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Biomedical subjects

M Novák

Publications and source records attributed to M Novák.

At least 19 recordsLinked to original sources

Implantation of p(HEMA)-collagen composite into bone.

The replacement of bone defects is very important in clinical practice. This study compares biological properties of poly(2-hydroxyethyl methacrylate)-collagen composite with those exhibited by pure p(HEMA), an insoluble fraction of calf skin collagen (ISC-40) and demineralized bone matrix after implantation into pig or dog femurs. The levels of biodegradation or destruction of implants and healing of bone defects were studied using X-ray photography, histology and enzyme histochemistry. The results indicated a significant effect of collagen on biological destruction of the p(HEMA)-composite implants; even a minute amount of collagen influences this process dramatically. A stimulatory action of collagen on new bone formation may be of importance in bone defect healing.

Animals

Amlodipine in patients with stable angina pectoris treated with nitrates and beta-blockers. The influence on exercise tolerance, systolic and diastolic functions of the left ventricle.

The effects of 5 and 10 mg of amlodipine and of placebo were compared in 21 patients with stable angina pectoris and multivessel coronary artery disease. The blind comparison was performed by means of bicycle ergometry and stress echocardiography using esophageal stimulation of the left heart atrium. All patients subsequently received placebo, amlodipine 5 mg and 10 mg for 2 weeks. In bicycle ergometry both doses of amlodipine in comparison with placebo significantly lowered the ST segment depression in lead V5 and prolonged the time to onset of angina. The exercise duration was significantly prolonged only after 10 mg of amlodipine. In stress echocardiography 10 mg of amlodipine significantly improved ejection fraction and reduced wall motion score during stimulation and increased peak velocity of relaxation of left ventricular posterior wall at rest and immediately after stimulation. In the patients with left ventricular end-diastolic pressure < or = 20 mmHg, amlodipine reduced the ratio of peak transmitral flow velocity in atrial contraction to that in early diastole (A/E) at rest and shortened deceleration time at rest and immediately after stimulation. Amlodipine in patients with stable angina pectoris significantly improved the exercise tolerance and the function of the left ventricle in a dose-dependent way. Amlodipine was well tolerated.

Amlodipine

Common and different antigenic properties of the rabies virus glycoprotein of strains SAD-Vnukovo and Pitman-Moore.

Two fixed rabies virus strains, SAD-Vnukovo and Pitman-Moore (PM) were used as combined immunogens for the generation of hybridomas secreting specific monoclonal antibodies (MoAbs). The obtained hybridomas were primarily screened by an ELISA for production of MoAbs to antigen of SAD-Vnukovo strain. Six positive clones were established. A panel of MoAbs has been characterized according to reactivity in immunofluorescence, immunoblot, ELISA and neutralization tests. All MoAbs were positive in immunofluorescence when cells infected with the SAD-Vnukovo strain were used. By immunoblot, four MoAbs showed specificity for the viral glycoprotein of both SAD-Vnukovo and PM rabies strains. This pattern of reactivity indicated the existence of shared conformation-independent epitopes located on the related antigens. However, in ELISA, the tested MoAbs did not recognize viral glycoproteins of the PM strain. This indicates, that the different strain-specific conformations of the native glycoprotein determine the accessibility of the common linear determinants for respective antibodies. Only one antibody, with conformation-dependent glycoprotein specificity, was capable to neutralize the CVS strain of rabies virus.

Animals

[Modern cardiac pacing. I. Dual-chamber pacemakers: 10 years' experience].

Dual chamber cardiac pacemakers restoring an impaired atrioventricular synchrony meet a demand of contemporary so-called physiologic cardiac pacing. 39 dual chamber (DDD) pacers were implanted in 1982-1991 in our center. They improved both well-being and hemodynamic values (doppler echocardiography) more distinctly than common ventricular demand devices did. P-wave driven ventricular pacing in normal sinus node function (in 40 per cent of our DDD patients) made a frequency response in physical exercise possible. A short atrioventricular delay in DDD pacing proved to be helpful in the treatment for reentry tachycardias refractory to antiarrhythmic drug administration. Demanding implant, high price, lengthy programming as well as a higher incidence of complications (30.7 per cent) as compared to ventricular pacemakers (7.6 per cent) were the main problems of DDD ones.

Adult

[Modern cardiac pacing. II. Rate responsive pacemakers: clinical experience].

Rate responsive cardiac pacemakers adapting their pacing frequency according to physical effort are able to solve not only a bradycardia, but a chronotropic incompetence too. 23 rate responsive pulse generators, implanted in 1987-1991 in our center, simulated the physiological conditions and in this way they significantly improved both working capacity in bicycle stress test (p < 0.0001) and well-being in comparison with ordinary demand pacers. The incidence of complications did not exceed that in simple common pacemakers, but the rate adaptive ones were expensive and their programming was time consuming. In all three rate adaptive principles used their non-specific response revealed some imperfection of sensor driven devices. In addition, both in QT and in respiratory dependent systems their pretty proportional frequency response was delayed, while the irregular pacing rate in body activity sensor was not very proportionate to the physical exercise. The non-specific sensor response may be reduced by a combination of biologic sensors.

Adult

Immunoblot analysis of antibody response in mice infected with Coxiella burnetii phase I.

Mouse sera collected from day 4 to day 133 postinfection (p.i.) with phase I Coxiella burnetii strain Nine Mile were analysed by immunoblotting with phase I C. burnetii cell lysate. Antibodies of IgG class protein antigens were revealed already on day 10 p.i. (60, 49 and 27 kD proteins), followed by those to 77 kD protein from day 18 p.i. and to further 7 (from 42 to 70 kD) proteins from day 28 p.i. IgG antibody reaction was observed also with 5 antigens in 14-20 kD region corresponding to lipopolysaccharides from day 22 p.i. Surprisingly, antibodies of IgM type appeared later (from day 22 p.i.) and were directed only to protein antigens, most markedly to 60 and 77 kD proteins. Differences in immunoblot patterns observed with the serum collected on day 72 p.i. before and after absorption to phase I and phase II C. burnetii cells, and to phase I cells treated by trichloroacetic acid (TCA) or KIO4, indicate the surface localization of protein phase I antigenic epitopes, which can be destroyed partly by TCA and almost completely by KIO4 treatment.

Animals

[Comparison of the effects of diltiazem and isradipine in adrenergic beta receptor blockade in patients with stable angina pectoris].

In 20 patients with stable angina II-III according to NYHA by means of ergometry the effect of short-term administration of dilthiazem (90 mg in three doses), placebo and isradipine (5 mg in three doses) in block of beta-receptors of the sympathetic nerve (metipranolol 3 x 10 mg/day) was compared. As compared with placebo, dilthiazem and isradipine retarded significantly the development of stenocardia, reduced the S-T depression in lead V5 and increased the total work output during ergometry. Based on the results of this and previous work (9) it may be stated that concurrent administration of metipranolol reduced the frequency of side-effects of isradipine and prevented the reflex rise of the heart rate following its short-terms administration. The authors conclude that starting treatment of stable angina with isradipine is safer and more effective in combination with metipranolol than when monotherapy is used. Dilthiazem must be administered with metipranolol carefully with regard to possible development of severe bradycardia and its suitable dose should be established by titration.

Adult

[Bispecific antibodies: present status and possibile applications].

The review article information on the current status in the research regarding bispecific antibodies. The theoretical and methodical aspects of preparation of heterohybridomas secreting bifunctional monoclonal antibodies are discussed in details. The question of purification of the antibody fraction with dual specificity is also addressed. The possible application of bispecific antibodies in human medicine for immunodiagnostics and aimed immunotherapy is described. (Fig. 7, Ref. 22.).

Antibody Specificity

[Drug therapy in vascular occlusions of the lower extremities].

The authors report their three-year experience with application of thrombolytic treatment in 31 patients with vascular occlusions of the lower extremities. They were successful in two thirds of the patients. The authors analyze the advantages and shortcomings of systemic or selective administration of antithrombotic therapy. Concurrent administration of hyperbaric oxygen is a rational therapy.

Adult

Analysis of human blood plasma triacylglycerols using capillary gas chromatography, silver ion thin-layer chromatographic fractionation and desorption chemical ionization mass spectrometry.

The identification and quantitation from pooled human plasma of over 50 molecular species of triacylglycerols, including 22 not previously reported, are reported. The triacylglycerols were first resolved by silver ion thin-layer chromatography into seven fractions, which were independently analysed by polarizable capillary gas chromatography and desorption chemical ionization mass spectrometry in the presence of an internal standard. The two methods gave similar values for the estimates of oligoenoic species, but the former method underestimated the polyenes (due mainly to significant losses caused by thermal degradation), and the latter method overestimated the saturates. The results show that an effective analysis of molecular species of plasma triacylglycerols cannot be obtained by either technique alone.

Chromatography, Gas

[The effect of nifedipine and diltiazem on left ventricular function in patients with stable angina pectoris and severe left ventricular dysfunction].

In a double blind crossover five-week trial with a randomized onset in 12 patients with normal blood pressure, stable angina pectoris and more severe left ventricular dysfunction (ejection fraction less than or equal to 40%) the effect of placebo nifedipine and diltiazem on left ventricular function and tolerance of exercise was compared. The investigation was done by means of echocardiography after a load with stimulation of the heart by an oesophageal electrode. As compared with placebo, only diltiazem retarded significantly the period before development of stenocardia on stimulation of the heart. There was no significant difference between nifedipine and diltiazem as regards the effect exerted on the ejection fraction and time which elapsed after stimulation before stenocardia developed. The authors observed an unequal response of patients to the administration of nifedipine and diltiazem (some patients had less favourable findings, although they were not subjectively aware of this deterioration). Therefore these drugs must be administered to patients with angina pectoris and more severe left ventricular dysfunction with care and only if other drugs (nitrates or angiotensin convertase inhibitors) do not eliminate ischaemia and pain.

Adult

Are the acid-labile interferon alpha and interferon omega-1 identical?

The interferon (IFN) activity found in human leukocyte IFN alpha preparations, autoimmune and AIDS sera, and others was reported to have distinct antigenic and deviating biological properties. This led to its vague designation as acid-labile and thermolabile IFN alpha. However, using specific monoclonal antibodies, the acid-labile component of IFN alpha (not exposed to pH 2) and recombinant IFN omega 1 showed significant relatedness. Monoclonal antibody T19, generated with virus-induced leukocyte IFN alpha that had not been exposed to pH 2, neutralized both the antiviral and antiproliferative activities of IFN omega-1, and vice versa; monoclonal antibody OMG 5, specific for recombinant IFN omega-1, cross-neutralized the antiviral and antiproliferative effects of the acid-labile component of leukocyte IFN alpha. When these two IFN preparations were incubated at pH 2 for 72 hr, their biological activity significantly decreased.

Animals

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