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Biomedical subjects

J Cerný

Publications and source records attributed to J Cerný.

At least 37 records · Page 2Linked to original sources
PubMed2000

The possible role of human cytomegalovirus (HCMV) in the origin of atherosclerosis.

BACKGROUND: The biological properties of some herpesviruses such as the ability of latent persistency in the host cells and the presence of viral DNA in atherosclerotic lesions, suggest the possible role of herpesviruses in the development of atherosclerosis. Although many authors proved the presence of viral DNA in arterial wall tissue, the role of herpesviruses in the origin and progress of atherogenesis still remains unclear. OBJECTIVES: The aim of this study was to confirm the presence of viral DNA in arterial wall and to associate the presence of these viruses with the development of atherosclerosis in patients with ischemic heart disease (IHD). STUDY DESIGN: A possible role of HCMV, EBV and HHV6 in the development of atherosclerosis was tested in 244 IHD patients and 87 coronarographically negative controls. The presence of viral DNA in aortic and venous walls, as well as in a peripheral blood samples was tested by the use of polymerase chain reaction (PCR) accompanied by, immunological tests for anti-virus antibodies IgM and IgG types for all experimental groups. RESULTS: The genomic DNA of HCMV was found in 76 and 59%, DNA of EBV in 59 and 50%, and DNA of HHV6 in 0.08 and 0.0%, of arterial walls of IHD patients and non-ischemic control group, respectively. No viral DNA was found in venous samples. Significant association (P < 0.01) has been proved between CMV infection and IHD. CONCLUSIONS: Our results suggest that HCMV and EBV can be found in the arterial wall, so that the arterial wall could be a potential site of persistency of those viruses. We also proved a significant association between the presence of HCMV DNA in aortic walls and atherosclerosis. Despite of the high genetic and biological similarity between CMV and HHV6 no substantial role of HHV6 in atherosclerosis has been proved.

Aorta↗
PubMed2000

CDw149 antibodies recognize a clustered subset of CD47 molecules associated with cytoplasmic signaling molecules.

One of the recently described antigens broadly expressed on human leukocytes is CDw149, which was defined at the 6th Human Leukocyte Differentiation Antigen (HLDA) Workshop by means of 2 monoclonal antibodies (mAbs). Molecular characterization of this antigen has been lacking. In the present study we demonstrate that these anti-CDw149 mAbs actually recognize a clustered subset of a well-defined membrane protein, CD47, also known as integrin-associated protein (IAP). This clustered subset is present on leukocytes but not erythrocytes. The anti-CDw149 mAbs bind with only low affinity to a monomeric (unclustered) subset of CD47 but with high avidity to the CD47 clusters. A fraction of CD47 is associated with large complexes containing cytoplasmic signaling molecules (Src family kinases and heterotrimeric G-proteins) similar to glycosphingolipid-enriched microdomains (GEMs), which may explain the previously described signaling capacity of CD47. The low-affinity anti-CD47 mAbs may be useful tools targeting specific receptor complexes involved in cell activation. Specific reactivity of low-affinity mAbs with clustered subsets of cell surface antigens may more generally explain the nature of poorly defined "activation forms" or activation neoepitopes described previously for several cell surface molecules.

Antibodies, Monoclonal↗
PubMed2000

Hemodynamic measurement in liver transplantation. Piggyback versus conventional techniques.

The piggyback technique in venous outflow tract reconstruction has been proposed as an alternative to the conventional technique in liver transplantation. Maintaining caval flow during the anhepatic phase with hemodynamic stability is regarded as one of the main advantages of this method. Between November 1994 and November 1998, the piggyback technique was used in 47 patients in our Center. Hemodynamic measurements during the operation showed hyperdynamic circulation with an increase in cardiac output (9.3+/-3.5 L/min) and the calculated cardiac index (5.0+/-1.9 L/min/m2). There was a statistically significant increase in heart rate and a decrease in systolic arterial pressure, cardiac output (CO) and cardiac index (CI) during inferior vena cava clamping ( simulated conventional technique). Only a non-significant decrease in CO and CI was observed during the partial clamp on the inferior vena cava (piggyback technique). Out of those two techniques, piggyback proved to be a safer approach to venous outflow tract reconstruction from the hemodynamic point of view.

Adolescent↗
PubMed2000

[Transplantation of the heart--indications, complications, therapy--our experience from investigations of 100 patients after cardiac transplantation].

Transplantation of the heart has become an accepted method for the treatment of terminal cardiac failure. Despite obvious advances in the care of patients after trasplantation a number of problems exist. The authors summarize their experience with the long-term follow-up of 100 adult patients with transplantations made in the Brno Centre of Cardiovascular and Transplantation Surgery. One-year survival in the group of patients is 80%, three-year survival 69%. The authors discuss indications and contraindications of cardiac transplantations, necessary preoperative and postoperative examinations, they follow-up the most serious complications during the posttransplantation period. They mention therapeutic possibilities and outline briefly the perspectives of care of patients after cardiac transplantation. Despite the number of problems encountered transplantation of the heart is for indicated patients with cardiac failure a unique chance to improve the prognosis of survival and the quality of life.

Adult↗
PubMed1999

Thyrotropin-releasing hormone-induced depletion of G(q)alpha/G(11)alpha proteins from detergent-insensitive membrane domains.

The role of detergent-insensitive membrane domains (DIMs) in desensitisation of the G protein-coupled receptor-mediated hormone response was studied in clone E2M11 of HEK293 cells which stably express high levels of both thyrotropin-releasing hormone (TRH) receptors and G(11)alpha G protein. DIMs were prepared by flotation in equilibrium sucrose density gradients and characterised by a panel of membrane markers representing peripheral, glycosylphosphatidylinositol-bound as well as integral membrane proteins (caveolin, CD29, CD55, CD59, CD147, the alpha subunit of Na, K-ATPase) and enzyme activities (alkaline phosphatase, adenylyl cyclase). Caveolin-containing DIMs represented only a small fraction of the overall pool of G(q)alpha/G(11)alpha-rich domains. Prolonged stimulation of E2M11 cells with TRH resulted in dramatic depletion of G(q)alpha/G(11)alpha from all DIMs, which was paralleled by a concomitant G(q)alpha/G(11)alpha increase in the high-density gradient fractions containing the bulk-phase membrane constituents soluble in 1% Triton X-100. Distribution of membrane markers was unchanged under these conditions. Membrane domains thus represent a substantial structural determinant of the G protein pool relevant to desensitisation of hormone action.

Adenylyl Cyclases↗
PubMed1999

Do the presence and amount of dysfunctional but viable myocardium affect the perioperative outcome of coronary artery bypass graft surgery?

The aim of our study was to assess the influence of the presence and amount of dysfunctional but viable myocardium on the perioperative outcomes in patients with coronary artery disease and moderate-to-severe left ventricular systolic dysfunction, who underwent coronary artery bypass graft surgery. Viability evaluation with low-dose dobutamine echocardiography was performed in 302 consecutive patients with coronary artery disease and left ventricular ejection fraction < or =40%, who were referred for coronary angiography and potential coronary revascularization. To quantify the amount of dysfunctional but viable myocardium, wall motion was scored using a 16-segment model. The dysfunctional segments were defined as viable if they exhibited improvement in their thickening by at least one grade. One hundred and twenty-seven patients underwent coronary artery bypass graft surgery. The perioperative outcomes were evaluated in 122 of them. Five patients were excluded because of inability to revascularize all vessels supplying dysfunctional but viable myocardial segments. Twenty-five patients exhibited a large amount of dysfunctional but viable myocardium (> or =6 segments, group A), 59 patients had a small amount of such myocardium (2-5 segments, group B), and 38 patients were found to have their dysfunctional myocardium irreversibly damaged (group C). The perioperative mortality in groups A, B, and C was 4, 10, and 11% (all P = NS), respectively. The rate of perioperative Q-wave myocardial infarction was 8, 10, and 3% (all P = NS), respectively. Similarly, there were no significant differences among the groups with respect to perioperative outcome variables including ventricular arrhythmias, duration and magnitude of catecholamine support, renal failure, pulmonary edema, and need for mechanical ventricular support or artificial ventilation. In patients with coronary artery disease and moderate-to-severe left ventricular dysfunction who underwent coronary artery bypass graft surgery, the presence and amount of dysfunctional but viable myocardium did not influence the perioperative outcome.

Adult↗
PubMed1999

GPI-microdomains: a role in signalling via immunoreceptors.

Glycosylphosphatidylinositol (GPI)-anchored proteins and glycosphingolipids are assembled on the leukocyte surface within membrane microdomains, which also accommodate a set of cytoplasmic signalling molecules (Src family kinases, G-proteins, linker proteins). Recent results suggest that these membrane specializations mediate not only signal transduction via GPI-proteins and glycolipids but also play important roles in initiation of signalling via immunoreceptors.

Animals↗
PubMed1999

Characterization of the human leukocyte GPI-anchored glycoprotein CDw108 and its relation to other similar molecules.

The CDw108 glycoprotein is expressed on the surface of some leukemic cell lines, erythrocytes and on activated lymphocytes. Its surface expression is rapidly upregulated following various activating stimuli (PHA, PWM, Con A, PMA, anti-CD3) and subsequently gradually decreases. The molecule is anchored in the membrane via glycosylphosphatidylinositol (GPI) moiety, it has molecular mass of 75-80 kDa and pI of 5.0-5.5. Endoglycosidase F and H reduce its apparent size as determined by SDS PAGE by approx. 15 and 22 kDa, respectively. It is a component of large, detergent-resistant GPI-complexes associated with protein kinases. In addition to the previously described identity of CDw108 with the JMH blood group antigen, we demonstrate here its identity to the previously described glycoprotein recognized by monoclonal antibodies H105 and KS.2, and exclude its identity with another GPI-anchored glycoprotein of similar size, melanotransferrin (gp97).

Antigens, CD↗
PubMed1999

T cell activation-associated epitopes of CD147 in regulation of the T cell response, and their definition by antibody affinity and antigen density.

CD147 is a broadly expressed cell surface glycoprotein of the Ig superfamily whose expression is up-regulated upon T cell activation. In order to elucidate a possible role of CD147 in T cell biology, we established 15 specific mAb. Seven distinct epitopes were defined by the mAb panel. Most of the mAb bound only to phytohemagglutinin (PHA)-activated but not resting T cells. We demonstrate that this was not because of true expression of activation-dependent neoepitopes but rather due to bivalent binding of the relatively low-affinity mAb (affinity constant KA values between 2.25 x 10(8) and 7 x 10(9) M-1) to the more densely expressed and/or more clustered CD147 molecules on the activated T cells. In contrast, the mAb with higher affinity (KA > 7 x 10(9) M-1) could stably bind in a monovalent fashion even to the relatively low dense CD147 molecules on resting T cells. This model might more generally explain the nature of 'activation epitopes' described previously in other leukocyte surface molecules. Finally, we provide evidence that induction of ordered dimerization of CD147 by a mAb directed to a unique epitope results in strong inhibition of CD3-mediated T cell activation.

Animals↗
PubMed1999

[Reconstruction of the venous outflow in liver transplantation using the "piggyback" technique].

The piggyback technique in venous outflow tract reconstruction has been proposed as an alternative to the conventional technique in liver transplantation. Between November 1994 and November 1997 this technique was used in 29 patients in our institute. Most of the patients were operated on without veno-venous bypass and we observed no complications concerning venous outflow tract reconstruction and no renal failure. Hemodynamic measurements during the operation showed only an insignificant decrease in cardiac index during the partial clamp on the inferior vena cava. The piggyback technique proved to be a convenient and safe approach to the venous outflow tract reconstruction in a majority of liver transplantations and has been used routinely in our institute.

Adolescent↗
PubMed1998

T cell receptor signalling results in rapid tyrosine phosphorylation of the linker protein LAT present in detergent-resistant membrane microdomains.

Stimulation of human T cell line Jurkat results in rapid tyrosine phosphorylation of a 35-38 kDa protein that is found in large and buoyant detergent-resistant membrane microdomains containing also glycosylphosphatidylinositol (GPI)-anchored proteins, glycolipids and Src-family protein tyrosine kinases ("GPI-microdomains"). The pp35-38 was found to be identical to LAT, a recently cloned key component of the T-cell receptor signalling pathway. Moreover, a modified form of protein tyrosine kinase Lck (pp60) was newly detected in the GPI-microdomains of the anti-CD3-stimulated Jurkat cells. These data support the idea that GPI-microdomains play important roles in immunoreceptor signalling.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Incorporation of leucocyte GPI-anchored proteins and protein tyrosine kinases into lipid-rich membrane domains of COS-7 cells.

Several human leucocyte surface glycoproteins and two lymphoid protein kinases were transiently expressed in monkey COS-7 fibroblastoid cells. All glycosylphospha-tidylinositol (GPI)-anchored proteins (CD14, CD16B, CD48, CD59, CD87 and GPI-anchored versions of CD2 and CD25) and protein tyrosine kinase (PTK) Lck but not transmembrane proteins (CD2, CD4, CD5, CD6, CD8) and PTK ZAP-70 were in part localized in buoyant, lipid-rich, detergent-resistant membrane GPI-microdomains of the COS cells. Endogenous GPI-microdomains of COS cells appear to be, in contrast to those present in leucocytes, essentially devoid of associated PTKs. Our results indicate that GPI-anchor is sufficient to target proteins to these membrane specializations even if expressed ectopically. Moreover, the N-terminal double acylation of the PTK Lck appears to be functional also in COS cells and targets the enzyme to the membrane GPI-microdomains implicated in receptor signalling.

Acylation↗
PubMed1998

Phagocyte-induced oxidative stress in patients with haemodialysis treatment and organ transplantation.

The aim of the study was to examine the phagocyte-derived production of reactive oxygen species (ROS), lipoperoxidation and the total radical-trapping antioxidant parameter (TRAP) in patients undergoing regular haemodialysis (HD) followed by kidney transplantation (n = 13). A significant increase in both spontaneous and activated ROS generation was found during the post-transplantation period in days 1-3. This effect was caused mainly by an increased number of neutrophils. On the other hand, the TRAP parameter was decreased in HD patients. After kidney transplantation, the TRAP parameter increased, reaching the level of healthy controls at the end of the first week after surgery. Increase in MDA level was determined after HD and kidney transplantation. It can be concluded from the results obtained that phagocyte mobilisation and increased oxidative stress after HD and kidney transplantation were associated with the insufficient activity of extracellular antioxidant mechanisms resulting in increased lipid peroxidation.

Humans↗
PubMed1998

Signal transduction in leucocytes via GPI-anchored proteins: an experimental artefact or an aspect of immunoreceptor function?

Membrane proteins anchored in the membrane via a glycolipid glycosylphosphatidylinositol (GPI) as well as some glycolipids are able to transduce signals and induce diverse functional responses in cells upon their cross-linking via antibodies or natural ligands. In some cases this signaling capacity seems to be due to associations of these molecules with specific transmembrane proteins. GPI-anchored proteins are components of membrane microdomains enriched in glycosphingolipids and cholesterol and devoid of most transmembrane proteins. These membrane specializations are relatively resistant to solubilization in solutions of some mild detergents at low temperatures. These 'GPI-microdomains' contain also cytoplasmic signaling molecules such as Src-family protein tyrosine kinases and trimeric G-proteins. Thus, at least some signaling elicited upon cross-linking of GPI-anchored proteins and glycolipids may be due to perturbation of the signaling molecules associated with these microdomains. It is suggested that these specialized areas of the membrane rich in signaling molecules interact with immunoreceptors (TCR, BCR, Fc receptors) cross-linked upon their interactions with ligands and importantly contribute to initiation of proximal phases of their signaling pathways.

Animals↗