivity after 24 to 48 hr. The observed sequence of changes in hepatic extracellular matrix proteins after galactosamine injection resembles the repair reaction in other tissues and may reflect the particular function that each carries out during the process of liver healing after toxic injury.
    Hepatology 03/1992; 15(3):423-31. DOI:10.1002/hep.1840150312 · 11.19 Impact Factor
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    ABSTRACT: Granulomatous inflammation is a specific type of chronic inflammation in which macrophages and T-cell-mediated immunity to the inciting agent play a pivotal role. In the present study, granulomatous hepatitis was induced in rats by the administration of a single intravenous dose of porcine intestinal alkaline phosphatase. The cellular composition of the hepatic granulomas was analyzed in-situ with a number of recently developed mouse anti-rat monoclonal antibodies to cells of the monocyte-macrophage lineage and lymphocyte subsets. Well-developed granulomas consisted of aggregates of macrophages with central modification into epithelioid cells, a peripheral rim of T- and B-lymphoid cells, including considerable numbers of immunoblasts and plasma cells. In addition, the periphery of the granulomas contained many fat storing cells, a sinusoidal cell type thought to play a central role in hepatic fibrosis. Moreover, intense immunostaining for the extracellular matrix proteins fibronectin and collagen type III was observed at the periphery of the lesions. The granulomas persisted for long periods without eliciting liver cirrhosis. Alkaline phosphatase induced hepatic granulomas in the rat may help to elucidate the contribution of cells of the B-lineage to chronic granulomatous inflammation.
    Virchows Archiv B Cell Pathology 02/1992; 62(1):35-43. DOI:10.1007/BF02899663
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    ABSTRACT: Mesangial cell (MC) proliferation and extracellular matrix (ECM) formation are hallmarks of chronic glomerular disease. The present in vitro study examined the effects of the vasoactive agents angiotensin II (Ang II), arginine vasopressin (AVP), and serotonin (5-HT) on growth and protein biosynthesis of cultured rat MCs after 72 hours of incubation. AVP and 5-HT (10(-6) M) significantly increased DNA synthesis and growth of quiescent subconfluent MCs to levels of 25 and 45%, respectively, of the optimal stimulatory effect of 10% fetal calf serum (FCS) (both P less than 0.001). The mitogenic effect of Ang II was 10% of the 10% FCS effect (P less than 0.01). ECM production was studied by ELISA assay for fibronectin (FN) secreted into the culture medium (SeFN) and cell-associated FN, that is, intra- and pericellular FN (CaFN). In all incubations, highly significant negative linear relationships were found between the numbers of MCs per well and quantities of both SeFN and CaFN after normalization of the data by logarithmic transformation (SeFN: r values greater than -0.9705; CaFN: r greater than -0.9620; P less than 0.001). Thus, increasing cell densities progressively suppressed ECM formation by MCs. The ECM production was found to be independent of growth activity. AVP significantly increased SeFN (P less than 0.05) and decreased CaFN (P less than 0.001) in subconfluent cultures; Ang II and 5-HT had no effect. Metabolic labeling with 35S-methionine (18 hr, 200 microCi/ml medium) and 2-D electrophoresis of MC lysates resulted in resolution of greater than 500 different radiolabeled intracellular proteins in molecular weight from 110 to 20 Kd over an isoelectric interval of 5.0 to 7.0.(ABSTRACT TRUNCATED AT 250 WORDS)
    Kidney International 02/1992; 41(1):124-31. DOI:10.1038/ki.1992.16 · 8.52 Impact Factor
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    ABSTRACT: Locally advanced cancer of the cardia and fundus might be cured by surgical resection. Poor results after surgery in stage IIIB and stage IV disease prompted a study of neoadjuvant chemotherapy. Treatment included four cycles of high doses of methotrexate (1.5 g/m2) and high doses of 5-fluorouracil (1.5 g/m2) followed by surgery in those patients with lesions then found to be resectable. Twenty patients with tumours staged as IIIB or IV were entered; 17 patients completed the four courses of chemotherapy and 14 underwent re-exploration. Eight patients achieved tumour reduction enabling resection. Five patients underwent total gastrectomy with distal pancreatectomy and splenectomy en bloc and three patients had an oesophagogastrectomy. There were no treatment-related deaths and toxicity was tolerable. Two patients were alive 54 and 41 months after chemotherapy with no evidence of disease. Locoregional recurrence developed in five patients and metastatic disease in one. Their median survival was 22 months.
    British Journal of Surgery 08/1991; 78(8):955-8. DOI:10.1002/bjs.1800780820 · 5.21 Impact Factor
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    ABSTRACT: The present study was undertaken to estimate the relative impact of a number of clinicopathologic and glomerular structural changes on severity and composition of focal and segmental glomerular sclerosis (FGS) in rats subjected to renal ablation. Groups of eight 1 1/2-nephrectomized (Nx) and sham-operated (Sh) male Wistar rats were studied at intervals of 2, 4, 8, 12, and 16 weeks. At sacrifice, kidney tissue was embedded in glycolmethacrylate to achieve optimal morphology for light microscopy, immunohistochemistry, and morphometry. FGS lesions were defined by the presence of focal and segmental glomerular scarring and collapse of the glomerular tuft with increased mesangial cellularity (MC), mesangial matrix expansion (MME), and adhesions between the tuft and Bowman's capsule (Adh). The severity of FGS and extent of MC, MME, and Adh was graded seimquantitatively to establish an injury score. The dependence of FGS injury score and of the scores of MC, MME, and Adh on a variety of clinicopathologic and glomerular structural alterations, taking account of possible correlations among them, was estimated with partial correlation and multiple linear regression analysis. The structural parameters included hyalinosis (H, PAS stain), glomerular lipid deposits (GLD, Oil Red O stain), glomerular volume expansion (GVE, morphometry), glomerular cellular proliferation (labeling of S-phase cells by 5 bromo-2'-deoxyuridine, BrdU)--and glomerular influx of macrophages (m phi), T cells, natural killer cells, and granulocytes (immunohistochemistry with mouse monoclonal antibodies). The clinicopathologic variables were urinary protein excretion (UP), fasting serum cholesterol levels (FChol), body weight (BW), total wet kidney weight (KW), heart weight (HW), and systolic blood pressure (SBP). The best fitting linear regression model, explaining 91% of the total variation of the FGS injury score (multiple r2 = 0.91), included UP as the main clinical, and H as the main structural variable. MC was explained best by BrdU incorporation (multiple r2 = 0.77). The optimal regression model describing MME contained the variables H, m phi, and FChol (multiple r2 = 0.84). The extent of Adh formation was optimally described by UP, m phi, and FChol (multiple r2 = .88). In conclusion, although none of these statistically significant associations indicate causal relationships, they identify - in addition to UP, H, and cellular proliferation - FChol as a major clinical determinant and glomerular m phi influx as a major structural alteration associated with FGS in the setting of renal ablation.(ABSTRACT TRUNCATED AT 400 WORDS)
    Laboratory Investigation 07/1991; 64(6):754-65. · 3.83 Impact Factor
  • International Society on Amyloidosis, Oslo, Norway; 08/1990

Publication Stats

1k Citations
227.11 Total Impact Points


  • 1994
    • Laboratories of Pathology Eastern-Netherlands
      Enschede, Overijssel, Netherlands
  • 1980–1993
    • University of Groningen
      Groningen, Groningen, Netherlands
  • 1992
    • Bielefeld University
      Bielefeld, North Rhine-Westphalia, Germany
  • 1987–1991
    • Universitair Medisch Centrum Groningen
      • • Department of Internal Medicine
      • • Department of Surgery
      Groningen, Groningen, Netherlands