PubMed Health⌕ Search

Biomedical subjects

C Gläser

Publications and source records attributed to C Gläser.

15 recordsLinked to original sources
PubMed2004

Plasma levels of transforming growth factor-1beta and alpha2-macroglobulin before and after radical prostatectomy: association to clinicopathological parameters.

BACKGROUND: To study the levels of transforming growth factor-1beta (TGF-beta1) and of alpha2-macroglobulin (alpha2-M), a high affinity binding protein of TGF-beta1, in comparison to prostate-specific antigen (PSA) in prostate cancer (PCa) patients before and up to 12 months after prostatectomy, and to correlate the results with clinicopathological parameters. METHODS: Eighty-one patients who underwent radical prostatectomy for PCa were included in this study. Pre- and postoperatively, plasma levels of TGF-beta1, alpha2-M and PSA were measured in the same samples by ELISA, and were correlated with pathological parameters and clinical outcomes. RESULTS: The preoperative TGF-beta1 levels were significantly elevated as compared to the controls; they showed a positive correlation with the Gleason score. Patients with initial androgen-deprivation therapy had lower TGF-beta1 levels than untreated patients. Elevated concentrations of TGF-beta1 levelled off 12 months after prostatectomy approaching values of healthy individuals. Decreased plasma levels of total and transformed alpha2-M (proteinase-complexed form) were observed in PCa. Preoperative levels of TGF-beta1 but not of alpha2-M seem to be influenced by the body mass index (BMI). CONCLUSIONS: Elevated TGF-beta1 and decreased alpha2-M were consistently found in patients with PCa, and may be considered as risk factors for tumor development and progression. In comparison to PSA, the TGF-beta1 levels displayed a slow decline after radical prostatectomy; this indicates that TGF-beta1 is mainly produced outside the prostatic tissue. Since TGF-beta1 levels are influenced by the BMI, this indicates that PCa might be sensitive to diet.

Aged↗
PubMed2003

Human alpha2-macroglobulin: genotype-phenotype relation.

A pentanucleotide deletion polymorphism in the gene of alpha2-macrolgobulin (alpha2-M) is suggested to be associated with late-onset Alzheimer's disease (AD), though controversial results have been reported. The underlying assumption is that the intronic pentanucleotide deletion may affect the biological function and quantity of the inhibitor and thus contribute to the AD pathology. In the present study we have analyzed the distribution of the deletion polymorphism within a group of 227 healthy Caucasians. In parallel studies, we determined the plasma concentrations of total and transformed alpha2-M. A strong correlation of the total concentration of alpha2-M with age was ascertained (r(s) = -0.54, P < 0.001). However, no significant correlation between age and the genotypes (P = 0.68) was detected, and no statistically significant effect of the genotype on the concentrations of total and transformed alpha2-M was found (P = 0.49 and 0.96, respectively). A significant correlation was observed between total and transformed alpha2-M in the genotype groups Ins/Ins (r(s) = 0.56, P < 0.001) and Ins/Del (r(s) = 0.35, P < 0.004). Furthermore, in the entire data set, a significantly elevated concentration of total alpha2-M was found in females as compared to males (P = 0.003). There was a slight but nonsignificant difference in the genotype distributions between males and females (P = 0.14). To test the proposed existence of genotype-specific alterations of functional properties of alpha2-M, we isolated alpha2-M from the plasma of carriers with different genetic background and analyzed the alpha2-M subunit structure as well as the binding of the inhibitor to growth factors/cytokines, to amyloid-beta and to the receptor. The experiments failed to reveal any genotype-specific functional alterations of the alpha2-M. The absence of abnormalities in alpha2-M mRNA and protein suggests that the alpha2-M deletion polymorphism is probably not associated with functional deficiencies important in AD pathology. However, it can be speculated that the observed general age-related alpha2-M deficiency may lead to accelerated accumulation of amyloid-beta, which might be relevant to AD pathology.

Adult↗
PubMed2000

Angiotensin-converting enzyme gene insertion/deletion polymorphism and carotid artery wall thickness in patients with peripheral arterial occlusive disease.

BACKGROUND: It has been suggested that the deletion polymorphism of the angiotensin converting enzyme (ACE) gene is linked to a high risk of cardiovascular disease. The relationship between the insertion/deletion (I/D) polymorphism of the ACE gene and the carotid intima-media thickness in patients with peripheral arterial occlusive disease is unknown. We tested the hypothesis that the early progression of atherosclerosis in the extracranial carotid arteries in patients with peripheral arterial disease is associated with a genetic predisposition. METHODS: This prospective trial included 98 patients who only had manifestations of arteriosclerotic disease in peripheral arterial vascular regions of the lower extremities (stable stage II PAOD). Maximal common carotid intima-media thickness (mIMT) was measured using high resolution B-mode ultrasonography. Determinations of ACE gene polymorphism were made using a polymerase chain reaction technique. Multivariate regression analysis was performed to assess the influence of ACE genotypes, ACE activity and vascular risk factors on intima-media thickness. RESULTS: There was no significant association between intima-media thickness and ACE gene polymorphism. History of symptomatic peripheral arterial disease without local or systemic progression exists in subjects with the II-genotype significantly longer than in subjects with the DD genotype (p=0.01). With the presence of an II-genotype, there was also a tendency towards a thinner intima-media thickness. We found significant correlations between intima-media thickness and age (p<0.0001), fasting serum insulin (p=0.001), and lipoprotein (a) (p=0.008). CONCLUSIONS: In the present study involving patients with stage II peripheral arterial occlusive disease, ACE gene polymorphism could not be identified as a determining marker for the development of intima-media thickening in the common carotid artery. However, it can be assumed that there is a reduced risk for the systemic progression of atherosclerosis in patients with the II genotype.

Arterial Occlusive Diseases↗
PubMed1999

Functional characterization of atherosclerosis-associated Ser128Arg and Leu554Phe E-selectin mutations.

The cellular adhesion molecule E-selectin is expressed on activated endothelial cells, and is involved in the process of adherence of blood cells to vessel endothelium in inflammatory events such as atherosclerosis. In a recent study we found a Ser128Arg mutation in the EGF domain as well as a Leu554Phe mutation in the membrane domain of E-selectin. We also established increased frequencies of both mutations among young patients with severe coronary atherosclerosis. In the present study we investigated the influence of these mutations on cell adhesion and on the release of soluble E-selectin. Mutants were created by site-directed mutagenesis and COS cells were transfected with E-selectin, either wild-type or mutant. Antibody-binding studies and cell-adhesion assays were performed on transfected COS cells and on interleukin-1 beta-stimulated HUVECs. Soluble E-selectin in supernatants of wild type and Leu554Phe mutant-transfected COS cells was measured by ELISA. We discovered significant differences in the strength of HL-60 cell adhesion for the Ser128Arg mutant: in comparison with the wild type, the strength of adhesion to the mutant was reduced on transfected COS cells (P < 0.01) as well as on stimulated HUVECs (P < 0.01). Significantly diminished release of soluble E-selectin was detected for the Leu554Phe membrane domain mutant, in comparison with the wild type. In summary, the mutations studied here influence the E-selectin function in vitro and may be considered as one of the risk factors involved in the complex pathogenesis of atherosclerosis.

Animals↗
PubMed1998

Low-density lipoprotein receptor-related protein in atherosclerosis development: up-regulation of gene expression in patients with coronary obstruction.

The low-density lipoprotein receptor-related protein (LRP) is a multifunctional cell-surface receptor that binds and mediates the endocytosis of several structurally and functionally distinct ligands. Involved in a variety of biological processes, including the regulation of the coagulation-fibrinolysis balance, the lipoprotein metabolism, cellular migration, proliferative processes and degenerative diseases, it has very recently become an interesting candidate for functional studies of the development of atherosclerosis. We investigated the individual cellular LRP gene expressions in 100 patients with angiographically confirmed severe coronary obstructions (myocardial infarction, patients with coronary angioplasty and patients with coronary bypass). Using a competitive reverse transcriptase polymerase chain reaction analysis we measured the specific LRP mRNA levels in monocytes from venous blood. In comparison with 110 unselected controls (122.1 ag/cell) the patient group demonstrated significantly higher LRP message levels (171.92 ag/cell). We found the most evident increase in the coronary angioplasty group (+43.5%). Investigating the intraindividual range of expression in healthy controls over a period of 4 weeks, we found nearly constant individual levels. Our results demonstrate a significant correlation of increased LRP mRNA levels with atherosclerotic processes (P<0.001), suggest an important implication of the LRP in atherosclerotic vascular processes, and emphasize the inclusion of LRP investigations in risk constellation studies.

Adult↗
PubMed1998

Different expression of the alpha2-macroglobulin receptor/low-density lipoprotein receptor-related protein in human keratinocytes and fibroblasts.

We compared, using a combination of different immunological methods and by competitive PCR, the expression of the alpha2-macroglobulin receptor/low-density lipoprotein receptor-related protein (alpha2-M-R/LRP) in human keratinocytes and fibroblasts. This receptor has previously been found in skin only in dermal cells associated with fibroblasts and dendritic cells. For immunodetection we used mouse monoclonal antibodies against the two subunits of the receptor and against the receptor-associated protein (RAP), known as the regulatory protein of the receptor activity. The alpha2-M-R/LRP was found to be predominantly located intracellularly in keratinocytes whereas a distinct labelling of the outer membrane surface was found in fibroblasts. RAP is abundant in fibroblasts but is less expressed in keratinocytes. In frozen skin sections receptor immunoreactivity was detected in the epidermis with increased reactivity of basal keratinocytes, as well as in the dermis in association with dermal fibroblasts. By immunoprecipitation of biotinylated cell extracts, polypeptides were identified corresponding to the alpha-subunit and beta-subunit of the receptor as well as to the coprecipitating RAP. Competitive PCR revealed the presence of 67.9 and 2049.7 ag of alpha2-M-R/LRP mRNA per cell in keratinocytes and fibroblasts, respectively. The results demonstrate that both cell types express alpha-M-R/LRP mRNA and contain receptor protein as well as RAP but in different quantities and subcellular localizations.

Animals↗
PubMed1998

Angiotensin-converting enzyme gene insertion/deletion polymorphism and peripheral arterial occlusive disease.

BACKGROUND: The deletion polymorphism of the ACE gene is linked to a high risk of cardiovascular disease due to the permanent activation of the local and systemic renin-angiotensin systems (RAS). The aim of this prospective study was 1. to compare the ACE insertion/deletion polymorphism in individuals with a healthy vasculature with that of patients suffering from peripheral arterial occlusive disease (PAOD), and 2. to determine whether associations existed between specific clinical parameters and the ACE genotype which the PAOD patients expressed. PATIENTS AND METHODS: Determinations of ACE I/D gene polymorphism were made using a polymerase chain reaction (PCR) technique on 98 patients with clinical stage II PAOD according to Fontaine and 240 healthy individuals who served as controls. All patients and controls came from central Germany. Clinical variables which included duration of clinical symptoms, a familial history of the disease, arteriosclerosis score (ASF, providing an estimate of the extent of atheromatosis at femoral artery bifurcation) and plasma ACE activity were correlated with the genotypes taking the cardiovascular disease risk factors which were present into consideration. RESULTS: Differences in ACE genotypes between patients with PAOD (D/I: 0.57/0.43) and control group individuals (D/I: 0.59/0.41) were not observed. In comparison with the II genotype, the DD genotype was associated with a shorter duration of disease (p = 0.01), a positive family medical history (p = 0.022) and a higher plasma ACE activity (p = 0.026). The ASF did not correlate with the ACE I/D gene polymorphism. CONCLUSION: Evidence that the deletion allele is linked to the manifestation of PAOD could not be found in the patients studied. One can assume, however, that the deletion allele has a progression promoting effect on the disease.

Aged↗
PubMed1997

Relationship of polymorphisms in the renin-angiotensin system and in E-selectin of patients with early severe coronary heart disease.

Previous association studies between angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) polymorphisms and several cardiovascular diseases have reported variable results. Therefore we examined the association of the DNA variants of ACE and AGT with early, severe coronary heart disease (CHD). In addition, we compared the genotypes of both polymorphisms and the recently discovered polymorphism in the E-selectin gene in both patients and an unselected population. This study included 113 patients with severe CHD (50 years old or less) and up to 197 control subjects. The frequencies of the ACE I/D variants were 48% I and 52% D in the controls and 46% I and 54% D in the patients. The frequencies of the AGT-M235T polymorphism were 60.8% M and 39.2% T in controls and 49.1% M and 50.9% T in the patients. The frequencies of the S128R polymorphism of the E-selectin were 91.3% S and 8.7% R in controls and 84.5% S and 15.5% R in the patients. In our studies the DD genotype of ACE was not associated with early severe CHD. We found a correlation between the M235T molecular variant of AGT and the S128R variant of E-selectin to early severe CHD.

Adult↗
PubMed1994

E-selectin polymorphism and atherosclerosis: an association study.

Adhesion molecules like the members of the selectin family participate in the interaction between leukocytes and the endothelium. They are also involved in the pathogenesis of atherosclerotic processes. To contribute to the analysis of the genetic background of atherosclerosis we searched for DNA polymorphisms in the genes encoding adhesion molecules especially E-selectin which seems to be expressed only in activated endothelium. An adenine to cytosine substitution for cDNA position 561 resulting in an amino acid exchange from serine to arginine (position 128) was detected in the epidermal growth factor like domain. A significantly higher mutation frequency (P = 0.02) was observed in 97 patients aged 50 years or less with angiographically proven severe atherosclerosis (allele frequency of arginine 0.155) compared with an unselected population (allele frequency of arginine 0.088) as well as in 40 patients aged 40 years or less (allele frequency of arginine 0.21, P = 0.0025). These data suggest that the 128-serine/arginine polymorphism is associated with a higher risk for early severe atherosclerosis.

Adult↗
PubMed1990

Immunogold labelling of membrane receptors for scanning electron microscopical investigations of genetically determined disorders of lipid metabolism.

Receptors binding of low-density lipoprotein at surfaces of human lymphocytes was studied by immunochemical and scanning electron microscopical methods. Using colloidal gold sol binding ability of cells from several probands could be demonstrated by immunolabelling. We investigated cell material from normolipidaemic persons and from patients with heterozygote autosomal monogenic hypercholesterolaemia. We found a distinct decrease of labelled gold particles at the cell surface of patients with this disorder of lipid metabolism. The simple extraction possibility of lymphocytes from human venous blood and the demonstrated scanning electron microscopical results recommend the described procedure for genetic application.

Apolipoproteins↗
PubMed1988

[Scanning electron microscopy studies in the detection of apo-B,E receptor activity of the lymphocyte membrane for diagnostic verification of genetically determined disorders of lipid metabolism].

We present a scanning electron microscopic method for determining the quantity of the apo B,E-receptors at the surface of lymphocytes. We used human lymphocytes from venous blood. Gold particles, 50 nm in diameter, were conjugated to the receptors by indirect coupling. We visualized the gold particles by means of an electron microscope (JEM 100 S with scanning attachment ASID). The lymphocytes of control persons and of patients with primary hyperlipoproteinaemias were analysed. Scanning electron microscopic assay of labelled apo-B,E-receptors was shown to allow the rapid and accurate identification of patients with autosomal monogenic hypercholesterolaemia.

Cell Membrane↗
PubMed1987

[Significance of the genetics of haptoglobin types in the demarcation of subgroups of juvenile chronic arthritis].

According to the at present valid definition and due to its different clinical subgroups as well as to the different therapeutic influencibility and prognosis the juvenile chronic arthritis represents a very heterogeneous feature of a disease. Systems of genetic markers increasingly obtain importance for the exact clinical specification of the juvenile chronic arthritis. The investigations described in this paper show a significant correlation of the genetically determined haptoglobin variants to the subgroups of the juvenile chronic arthritis. By means of the careful nosological differentiation which goes beyond the usual principles of subdivision the type of haptoglobin gives a diagnostic enrichment in the assessment of the juvenile chronic arthritis.

Adolescent↗