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R Loginov

Publications and source records attributed to R Loginov.

14 recordsLinked to original sources
PubMed2006

Cytomegalovirus and proliferative signals in the vascular wall of CABG patients.

OBJECTIVE: To further elucidate the mechanism by which cytomegalovirus (CMV) may promote atherosclerosis, we studied the expression pattern of cellular inflammatory and proliferative signals in the aortic wall of CMV(+) and CMV(-) patients undergoing coronary artery bypass grafting (CABG). METHODS: Aortic biopsies and blood samples of 68 CABG patients were investigated for CMV-DNA by PCR and IN SITU hybridisation. Expression of pp65 antigen, adhesion molecules (ICAM-1, VCAM-1, E-selectin), growth factors (PDGF-AA, TGF-beta), and the cellular proliferation factor Ki-67 was studied by immunohistochemistry. Logistic regression was used to test the correlation between the presence of CMV, vascular inflammation, and traditional noninflammatory risk factors for atherosclerosis. RESULTS: CMV-DNA was detected in the aortic tissue of 52 (76%) patients, and was localised predominantly in vascular smooth muscle cells. In CMV(+) patients, the expression of adhesion molecules and growth factors in the aortic endothelium was increased compared with CMV(-) patients. A positive correlation of elevated CRP, the induction of adhesion molecules and growth factors and CMV(+) was found. Female gender, smoking, and hyperlipidaemia were identified as risk factors for CMV(+). CONCLUSIONS: CMV-DNA in smooth muscle cells induces local growth factor expression as well as endothelial activation, both of which can promote the progression of atherosclerosis. Since traditional atherogenic risk factors increase the likelihood of aortic CMV manifestation, we suggest that CMV plays a crucial role in mediating the progression of atherosclerosis.

Aged↗
PubMed2005

HHV-6-DNAemia related to CMV-DNAemia after liver transplantation.

In addition to cytomegalovirus (CMV), activation of other betaherpesviruses, especially human herpesvirus 6 (HHV-6), has been reported in liver transplant patients. The purpose of this study was to investigate the posttransplant HHV-6-DNAemia in relation to CMV-DNAemia in liver transplant patients. Thirty-one adult liver allograft recipients were regularly monitored for CMV and HHV-6 during the first 3 months after transplantation. For the diagnosis of CMV infections, pp65-antigenemia assay and quantitative DNA-PCR were used. HHV-6 was demonstrated by using quantitative DNA-PCR and HHV-6 antigenemia test. Altogether 253 blood specimens of 31 recipients were analyzed. In addition, CMV and HHV-6 specific antigens were demonstrated by immunohistochemistry in liver biopsy specimens in the case of graft dysfunction. Thirteen patients (40%) developed a clinically significant CMV infection, at a mean of 33 days (range 5 to 62 days) after transplantation and were treated with intravenous ganciclovir. The peak viral loads of these symptomatic CMV infections were high (CMV-DNA 34210 +/- 37557 copies/mL plasma). Six additional asymptomatic patients demonstrated significantly lower CMV-DNAemia levels (1020 +/- 1008 copies/mL, P < .05), and were not treated. Concurrently with CMV, HHV-6 DNAemia and antigenemia were detected in 17 of 19 patients, mean 11 days (range 6 to 24 days) after transplantation. HHV-6 appeared prior to CMV in most cases (12 of 17). However, the peak viral loads were low (HHV-6-DNA <1500 copies/mL blood), even in the five patients who demonstrated HHV-6 antigens on liver biopsy. All CMV infections were successfully treated with ganciclovir and the CMV DNAemia/antigenemia subsided. HHV-6 also responded to the antiviral treatment, but more slowly and less clearly. In conclusion, HHV-6 activations were common and usually associated with CMV infection in liver transplant patients. Further investigation of the clinical significance of HHV-6 DNAemia/antigenemia is necessary.

Adult↗
PubMed2003

Detection of CMV-DNA in peripheral blood leukocytes of liver transplant patients after ganciclovir treatment.

Cytomegalovirus (CMV) infections are common after transplantation, but usually successfully treated with antivirals. In this study, the detection of CMV-DNA in peripheral blood leukocytes was monitored and compared with CMVpp65-antigenemia in liver transplant patients receiving ganciclovir treatment. Twenty adult liver transplant recipients were frequently monitored for CMV up to 6 months after transplantation. CMV infections were diagnosed by pp65-antigenemia and the same specimens were used for CMV-DNA in situ hybridization. Altogether 202 blood specimens were analyzed. During the first 6 months, 14/20 patients developed CMV antigenemia and 11 were treated with ganciclovir. In all patients, CMV-DNA was detected before antigenemia (mean 15 days earlier). All patients responded to ganciclovir and pp65-antigenemia disappeared. However, 8/11 demonstrated persistence of CMV-DNA for up to 6 months. Recurrences appeared in 6/11 patients. In conclusion, detection of CMV-DNA preceded pp65-antigenemia. Persistence of CMV-DNA demonstrates that the virus is not eliminated by ganciclovir and recurrences can be expected.

Antiviral Agents↗
PubMed2000

Sequential analysis of adhesion molecules and their ligands in rat renal allografts during the development of chronic rejection.

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are important in endothelial cell-leukocyte interactions. In this sequential study, the expression of ICAM-1 and VCAM-1 and their ligands LFA-1 and VLA-4 as well as major histocompatibility complex class II antigens (MHC class II), and interleukin-2-receptor (IL-2R) were investigated during the development of chronic renal allograft rejection in a rat model. The time-related expression of adhesion molecules and their ligands in the graft was correlated to the chronic allograft damage index (CADI). In association with an initial short immune activation, there was a significant ICAM-1 and VCAM-1 induction in the vascular endothelium and the tubular epithelium. In the interstitium, there was infiltration of lymphocytes expressing ligand molecules VLA-4 and LFA-1, as well as activation markers MHC class II and IL-2R. Thereafter, the expression declined together with the increase of CADI-values. In end-stage chronic rejection, there was practically no expression of ICAM-1 and VCAM-1. In the interstitium, there were only few ligand-expressing leukocytes. In conclusion, adhesion molecules and their ligands are involved in the induction phase of the process but no longer in the later stages of chronic rejection.

Animals↗
PubMed1999

Antiviral and immunomodulatory effects of desferrioxamine in cytomegalovirus-infected rat liver allografts with rejection.

BACKGROUND: Cytomegalovirus (CMV) infection is associated with acute and chronic allograft rejection. We have recently shown that rat CMV increases portal inflammation and bile duct destruction in a model of rat liver allograft rejection. Desferrioxamine (DFO), an iron chelator and antioxidant, has recently been demonstrated to have antiviral as well as immunomodulatory effects in vitro. We therefore investigated whether DFO inhibits (a) CMV infection and (b) graft destruction in our rat model. METHOD: One day after liver transplantation, PVG (RT1c) into BN(RT1n), the rats were infected with rat CMV (RCMV, Maastricht strain; 10(5) plaque-forming units i.p.). The effects of 100 mg/kg body weight and 200 mg/kg body weight DFO were examined. RESULTS: In the untreated group, the grafts were uniformly RCMV culture-positive. In the group receiving 200 mg/kg DFO, RCMV replication was effectively inhibited. Inflammatory response in the graft, and especially the number of macrophages, was significantly reduced by DFO. Portal inflammation and bile duct destruction were also significantly reduced. In the untreated group, the bile duct epithelial cells were found to be strongly positive for tumor necrosis factor-alpha and this expression was clearly decreased by DFO. In addition, DFO significantly inhibited vascular cell adhesion molecule-1 expression on sinusoidal endothelial cells. CONCLUSIONS: Our in vivo transplant study strongly supports the inhibitory effects of metal chelators on CMV infection and their possible usefulness in the treatment of CMV-induced pathogenic changes.

Adjuvants, Immunologic↗
PubMed1999

Time-related effects of cytomegalovirus infection on the development of chronic renal allograft rejection in a rat model.

Cytomegalovirus (CMV) infection is a risk factor for chronic allograft rejection. The histological findings of chronic renal allograft rejection include inflammation, vascular intimal thickening, glomerulosclerosis, tubular atrophy and fibrosis. We have developed a rat model of renal transplantation in which transplants, after an early inflammatory episode, end up with chronic rejection within 60 days. During the early phase of the process in this model, CMV increased and prolonged the inflammatory response, the expression of adhesion molecules, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and their ligands, lymphocyte function antigen-1 and very late antigen-4 in the graft. Simultaneously, the production of various growth factors, such as transforming growth factor beta, platelet-derived growth factor and connective tissue growth factor was upregulated, which induce smooth muscle cell proliferation in the vascular wall and collagen synthesis by fibroblasts. Chronic rejection developed within 20 days in CMV-infected grafts. In summary, CMV infection accelerated and enhanced the early immune response, the induction of growth factors and collagen synthesis, and the development of chronic rejection in renal allografts.

Animals↗
PubMed1997

Persistent cytomegalovirus in liver allografts with chronic rejection.

Cytomegalovirus (CMV) infection is one of the suggested risk factors for chronic allograft rejection. Clinical and experimental studies have shown that CMV is somehow implicated in rejection mechanisms and in the generation of graft arteriosclerosis, characteristic of chronic rejection. In liver transplantation, there is also evidence of an association between CMV and vanishing bile duct-syndrome (VBDS), which is characteristic of chronic liver allograft rejection. In this study, the role of posttransplant CMV infection and of acute rejection in the patients with irreversible, histologically confirmed chronic liver rejection with VBDS and vasculopathy was analyzed. Ten of 200 (5%) consecutive liver transplants were lost due to chronic rejection, from between 5 and 28 months from transplantation. In these 10 patients, acute rejections were frequent, and nine of ten patients had at least one episode of rejection early after transplantation. All patients (10 of 10) had a history of CMV infection usually following acute rejection. To investigate the role of CMV in chronic rejection, nine available removed grafts were examined for the presence of the CMV genome by DNA-hybridization in situ using a biotinylated CMV-DNA probe. Persistent CMV-DNA was found in all of those available grafts with chronic rejection. CMV-DNA was strongly expressed in the remaining bile ducts and moderately expressed in the endothelial cells of the vascular structures, the CMV positivity of hepatocytes varied from graft to graft. Thus, persistent CMV genome was found in those structures that are the major targets of the chronic rejection process in the liver. These findings support the previous suggestion of an association between CMV and chronic allograft rejection.

Bile Ducts↗
PubMed1994

CMV-induced class II antigen expression in various rat organs.

Cytomegalovirus (CMV) is thought to trigger acute or chronic allograft rejection by inducing the expression of MHC class II antigens in the graft. This induction may be mediated by gamma-interferon or directly by CMV. In this study, we have investigated which structures in the rat kidney, liver, and heart are responsive to CMV-induced class II expression in vivo. Rats were infected with rat CMV, the organs were harvested during the acute phase of infection, and the virus was demonstrated by culture from each organ. Direct CMV antigen detection was performed on frozen sections to demonstrate the detailed localization of CMV in the organs. In the kidney, CMV antigens were found in the vascular endothelium, in tubular cells, and scattered in the glomeruli. In the liver, the vascular structures and parenchyma contained CMV antigens. In the heart, CMV antigens were seen only in the capillary endothelium. Class II antigen expression was demonstrated by a monoclonal antibody and immunoperoxidase techniques. The induction of class II molecules was recorded in exactly the same cellular structures as those in which CMV antigens were detected.

Animals↗