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Biomedical subjects

L Borecký

Publications and source records attributed to L Borecký.

At least 19 recordsLinked to original sources
PubMed1995

Increased effects of topically applied interferon on herpes simplex virus-induced lesions by caffeine.

Caffeine (Cf, 0.15-0.6 mg/ml) and human leukocyte interferon (IFN, > 5 x 10(2) IU/ml) partially inhibited the replication of herpes simplex virus type 1 (HSV-1) in human diploid LEP cells and HaCaT cells. When the two drugs were applied simultaneously the inhibitory effects exceeded those achieved with either substance alone. In the subsequent clinical trial, which was conducted as a one-center, randomised, and placebo-controlled study, the same substances included in either ointment or solution were used for topical treatment of recurrent herpetic lesions. Of 115 patients taken into the study 20 were treated with Cf only (50 mg/g of ointment or solution), 25 with IFN only (5 x 10(4) IU/g), 25 with mixture of Cf and IFN (same concentrations) and 45 with placebo. Both the healing time (HT, period between the prodromes and reepithelization) and the spreading time (ST, period between the prodromes and the appearance of the last new lesion) were recorded in each patient. While the placebo effects were negligible, the other treatments tended to abort the lesions. HT was shortened by at least 4 days in 75% of patients treated with Cf alone, in 88% of those treated with IFN alone, and in all patients treated with their mixture. The effects on ST were less marked; in the case of Cf alone they were negligible. A shortening of ST by at least 2 days was recorded in 40% and 60% of patients treated with IFN alone and the drug mixture, respectively. Statistical analysis confirmed that both in terms of HT and ST the disease was more significantly alleviated by the mixture of Cf and IFN than by either drug alone.

Administration, Topical↗
PubMed1993

Porcine leukocyte interferon exhibits close antigenic relatedness to human interferon alpha 2, but not to human interferon alpha 1.

As reported by others using polyclonal antisera, natural human and porcine interferons (IFN)-alpha are antigenically related. Using monoclonal antibodies (mAb) in neutralization and ELISA experiments, we found differences in the subtype/antigenic composition between virus-induced porcine and human leukocyte preparations. Human leukocyte IFN-alpha contains two major antigenically distinct subtypes, IFN-alpha 1 and IFN-alpha 2. However, swine leukocytes produced only a single predominant species of IFN-alpha with high antigenic homology to human IFN-alpha 2. Moreover, we were unable to detect close antigenic relatedness between recombinant porcine and human IFN-alpha 1 subtypes.

Animals↗
PubMed1993

Peptide-mapping of three neutralizing epitopes into predicted biologically active sites of human interferon-alpha 2.

Immunologically less reactive but functionally relevant structures were identified on human interferon (IFN)-alpha 2 by three neutralizing monoclonal antibodies (mAb). The binding sites of these mAbs were mapped using a set of synthetic peptides that covered the amino acid sequence of two predicted biologically active segments in the regions 31-53 and 63-85 of IFN-alpha 2. We measured the capacity of fragments to inhibit the IFN-neutralizing activity of mAbs and located three linear epitopes around residues 42-53, 63-76 and 77-85 of the IFN-alpha 2 molecule.

Amino Acid Sequence↗
PubMed1993

Cytokines: the fourth homeostatic system.

The cytokines represent a network of small polypeptides produced by a variety of immune, blood and somatic cells. They can be considered the fourth homeostatic system serving the integrity of the organism. The cytokines cooperate with, substitute or, regulate the activity of cells and products of hormonal, neural and immune systems and function as physiological and/or emergency regulators. The attempts to exploit them in the therapy of viral and/or neoplastic diseases brought, so far, only partial success. However, they remain the goal of a new, more physiological therapy.

Animals↗
PubMed1993

In vitro antiproliferative effect of interferon alpha in solid tumors: a potential predictive test.

An in vitro test for the antiproliferative effect of human leukocyte interferon (IFN-alpha) was performed in primary cultures of tumor cells obtained from 32 patients with either malignant melanoma (13), renal carcinoma (4) or bladder carcinoma (15). Our results demonstrated activity of IFN in all three groups of solid tumors. However, appreciable differences in sensitivity to antiproliferative effect of IFN between individual tumors of the same type were found. The potential of this antiproliferative test for prediction of treatment response in IFN-therapy is discussed.

Adult↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

Interferon after 30 years.

IFN is a product of a growing family of IFN-genes in the vertebrate cell. It is a polypeptide which fits the definition both of lymphokines and/or "local" hormones, and, cannot be anymore considered an "autonomous antiviral factor", as postulated originally. Rather, IFN increasingly seems to play in the organism the role of a "master-lymphokine" that mediates, potentiates or regulates the effects of various lymphokines in differentiation, growth and antigen expression of cells. The antiviral, antiproliferative, cell- and antigen-activating activities of IFN formed the basis for expectations that IFN will be utilized in therapy. These expectations were only partially fulfilled. In some diseases, however, the results of clinical tests are convincing. In such tests, we learned that the successful application of IFN in disease requires other strategies than with cytostatics etc. IFN may be deleterious for the organism when present for a long time in circulation and/or applied in high doses. This follows both from observed side effects of IFN and from the mitigating effect of anti-IFN sera in some diseases.

Animals↗
PubMed1989

Abnormal macrophages and NK cell cytotoxicity in human systemic lupus erythematosus and the role of interferon and serum factors.

Macrophage (MO) and natural killer (NK) cell mediated cytotoxicity to K562 target cells were strikingly decreased in patients with systemic lupus erythematosus (SLE). SLE NK cells failed to release soluble factor(s) for lysing the targets. IFN-induced enhancement of both types of cytotoxicity was impaired. NK cells from healthy subjects kept their activity in culture with or without IFN for more than six days whereas SLE NK cell activity declined to zero at day 3. So, the increased IFN level of many SLE patients and a possible prior IFN priming effect seemed unrelated to the insensitivity to exogenous IFN in vitro. Inhibition factor(s) of SLE serum suppressed NK cytotoxicity in the presence of IFN whereas IFN sensitivity of MO remained unaffected indicating the complex regulation by serum components of immune reactions.

Chromium Radioisotopes↗
PubMed1989

Monoclonal antibodies neutralizing human leukocyte acid- and thermolabile interferon alpha.

Using a high titred human leukocyte IFN alpha preparation which contained both acid- and thermolabile (AL-IFN alpha) and acid- and thermostable IFN alpha species in 9:1 proportion for immunization of BALB/c mice, five hybridomas secreting monoclonal antibodies that reacted with AL-IFN alpha were obtained. In antiviral and antiproliferative tests on HL-60 cells, their products showed high degree of specificity for AL-IFN alpha. The results suggest that both the "normal" leukocyte AL-IFN alpha and the IFN alpha found in sera of autoimmune and other chronic patients might belong to the same subtype of IFN alpha.

Animals↗
PubMed1989

Murine monoclonal antibodies against human fibroblast (beta) interferon. Correlation of the neutralization of antiviral and antiproliferative activities.

Eight mouse hybridoma lines secreting monoclonal antibodies (MoAb) to human fibroblast interferon (HuIFN-beta) were established. All MoAbs were capable of neutralizing two different biological activities of HuIFN-beta: the antiviral activity and the antiproliferative activity. Positive correlation was demonstrated between the ability of hybridoma culture supernatants to neutralize the antiviral and antiproliferative effects of human fibroblast IFN. The neutralizing capacity of individual hybridoma culture supernatants depended on the concentration of MoAb in the sample. Only one of IFN-neutralizing MoAbs has shown binding capacity to human fibroblast IFN when used in enzyme immunoassay as solid-phase antigen. This MoAb was purified to homogeneity and its specific neutralizing activity against HuIFN-beta was calculated (3.5 X 10(4) I.U. per mg).

Animals↗
PubMed1988

Activation of NK cells in subjects exposed to mild hyper- or hypothermic load.

The effect of mild hyper- and hypothermic stress on release of selected hormones (somatotropin, noradrenaline, etc.), interferon (IFN), and activity of NK cells in the blood was examined in groups of young males during a 30 min exposure to 39 degrees C and 4 degrees C. A quick release of somatotropin was registered in 44% of examinees in the hyperthermic group, while the persons exposed to 4 degrees C reacted with a release of noradrenaline only. Concurrently, an elevation of NK cell activity was observed both in the subgroup releasing somatotropin after hyperthermic stress and in the group exposed to cold. Since these forms of mild stress did not lead to an appearance of IFN in the serum, the possibility of an NK cell activating effect of somatotropin and/or the adrenal hormones was tested. While the adrenal hormones stimulated the NK cell activity in vitro, no support for a similar role for somatotropin was found.

Adult↗
PubMed1988

Human interferon alfa therapy and hepatitis B virus markers in the serum of patients with chronic course of illness.

Dynamics of serum levels of HBsAg, HBeAg and anti HBc were followed during human interferon alpha (Hu IFN alpha) therapy of patients with chronic active or chronic persistent hepatitis B. More or less expressed oscillations of HBsAg serum levels seen in two out of our six treated patients seemed to occur due to IFN effect. Little and seldom changes were observed in HBeAg and anti HBc serum levels. The profiles of HBsAg serum levels of interferon-treated patients compared with the profiles of "conventionally" treated patients disclosed occurrence of spontaneous or perhaps interferon-induced cyclic elevations and depressions of HBsAg blood levels. The possible significance of this phenomenon is discussed.

Adult↗