N-octanoyl Dopamine Attenuates the Development of Transplant Vasculopathy in Rat Aortic Allografts Via Smooth Muscle Cell Protective Mechanisms.

Background: Transplant vasculopathy (TV) is a major cause for late graft loss after cardiac transplantation. Endothelial damage and T cell infiltration play a pivotal role in the development of TV. Because N-octanoyl dopamine (NOD) inhibits vascular inflammation and suppresses T cell activation in vitro, we here tested the hypothesis that NOD treatment ameliorates TV.

Overexpression of Cystathionine γ-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3.

Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine (polyQ) disorder caused by a CAG repeat expansion in the ataxin-3 () gene resulting in toxic protein aggregation. Inflammation and oxidative stress are considered secondary factors contributing to the progression of this neurodegenerative disease. There is no cure that halts or reverses the progressive neurodegeneration of SCA3.

Correlation of microRNA-16, microRNA-21 and microRNA-101 expression with cyclooxygenase-2 expression and angiogenic factors in cirrhotic and noncirrhotic human hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a classical example of inflammation-linked cancer and is characterized by hypervascularity suggesting rich angiogenesis. Cycloxygenase-2 (COX-2) is a potent mediator of inflammation and is considered to upregulate angiogenesis. The aims of the study are (1) to analyze expression of Cox-2 mRNA, Cox-2 protein, miR-16, miR-21 and miR-101 in HCC and adjacent liver parenchyma in cirrhotic and noncirrhotic liver, (2) to investigate the relation between COX-2 expression, miR-21 expression and angiogenic factors in these tissues and (3) to investigate the association between miR-16 and miR-101 and COX-2 expression.

Smoking during pregnancy influences the maternal immune response in mice and humans.

Objective: During pregnancy the maternal immune system has to adapt its response to accommodate the fetus. The objective of this study was to analyze the effects of smoking on the maternal immune system.

Study Design: First-trimester decidual tissue and peripheral blood of smoking and nonsmoking women were analyzed by real time reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry.

Altered expression of immune-associated genes in first-trimester human decidua of pregnancies later complicated with hypertension or foetal growth restriction.

During pregnancy the maternal immune system has to coordinate uterine spiral-artery remodelling, trophoblast invasion, and acceptance of the semi-allogenic fetus simultaneously. As dysregulation of the immune system is associated with adverse pregnancy outcomes, we analysed first-trimester deciduas of pregnancies for immune parameters in later complicated pregnancies. Higher IL6 and macrophage mRNA expression, and lower ratios of regulatory macrophages were found in first-trimester deciduas of pregnancies later complicated with pregnancy-induced hypertension.

Renal effects of long-term darbepoetin alpha treatment in hypertensive TGR(mRen2)27 rats.

Introduction: Erytropoietin (EPO) has cytoprotective and angiogenic properties and has a beneficial effect in ischaemic conditions. Since the development of renal interstitial abnormalities are often associated with ischaemia, we studied the effects of the long-acting EPO analogue darbepoetin alpha (DA) on kidney damage in TGR(mRen2)27 (Ren2) rats.

Materials And Methods: Ren2 rats were randomised to DA or vehicle (VEH) or to DA + angiotensin converting enzyme inhibitor (ACEi) or VEH + ACEi.

Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma.

Background: Flat epithelial atypia (FEA) of the breast is characterised by a few layers of mildly atypical luminal epithelial cells. Genetic changes found in ductal carcinoma in situ (DCIS) and invasive ductal breast cancer (IDC) are also found in FEA, albeit at a lower concentration. So far, miRNA expression changes associated with invasive breast cancer, like miR-21, have not been studied in FEA.

ADAM19 expression in human nephrogenesis and renal disease: associations with clinical and structural deterioration.

ADAM19, an enzyme from the ADAM (a disintegrin and metalloproteinase) family, is involved in various cell-cell and cell-matrix interactions. It can cleave epidermal growth factor (EGF)-like growth factors, such as heparin-binding (HB)-EGF and neuregulin (NRG), from the cell membrane. ADAM-mediated EGF receptor activation is crucial in the development of renal pathology.

Upregulation of ADAM19 in chronic allograft nephropathy.

ADAM19 (a disintegrin and metalloproteinase 19) is involved in cell-cell and cell-matrix interactions and tumor necrosis factor (TNF)-alpha shedding. We studied ADAM19 in chronic allograft nephropathy (CAN) nephrectomies and in normal human kidneys. Reverse transcriptase (RT) PCR revealed an upregulation of ADAM19 mRNA in CAN when compared with control kidneys (p = 0.

Enhanced ecto-apyrase activity of stimulated endothelial or mesangial cells is downregulated by glucocorticoids in vitro.

Endothelial as well as mesangial cells show enhanced activity of ecto-apyrase following pro-inflammatory stimulation in vitro. Since this ecto-enzyme appears to be able to regulate plasma hemopexin, which latter molecule plays a role in the pathogenesis of corticosteroid responsive nephrotic syndrome, the question was raised whether glucocorticoids are potentially able to downregulate ecto-apyrase activity of these cells. Therefore, cell cultures of endothelial or mesangial were stimulated with or without lipopolysaccharide (10 ng/ml).

Specific MAP-kinase blockade protects against renal damage in homozygous TGR(mRen2)27 rats.

Angiotensin II (AngII) plays an important role in renal damage by acting on hemodynamics, cell-growth, proliferation, and fibrosis, mainly by effects on the AngII type 1 (AT(1)) receptor. The AT(1) receptor activates several intracellular signaling molecules such as mitogen-activated protein kinases extracellular signal-regulated kinase (ERK) and p38, but their role in AngII-mediated renal damage is not well characterized. We therefore investigated whether pharmacologic blockade of ERK and p38 could prevent renal damage in high-renin homozygous transgenic rats (Ren2), with the effects of an AT(1) receptor antagonist (AT(1)-RA) as a reference.

Bone mineral density in children, adolescents and adults with glycogen storage disease type Ia: a cross-sectional and longitudinal study.

The occurrence of (symptoms related to) osteopenia is a known complication in glycogen storage disease type Ia (GSD Ia) patients. However, only limited information is available about bone mineral density (BMD). Using dual energy x-ray absorptiometry, we studied both cross-sectional and longitudinal lumbar spine areal BMD (BMD(areal) in g/cm2), areal BMD corrected for delayed bone maturation (BMD(bone age) in g/cm2), and volumetric BMD (BMD(vol) in g/cm3).

Distribution of cytoskeletal proteins, integrins, leukocyte adhesion molecules and extracellular matrix proteins in plastic-embedded human and rat kidneys.

Objective: To study the distribution of cytoskeletal proteins (actin, alpha-actinin, vinculin, beta-tubulin, keratin, vimentin, desmin), adhesion molecules for cell-matrix interations (very later antigens [VLA1-61, beta1, beta2 [CD18], vitronectin receptor [alphavbeta3], CD 11b), leukocyte adhesion molecules (ICAM-1) and extracellular matrix proteins (collagen IV, fibronectin, laminin, vitronectin) in human and rat kidneys by using a superior processing and immunohistochemical staining technique.

Study Design: Human and rat kidneys were fixed in 2% paraformaldehyde, dehydrated in acetone and processed in a new, low-toxic glycol, methacrylate mixture, especially developed for immunohistochemistry. Both the glomeruli and the interstitial areas were carefully examined and scored semiquantitatively.

Proteoglycan changes in the extracellular matrix of lung tissue from patients with pulmonary emphysema.

To characterize the changes in the extracellular matrix in smoking-related pulmonary emphysema, we undertook immunohistochemical studies in lung tissues from controls (n = 7), from patients with mild (n = 11) and severe (n = 8) emphysema, and from patients with lung fibrosis (n = 6). We studied collagens, laminin, fibronectin, proteoglycans (PGs), and beta1-integrins. The majority of the patients with severe emphysema showed diminished staining for the interstitial PGs, decorin and biglycan, in the peribronchiolar area, compared with patients in the control and fibrosis groups.

Differential effects of nitric oxide synthase inhibitors on endotoxin-induced liver damage in rats.

Background & Aims: During endotoxemia, expression of inducible nitric oxide synthase (iNOS) and nitric oxide production in the liver is increased. NO has been suggested to have a hepatoprotective function. The aim of this study was to investigate the distribution of iNOS and the effect of different NO synthase inhibitors on liver damage and hemodynamics during endotoxemia.

Characterization of a rat glomerular visceral epithelial cell line.

Cultures of glomerular epithelial cells (GEC) are currently used to identify important cellular and molecular mechanisms involved in the pathogenesis of renal diseases. However, there is still controversy in the literature as to the visceral or parietal origin of cultured GEC. Our aim was to firmly establish the nature of a GEC cell line.

Biological alterations of rat podocytes cultured under basolateral hydrostatic pressure.

In vivo, glomerular visceral epithelial cells (GVEC), or podocytes, are morphologically highly differentiated cells which are in close contact with adjacent cells by complex interdigitating foot processes. In vitro, the dedifferentiated appearance of podocytes hampers investigations on podocyte structure and function. Cultured podocytes resemble simple epithelium in several ways with apical tight junctions and absence of foot processes.

Interferon-gamma (IFN-gamma) and IL-4 expressed during mercury-induced membranous nephropathy are toxic for cultured podocytes.

The subepithelial immune deposits of Dorus Zadel Black (DZB) rats with mercury-induced membranous nephropathy consist of autoantibodies directed to laminin P1 and of complement. The animals develop massive proteinuria within 10-14 days which is associated with obliteration of foot processes of glomerular visceral epithelial cells (GVEC), or podocytes. Previous studies indicate that these autoantibodies are probably not the sole mediator of proteinuria and GVEC damage.

Podocyte expression of MHC class I and II and intercellular adhesion molecule-1 (ICAM-1) in experimental pauci-immune crescentic glomerulonephritis.

We examined immunopathological changes of podocytes in vivo which, based on in vitro studies, are thought to be relevant for the pathogenesis of renal diseases. We investigated the alterations of podocytes in local inflammation in a recently developed model of pauci-immune necrotizing crescentic glomerulonephritis (NCGN) in the rat. Frozen and plastic embedded kidney sections at different time points of the disease were incubated with antibodies directed to MHC class I, MHC class II, ICAM-1 and to relevant cytokines.

Puromycin aminonucleoside and adriamycin disturb cytoskeletal and extracellular matrix protein organization, but not protein synthesis of cultured glomerular epithelial cells.

Puromycin aminonucleoside (PA) and Adriamycin (ADR) cause glomerular proteinuria associated with degenerative alterations of glomerular visceral epithelial cells (GVEC) and detachment from the glomerular basement membrane when administered to rats. This in vitro study was performed to define, in detail, the quantitative and qualitative changes of a number of adhesion-associated proteins (cytoskeletal, extracellular matrix and integrin proteins) upon exposure to PA and ADR. By immunofluorescence we observed: (1) dose- and incubation-time-dependent filament pattern changes and decreased staining of the cytoskeletal proteins actin, vimentin, keratin, and beta-tubulin; (2) an altered distribution, and decreased expression of the extracellular matrix proteins laminin and heparan sulfate and (3) a loss of the beta 1-integrin focal adhesions upon exposure to PA and ADR.

Quantification of glomerular epithelial cell adhesion by using anti-DNA antibodies in ELISA.

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.

[Milker's fever, an occupational disease on the increase].

In order to obtain a better picture of the course of dairy farm fever, a leptospirosis caused by hardjo, an inquiry by means of questionnaires was conducted into its symptomatology and its trade-connected risk factors. The inquiry was performed in 32 seropositive dairy farmers and a matched-pair control group. All persons involved were living or working on contaminated farms.

Early induction of MHC antigens in human liver grafts. An immunohistologic study.

The present study documents major histocompatibility complex (MHC) Class I and II expression during early acute rejection of human liver grafts. Serial graft biopsies (pretransplant, time zero, and 1 week) were studied. Ten patients received azathioprine (AZA) and prednisone; the other six patients were treated with quadruple therapy (azathioprine, cyclosporine A, prednisone, and cyclophosphamide).

Acute rejection in human liver grafts: a comparative histologic study of cases maintained on azathioprine and prednisone versus cyclosporine A and low-dose steroids.

The morphology of acute rejection (AR) in biopsies of liver allografts obtained in the first 2 weeks after transplantation was analyzed. Material from patients maintained on azathioprine and prednisone (AZA; Groningen, The Netherlands) was compared with that of patients receiving cyclosporine A and prednisone (with or without azathioprine) in low doses (CSA; Minneapolis). Strict selection criteria were applied to exclude circulatory and biliary complications and viral infection in this early observation period after transplantation.