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J Heger

Publications and source records attributed to J Heger.

At least 19 recordsLinked to original sources
PubMed2006

Repression of anti-apoptotic genes via AP-1 as a mechanism of apoptosis induction in ventricular cardiomyocytes.

Nitric oxide (NO) is increased under several pathophysiological, mainly inflammatory processes in the heart and has been characterized as an inducer of apoptosis in cardiomyocytes. The transcription factor activating protein-1 (AP-1) has been identified as a mediator of NO-induced apoptosis. Genes that are regulated by AP-1 under apoptotic conditions have not been identified yet. Therefore, we performed a microarray analysis with subsequent real-time polymerase chain reaction (PCR) to identify genes regulated by AP-1 in NO-induced ventricular cardiomyocytes of rats and tested the functional role of these genes in apoptosis. Cardiomyocytes were transformed with AP-1 decoy oligonucleotides for inhibition of AP-1 activity. These, as well as non-transformed control cells, were stimulated with the NO donor (+/-)-S-nitroso-N-acetylpenicillamine (SNAP, 100 microM) for 2 h. Some of the genes with differential gene expression on microarrays were further analysed by real-time PCR. Genes that are induced by SNAP were not identified. However, four genes, pyridoxal kinase, heat shock protein 10 (Hsp10), antigen identified by monoclonal antibodies 4F2 (4F2) and myosin light chain 2, were downregulated by SNAP in presence of AP-1. Pyridoxal kinase, Hsp10 and 4F2 have anti-apoptotic effects in unstimulated cells because downregulation of their expression by antisense oligos induced apoptosis in cardiomyocytes. An involvement of these genes in NO-induced apoptosis could only be proven for pyridoxal kinase. In conclusion, using microarray technology, we identified three anti-apoptotic genes (Hsp10, 4F2 and pyridoxal kinase) in ventricular cardiomyocytes, which may help the cells to resist some apoptotic stimuli. The downregulation of these genes results in cardiomyocyte apoptosis. Prevention of their downregulation may protect cardiomyocytes against apoptotic stimuli, and this may be of therapeutic benefit.

Animals↗
PubMed2006

Angiotensin II stimulates apoptosis via TGF-beta1 signaling in ventricular cardiomyocytes of rat.

Elevations in angiotensin II (AngII) and transforming growth factor (TGF-beta1) levels are often found under conditions leading to progression of heart failure. From several studies, it is evident that AngII enhances TGF-beta1 expression via activator protein 1 (AP-1) activation, and that this pathway is involved in hypertrophic growth of the heart muscle and in the development of cardiac fibrosis. We now continued characterization of the signaling pathway stimulated by AngII in ventricular cardiomyocytes of rat and analyzed if the enhancement of TGF-beta1 expression by AngII may also contribute to apoptosis induction, which is another predictor of heart failure progression. Stimulation of cardiomyocytes with 100 nM AngII for 2 h activated the transcription factors AP-1 and GATA by 68.6+/-23.9 or 70.7+/-9.8%. Induction of both factors was mediated by p38 mitogen-activated protein kinase (MAPK) because it was totally blocked using a specific inhibitor of the kinase (SB202190). When GATA was inhibited by transformation of cardiomyocytes with decoy oligonucleotides, AngII could not enhance TGF-beta1 expression. This inhibition was observed on the mRNA level in real-time polymerase chain reaction and on the protein level in Western blots. As a consequence, upon AngII stimulation for 24 h, release of TGF-beta1 from cardiomyocytes was also reduced from 240.5+/-50.4 to 130.5+/-22.1% (p<0.05). In contrast to the early induction of GATA and AP-1, the transcription factor similar to mothers against decapentaplegic homolog (SMAD) was induced by AngII after 24 h. This stimulation was dependent on TGF-beta1 because it was blocked by antibodies specific for TGF-beta1. Twenty-four hours after AngII addition, the number of apoptotic cardiomyocytes increased by 6.5+/-1.2%, and this apoptosis induction was blocked when SMAD activity was inhibited by transformation of cardiomyocytes with SMAD decoy oligonucleotides. In conclusion, the transcription factors AP-1 and GATA are activated by p38 MAPK upon AngII stimulation, and both are needed to enhance TGF-beta1 expression in ventricular cardiomyocytes. TGF-beta1 acts in an autocrine loop on the cells to induce apoptosis via SMAD signaling. Thus, the often-found correlation between AngII, TGF-beta1, AP-1, and SMAD in pathogenesis of heart disease reflects the proapoptotic signaling pathway induced by AngII in cardiomyocytes.

Angiotensin II↗
PubMed2004

[Slovak nomenclature of organic chemistry].

The paper describes the beginnings of Slovak nomenclature of organic compounds and the application of CNOC IUPAC rules in the Slovak language, comparing the different conditions of the origin of national nomenclature in the Czech and Slovak parts of former Czechoslovakia.

Chemistry, Organic↗
PubMed2003

Efficiency of amino acid utilization in the growing pig at suboptimal levels of intake: branched-chain amino acids, histidine and phenylalanine + tyrosine.

Five balance experiments on growing pigs were carried out to study the marginal efficiency of utilization of isoleucine, leucine, valine, histidine and phenylalanine + tyrosine and to estimate their requirements for maintenance. Purified diets based on casein and crystalline amino acids as the sole source of N contained graded levels of each amino acid, corresponding to protein accretion rates of 0, 33, 66, 99 and 132 g/day, respectively. All other essential amino acids were given in a 30% excess. N retention increased linearly (p < 0.01) as the dietary concentration of the limiting amino acid increased. Based on linear regression equations relating amino acid deposition in body protein to amino acid intake, marginal efficiencies of ileal digestible amino acid utilization were calculated to be isoleucine - 0.81, leucine - 0.81, valine - 0.82, histidine - 1.17 and phenylalanine + tyrosine - 0.67. Extrapolating the regression equations to zero N retention, the daily requirements of amino acids for N equilibrium were estimated to be (mg/kg0.75) isoleucine - 18, leucine - 33, valine - 23, histidine - 14 and phenylalanine + tyrosine - 43.

Amino Acids, Essential↗
PubMed2002

Efficiency of amino acid utilization in the growing pig at suboptimal levels of intake: lysine, threonine, sulphur amino acids and tryptophan.

A series of N balance experiments using growing pigs was conducted to study the efficiency of utilization of lysine, threonine, sulphur amino acids and tryptophan and to estimate their maintenance requirements. Purified diets based on casein and crystalline amino acids as the sole source of N contained graded levels of each amino acid, corresponding to expected protein accretion rate of 0, 33, 66, 99 and 132 g/day, respectively. N retention increased linearly (p < 0.01) as the dietary concentration of the limiting amino acid increased. Based on linear regression equations relating amino acid deposition in body protein to amino acid intake, marginal efficiencies of ileal digestible amino acid utilization were calculated to be lysine 0.91, threonine 0.83, sulphur amino acids 0.85 and tryptophan 0.66. Extrapolating the regression equations to zero N retention, the daily requirements of amino acids for N equilibrium were estimated to be (mg/kg(0.75)) lysine 39, threonine 49, sulphur amino acids 46 and tryptophan 16.

Amino Acids↗
PubMed2001

Effect of nonessential amino acids on nitrogen retention in growing pigs fed on a protein-free diet supplemented with sulphur amino acids, threonine and tryptophan.

Two N balance experiments were conducted on growing pigs to study the effect of essential and nonessential amino acids added to a protein-free diet on N retention. In Expt. 1, the addition of sulphur amino acids, threonine and tryptophan to a protein-free diet at levels two times the maintenance requirements reduced (p > 0.1) daily N loss from -131 to -108 mg/kg(0.75). A further addition of nonessential amino acids equivalent to 250 mg N/kg(0.75)/d resulted in a marked increase (p < 0.01) in daily N retention to 28 mg/kg(0.75). In Expt. 2, nonessential amino acids were added to a protein-free diet supplemented with sulphur amino acids, threonine and tryptophan at levels corresponding to 100, 200 and 300 mg N/kg(0.75)/d. N retention increased linearly as dietary nonessential N increased. The slope of the best-fit regression line indicated that the marginal efficiency of nonessential N utilization for protein accretion was 0.26. The results suggest that nonessential amino acids may be a limiting factor for the re-utilization of amino acids released by body protein breakdown or that they may serve as precursors for de novo synthesis of amino acids by gut microorganisms, thus contributing to the amino acid requirements of the pig.

Amino Acids↗
PubMed2000

Post-translational modification of the myxoma-virus anti-inflammatory serpin SERP-1 by a virally encoded sialyltransferase.

SERP-1 is a secreted serpin (serine-proteinase inhibitor) encoded by myxoma virus, a poxvirus pathogen of rabbits. SERP-1 is required for myxoma-virus virulence, and the purified protein has been shown to possess independent anti-inflammatory activity in animal models of restenosis and antigen-induced arthritis. As an inhibitor of serine proteinases, SERP-1 acts against tissue-type plasminogen activator, urokinase-type plasminogen activator, plasmin, thrombin and Factor Xa. In the present study, examination of SERP-1 glycosylation-site mutants showed that the N-linked glycosylation of Asn(172) was essential for SERP-1 secretion, whereas mutation of Asn(99) decreased secretion efficiency, indicating that N-linked glycosylation plays an essential role in the processing and trafficking of SERP-1. Furthermore, comparison of SERP-1 from wild-type myxoma virus and a virus containing a targeted disruption of the MST3N sialyltransferase locus demonstrated that SERP-1 is specifically modified by this myxoma-virus-encoded sialyltransferase, and is thus the first reported viral protein shown to by modified by a virally encoded glycosyltransferase. Sialylation of SERP-1 by the MST3N gene product creates a uniquely charged species of secreted SERP-1 that is distinct from SERP-1 produced from other eukaryotic expression systems, though this has no apparent effect upon the kinetics of in vitro proteinase inhibition. Rather, the role of viral sialylation of SERP-1 likely relates to masking antigenicity or targeting SERP-1 to specific sites of action in vivo.

Amino Acid Sequence↗
PubMed2000

[Conventional thrombendarterectomy with carotid patch plasty vs. eversion endarterectomy: technique, indications and results].

We report our experience with carotid surgery during the past 11 years and a prospective randomized study on 600 patients with conventional thromb-endarterectomy (TEA) versus eversion-endarterectomy (EEA). First results gave EEA a slight advantage, which could not be proved in the following years. Both methods are equivalent in terms of postoperative and long-term results. Follow-up showed one difference between the two methods: Restenosis occurred more often in the TEA-group (14.7% TEA versus 6.5% EEA). The frequency of symptomatic restenosis was the same in both groups (3.8% TEA versus 3.9% EEA). EEA did not show late restenosis. We attribute this to the avoidance of patch-suture and the introduction of patch material, as was observed by other authors. No ruptures of venous patches occurred in our study after primary implantation, while two venous grafts ruptured after substitution of an infected Dacron patch. Infection rate for the Dacron patch was below 0.2% and is therefore negligible. Duplex-ultrasound is indispensable in evaluating plaque-morphology, although sensitivity is low in the detection of dangerous atherosclerotic lesions (73.4% for the soft plaque, 31.9% for ulcerations). In view of these results and a critical analysis of the current literature, we see slight advantages for EEA over TEA inspite of equivalent operative results. However, EEA is a suitable procedure only in connection with subtile intraoperative control and in the hand of an experienced surgeon.

Angiography↗
PubMed1998

Effect of essential:total nitrogen ratio on protein utilization in the growing pig.

Two N balance experiments using growing pigs were conducted to study the effect of essential:total (E:T) N ratio on N retention and utilization. Purified diets contained casein and crystalline amino acids as the sole sources of N. E:T values ranged from 0.25 to 0.86 while either the concentration of total N (Expt. 1) or essential N (Expt 2) was kept constant. At a constant concentration of total dietary N, N retention and total N utilization were maximized with an E:T value of approximately 0.6, while essential N utilization gradually decreased as E:T increased. At a constant level of essential N, N retention remained unchanged until the E:T value reached 0.48 and then decreased. In Expt 2, maximum total N utilization was attained with an E:T value of 0.66 while N excretion and essential N utilization decreased with increased E:T value. These results suggest that under conditions of optimal protein utilization, essential amino acids are partially degraded and used for the synthesis of non-essential amino acids.

Amino Acids↗
PubMed1990

Sequence of amino acid limitation in triticale.

Nitrogen balance experiments were conducted on growing rats to study the sequence of limitation of amino acids in triticale protein. All essential amino acids were added to a triticale-based diet to adjust their total dietary levels to 110% of the requirement. From this complete supplement, individual amino acids were successively removed and nitrogen balance (NB) and biological value of protein (BV) were measured. Based on the extent of response to removal of amino acids, the sequence of limitation was determined to be lysine, threonine, methionine and valine. The removal of histidine, isoleucine or tryptophan had no effect on NB or BV.

Amino Acids↗
PubMed1990

Sequence of amino acid limitation in triticale.

Nitrogen balance experiments were conducted on growing rats to study the sequence of limitation of amino acids in triticale protein. All essential amino acids were added to a triticale-based diet to adjust their total dietary levels to 110% of the requirement. From this complete supplement, individual amino acids were successively removed and nitrogen balance (NB) and biological value of protein (BV) were measured. Based on the extent of response to removal of amino acids, the sequence of limitation was estimated to be lysine, threonine, methionine and valine. The removal of histidine, isoleucine or tryptophan had no effect on NB or BV.

Amino Acids↗
PubMed1990

Estimation of optimum amino acid supplements to triticale.

Based on the nitrogen balance (NB) data and the efficiency of amino acid utilization, optimum supplements of limiting amino acids (AA) to triticale were calculated and their effect on true N digestibility (TD), biological value of protein (BV) and net protein utilization (NPU) of a triticale-based diet was evaluated. To determine if AA balance must be considered in the calculation of the optimum supplements, the effect of a 20% or 40% excess of essential AA in lysine-, methionine-, threonine- or tryptophan-deficient diets was also studied. The AA excess had no significant effect on NB in diets deficient in lysine, methionine or threonine. However, NB in rats fed on the tryptophan-deficient diet increased as the AA excess increased. BV of the diet containing the optimized supplements of lysine, threonine, methionine and valine was comparable to that of lactalbumin or to the diet supplemented with all essential AA. The deletion of valine from the optimized supplement caused an insignificant decrease in BV. Due to the lower TD, NPU of diets containing the optimized AA supplements was lower than that of the diet containing all essential AA or of the lactalbumin-based diet.

Amino Acids↗
PubMed1990

Non-essential nitrogen and protein utilization in the growing rat.

Three series of nitrogen-balance experiments were carried out on growing rats fed on purified isonitrogenous diets (16 g N/kg) to study the importance of non-essential N and the essential:total N (E:T) ratio for attaining maximum N balance (NB) and biological value (BV) of protein. Minimum dietary levels of asparagine, proline and glutamic acid required for maximum NB and BV were estimated to be 1.0, 2.0 and 5.0 g/kg respectively. In an essential amino acid-based diet, the levels of individual amino acids were successively reduced to 110% of the requirement. Reducing the level of arginine, lysine or methionine + cystine resulted in a significant increase in NB and BV while the response of rats given the isoleucine-reduced diet significantly decreased. Addition of asparagine, proline and glutamic acid in the estimated minimum amounts to an essential amino acid-based diet resulted in a significant increase in NB and BV. A further significant increase was found when the levels of arginine, lysine and methionine + cystine in the diet were reduced to 110% of the requirement. The performance of rats fed on the latter diet was similar to that of rats given a diet with the optimum E:T ratio. It is concluded that the optimum protein utilization may be influenced by the presence of some non-essential amino acids and by the surplus of some essential amino acids rather than by the E:T ratio per se.

Amino Acids, Essential↗
PubMed1986

Weight gain, feed conversion efficiency and plasma free lysine as response criteria in evaluating supplements of lysine plus threonine and lysine plus tryptophan to deficient diets for rats.

Two experiments were conducted on growing male SPF-rats to compare weight gain, feed conversion efficiency and plasma free lysine concentration as response criteria in evaluating adequacy of lysine plus threonine and lysine plus tryptophan supplements to the deficient diets. Two basal semisynthetic diets were prepared limiting in lysine and threonine (Expt. 1) and lysine and tryptophan (Expt. 2). The addition of graded supplements to the basal diets of L-lysine X HCl alone (0.2; 0.4; 0.6; 0.8 and 1.0% of diet) induced imbalance of amino acids resulting in low level of daily weight gain and feed conversion efficiency. Plasma free lysine concentration started to grow linearly from the first supplement of L-lysine X HCl. If rats were fed the diets containing identical supplements of L-lysine X HCl in combination with two supplements of L-threonine (0.2 and 0.4% of diet, Expt. 1) or L-tryptophan (0.05 and 0.1% of diet, Expt. 2), plasma free lysine started to increase before supplements of amino acids were adequate to support maximum weight gain and feed conversion efficiency. this difference in response seems to be caused by different feeding regiment during the growth period of the experiments (ad libitum) and training period prior to blood sampling (feeding twice daily).

Animal Feed↗
PubMed1985

Efficiency of utilization of essential amino acids in growing rats at different levels of intake.

Nitrogen balance was studied in growing male SPF-rats fed on diets in which each essential amino acid was varied from zero to about 120% of optimum requirement. From the balance results, optimum and maintenance requirements were estimated as well as the efficiency of utilization of amino acids for growth and growth + maintenance. N balance increased with increasing dietary level of the deficient amino acid; the response gradually diminished as the content of the amino acid approached optimum. At zero level of intake, negative N balance was found for all amino acids except histidine. The highest loss of body N was found in the sulphur-amino-acid-free diet and the lowest one in the lysine-free diet. Maximal utilization of essential amino acids for growth was found at dietary levels corresponding to 30-60% of optimum requirement and ranged from about 0.65 to 0.85 except for S amino acids and histidine. The utilization of S amino acids was about 0.55 while that of histidine exceeded 1.0. The utilization of amino acids for growth + maintenance was maximal at the lowest levels of intake and gradually decreased as the dietary concentration of the limiting amino acid increased. At dietary levels near optimum the utilization was about 0.6-0.7, except for S amino acids where the utilization was less than 0.5.

Amino Acids, Essential↗
PubMed1983

Gastric cascade: a diagnosis without clinical importance?

The clinical importance of the radiological diagnosis gastric cascade has been discussed for many years. In the present study, a group of patients with gastric cascades as their only radiologic gastric finding was compared with a group of patients without any pathological radiologic findings in their stomach. No statistically significant difference was found with regard to abdominal symptoms between the two groups. Furthermore, it was shown that even a slight bending of the body is sufficient to eliminate totally a gastric cascade.

Adult↗