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Biomedical subjects

P Galajda

Publications and source records attributed to P Galajda.

At least 19 recordsLinked to original sources
PubMed2006

HER-2 [Ile655Val] polymorphism in association with breast cancer risk: a population-based case-control study in Slovakia.

Breast cancer belongs to the most frequent types of cancer affecting women and it occurs at any age. Around 1600-1800 women are getting ill annually in the Slovak republic. One of the most important factors in connection with cancer genesis refers to changes in specific genes. HER-2 proto-oncogene belongs to low penetrating genes, which increase susceptibility to breast cancer genesis. Clinical studies demonstrated an association between polymorphism at codon 655 of this gene and increased risk for breast cancer development. The aim of this case-control based prospective study was to determine the distribution of HER-2 genotype and its association with risk factors of breast cancer in the population of women in Slovak republic. HER-2 genotypes were determined with PCR-RFLP method. The DNA was isolated from white blood cell nuclei. The frequency of Val allele in the cancer group was 29.79% and was higher than in the control group 15.84% (p<0.05). The presence of the heterozygote (Ile/Val) genotype was identified in 46.81% of patients in the case group and in 28.33% in healthy individuals, and the homozygote (Val/Val) genotype in 6.38% and 1.67, respectively (p<0.01). The risk of breast cancer development for carriers of one valine (Val) allele in genotype was two-times lower (OR=2.47) than for carriers of two Val alleles (OR=5.73) (p<0.05). Risk of cancer genesis for Val allele carriers was higher in multiparas (OR=2.90), among women with positive family history of breast cancer (OR=5.0), BMI>24 (kg/m2), and late menopause (OR=1.5). Contraceptives in anamnesis contrariwise showed tend to decrease the risk in Val allele carriers (OR=0.3). In conclusion, this study revealed relatively high frequency of the Val allele among the women population of the Slovak republic. Ile655Val polymorphism of HER-2 gene was associated with a statistically significantly increased risk of breast cancer all above in homozygotes for Val allele.

Adult↗
PubMed2004

[Glomerulonephritides, histology forms, way of treatment and therapeutic effect in our patients].

Authors present a group of patients in the article who were monitored at a nephrology outpatient department of the University Hospital in Martin between years 1997 and 2001 for nephritic or nephrotic syndrome. Indications, contraindications and ways of histology examinations of kidneys in their department are discussed in the beginning of the work. Than prevalence of individual types of glomerulonephritides as well as way and length of therapy based on histology picture are discussed in the monitored group of patients. In the end results of therapeutic response are presented. Among other things, authors came to a conclusion that it is the least possible to manage the disease when histology results show sclerotisation of glomerules and in cases of frequent relapses in prolipherative forms of glomerulonephritides.

Adolescent↗
PubMed2001

Labeling phosphorylated LHCII with microspheres for tracking studies and force measurements.

We report a method to selectively label phosphorylated, membrane proteins with microscopic particles. This technology is particularly useful in single particle studies. In such studies, the particles may serve to visualize protein diffusion and/or as 'handles' to study the force of interaction between the labeled protein and the membrane matrix. In the latter kind of experiments, forces can be applied and measured by calibrated optical tweezers. Optical tweezers were used in this work to test the strength of the particle labeling. Labeling a single protein with a particle produces a long-lived, distinct tag and is particularly useful for proteins in photosynthetic membranes, which contain endogenous fluorophores that would render single fluorescent proteins difficult to detect.

Chloroplasts↗
PubMed2001

Increased platelet glycoprotein V levels in patients with coronary and peripheral atherosclerosis--the influence of aspirin and cigarette smoking.

As platelet hyperactivity is important in atherosclerosis and smoking, we hypothesized higher levels of soluble platelet membrane glycoprotein V (gpV) in 95 patients with peripheral artery disease (PAD) and 92 with coronary artery disease (CAD) compared to 99 healthy controls, and examined the effects of aspirin and of smoking two cigarettes on soluble gpV and platelet function. Soluble gpV (ELISA) was significantly raised in, but not between, both PAD and CAD patients, compared to controls (p < 0.05). In multivariate analysis, systolic blood pressure, smoking and atherosclerosis (all p < 0.01) were significant influences on soluble gpV in the whole study cohort. There was a weak correlation between soluble gpV and another platelet marker, soluble P selectin (p = 0.048). Acute smoking in 14 subjects increased platelet aggregability and beta-thromboglobulin, but not soluble gpV: there were no changes in 11 non-smokers. Five days consumption of aspirin (325 mg daily) by 14 subjects did not influence levels of soluble gpV. Our data indicate that soluble gpV may be a useful new marker of platelet activation in atherosclerosis, but may be influenced by smoking status and blood pressure.

Adenosine Diphosphate↗
PubMed2000

[Latent autoimmune (type 1) diabetes mellitus in patients originally classified as type 2. Divergence of etiologic markers].

BACKGROUND: To assess the prevalence of markers of autoimmune insulitis (AII) in patients classified originally as having Type-2 diabetes mellitus (Type-2 DM). 386 patients subdivided according to the BMI, C-peptide and type of treatment. METHODS AND RESULTS: Age, BMI, C-peptide, Glutamic acid decarboxylase autoantibodies (GADA), HLA-DR/,-DQ alleles. Prevalence of GADA varied from < 5% in obese patients with normal/increased C-peptide to > 30% in non-obese patients with low C-peptide. In majority of GADA positive patients, the Type-1 DM high-risk HLA-DRB1*, HLA-DQB1* alleles have been found. Among them HLA-DRB1*0302 and HLA-DRB1*0201 were more frequent than HLA-DRB1*040x and HL:A-DQB1*0302. CONCLUSIONS: Significant fraction of patients classified initially as Type-2 DM may have in fact Type-1 DM. Such patients can be recognized on the basis of assessment of serological (GADA) and immuno-genetical (HLA-DR/,-DQ alleles) markers. In some patients clinical, metabolic, immune, and immunogenetic markers may disagree. This divergence stresses multifactorial genesis of diabetes. Moreover, it can also suggest that both autoimmune insulitis and insulin resistance may coexist in parallel.

Adult↗
PubMed1999

Chloride ion binding to bacteriorhodopsin at low pH: an infrared spectroscopic study.

Bacteriorhodopsin (bR) and halorhodopsin (hR) are light-induced ion pumps in the cell membrane of Halobacterium salinarium. Under normal conditions bR is an outward proton transporter, whereas hR is an inward Cl- transporter. There is strong evidence that at very low pH and in the presence of Cl-, bR transports Cl- ions into the cell, similarly to hR. The chloride pumping activity of bR is connected to the so-called acid purple state. To account for the observed effects in bR a tentative complex counterion was suggested for the protonated Schiff base of the retinal chromophore. It would consist of three charged residues: Asp-85, Asp-212, and Arg-82. This quadruplet (including the Schiff base) would also serve as a Cl- binding site at low pH. We used Fourier transform infrared difference spectroscopy to study the structural changes during the transitions between the normal, acid blue, and acid purple states. Asp-85 and Asp-212 were shown to participate in the transitions. During the normal-to-acid blue transition, Asp-85 protonates. When the pH is further lowered in the presence of Cl-, Cl- binds and Asp-212 also protonates. The binding of Cl- and the protonation of Asp-212 occur simultaneously, but take place only when Asp-85 is already protonated. It is suggested that HCl is taken up in undissociated form in exchange for a neutral water molecule.

Arginine↗
PubMed1999

[A multicompartmental and multifactorial model of production of plasminogen activator inhibitor (PAI-1). II. Clinical study in patients with insulin resistance].

PAI-1 levels are closely associated with insulin resistance (IR) syndrome, including patients with obesity, hypertension, hypertriglyceridaemia and type 2 diabetes mellitus (DM). Clinical studies demonstrated PAI-1 correlations with insulin (IRI), triglycerides (TG) and body mass index (BMI) values, but these relations have not been confirmed in all studies. In obesity PAI-1 levels correlate with IRI and BMI in the relation to increased adipocyte PAI-1 production, which is dependent on stimulative insulin action. In the case of endothelial hyperproduction in patients with IR elevated PAI-1 levels correlate with TG values. Insulin inhibits induced endothelial PAI-1 production. PAI-1 levels in patients with IR represent cumulative production in described tissues.

Adipocytes↗
PubMed1998

[Successful treatment of hemothorax with recombinant factor VIIa in a hemophilic child with inhibitor].

rFVIIa is at present the most progressive treatment in different haemorrhages and operations in patients with haemophilia A and a high titre of inhibitor. As apparent from the presented case of a 4-year-old boy with haemorrhage into the pleural cavity, rFVIIa is sufficiently effective to induce haemostasis, while it is safe and has no side-effects. It does not induce systemic activation of haemostasis. Its application requires, due to the high price, that all criteria should be met which were elaborated for the Slovak Republic in the National centre of haemostasis and thrombosis.

Child, Preschool↗
PubMed1998

[Tissue plasminogen activator and diabetes mellitus].

tPA has been the independent risk factor of the thrombosis associated with atherosclerosis. There are increased tPA levels in type 1 diabetic patients with vascular complications and tPA is endothelial injury marker in this case. In type 2 diabetes mellitus elevated tPA antigen levels in early disease stage are caused by increased production of complexes with inhibitor (PAI-1) and tPA or fibrinolytic activity has been decreased.

Diabetes Mellitus↗
PubMed1998

[A new model of hemostasis].

Haemostasis is a complexly controlled process which takes place in two stages. The first initial stage leads to the formation of a small amount of thrombin. The crucial step of initiation is the bond between the activated factor VIIa and the tissue factor. It is regulated by interaction between factors promoting and inhibiting the process of thrombogenesis. The initiation of haemostasis must be associated with the formation of the thrombus and for effective fibrinogenesis the second stage, amplification of haemostasis, is necessary. A new two-stage model of coagulation imitates the process of haemostasis in vivo as the classical MacFarlan cascade model and makes it possible to explain the pathogenesis of prothrombotic conditions.

Hemostasis↗
PubMed1998

[A multicomparmental and multifactorial model of production of plasminogen activator inhibitor (PAI-1). I. Experimental studies].

Hypofibrinolysis caused by increased PAI-1 levels in patients with insulin resistance (IR) is one of the most common acquired prothrombotic states with higher risk of arterial thrombosis associated with atherosclerosis. Increased PAI-1 levels are caused by PAI-1 hyperproduction in various compartments owing to various factors (multicompartmental and multifactorial model). Metabolic compartment, including visceral adipocytes and hepatocytes, is sensitive on stimulative action of insulin, proinsulin and some cytokines. This pool is responsible for elevated PAI-1 levels in obesity. Vascular compartment, including mainly endothelium, is sensitive on thrombin, angiotensin IV, cytokines, biological active lipids and oxidative stress effect, while insulin inhibits cytokine induced PAI-1 production on contrary. This compartment is responsible for elevated PAI-1 levels in patients with type 2 diabetes mellitus and hypertension with endothelial dysfunction. PAI-1 levels in patients with IR represent cumulative production in described compartments.

Adipocytes↗
PubMed1998

[Glutamic acid decarboxylase autoantibodies (antiGAD-Ab) in patients with non-insulin dependent diabetes mellitus (NIDDM)].

AIM OF STUDY: To assess the prevalence of markers of autoimmune destruction of pancreatic beta-cells in patients with non-insulin dependent diabetes mellitus (NIDDM). SUBJECTS: 127 hospitalized NIDDM patients subdivided to the following subgroups: non-obese with C-peptide < 0.3 nmol/l (NIDDM-(-)), non-obese with C-peptide > 0.3 nmol/l (NIDDM-(+)), obese with C-peptide < 0.3 nmol/l (NIDDM+(-)) and obese with C-peptide > 0.3 nmol/l (NIDDM2+). METHODS AND MEASURED PARAMETERS: Age, BMI, C-peptide, autoantibodies to glutamic acid decarboxylase (antiGAD-Ab), autoantibodies to islet cells (ICA), markers of specific cellular immunity CD4, CD8, CD19, CD4/CD8, CD4/CD45/RA+, CD4/CD45/RA-, NK (CD16+56), CD3/HLADR, organ specific/non-specific autoantibodies. RESULTS: AntiGAD-Ab were positive in 5/15 (33.3%) NIDDM-(-), 1/32 (3.1%) NIDDM-(+), 2/9 (22.2%) NIDDM+(-) and in 3/71 (4.2%) NIDDM2+. The positivity of antiGAD-Ab in NIDDM-(-) and NIDDM+(-) was significantly higher (p < 0.05) than in NIDDM-(+) and NIDDM2+. CONCLUSION: Some patients with manifestation of diabetes in older age initially classified and treated as having NIDDM may have in fact slowly evolving autoimmune insulin-dependent diabetes mellitus (LADA). These patients can be identified by measurement of antiGAD-Ab or other markers (ICA, IA-2) of autoimmune destruction of pancreatic beta-cells (AID). Moreover, in some patients both AID and insulin resistance may coexist in parallel.

Adult↗
PubMed1998

[Plasminogen activator inhibitor (PAI-1) and diabetes mellitus. II. PAI-1 in insulin resistant conditions].

Insulin resistance (IR) is associated with an elevated PAI-1 level and by correlation with insulin and triacylglycerol (TG) levels. While in IR non-diabetics this relationship is close, in patients with NIDDM the mutual relationship is less marked and there are other factors which raise the PAI-1 levels such as proinsulin, oxidation stress or cytokines. Therefore achievement of satisfactory metabolic control, reduction of insulin and TG levels need not be associated with normalization of PAI-1. As it is an independent risk factor of atherosclerosis, further examinations are necessary in order to differentiate in more detail the possible causes of its rising level in order to obtain a rational basis for effective therapy.

Diabetes Mellitus↗
PubMed1997

Endothelial markers in diabetes mellitus.

In this study we examined 22 NIDDM patients without vascular complications and 17 age-matched healthy blood donors. Von Willebrand factor (vWF) levels were significantly increased in NIDDM patients compared to healthy blood donors (1.33 +/- 0.39 vs 1.01 +/- 0.27 IU/ml p = 0.006), while thrombomodulin (TM) levels were similar in the both groups. vWF levels correlated with calcium dependent secretion parameters such as C-peptide (r = 0.680, p < 0.001) and PF4 (r = 0.613, p < 0.01) and did not correlate with calcium-independent markers of endothelial injury such as TM (r = 0.287, p = 0.196) and TFPI (r = 0.296, p = 0.181). Therefore it seems that increased levels of Cai-dependent endothelial and platelet activation markers may precede the signs of endothelial damage. This hypothesis requires further research.

Adult↗
PubMed1997

[What does the relation of digoxin-like immunoactivity and serum insulin levels in pregnant women signify?].

BACKGROUND: Digoxin-like immunoactivity (DLIA) reflects the presence of endogenous substances which are close to cardiac glycosides. These substances via inhibition of Na(+)-K(+)-ATPase increase intracellular calcium stores (Ca2+i) and may modulate various Ca(2+)-dependent mechanisms. Although DLIA are known primarily as hypertension and natriuresis promoting factors, several recent works have suggested that DLIA relates also to diabetes mellitus. The main stimulus for DLIA secretion represents volume-expansion. AIM OF STUDY: To assess relation of DLIA to glucose tolerance and insulin levels in pregnant women (PW). SUBJECTS AND METHODS: 1) 67 PW (DLIA measured by RIA-kit HUMA-LAB Kosice), 2) 53 PW (DLIA measured by RIA-kit ORION). PW were subdivided according to the glucose tolerance and insulin concentrations. RESULTS: 1. DLIA in hyperinsulinemic PW were significantly higher than in those with normal insulin levels. 2. DLIA significantly correlated with insulin levels as well as with insulinogenic index. 3. The increase in plasma glucose and insulinemia during OGTT was accompanied by a decrease in DLIA. These findings were independent of other measured parameters (age, body mass index, pregnancy induced weight gain, blood pressure and steroid hormones). CONCLUSIONS: These findings suggest that DLIA does not respond only to changes regarding sodium-retention and volume-expansion, but also to changes in glucose and insulin metabolism. Thus, DLIA could represent one of the markers of "specific" neurohumoral activation. However, the question of whether an elevation in DLIA may consequently modulate mechanisms of insulin secretion, insulin sensitivity, vascular reactivity and other Ca2+i-dependent mechanisms remains speculative. (Tab. 4, Fig. 4, Ref. 41).

Blood Glucose↗
PubMed1997

[Plasminogen activator inhibitor (PAI-1) and diabetes mellitus. I. Regulation of PAI-1 levels].

Elevated PAI-1 levels were described in different insulin resistant conditions, incl. diabetes mellitus type II. In its formation probably several stimulating factors participate. Hitherto accomplished studies suggest not only the important effect of insulin acting synergically with very low density. lipoproteins (VLDL) on hepatocytes but also the importance of the endothelial pool where the action of proinsulin, VLDL and cytokines in synergy with Cai-dependent stimuli (oxidation stress, thrombin) is involved. Under certain circumstances also another adipocyte compartment may play a role, and a significant role of thrombocytes in raising the PAI-1 level cannot be ruled out either. A more detailed analysis of the raised PAI-1 level in different patients could extend the possibilities of therapeutic reduction of levels of this important risk factor of atherosclerosis.

Diabetes Mellitus, Type 2↗