PubMed Health⌕ Search

Biomedical subjects

M Novák

Publications and source records attributed to M Novák.

At least 55 records · Page 3Linked to original sources

Distinct effect of pH 2 on a common antigenic structure found in human interferons-alpha 1 and -alpha 2 in the region 30-35.

The antigenic similarity between molecules of recombinant human interferon-alpha 1 (IFN-alpha 1) and recombinant human IFN-alpha 2 was demonstrated with neutralizing monoclonal antibody (mAb) 1-46. The common epitope for the mAb 1-46 was localized into amino-terminal region of IFN-alpha molecule around residues 30-35. Following pH 2 treatment, the biological activity of both IFN-alpha 1 and IFN-alpha 2 was retained but the antigenic relatedness between corresponding sequences 30-35 was diminished. The common structure on the IFN-alpha 1 molecule proved acid stable and the mAb 1-46 retained the ability to neutralize the pH 2 treated IFN-alpha 1. However, the neutralization of pH 2-treated IFN-alpha 2 by specific antibody was completely suppressed. These results complemented our earlier finding of the dramatic effect of acidic pH on the antigenic structure of region 132-137 of the IFN-alpha 2 molecule. We conclude that pH 2 may induce a conformational rearrangement of the IFN-alpha 2 molecule, resulting in an altered tertiary structure with deviating antigenic characteristics.

Acids↗

Enhancement of neutralizing efficacy by combining three monoclonal antibodies to human interferon-alpha.

Three murine monoclonal antibodies (mAb) directed to distinct epitopes on recombinant human interferon (IFN)-alpha 1, and three mAb recognizing distinct epitopes on recombinant human interferon (IFN) alpha 1, and three mAb recognizing distinct epitopes on recombinant human IFN-alpha sc, were studied by IFN-neutralizing assays. The efficacy of neutralization of the anti-viral and the anti-proliferative activities of IFN-alpha 1, or IFN-alpha 2c, by the specific antibodies used, individually or in combination, were evaluated. In comparison with single mAb, the mixtures of three mAb against IFN-alpha 1 or three mAb against IFN-alpha 2c were capable of neutralizing more than 10-times larger amounts of IFN-alpha 1 and alpha 2c, respectively. The strong potentiation of the neutralization efficacy resulting from mixing different mAb was demonstrated by neutralization of the anti-viral as well as the anti-proliferative activities of both recombinant IFN. The neutralization experiments support the interpretation that the observed potentiation results from simultaneous interaction of anti-IFN mAb with different epitope specificity.

Antibodies, Monoclonal↗

[Comparison of the effects of nifedipine and diltiazem in patients with stable angina pectoris of various severity and pathomorphology of the coronary arteries].

In a double blind 7-week randomized study the authors compared in 29 patients with stable angina the action of placebo, nifedipine and diltiazem. Nifedipine was administered in amounts of 60 mg/day for three weeks, diltiazem 270 mg/day also for three weeks. Nifedipine and diltiazem exerted a significant antianginous action in patients with occluded but collateralized coronary arteries (group A), as well as in patients without collaterals (group B). In both these groups diltiazem improved the load tolerance significantly more than nifedipine. Nifedipine and diltiazem were useful also in patients with mild (group E), medium (group D) and severe (group C) affections of the coronary arteries. Groups C and E differed significantly as to the different effect of nifedipine and diltiazem on load S-T depressions (in group C diltiazem was significantly more effective, in group E nifedipine was insignificantly better), and it was not possible to explain these differences by a different effect on Robinson's index. The authors conclude that neither nifedipine nor diltiazem led in the amounts used to the "steal phenomenon" with clinical impact. In patients with mild affections of the coronary arteries their antiischaemic and antianginous action was similar, in patients with severe affection of the coronary arteries diltiazem was more effective.

Adult↗

[Intravenous streptokinase in the treatment of acute myocardial infarct].

In 314 patients with a first myocardial infarction, admitted within four hours after development of symptoms, the authors used in addition to standard therapy heparin treatment in 205 and streptokinase treatment (1.5 mil. u. i.v. with subsequent i.v. heparin administration) in 109 patients. Thrombolytic treatment was more effective, it reduced the lethality by 55.7% and was associated with a lower incidence of complications during the first 30 days. The reduced lethality, however, did not reach statistical significance because of the small number of patients and the low mortality rate in both groups. The left ventricular ejection fraction was practically equal in both groups after six weeks. Undesirable effects of thrombolytic therapy were rare and did not seriously threaten the patients. Provided contraindications are carefully respected, this treatment is safe and its routine use in the treatment of new myocardial infarctions must be supported. Streptokinase remains the drug of choice because it is equally effective as other available fibrinolytics and is the cheapest one.

Adult↗

Antigenic link between human interferons-alpha and -beta: the common epitope 1.

An until now unobserved consistent antigenic structure, tentatively named "common epitope 1," was detected on molecules of human recombinant (rHu) IFN-alpha 2 and natural HuIFN-beta by testing with monoclonal and polyclonal antibodies. The monoclonal antibody B6, obtained after immunization of BALB/c mice with human fibroblast IFN-beta, was capable of binding and neutralizing both IFN-alpha 2 and natural IFN-beta. The neutralizing activity of monoclonal antibody B6 was completely inhibited by a synthetic hexapeptide which corresponded to the amino acid sequence of IFN-alpha 2 in positions 132-137. Although a corresponding sequence of amino acids in the IFN-beta molecule was localized to the region 134-139 and shows only a 66% homology with the assumed IFN-alpha 2 binding site, lysine at position 132 in IFN-alpha 2 and at position 134 in IFN-beta seems to be crucial for establishment of the common epitope. Its existence was supported by experiments using polyclonal antibodies. Antiserum to IFN-alpha 2 showed cross-neutralization with IFN-beta, and vice versa, antiserum to IFN-beta cross-reacted with IFN-alpha 2. The ability for cross-neutralization by both polyclonal antisera was abolished in the presence of IFN-alpha 2 hexapeptide SH 132-137. No cross-reacting epitope could be detected on the IFN-alpha 1 molecule. These findings are the first evidence of a homology between human IFNs of alpha and beta types at the antigenic level. They indicate that the antigenic distinction between IFNs of alpha and beta types is not absolute.

Amino Acid Sequence↗

DSA diagnosis of pulmonary embolization from intracardial thrombus in a patient with permanent pacing catheter.

Pulmonary embolization in patients with implanted pacemakers is rare and an intracardiac thrombus attached to the distal end of a newly implanted ventricular endocardial electrode following removal of a previously implanted lead is a curiosity. We have documented such a case by digital subtraction angiography, a minimally invasive procedure that demonstrates both an intracardiac thrombus and secondary pulmonary embolization in a single procedure, which also allows simplified follow-up evaluation following therapy.

Angiography, Digital Subtraction↗

Modification of the antigenic structure of human interferon alpha-2 by PH 2 treatment: a further support for the antigenic relationship between alpha and beta interferons.

We have recently reported that a unique antigenic structure, designated as Common epitope 1, was found to be shared by human recombinant IFN alpha-2 and the human fibroblast IFN beta. The Common epitope 1 was identified with the aid of a synthetic IFN alpha-2 fragment SH 132-137. Based on this observation, we proposed the hypothesis that an antigenic relationship should exist also between natural human leukocyte IFN alpha and natural human fibroblast IFN beta. However, we were not able to detect any Common epitope 1 in preparations of conventional human leukocyte IFN alpha. In the present study, we were looking for a possible explanation of absence of the Common epitope 1 in conventional leukocyte IFN alpha. First, we demonstrated its acid labile nature in the recombinant IFN alpha-2 molecule and second, we proposed that the pH 2 lability of this unique epitope might be responsible for the lack of antigenicity also in pH 2-treated (conventional) leukocyte IFN alpha preparations. Actually, when pH 2 non-treated leukocyte IFN alpha was examined, we succeeded in demonstration of the Common epitope 1 in IFN-preparation. Moreover, anti-serum against pH 2 non-treated IFN alpha was capable of neutralizing both the conventional i.e. pH 2-treated leukocyte IFN alpha and fibroblast IFN beta. It is concluded that the nomenclature distinguishing two classes (i.e. alpha and beta as class I and gamma as class II) of IFNs is more appropriate than the current official nomenclature distinguishing three antigenic classes of IFNs.

Animals↗

[False aneurysm of the anterior tibial artery as a sequela of complicated foreleg fracture].

The authors discuss the aetiology, diagnosis and therapy of false aneurysms and mention their possible occurrence at different sites, whereby they emphasize the rare occurrence of pseudoaneurysms in conjunction with fractures of the bones of the extremities. The rare nature of the mentioned complication stimulated the authors to present a case-history of a pseudoaneurysm of the anterior tibial artery.

Aged↗

[Recording of monophasic action potentials using a contact catheter in humans. Preliminary report].

Investigations of a monophasic action potential (MAP) at a cellular level in experiments provided basic findings on the course of the electric activity in cells in various cardiac compartments and tissues under physiological conditions and various pathological states and has become an indispensible part of the evaluation of electrophysiological properties of various cardiovascular drugs, in particular antiarrhythmic drugs. A record corresponding to the MAP can be obtained also from the surface of the human endocardium during catheterization by means of a Franz contact catheter. MAP is induced by pressure depolarization after applying the catheter to the endocardium of different cardiac compartments. The objective of the author's preliminary communication is to present the initial experience with the MAP record from right-sided cardiac compartments during a routine electrophysiological examination in five patients at rest, during increasing stimulation of the atria and ventricles and after administration of some antiarrhythmic drugs. The authors evaluated the duration of MAP, the duration of 10%, 50% and 90% repolarization, the MAP amplitude, the activation time, repolarization time and the incidence of spontaneous diastolic depolarization. The recording and evaluation of MAP during the routine electrophysiological examination can contribute to the understanding of the development of arrhythmias, the action of antiarrhythmic drugs and to the evaluation of ischaemic changes of the myocardium. The clinical impact of MAP records is not clear so far and its assessment will call for further experience with this method.

Action Potentials↗

[Why are there anti-cardiolipin antibodies in patients with infectious mononucleosis and in patients with systemic lupus erythematosus?].

The phenomenon of anticardiolipin antibodies (aCL) is in recent years the subject of interest as it is connected with manifestations of thromboses at different sites, with repeated miscarriages in pregnant women and with thrombocytopenia. As compared with the original finding in patients with systemic lupus erythematosus (SLE), the authors find they are present also in infection with the Epstein-Barr virus--in patients with acute infectious mononucleosis, in as many as 61% of a total number of 77 examined patients; in a group of 60 patients with SLE in 41% and in a group of healthy controls in 3.9%. aCL differ, however, as regards the distribution of isotypes--aCL of class IgM are found mainly in infectious mononucleosis, class IgG in patients with SLE. The authors discuss problems associated with the development and practical importance of these antibodies.

Adolescent↗

[Silent stress ischemia in patients after aortocoronary bypass].

In a group of 37 patients with chronic stable angina the authors compared results of bicycle ergometry after a load before and after coronary artery bypass grafting. The group included only patients who had to terminate initial ergometry performed during the last two months before operation on account of stenocardia and signs of myocardial ischaemia on the ECG tracing. On average 20 months after coronary artery bypass grafting ergometry was repeated. Nineteen patients (51%) lacked electrocardiographic signs of myocardial ischaemia, 18 patients (49%) suffered from ischaemia after a load (depression S-T greater than or equal to 2 mm). Of these in 18 patients 8 (44%) no stenocardial attacks were present in another 5 (28%) stenocardia developed only when the depressions were S-T greater than 2 mm. Six patients (33%) had depressions S-T greater than or equal to 3.5 mm at a time when during ergometry they had no complaints and were engaged in similar work loads occasionally also at home. The authors conclude that in the investigated group silent ischaemia after a load was frequent in patients after a coronary artery bypass grafting and frequently it was severe. Patients after coronary artery bypass grafting developed stencardia only after greater S-T depressions than before operation. All patients after coronary artery bypass grafting should be checked by means of loading tests.

Adult↗

[Calculation of percentage of hearing loss in speech audiometry].

In a previous paper the authors explained, based on statistical analysis, the use of mixed Czech verbal audiometry for the percentage evaluation of auditory losses. In the present work the above problems are discussed and an actual example of calculation of auditory losses is given. Based on statistical processing of more than 200 sound and verbal audiograms a table was prepared where the number is inserted corresponding to the sum of 50% and 100% comprehensibility of a mixed verbal set in dB. A reading of the percentage hearing loss is then taken. In case of discrimination loss in verbal audiometry its value is added to the sum of 50% and maximum attained comprehensibility. If the thus calculated percentage hearing loss in verbal audiometry differs from the hearing loss assessed according to Fowler and Sabine in sound audiometry, in the final evaluation the mean of the two percentage values is used.

Adult↗

[Gastric volvulus].

Patient with gastric volvulus of secondary type due to paraesophageal hernia is reported. The possibility of gastric volvulus has to be considered in light of the severity of the condition and its relatively rare occurrence. Contrast esophagography and swallow in the lateral projection will confirm the diagnosis.

Humans↗

[Correlation of speech audiometry with the Fowler and Sabin method of hearing loss evaluation].

Evaluation of hearing losses for the purpose of granting pensions, for forensic purposes or for claims of damages is very important and it should not be based on a single examination method i.e., sound audiometry, which does not evaluate the entire auditory analyzer and does not fully appreciate the social usability of hearing. Statistical analysis and mutual correlations between monosyllabic audiometry, mixed and 3-4 syllabic audiometry and sound audiometry revealed that evaluation of hearing losses according to Fowler and Sabine correlates least with mixed verbal audiometry, although mixed verbal set-ups are typical for the Czech language as regards the structure and frequency of words. The authors recommended therefore the use of mixed verbal audiometry for the percentage evaluation of hearing losses. The actual proposal with a table of calculated hearing losses will be in a subsequent communication.

Adult↗

Human acid- and thermolabile alpha-interferon-like substance: selective reactivity with a monoclonal antibody.

An acid- and thermolabile alpha-interferon-like substance, designated AL-IFN-alpha, has been found in non-processed normal human leukocyte IFN preparations as well as sera from patients with autoimmune or other chronic diseases. Little is known about origin, production and biological activity of these IFN activities. Monoclonal antibodies were obtained which proved highly selective in neutralizing AL-IFN-alpha in both anti-proliferative and antiviral tests. While the monoclonal antibodies were strict specific, polyclonal antibodies against various interferons showed less specificity in these tests. The results suggest that AL-IFN-alpha represents an antigenically distinct IFN-alpha subtype or, alternatively, a new lymphokine with antiproliferative and antiviral activity.

Acids↗