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Biomedical subjects

P Hájek

Publications and source records attributed to P Hájek.

At least 19 recordsLinked to original sources

Pregnancy-associated plasma protein A and proform eosinophilic major basic protein in the detection of different types of coronary artery disease.

Kryptor system was proven to be a rapid, standard method for pregnancy-associated plasma protein A and proform eosinophilic major basic protein (PAPP-A/proMBP) complex detection in coronary artery disease (CAD). No age and/or gender differences in 51 controls and 110 stable coronary artery disease (SCAD) patients were found. SCAD patients did not differ from controls and no difference in PAPP-A/proMBP levels with regards to the number of affected vessels was found. In 21 unstable angina pectoris (UAP), in 35 without and 66 with ST elevation acute myocardial infarctions (NSTEMI, STEMI respectively) patients PAPP-A/proMBP levels were increased (P=0.004 and P<0.0005, respectively). PAPP-A/proMBP levels did not correlate with cardiac troponin I (cTnI) in STEMI and NSTEMI patients. PAPP-A/ proMBP increase was more frequent than cTnI (P=0.036) within the early phase of STEMI. In NSTEMI patients PAPP-A/proMBP positivity was present in 50% of cTnI negative cases. Receiver operating characteristic (ROC) analysis revealed the highest diagnostic accuracy of PAPP-A/proMBP (0.919) in STEMI cTnI positive cases. The highest specificity/sensitivity PAPP-A/proMBP levels for particular acute coronary syndrome (ACS) types were 10.65-14.75 mIU/l. Combination of PAPP-A/proMBP with cTnI increases their diagnostic efficacy within the early phase of ACS. Our results suggest that PAPP-A/proMBP complex is involved in processes preceding vulnerable plaque development in ACS.

Acute Coronary Syndrome↗

The role of tissue factor in thrombosis and hemostasis.

The tissue factor (TF) is one of the most important regulators of arterial thrombosis. Because arterial thrombosis is the pathophysiologic background of acute coronary syndrome, the possible impact of blocking the arterial thrombosis on its onset is a challenging problem. The investigations of TF brought a new concept of "cell-based coagulation model" which highlighted the question of blood-borne TF as a source of TF in circulating blood. In this review we summarize essential information on the pathophysiology, molecular structure, expression and distribution of TF and we propose a novel concept of blood-borne TF, suggesting the possibilities of inhibition of the coagulation cascade with newly synthetized drugs.

Animals↗

Clinical and demographic characteristics of psychiatric patients seropositive for Borrelia burgdorferi.

PURPOSE: Borrelia burgdorferi (Bb) infection can affect the central nervous system and possibly lead to psychiatric disorders. We compared clinical and demographic variables in Bb seropositive and seronegative psychiatric patients and healthy controls. METHOD: Nine hundred and twenty-six consecutive psychiatric patients were screened for antibodies to Bb and compared with 884 simultaneously recruited healthy subjects. RESULTS: Contrary to healthy controls, seropositive psychiatric patients were significantly younger than seronegative ones. None of the studied psychiatric diagnostic categories exhibited stronger association with seropositivity. There were no differences between seropositive and seronegative psychiatric patients in hospitalization length, proportion of previously hospitalized patients and proportion of subjects with family history of psychiatric disorders. CONCLUSION: These findings elaborate on potential association between Bb infection and psychiatric morbidity, but fail to identify any specific clinical 'signature' of Bb infection.

Adult↗

[Assessment of speed of an anti-platelet effect after two different doses of acetylsalicylic acid by flocculation].

UNLABELLED: Acetylsalicylic acid inhibits aggregation of blood platelets through affecting arachidon acid metabolism--a precursor of thromboxan which is a strong platelet aggregation inhibitor. A standard method for measurement of aggregation activity blockade (in percents) of platelet rich plasma is turbidimetric aggregomethry based on spectrophotometric principle. According to results of recent studies administration of acetylsalicylic acid is one of the basic pillars of prevention of thrombotic complications in atherosclerotic arterial disease. Acetylsalicylic acid doses differ from study to study. An aim of our work was to measure speed of two different doses of acetylsalicylic acid. RESULTS: Level of aggregation activity blockade in samples of platelet rich plasma was measured by aggregometry in 26 healthy volunteers after administration of four inductors of thrombocyte aggregation (arachidon acid, adenosindiphosphate, collagen, and ristocetin). The samples were taken before administration and 120, 240, and 360 minutes after single peroral administration of 100 or 400 mg of acetylsalicylic acid. Samples of plasma were analysed immediately after sampling. Before drug administration there was no aggregation activity in 27.7% of the sample after arachidon acid administration, 28.3% after ADP administration, 21.5% after collagen administration and 25.3% after ristocetin administration. After administration of 400 mg of acetylsalicylic acid and administration of arachidon acid as an inductor 89.9% of the aggregation activity of the sample was blocked after 120 minutes, 89.6% after 240 minutes, and 90.6% after 360 minutes. After administration of adenosindiphosphate as an inductor 71.7% of the aggregation activity of the sample was blocked after 120 minutes, 68.3% after 240 minutes, and 69.9% after 360 minutes. And, after administration of ristocetin as an inductor 64% of the aggregation activity of the sample was blocked after 120 minutes, 66.4% after 240 minutes, and 54% after 360 minutes. Blockade of aggregation activity after collagen administration was not statistically significant. After administration of 100 mg of acetylsalicylic acid and administration of arachidon acid 83.8% of the aggregation activity of the sample was blocked after 120 minutes, 89.2% after 240 minutes, and 89.6% after 360 minutes. After adenosindiphosphate administration statistically significant blockade of aggregation activity was achieved after 360 minutes in the 56.7% of the sample. Also after collagen administration 42.5% of aggregation activity of the sample was blocked significantly after 360 minutes while ristocetin has not proved to influence aggregation in a statistically significant manner. CONCLUSION: Both doses of acetylsalicylic acid influenced aggregation activity of platelets in a statistically significant manner as soon as after 120 minutes following their peroral administration. However, they had different ability to influence platelets response to alternative ways of activation--by adenosindiphosphate, collagen, and ristocetin. 400 mg dose blocked these ways while 100 mg dose was efficient in blocking these ways after 360 minutes and in case of ristocetin--an inductor used to monitor platelet adhesion ability--100 mg dose has not led to statistically significant blockade at all.

Adenosine Diphosphate↗

[Deferral of coronary intervention based on measurement of myocardial fractional flow reserve].

BACKGROUND: Myocardial fractional flow reserve (FFR) is a useful method in assessment of functional significance of coronary stenosis. Deferral of intervention of angiographically intermediate lesion based on FFR measurement is safe in selected patient population as previously described. The aim of the study was to assess mid-term results after deferring coronary intervention of intermediate lesion in a non-selected patient population with no respect to the extent of coronary artery disease and to the results of stress tests if performed. METHODS: A coronary intervention of angiographically intermediate lesion (40 - 70% according to QCA) was deferred in a group of 50 consecutive patients (33 men, mean age 60.8 +/- 10.2 y.) on the basis of FFR > or = 0.75 (mean FFR 0.89 +/- 0.06). FFR was measured in 62 lesions (mean stenosis diameter 55 +/- 7%, left anterior descending 34 lesions, circumflex artery 13 lesions, right coronary artery 15 lesions). One-vessel disease was presented in 14 pts (28%), 36 pts (72%) presented with multivessel disease (two-vessel disease in 27 pts - 54% and three-vessel disease in 9 pts - 18%). Stress test was positive in 15 pts, in 1 pts. negative, and in 3 pts. non-diagnostic. All-cause mortality, cardiac mortality, non-fatal myocardial infarction (MI) and ischemia driven target vessel revascularization (TLR) were recorded during follow-up. Severity of angina pectoris (CCS classification) and a need for antianginal treatment (beta-blockers, nitrates, calcium channel blockers) at the baseline and at the end of clinical follow-up was recorded. RESULTS: Follow-up was completed in 49 patients (98%). Mean time of follow-up is 15.4 +/- 2 months (range 12 - 22 months, median 15 months), two patients died (4 %)--one from colon cancer, the other patient died from lung cancer, there was not any cardiac death recorded, two patients (4%) had target vessel revascularization. Estimated 22 months event-free (all-cause death, MI, TLR) survival was (mean +/- SEM) 86 +/- 7%. There was a significant difference in symptom severity--mean grade of angina pectoris at baseline was 1.8 +/- 1.3, at follow-up 1.1 +/- 1.0 (p < 0.05). There was not difference in use of antianginal drugs was same at baseline and at follow-up (1.7 +/- 0.8 vs. 1.7 +/- 0.7). Thirty-five patients (71%) were treated by statins. CONCLUSIONS: Deferring of coronary interventions of intermediate stenosis based on FFR measurement is safe in a mid-term follow-up. Despite of the same intensity of antianginal treatment there was a significant decrease in symptom severity.

Aged↗

[Angiographically marginally significant coronary stenoses--postponement of intervention based on measurement of myocardial fractional flow reserve].

INTRODUCTION: When evaluating angiographically marginal coronary stenoses (i.e. 40-70% reduction of the diameter of the arterial lumen) it is under certain conditions difficult to decide on their actual functional impact. Assessment of the fractional flow reserve (FFR) is a simple method based on assessment of intracoronary pressures during pharmacologically induced hyperaemia. For the severity of stenosis according to previous studies the liminal values is FFR lower than 0.75; furthermore it was proved that intervention of angiographically marginal stenoses with FFR values of 0.75 or more can be safely postponed. OBJECTIVE: Test the safety of FFR examination and take in a group of patients with marginally severe stenosis further steps according to results of FFR assessment. MATERIAL AND METHODS: During the period from January to Juky 2000 FFR assessments were made in a total of 34 patients (11 women, 23 men, mean age 62 +/- 12 years) who suffered from marginal stenosis of some coronary vessel. The FFR examination took place under pharmacologically induced hyperaemia after intracoronary adenosine administration. RESULTS: Measurements were made in a total of 41 stenoses. Only in two a value lower than 0.75 was found. In these patients coronary intervention was implemented; intervention was also made in two patients on account of technical problems and inconsistent results of FFR measurements. A FFR value of 0.75 or less was found in 37 stenoses (90%) and intervention was therefore postponed. Examination and the immediate subsequent course were without complications. CONCLUSION: According to initial experience FFR examination is a safe, simple and easily reproducible method. Based on the results of assessment and knowledge of the accomplished studies in the group of marginally significant stenoses in a great proportion of patients coronary intervention was postponed.

Coronary Angiography↗

Lack of complex I activity in human cells carrying a mutation in MtDNA-encoded ND4 subunit is corrected by the Saccharomyces cerevisiae NADH-quinone oxidoreductase (NDI1) gene.

The gene for the single subunit, rotenone-insensitive, and flavone-sensitive internal NADH-quinone oxidoreductase of Saccharomyces cerevisiae (NDI1) can completely restore the NADH dehydrogenase activity in mutant human cells that lack the essential mitochondrial DNA (mtDNA)-encoded subunit ND4. In particular, the NDI1 gene was introduced into the nuclear genome of the human 143B.TK(-) cell line derivative C4T, which carries a homoplasmic frameshift mutation in the ND4 gene. Two transformants with a low or high level of expression of the exogenous gene were chosen for a detailed analysis. In these cells the corresponding protein is localized in mitochondria, its NADH-binding site faces the matrix compartment as in yeast mitochondria, and in perfect correlation with its abundance restores partially or fully NADH-dependent respiration that is rotenone-insensitive, flavone-sensitive, and antimycin A-sensitive. Thus the yeast enzyme has become coupled to the downstream portion of the human respiratory chain. Furthermore, the P:O ratio with malate/glutamate-dependent respiration in the transformants is approximately two-thirds of that of the wild-type 143B.TK(-) cells, as expected from the lack of proton pumping activity in the yeast enzyme. Finally, whereas the original mutant cell line C4T fails to grow in medium containing galactose instead of glucose, the high NDI1-expressing transformant has a fully restored capacity to grow in galactose medium. The present observations substantially expand the potential of the yeast NDI1 gene for the therapy of mitochondrial diseases involving complex I deficiency.

Binding Sites↗

Rate-limiting step preceding cytochrome c release in cells primed for Fas-mediated apoptosis revealed by analysis of cellular mosaicism of respiratory changes.

In the present work, Jurkat cells undergoing anti-Fas antibody (anti-Fas)-triggered apoptosis exhibited in increasing proportion a massive release of cytochrome c from mitochondria, as revealed by double-labeling confocal immunofluorescence microscopy. The cytochrome c release was followed by a progressive reduction in the respiratory activity of the last respiratory enzyme, cytochrome c oxidase (COX), and with a little delay, by a decrease in overall endogenous respiration rate, as measured in vivo in the whole cell population. Furthermore, in vivo titration experiments showed that an approximately 30% excess of COX capacity over that required to support endogenous respiration, found in naive cells, was maintained in anti-Fas-treated cells having lost approximately 40% of their COX respiratory activity. This observation strongly suggested that only a subpopulation of anti-Fas-treated cells, which maintained the excess of COX capacity, respired. Fractionation of cells on annexin V-coated paramagnetic beads did indeed separate a subpopulation of annexin V-binding apoptotic cells with fully released cytochrome c and completely lacking respiration, and a nonbound cell subpopulation exhibiting nearly intact respiration and in their great majority preserving the mitochondrial cytochrome c localization. The above findings showed a cellular mosaicism in cytochrome c release and respiration loss, and revealed the occurrence of a rate-limiting step preceding cytochrome c release in the apoptotic cascade. Furthermore, the striking observation that controlled digitonin treatment caused a massive and very rapid release of cytochrome c and complete loss of respiration in the still respiring anti-Fas-treated cells, but not in naive cells, indicated that the cells responding to digitonin had already been primed for apoptosis, and that this treatment bypassed or accelerated the rate-limiting step most probably at the level of the mitochondrial outer membrane.

Amino Acid Chloromethyl Ketones↗

Overproduction of PDR3 suppresses mitochondrial import defects associated with a TOM70 null mutation by increasing the expression of TOM72 in Saccharomyces cerevisiae.

Most mitochondrial proteins are synthesized with cleavable amino-terminal targeting signals that interact with the mitochondrial import machinery to facilitate their import from the cytosol. We previously reported that the presequence of the F(1)-ATPase beta subunit precursor (pre-F(1)beta) acts as an intramolecular chaperone that maintains the precursor in an import-competent conformation prior to import (P. Hajek, J. Y. Koh, L. Jones, and D. M. Bedwell, Mol. Cell. Biol. 17:7169-7177, 1997). We also found that a mutant form of pre-F(1)beta with a minimal targeting signal (Delta 1,2 pre-F(1)beta) is inefficiently imported into mitochondria because it rapidly folds into an import-incompetent conformation. We have now analyzed the consequences of reducing the pre-F(1)beta targeting signal to a minimal unit in more detail. We found that Delta 1,2 pre-F(1)beta is more dependent upon the Tom70p receptor for import than WT pre-F(1)beta is, resulting in a growth defect on a nonfermentable carbon source at 15 degrees C. Experiments using an in vitro mitochondrial protein import system suggest that Tom70p functions to maintain a precursor containing the Delta 1,2 pre-F(1)beta import signal in an import-competent conformation. We also identified PDR3, a transcriptional regulator of the pleiotropic drug resistance network, as a multicopy suppressor of the mitochondrial import defects associated with Delta 1,2 pre-F(1)beta in a tom70 Delta strain. The overproduction of PDR3 mediated this effect by increasing the import of Delta 1,2 pre-F(1)beta into mitochondria. This increased the mitochondrial ATP synthase activity to the extent that growth of the mutant strain was restored under the selective conditions. Analysis of the transcription patterns of components of the mitochondrial outer membrane import machinery demonstrated that PDR3 overproduction increased the expression of TOM72, a little studied TOM70 homologue. These results suggest that Tom72p possesses overlapping functions with Tom70p and that the pleiotropic drug resistance network plays a previously unappreciated role in mitochondrial biogenesis.

Amino Acid Sequence↗

[Sonography findings in the carotid arteries in diabetics before aortocoronary bypass].

UNLABELLED: Neurological complications of patients during cardiac operations are closely associated with affections of the carotid arteries. The relationship of diabetes to these findings was not investigated so far. During the period between July 1 and Dec. 31 2000 the authors examined sonographically 127 patients indicated for aortocoronary bypass on account of affection of three arteries. Diabetes mellitus type 2 was present in 44 patients. A significant stenosis was detected in 4 (5%) without diabetes and in 5 (11%) patients with diabetes (p < 0.05), moreover in two patients with diabetes complete obstruction of the inner carotid was found. An insignificant stenosis (up to 70% was found in 3 (3%) of the patients without diabetes and in 3 (7%) patients with diabetes (p < 0.05). The thickness of the intima and media (IMT) was in patients with diabetes insignificantly greater (0.76 vs. 0.89 mm, NS). The mean index of echogenicity of plaques was in diabetic patients also insignificantly greater (2.1 vs. 2.9 NS). Atherosclerotic plaques greater than 2 mm were more frequent in diabetics (7.8% vs. 8 (18%), p < 0.05). A significantly more frequent finding of carotid stenosis or larger plaques was proved in patients with a history of CMP. Sonographic findings on the vertebral arteries were not associated with the presence of diabetes. CONCLUSION: Carotid sonography in patients of three arteries reveals in diabetic patients and in those with a history of CMP more frequent significant stenosis and the presence of major atherosclerotic plaques.

Aged↗

[Repair of traumatic lesions in peripheral nerves--introduction].

The reconstruction of traumatic lesions of peripheral nerves (PN) underwent the most significant improvement with the introduction of operating microscopes, microsurgical techniques and pertinent instruments, including microsutures. New information with respect to the pathophysiology of the degeneration and regeneration of peripheral nerves on a subcellular level also helped in the delineation of the rules and timing of optimal conditions for suturing. The present microtechnique seems to have reached its plateau with regard to capacity of available materials, technology and methodology. Despite this progress there is room for further improvement as addressed in this presentation. In this part of our work we would like to present a survey and analysis of the necessary theoretical knowledge of the basis of degeneration of a traumatized peripheral nerve at the level of molecular changes, as well as to indicate new technologies and materials. A detailed comparison of the classical method (microsuture) with the new technology (laser) has so far failed to demonstrate any significant difference. Therefore it appears necessary, when seeking advantages of the new methodology, to examine its application and not its quality, which will be the subject of the second part our work.

Humans↗

[Repair of traumatic lesions in peripheral nerves--initial experience with laser anastomosis].

Experience with conventional repair of peripheral nerves clearly indicates that there is still room for improvement, mainly in so far as functional results are concerned. It appears that the present microtechnique has reached its limitation given by physical and technological means, materials and methodology. The use of CO2 laser was tried on rat sciatic nerve. An equal number of nerves were severed surgically and sutured, using microsuture technique in one group and the same number of nerves were repaired using the CO2 laser technique. For the setting of the parameters, optimal for our purpose of reuniting the tissues, we have utilised morphological and electrophysiological qualitative and quantitative characteristics. The results were assessed by comparing both functionally and morphologically, the functional comparison being made electrophysiologically and the morphological comparison microscopically and morphometrically. The comparison shows a larger degree of scarring and constriction of the nerves anastomosed by classical microsuture than that of the laser technique. Action potentials going through the anastomosis have been noticed in both groups without significant difference in quality of CMAP, with the exception the latency.

Anastomosis, Surgical↗

[Monitoring cytomegalovirus infection using the 2-step nested polymerase chain reaction in patients with allogenic bone marrow transplantation].

Cytomegalovirus infections and their sequelae are the most serious complications in patients after allogenic bone marrow transplantations. Therefore in recent years quite rightly attention is paid to new diagnostic methods which make earlier and more sensitive detection of incipient CMV infection possible. The method of the two-stage polymerase chain reaction (PCR) was used for early detection of CMV infection and its possible further monitoring in 38 recipients of allogenic bone marrow. A positive result was recorded in 15 (39%) patients whereby in 10 (13%) repeated positivity was involved. In three in this group of patients (8%) CMV disease developed, always preceded by PCR positivity. Sensitivity, specificity, positive and negative predictive CMV PCR values were 100, 66, 20 and 100%. Concomitant comparison with serological examination (antibody titre class IgM/seroconversion) revealed the small contribution of serology (corresponding values are 67, 54, 11 and 95%) in patients after bone marrow transplantations. The presented results provide evidence of the contribution of PCR in the diagnosis of CMV in those patients where due to their high sensitivity and excellent predictive value it is possible to avoid the toxicity of unnecessary antiviral treatment.

Adolescent↗

CADIAG-2 and MYCIN-like systems.

CADIAG-2 and MYCIN-like systems are expert systems with numerous applications in medicine. CADIAG-2 is a fuzzy expert system based on max-min inference, while MYCIN-like systems use combining functions to calculate the global weights (degrees) of suggested diagnoses. This paper brings a comparison of CADIAG-2 and MYCIN-like systems. It studies relations between them and shows how CADIAG-2 can be embedded into MYCIN-like systems. An approach of inclusion of negative knowledge into CADIAG-2 is proposed. Some remarks regarding the acquisition of weights of rules are given as well.

Expert Systems↗

The amino terminus of the F1-ATPase beta-subunit precursor functions as an intramolecular chaperone to facilitate mitochondrial protein import.

Mitochondrial import signals have been shown to function in many steps of mitochondrial protein import. Previous studies have shown that the F1-ATPase beta-subunit precursor (pre-F1beta) of the yeast Saccharomyces cerevisiae contains an extended, functionally redundant mitochondrial import signal at its amino terminus. However, the full significance of this functionally redundant targeting sequence has not been determined. We now report that the extended pre-F1beta signal acts to maintain the precursor in an import-competent conformation prior to import, in addition to its previously characterized roles in mitochondrial targeting and translocation. We found that this extended signal is required for the efficient posttranslational mitochondrial import of pre-F1beta both in vivo and in vitro. To determine whether the pre-F1beta signal directly influences precursor conformation, fusion proteins that contain wild-type and mutant forms of the pre-F1beta import signal attached to the model passenger protein dihydrofolate reductase (DHFR) were constructed. Deletions that reduced the import signal to a minimal functional unit decreased both the half-time of precursor folding and the efficiency of mitochondrial import. To confirm that the reduced mitochondrial import associated with this truncated signal was due to a defect in its ability to maintain DHFR in a loosely folded conformation, we introduced structurally destabilizing missense mutations into the DHFR passenger to block precursor folding independently of the import signal. We found that the truncated signal imported this destabilized form of DHFR as efficiently as the intact targeting signal, indicating that the primary defect associated with the minimal signal is an inability to maintain the precursor in a loosely folded conformation. Our results suggest that the loss of this intramolecular chaperone function leads to defects in the early stages of the import process.

Adult↗

Nitrogen regulation of fatty acids and avermectins biosynthesis in Streptomyces avermitilis.

Fatty acid composition was analysed in the producer of avermectins, Streptomyces avermitilis C-18 grown in chemically defined medium with different nitrogen sources. Significant differences in nitrogen regulation of fatty acid biosynthesis were found in this strain in comparison with other streptomycetes studied so far. This finding could be explained at the level of regulation of branched-chain amino acid metabolism.

Amino Acids, Branched-Chain↗

Increase in cutaneous temperature induced by hypnotic suggestion of pain.

Eight patients with atopic eczema and six healthy subjects were given hypnotic suggestion to feel pain in the upper part of the back and in one case on the palm. An average local increase in skin temperature of 0.6 degrees C (detected by thermovision) occurred under this condition. For some patients cutaneous pain threshold was increased before the experiment by means of repetitive hypnotic suggestion of analgesia. These subjects reported feeling no pain subjectively, but the local change in skin temperature was equal in both cases. The results suggest a central mechanism induced by measuring changes in pain threshold in the skin, which changes are independent of local changes in blood flow.

Adolescent↗