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Biomedical subjects

V Vonka

Publications and source records attributed to V Vonka.

At least 55 records · Page 3Linked to original sources
PubMed1998

Prevalence of antibodies to human papillomaviruses in the general population of the Czech Republic.

Sera from 450 individuals between the age of 1 and 80 years, representing the general population of the Czech Republic, were tested for the presence of antibodies to human-papillomavirus(HPV)-derived antigens. The following antigens were used: (i) HPV1 virions; (ii) HPV16, -18 and -33-virus-like particles (VLP); (iii) peptides derived from L2 open reading frames (ORFs) of HPV16 and HPV6/11; (iv) peptides derived from HPV16 E2, E4 and E7 ORFs of HPV16. The prevalence of antibodies reactive with the capsid-derived antigens was age-dependent, while no clear age dependence was observed in the distribution of antibodies to peptides derived from HPV16 early proteins. In individual sera, high correlations between the presence of antibodies reactive with the 2 L2 peptides, also between the antibodies reactive with different VLPs, were found. While the simultaneous presence of the 2 L2 antibodies was frequently detected in individual sera in all age groups, the simultaneous occurrence of VLP antibodies was detected mostly in subjects older than 20 years. There were no significant differences in HPV-antibody distribution between men and women.

Adolescent↗
PubMed1998

Induction of anti-tumour immunity by suicide-gene-modified HPV-16-transformed hamster cells.

From K3/II, which is a highly oncogenic HPV16-transformed Syrian hamster cell line, thymidine-kinase(TK)-less cells, denoted B 49, were derived. B49 cells were transfected by a plasmid containing the herpes-simplex-virus TK gene (HSV TK) and several sub-lines expressing this gene were isolated from the transfected cultures. The HSV TK+ cells were highly sensitive to ganciclovir (GCV) and other anti-viral substances whose inhibitory effect is based on their phosphorylation by HSV TK. One of the cell lines, denoted KL1/6, exhibited relatively high stability of the HSV TK+ phenotype and was used in subsequent experiments. When KL1/6 cells were co-cultivated in the presence of GCV with various other cell lines of hamster, mouse or monkey origin, the by-stander effect (BE) was observed. GCV treatment of hamsters prevented development of tumours after the administration of KL1/6 cells but not K3/II cells. The treatment of animals with already established KL1/6-induced tumours resulted in tumour regression in all instances, but complete regression was observed only in animals carrying small tumours. The BE of KL1/6 cells on K3/II cells was also seen in vivo. In addition, concomitant immunity was observed in animals simultaneously inoculated with KL1/6 cells and K3/11 cells at 2 separate sites of the body. This effect was evident not only in animals in which KL1/6 tumours developed, but also in those in which tumour outgrowth was prevented by GCV treatment. In other experiments it was demonstrated that one KL1/6 + GCV treatment resulted in partial resistance, 2 such treatments in complete resistance to the challenge with K3/II cells.

Animals↗
PubMed1998

Effect of 3-beta-hydroxysteroid dehydrogenase gene deletion on virulence and immunogenicity of different vaccinia viruses and their recombinants.

3-beta-Hydroxysteroid dehydrogenase (3-beta-HSD) activity coded for by the A44L gene of vaccinia virus (VV) was demonstrated in CV-1 cultures infected by all five VV strains tested, viz. WR, Praha virus, DRYVAX Wyeth-derived virus (DD), LIVP and MVA. Deletion of the A44L gene in two Praha virus-derived clones (the moderately virulent P13 and the highly attenuated P20), the WR and DD viruses resulted in absence of 3-beta-HSD activity from infected cultures. The virulence for mice of P13 was not affected, and that of WR was only slightly decreased, by the A44L gene deletion. Recombinant VVs expressing either varicella-zoster virus glycoprotein E (VZV-gE) or hepatitis B virus preS2-S protein (HBV-preS2-S) and their respective A44L deleted mutants were used in immunogenicity tests in mice. In terms of antibody response to VV and the recombinant proteins, the deletion resulted in a lowering the immunogenicity in the moderately virulent clone P13 virus and its progenies. In the highly attenuated P20 and DD viruses and their progenies no effects were apparent.

3-Hydroxysteroid Dehydrogenases↗
PubMed1998

[Inflammatory stromal reaction in epithelial neoplasia of the uterine cervix in correlation with HPV infection].

260 cases of women with epithelial neoplasias of the uterine cervix were studied: HPV infection was detected by DNA in situ hybridization and serology, simultaneously structure and intensity of stromal inflammatory reaction (SR) were evaluated (semiquantitatively) as well as standard clinical immunological parametres investigated by serology. Results proved the same character of SR in intraepithelial lesions and invasive carcinomas and the intensity of SR increasing in relation to the gravity of epithelial dysplasia. There was not found any significant difference in SR between cases with detected HPV infection and cases lacking it. Summarized immunological parametres were in limits of normal reference range.

Female↗
PubMed1997

[Principles of gene therapy in tumors].

Gene therapy (GT) of cancer represents one of the most promising and exciting innovations in contemporary medicine. Several different strategies of GT of cancer have been developed. In spite of the rapid methodological progress their exploitation encounters a variety of problems. The most pertinent are associated with the use of vectors for gene transfer. Nowadays, virus-based vectors are preferred to the physical-chemical approaches. A special position in the methodology of cancer GT belongs to the so-called suicide genes. The expression of these genes in tumour cells results in their death provided they have been exposed to certain, originally innocuous substances. Combination of suicide genes with those coding for cytokines may eventually yield a very efficient means both for prevention and treatment of cancer. GT is connected with a number of considerable scientific, organizational and ethical problems. Coping with them requires extraordinary effort and well-organized and deliberate international cooperation.

Animals↗
PubMed1997

Correlation between the presence of anti HPV33 VLP antibodies and HPV DNA in cervical neoplasia patients.

The L1 capsid proteins derived from human papillomavirus (HPV) type 33 were expressed in a recombinant baculovirus system using Sf9 insect cells. Selected sera originating in women from case-control study carried out in Spain and Colombia found negative and positive for HPV16, 18, 31, 33 and 35 DNA were tested in ELISA for the presence of IgG antibodies to purified virus-like particles (VLP). The reactivity was type-restricted with the possible exception of HPV31.

Antibodies, Viral↗
PubMed1997

Human papillomavirus DNA and antibodies to human papillomaviruses 16 E2, L2, and E7 peptides as predictors of survival in patients with squamous cell cervical cancer.

PURPOSE: To assess whether human papillomavirus (HPV) DNA detection in cervical cancer specimens, or antibodies to selected HPV 16 peptides are predictors of tumor recurrence and long-term survival in patients with squamous cell invasive cervical cancer. SUBJECTS AND METHODS: Four hundred seventy-one cases included in two population-based case-control studies underwent follow-up evaluation. The survival and cause of death were ascertained for 410 cases (87%), with a median follow-up time of 4.6 years after diagnosis. HPV DNA was assessed using an L1 polymerase chain reaction (PCR)-based system and Southern hybridization (SH) on scraped cytologic specimens or biopsies. HPV 16 antibodies to E2, L2, and E7 peptides were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS: Clinical stage was the only independent prognostic factor for recurrence or survival. Although seropositivity to HPV 16 E7/3 peptide predicted a twofold excess risk of mortality (adjusted hazards ratio [HRa] = 2.0; 95% confidence interval [CI], 1.2 to 3.3), the association was restricted to stage I (HRa = 6.6; 95% CI, 1.2 to 37.6) and II (HRa = 5.9; 95% CI, 2.1 to 16.5) patients. The presence of HPV DNA (HRa = 0.9; 95% CI, 0.5 to 1.5), different estimates of the HPV viral load and the HPV type identified were not predictors of tumor recurrence or survival. CONCLUSION: The presence of antibodies to HPV 16 E7 proteins is of prognostic value in early-stage cervical cancer. Our results provide strong evidence that detection and typing of HPV DNA in cervical cells or tissues is not a prognostic factor for recurrence or survival.

Adult↗
PubMed1997

Putative regulatory sequence in human papillomavirus type 16 E2 open reading frame.

A 114 bp fragment of the human papillomavirus type 16 (HPV16) E2 open reading frame (nt. 3142-3255) containing a putative estrogen responsive element (ERE) was amplified and cloned into pBLCAT2 plasmid in both sense (p159-4) and anti-sense (p164) orientation. The plasmids were transfected into human breast-cancer cell line MCF-7 containing estrogen receptor and the cultures were kept in the presence or absence of beta-estradiol. The chloramphenicol acetyltransferase (CAT) activity was not influenced by estrogen. However, a silencer effect was observed both in cultures transfected with p159-4 and p164 plasmids. We prepared and cloned synthetic fragments containing the putative ERE and failed to prove that the palindrome in the putative ERE was responsible for the silencer activity.

Base Sequence↗
PubMed1996

Serological response to HPV16 in CIN-III and cervical cancer patients. Case-control studies in Spain and Colombia.

This study evaluates the association of antibodies against HPV-16-derived peptides with cervical cancer and estimates the sensitivity and specificity of the serological assays in relation to HPV DNA detection in cervical cells by PCR. Study subjects were derived from 4 case-control studies carried out in Spain and Colombia. Sera from 544 cases of CIN III and invasive cancer and of 543 age-matched controls were tested for antibodies to 5 peptides derived from E2, E7 (3 partially overlapping frames of HPV 16 denoted E7/ 1, E7/2, E7/3) and L2 open reading frames of HPV 16. HPV DNA was detected using a L1-PCR based method. Among cancer controls, antibody response to E2 and E7/1, E7/2, E7/3 was higher in Colombia (22.5%,7.2%,11.7%,12.6% respectively) than in Spain (17.1 %, 4.7%, 5.9%, 5.9%). E7 antibodies were related to stage, particularly in CIN III vs. invasive stages and less markedly within invasive stages. Detection of antibodies to the E7/1 was associated to CIN III (OR = 1.8). The risk of invasive cervical cancer was increased among those with antibodies to E2 (OR = 2.2), to E7/1 (OR = 4.2), to E7/2 (OR = 4.3), and to E7/3 (OR = 2.5). Presence of antibodies to all the 3 E7 peptides increased the risk of CIN III (OR = 5.6) and that of invasive cancer (OR = 17.5). High levels of antibodies to E7/1 or E7/2 or E7/3 increased the risk of invasive cervical cancer (OR for high levels of antibodies vs. negatives to E7/1 OR = 22.6; E7/2 OR = 7.5, E7/3 OR = 3.4). In the present analysis, antibodies to L2 were not associated with either CIN III or cervical cancer. Serological markers of HPV 16 detected less than half of the HPV-16-DNA-positive cases. It is concluded that antibodies to E2 and particularly E7 antigens are strongly associated with cervical cancer. Antibodies to E7 seem to be a moderate marker of tumor burden.

Adult↗
PubMed1996

Influence of the parental virus strain on the virulence and immunogenicity of recombinant vaccinia viruses expressing HBV preS2-S protein or VZV glycoprotein I.

Five triple-plaque purified vaccinia virus (VV) lines generated from smallpox Sevac VARIE vaccine (strain Praha) and three VV virus lines similarly derived from Wyeth DRYVAX vaccine were used for preparation of recombinants expressing the hepatitis B virus preS2-S gene. The same five Praha-derived virus lines were used to construct recombinants expressing the varicella-zoster virus (VZV) glycoprotein I (gpI) gene. Recombinants and their parental viruses were tested for the residual neurovirulence in mice. The virus lines and the recombinants derived therefrom differed markedly in this respect. Immunization of mice resulted in high levels of anti-HBsAg antibodies only in the case of recombinants derived from the relatively virulent viruses. In contrast, the levels of VZVgpI antibodies in mice were similar with all VV-VZV recombinants irrespective of the virulence of the parental virus line.

Animals↗
PubMed1995

Search for optimal parent for recombinant vaccinia virus vaccines. Study of three vaccinia virus vaccinal strains and several virus lines derived from them.

Three vaccinia virus strains (Praha, DD--a DRYVAX Wyeth vaccine-derived virus-and LIVP) were examined for growth in various cell cultures and for virulence and immunogenicity in mice. The viruses did not differ by their growth rates in monkey kidney cells (CV-1), human diploid cells (LEP), rat TK cells (RAT 2) or primary dog kidney cells. The immunogenicity of Praha and DD viruses was similar, the virus LIVP was somewhat more immunogenic. In terms of virulence in 3-day-old mice, the DD virus was the most attenuated. Single-plaque progenies were derived from the original smallpox vaccines VARIE Sevac (strain Praha) and DRYVAX Wyeth and tested for the above markers and DNA restriction patterns. The results obtained demonstrated biological and molecular heterogeneity of the original virus populations. Close linkage was observed between immunogenic activity and virulence in 3-day but not in 3-week mice. The results indicate that smallpox vaccine preparations may serve as an abundant source of virus mutants.

3T3 Cells↗
PubMed1995

[Potential carcinogenic factors in cervical intraepithelial neoplasia].

In a group of 22 women with cervical intraepithelial neoplasia and carcinoma of the cervix uteri and in a control group of 37 healthy women, a number of anamnestic and objective data about factors influencing these women and about consequences of such influence were analysed. Statistically significant differences between patients and controls were found in the character of work performed (physical vs. intellectual, p = 0.0312), the presence of stressing factors at the workplace (p = 0.02), a higher number of consumed meals per day in the control group (p = 0.0009), daily consumption of beer in a higher percentage of patients (p = 0.0015), the frequency of sexual intercourse in the last 2-3 months before the diagnosis of disease or examination (higher in controls, p = 0.0164) and subjective rating of sexual life in the fourth decade (better rating in controls, p = 0.0005). No differences were found between patients and controls in the number of sexual partners, the presence of antibodies against HSV-2 and other factors. According to data presented and data in the literature, external environment, some of the characteristics of sexual life and particularly infection with certain types of papillomaviruses have a certain influence on the development of cervical neoplasias.

Female↗
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↗
PubMed1995

[Detection and typing of HPV DNA in situ--improvement in diagnosis of lesions of the uterine cervix].

We examined the cervical samples from 63 female patients with various grades of cervical intraepithelial neoplasia (CIN), invasive squamous cell carcinoma (INCA) or inflammation. All the women with the diagnosis of CIN were selected on the basis of cytological prediction of HPV infection (koilocytosis, dyskeratosis). The analysis of human papillomavirus (HPV) genome by DNA hybridization in situ was done in all cases. Simultaneously, the immunohistochemical expression of papillomavirus common antigen (PVCA) and proliferating cell nuclear antigen PCNA/cykline was determined. The results confirm the correlation between high risk HPV types 16, 18, 33 and higher grade of dysplasia (CIN) as well as higher proliferative activity. On the other hand, the detection of HPV DNA does not correlate with PVCA expression or with cytological/histological diagnosis of koilocytosis. This finding shows that common cytological or histological examinations may be unreliable and in particular the significance of koilocytosis must be reevaluated.

Antigens, Viral↗
PubMed1994

[Construction of recombinant vaccinia viruses].

Expression system based on vaccinia virus (VV) is used both for recombinant protein production in vitro and as an alive vaccine. The article summarizes various strategies for recombinant VV construction, and describes preparation of recombinants expressing various forms of S and C genes of hepatitis B virus (HBV). It is shown, that the CV-1 cells infected with these recombinants synthesized the MS (middle) and the LS (large) polypeptides of the surface antigen (HBsAg) and the nucleocapsid antigen (HBcAg) polypeptide and the polypeptide HBeAg. Posttranslation modification of all expressed proteins was the same as at HBV infection.

Hepatitis B↗