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T Kovacs

Publications and source records attributed to T Kovacs.

At least 19 recordsLinked to original sources
PubMed2002

A(2) adenosine receptors regulate CFTR through PKA and PLA(2).

We investigated adenosine (Ado) activation of the cystic fibrosis transmembrane conductance regulator (CFTR) in vitro and in vivo. A(2B) Ado receptors were identified in Calu-3, IB-3-1, COS-7, and primary human airway cells. Ado elevated cAMP in Calu-3, IB-3-1, and COS-7 cells and activated protein kinase A-dependent halide efflux in Calu-3 cells. Ado promoted arachidonic acid release from Calu-3 cells, and phospholipase A(2) (PLA(2)) inhibition blocked Ado-activated halide efflux in Calu-3 and COS-7 cells expressing CFTR. Forskolin- and beta(2)-adrenergic receptor-stimulated efflux were not affected by the same treatment. Cytoplasmic PLA(2) (cPLA(2)) was identified in Calu-3, IB-3-1, and COS-7 cells, but cPLA(2) inhibition did not affect Ado-stimulated cAMP concentrations. In cftr(+) and cftr(-/-) mice, Ado stimulated nasal Cl(-) secretion that was CFTR dependent and sensitive to A(2) receptor and PLA(2) blockade. In COS-7 cells transiently expressing DeltaF508 CFTR, Ado activated halide efflux. Ado also activated G551D CFTR-dependent halide efflux when combined with arachidonic acid and phosphodiesterase inhibition. In conclusion, PLA(2) and protein kinase A both contribute to A(2) receptor activation of CFTR, and components of this signaling pathway can augment wild-type and mutant CFTR activity.

Adenylyl Cyclases↗
PubMed2001

Physiological responses to mixing in large scale bioreactors.

Escherichia coli fed-batch cultivations at 22 m3 scale were compared to corresponding laboratory scale processes and cultivations using a scale-down reactor furnished with a high-glucose concentration zone to mimic the conditions in a feed zone of the large bioreactor. Formate accumulated in the large reactor, indicating the existence of oxygen limitation zones. It is suggested that the reduced biomass yield at large scale partly is due to repeated production/re-assimilation of acetate from overflow metabolism and mixed acid fermentation products due to local moving zones with oxygen limitation. The conditions that generated mixed-acid fermentation in the scale-down reactor also induced a number of stress responses, monitored by analysis of mRNA of selected stress induced genes. The stress responses were relaxed when the cells returned to the substrate limited and oxygen sufficient compartment of the reactor. Corresponding analysis in the large reactor showed that the concentration of mRNA of four stress induced genes was lowest at the sampling port most distant from the feed zone. It is assumed that repeated induction/relaxation of stress responses in a large bioreactor may contribute to altered physiological properties of the cells grown in large-scale bioreactor. Flow cytometric analysis revealed reduced damage with respect to cytoplasmic membrane potential and integrity in cells grown in the dynamic environments of the large scale reactor and the scale-down reactor.

Acetic Acid↗
PubMed2001

The new proton pump inhibitor esomeprazole is effective as a maintenance therapy in GERD patients with healed erosive oesophagitis: a 6-month, randomized, double-blind, placebo-controlled study of efficacy and safety.

BACKGROUND: Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor to be developed as an optical isomer. In patients with erosive oesophagitis, esomeprazole has produced significantly greater healing rates and improved symptom resolution vs. omeprazole. AIM: This study assesses the efficacy of esomeprazole for preventing relapse in patients with healed oesophagitis. METHODS: In this 6-month US multicentre randomized double-blind placebo-controlled trial, 375 Helicobacter pylori-negative patients with endoscopically healed oesophagitis received esomeprazole 40 mg, 20 mg, 10 mg, or placebo once daily. The primary efficacy end-point was maintenance of healing at 6 months. Secondary end-points assessed changes in symptoms, and long-term safety and tolerability. RESULTS: Significantly (P < 0.001) more patients remained healed with esomeprazole 40 mg (87.9%), 20 mg (78.7%), or 10 mg (54.2%), than with placebo (29.1%). Relapse, when it occurred, was later with esomeprazole. Sustained resolution of heartburn was observed in the 40 mg and 20 mg groups; there was a high correlation between absence of heartburn and maintenance of healing. Adverse effects were mild, infrequent and not significantly different between groups. CONCLUSIONS: Esomeprazole is effective and well-tolerated in the maintenance of healing of erosive oesophagitis. Esomeprazole 40 mg and 20 mg offer significant clinical benefit to patients.

Administration, Oral↗
PubMed2001

FISH assessment of aneuploidy frequencies in mature and immature human spermatozoa classified by the absence or presence of cytoplasmic retention.

Previously, a relationship has been found between diminished cellular maturity of human spermatozoa and low-level expression of the testis-specific chaperone protein, HspA2. Because HspA2 is a component of the synaptonemal complex in rodents, and assuming that this is also the case in men, it was postulated that the frequency of chromosomal aneuploidies would be higher in immature versus mature spermatozoa. This question was examined in spermatozoa from semen and from 80% Percoll pellets (enriched for mature spermatozoa) of the same ejaculate in 10 oligozoospermic men. Immature spermatozoa with retained cytoplasm, which signifies spermiogenetic arrest, were identified by immunocytochemistry. Using fluorescence in-situ hybridization (FISH), approximately 7000 sperm nuclei were evaluated in each of the 20 fractions (142 086 spermatozoa in all) using centromeric probes for the X, Y and 17 chromosomes. The proportions of immature spermatozoa were 45.4 +/- 3.4 versus 26.6 +/- 2.2% in the two semen versus the Percoll groups (medians: 48.2 versus 25%, P < 0.001, n = 300 spermatozoa per fraction, total 6000 spermatozoa). There was also a concomitant decline in total disomy, total diploidy and total aneuploidy frequencies in the 80% Percoll versus semen fractions (0.17 versus 0.54%, 0.14 versus 0.26% and 0.31 versus 0.81% respectively, P < 0.001 in all comparisons). The mean decline of aneuploidies was 2.7-fold. With regard to the hypothesis that aneuploidies are related to sperm immaturity, there was a close correlation between the incidence of immature spermatozoa and disomies (r = 0.7, P < 0.001) but no correlation with diploidies (r = 0.03), indicating that disomies originate primarily in immature spermatozoa. It is suggested that the common factor underlying sperm immaturity and aneuploidies is the diminished expression of HspA2. In addition, the lack of this chaperone may also cause diminished cellular transport of proteins, such as DNA-repair enzymes or of the retention of cytoplasm that is extruded from normally maturing spermatozoa during spermiogenesis.

Aneuploidy↗
PubMed1998

Factors associated with atrial fibrillation in patients with mitral stenosis: a cardiac catheterization study.

Atrial fibrillation (AF) is frequently found in association with rheumatic mitral valve disease. To study the interrelation of factors contributing to the risk of AF in patients with mitral stenosis, we examined a cardiac catheterization database of a series of 314 patients. Patients with AF were older, 53.4 +/- 6.1 years versus 51.7 +/- 7.2 years (p = 0.03), and had a lower cardiac index, 2.3 +/- 0.6 L/min/m2 versus 2.6 +/- 0.7 L/min/m2 (p = 0.0002), than patients in sinus rhythm at catheterization. The mitral valve area was significantly smaller in patients with AF than in patients in sinus rhythm, 1.2 +/- 0.5 cm2 versus 1.6 +/- 0.7 cm2 (odds ratio 1.40/0.25 cm2 decrease; p = 0.0001) as was mitral valve index. The pressure-AF association with the highest statistical significance was seen with mean right atrial pressure, 10.6 +/- 4.9 mm Hg versus 7.6 +/- 3.8 mm Hg (odds ratio 2.24; p < 0.0001). Other variables with significant positive associations by univariate analysis were pulmonary artery wedge pressure, pulmonary artery mean pressure, and pulmonary resistance. When stepwise logistic multiple regression analysis was performed, the results indicated that both severity of mitral stenosis and increased right atrial pressure were independently associated with AF in this population with mitral stenosis. After adjustment was performed for these variables, age was not independently associated with AF.

Adult↗
PubMed1998

Gastric metaplasia of the duodenum: identification by an endoscopic selective mucosal staining technique.

BACKGROUND: To understand the pathophysiology of duodenal ulcer disease, it is important to identify and quantitate gastric metaplasia of the duodenum. Methylene blue dye is absorbed well by intestinal mucosa, but not by gastric mucosa. Our aim was to validate a methylene blue staining technique for measurement of gastric metaplasia in the duodenum. METHODS: Eight subjects with chronic duodenal ulcer disease and seven subjects with other upper intestinal disorders underwent duodenal methylene blue staining after application of a mucolytic agent. Biopsy specimens were obtained from blue-stained and pale unstained areas and assessed for gastric metaplasia histologically. RESULTS: Pink or pale unstained duodenal areas had more gastric surface cell metaplasia than blue-stained areas. Unstained duodenum was also more likely to have extensive (more than 25% of the biopsy specimens) gastric metaplasia (60%) than blue-stained areas (9%). Subjects with duodenal ulcer disease had more unstained mucosa than controls. CONCLUSION: Methylene blue staining of the duodenum is useful to identify and quantitate gastric metaplasia.

Aged↗
PubMed1997

The platelet Ca2+ transport ATPase system.

The Ca2+ signal accompanying cell function involves the activities of plasma membrane Ca2+ transport ATPases (PMCA) which transport Ca2+ ions out of the cell and those of sarco/endoplasmic reticulum Ca2+ transport ATPases (SERCA), which pump Ca2+ ions into intracellular Ca2+ pools. Although a platelet Ca2+ transport ATPase was described three decades ago, for a long time it remained poorly understood in terms of its cellular localization and identity. By integrating data obtained during recent years, including newly available information in the literature for the PMCAs and aspects of our work concerning the SERCAs, the present review will show how the overall view of the platelet Ca2+ATPase system has to be modified due to the presence of a number of Ca2+ATPases in these cells. These Ca2+ATPases include a typical 144 kDa PMCA protein, although its molecular identity still remains to be established, expressed together with a multi-SERCA system constituted by the ubiquitous 100 kDa SERCA 2b isoform, the 97 kDa SERCA 3 isoform and a new 97 kDa SERCA isoform recognized by the monoclonal antibody termed PL/IM 430 which also remains to be identified. The new paradigm of the platelet multi-Ca2+ATPase system will be discussed including: (i) the problems solved, as it has now become possible to reconciliate previous contradictory observations and (ii) those which still remain due to the fact that the platelet Ca2+ATPase system is more complex than previously assumed. Finally, to put this complexity of the platelet Ca2+ transport ATPase system into perspective, the biological significance of the multi-SERCA system in the context of Ca2+ signalling will be tentatively discussed in an attempt to produce a model of the organization of the intracellular Ca2+ pools in platelets.

Journal Article↗
PubMed1996

Spontaneous haematoma of the umbilical cord with a single umbilical artery.

A rare example of the partial rupture of the umbilical vein resulting in a cord haematoma is reported. CTG alterations made possible to anticipate the deterioration of the foetal condition and a healthy infant was delivered by emergency caesarean section. Cross sections of the umbilical cord revealed the lack of one of the umbilical arteries and the haematoma having interfered with the foetal circulation.

Adult↗
PubMed1996

Altered thermoregulatory responses to clonidine in streptozotocin-diabetic rats.

1. The effects of streptozotocin (STZ) treatment on alpha 2-adrenoceptor regulation of body temperature were studied by monitoring the response of colonic temperature to administration of clonidine. 2. A dose-dependent fall in colonic temperature occurred in control rats given clonidine challenge (0.05-2.0 mg kg-1, s.c.); this response was inhibited by prior administration of either yohimbine or idazoxan (2 mg kg-1, s.c.) but not by the peripherally-acting alpha 2-adrenoceptor antagonist L-659,066 (10 mg kg-1, s.c.). 3. In rats treated with STZ (65 mg kg-1, i.v.) administration of clonidine elicited a dose-independent hyperthermia (circa 1 degree C.); this effect was unaltered by prior administration of yohimbine or idazoxan. 4. Naloxone (5 mg kg-1, s.c.) elicited a small fall in temperature (< 1 degree C.) in both control and STZ-treated rats; naloxone pretreatment did not alter the temperature response to clonidine in either group. 5. Nicotinic acid (10 mg kg-1, s.c.) caused a similar small elevation in temperature in both groups. 6. Administration of replacement insulin to STZ-treated rats maintained weight gain and low blood glucose while the thermoregulatory response to clonidine slowly reverted to normal. 7. These results show that altered central temperature control is an element of the generalised abnormality of alpha 2-receptor function induced by STZ.

Adrenergic alpha-Agonists↗
PubMed1995

Role of calcium loading in early afterdepolarizations generated by Cs+ in canine and guinea pig Purkinje fibers.

INTRODUCTION: Our previous observations indicate that the Na+:Ca2+ exchange current (INa:Ca) plays an important role in early afterdepolarizations occurring at more negative Vm (L-EAD). The purpose of these studies was to examine the role of Ca(2+)-loading, which stimulates INa:Ca, in generation of L-EAD. METHODS AND RESULTS: Purkinje strands and preparations of ventricular myocardium from dogs and guinea pigs were superfused with oxygenated physiologic buffer solutions at 37 degrees C. To induce EADs, [K+]o was reduced to 2.0 to 3.0 mM and [Cs+]o (3.6 to 4.0 mM) was added at slow rates of < or = 0.3 Hz. Isometric contraction in canine Purkinje strands and guinea pig papillary muscles doubled in 1-hour exposure to Cs+ and low [K+]o at slow rates and the uptake of 45Ca2+ was approximately doubled after 30 minutes. Forty-three percent of Purkinje fibers developed L-EAD after a latent period of 17 to 123 minutes of exposure. Ouabain (0.2 microM) suppressed L-EAD within 10 minutes reversibly. Ca(2+)-loading (low [Na+]o or high [Ca2+]o) for 5 to 10 minutes before exposure to Cs+, low [K+]o, and slow rates resulted in rapid development of L-EAD in all preparations during subsequent exposure. In Ca(2+)-loaded preparations, delayed afterdepolarizations (DADs) as well as L-EADs developed. CONCLUSIONS: Reduction of K+ currents with Cs+, low [K+]o, and slow rates induced L-EAD in a fraction of Purkinje fibers after a latent period during which Ca(2+)-loading of the sarcoplasmic reticulum occurred, while fibers preloaded with Ca2+ developed L-EAD rapidly and uniformly. These findings indicate that Ca(2+)-loading is a critical condition for the development of L-EAD. Early suppression of L-EAD by ouabian suggests a dependence of L-EAD on low [Na+]i. These findings implicate INa:Ca in the generation of L-EAD.

Animals↗
PubMed1994

Correlated expression of the 97 kDa sarcoendoplasmic reticulum Ca(2+)-ATPase and Rap1B in platelets and various cell lines.

Evidence has accumulated that cyclic AMP (cAMP)-induced phosphorylation of a Ras-related protein (Rap1) regulates platelet Ca2+ transport. As this transport was recently found to be controlled by two isoforms of sarcoendoplasmic reticulum Ca(2+)-ATPase (SERCA), the 100 kDa SERCA2b and the newly identified 97 kDa SERCA, we attempted to establish which isoform is involved in this regulation. For this purpose, we studied the expression and regulation of both the SERCA and Rap1 isoforms in platelets, haemopoietic cells and various cancer cell lines. SERCA2b was shown to be equally expressed in all the cell lines tested, as determined by detection of its phosphoenzyme formation and by Western blotting using an isoform-specific antibody. In contrast, the expression of the 97 kDa SERCA, studied by the same methods, varied from total absence in the cancer cells to high levels in the megakaryocytic cell lines. With regard to the potential regulatory Rap1 proteins, Western blotting showed different expression of total Rap1 isoforms among the cell lineages, thus ruling out any possible relationship between Rap1 and SERCA2b. However, the expression of Rap1 proteins correlated with that of the 97 kDa SERCA isoform. More refined analysis of the rap1A and rap1B isoforms by reverse transcription PCR and by determining cAMP-induced phosphorylation of Rap1B, i.e. its functional mechanism, confirmed the correlation between Rap1B and the 97 kDa SERCA expression. This relationship was also established by the concerted up-regulation of these two proteins demonstrated in the pathological model of platelets from hypertensive rats. It is concluded that the expressions of 97 KDa SERCA and Rap1B are related, suggesting that regulation of the platelet Ca(2+)-ATPase system by cAMP-induced phosphorylation of Rap1B specifically involves the 97 kDa SERCA.

Animals↗
PubMed1993

Resolution of coronary ischemic syndrome due to dislodgement of intraluminal thrombus during diagnostic cardiac catheterization.

Dislodgement of an intraluminal coronary thrombus occurred in a patient with unstable angina during diagnostic cardiac catheterization. The thrombus propagated into the systemic circulation without clinical manifestation of embolism. The procedure rendered the patient asymptomatic. The case illustrates the role of intraluminal coronary thrombus in unstable angina.

Angina, Unstable↗
PubMed1992

[Late reinterventions after the surgical treatment of gastric and duodenal ulcer].

A number of 87 reinterventions performed during a 5-year-period for late complications of the gastric and duodenal ulcer surgery are analysed. In most of them (64 cases), the cause of the reintervention was a postoperative ulcer. A long afferent loop (6 cases), the dumping syndrome (4 cases), the stenosis of the anastomosis opening (6 cases) and the primitive neoplasm of the gastric stump (7 cases) represented other causes of reintervention. The immediate postoperative results were very good and good in 69 cases. The risks related to the specific character of this surgery materialized themselves in 14 postoperative complications (anastomotic fistulas, haemorrhages from the anastomosis, stress ulcers etc.), which required iterative operations; the postoperative death rate attained 3.4%. The analysis of these postgastrectomy syndromes is an opportunity to discuss about the failure factors in the surgery of the gastric and duodenal ulcer, the possibilities of exploration and the principles which should guide the reparative therapy.

Adult↗
PubMed1991

[Cephalic duodenopancreatectomy with preservation of the pylorus in treating a malignant tumor of Vater's ampulla].

The paper reports on the clinical observation of a patient with mechanical jaundice in which the biliary obstruction was caused by an ampulla of Vater. Cephalic duodenopancreatectomy with preservation of the pylorus was used. Distally the duodenum was excised to its intersection with the mesenteric vessels. For recovery of the digestive circuits, a loop excluded "en Y" à la Roux ascending transmesocolically was used. The anastomoses had the following stages: choledochojejunostomy (T-T) the most proximal; pancreatic-jejunal anastomosis (T-L); and the most distal, the duodeno-jejunal one (T-L). After surgery, the evolution was good, and the patient left the hospital with the wound cured. Starting from this observation, the authors discuss aspects connected with the technique of cephalic duodenopancreatectomy with or without preservation of the pylorus.

Adenocarcinoma↗
PubMed1990

Inhibition of the RNA polymerase of vesicular stomatitis virus by ppp5'A2'p5'A and related compounds.

The diadenylate triphosphates ppp5'A2'p5'A and ppp5'A3'p5'A were found to inhibit the purified RNA polymerase ('nucleocapsid') complex from vesicular stomatitis virus (VSV). The corresponding diadenylate monophosphate p5'A2'p5'A did not inhibit, nor did the triadenylate triphosphate ppp5'A2'p5'A2'p5'A; the diadenylate diphosphate pp5'A2'p5'A had intermediate inhibitory activity. Increasing the concentration of ATP, GTP or CTP in the reaction mixture decreased inhibition by ppp5'A2'p5'A, while UTP had minimal or no protective effect. ppp5'A2'p5'A did not protect the RNA polymerase from inactivation by N-ethylmaleimide. This suggests that the action of ppp5'A2'p5'A occurs at a site on the enzyme that is distinct from the N-ethylmaleimide-protecting, ATP-binding site characterized previously.

Adenine Nucleotides↗