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Biomedical subjects

V Mayer

Publications and source records attributed to V Mayer.

At least 19 recordsLinked to original sources

Creutzfeldt-Jakob disease risk and PRNP codon 129 polymorphism: necessity to revalue current data.

The polymorphism at codon 129 (M129V) of the prion protein gene (PRNP) is a recognized genetic marker for susceptibility to Creutzfeldt-Jakob disease (CJD) in the Caucasians. The distribution of this polymorphism in healthy individuals provides an important starting point for the evaluation of CJD risk in the general population. Early studies of reference population cohorts demonstrated that methionine/valine heterozygosity was the most frequent genotype. These studies were performed in relatively small numbers of control subjects and do not correspond with the findings of more recent investigations. In this study, we present an analysis of the codon M129V distribution in 613 corneal donors, representing one of the largest control groups examined to date. Methionine homozygotes represented 48.1%, valine homozygotes 8.7% and methionine/valine heterozygotes 43.2%. While age-related difference was not significant, differentiation according to the gender showed significant difference. The observed highest proportion of methionine homozygotes and statistically significant difference between genders as well as comparison with results obtained in other countries underline the need to re-evaluate the generally used reference data on M129V, including consideration of the gender, age and geographical distribution.

Amyloid↗

HIV infection and risk behaviour of commercial sex workers and intravenous drug users in Slovakia.

INTRODUCTION: Aim of the study was to determine risk behaviour and HIV prevalence among commercial sex workers (CSWs) and intravenous drug users (IDUs) in streets of Bratislava and B. Bystrica, SR. METHODS: HIV antibodies were tested from saliva using ELISA test. Anonymous questionnaire was completed. RESULTS: 121 persons (61 men and 60 women) were involved in the sociological study. Mean age of the participants was 21.9 years. 185.1% of subjects were from Bratislava. 108 participants were tested for the presence of HIV-antibodies, one was confirmed HIV-positive (0.82%). In the past 47.9% of participants and 22.3% of their partners were tested for the presence of HIV-antibodies. 10.8% of subjects proclaimed that they suffered from other sexually transmitted infection (STI) in the past HIV testing of participants significantly correlated with the testing for other STI (p<0.002) as well as with HBV/HCV (p<0.001). 58 participants were using tattooing (47.9%). 46.3% of all participants never used condoms with partners. 31.4% of respondents proclaimed disruption of condom during sexual intercourse. Significant correlation was found between testing of participants for other STI and usage of condoms with their partners (p<0.013). Women used condoms more often by sexual contacts with partners than men used condoms (p<0.094). They were also significantly more tested for other STI in the past (p<0.021) and they suffered from other STI more often than men (p<0.033). 26.5% of person--only women--were involved in commercial sex work. 93.5% of them were taking drugs as well, 21.8% suffered for other STI in the past They were working in sex business on average for 26 months. The average number of their clients per week was 12.3. CSWs used condoms more often with clients than with partners. 98.2% of all participants were taking drugs, 93% of them intravenously. 24.6% of IDUs always used new or their own needles and syringes, while 69.4% shared equipments with the other users. IDUs drug users used condoms significantly less often with their partners than did CSWs (p<0.006). CSWs were significantly more often tested for other STI (p<0.001) and they also more often suffered for other STI than IDUs (p<0.045). CONCLUSION: More effort should be done to decrease risk behaviour revealed in the groups of CSWs and drug users.

Adolescent↗

Initial RNA expression in human monocytes after multiple injury: a screening pilot study on potentially trauma-sensitive factors by using the microarray-technique.

BACKGROUND: Pathological affection of the immune system is one of the initiating mechanisms for the induction of multiple organ failure (MOF) in patients suffering from multiple injuries. Potential responsible intracellular mechanisms such as initial monocyte mRNA expression of specific mediators remain poorly studied, so far. Hence, we applied the microarray technique for screening of a wide variety of genes in circulating monocytes of multiple injured patients and compare the molecular results to the clinical course of the patients (MOF-score). METHODS: In our prospective pilot study 6 patients were enclosed presenting with blunt multiple injuries (Injury Severity Score 16 to 57 points). Monocytes were isolated out of sequentially drawn samples (6, 12, 24 and 48 hours after trauma) using magnetic cell sorting (CD14) and a human microarray system was used (Atlas stress 1.2, Clontech, 1176 genes). Alterations in the sequential samples were identified by calculating ratios to baseline levels on admission and cluster analysis was performed (Spotfire Decision). RESULTS: Only 86 (ca.5%) genes displayed an obvious signal. The house-keeping genes clustered well together in all patients in contrast to a substantial inter-individual variability of the other signal giving genes. No mediator burst of the classical pro- or anti-inflammatory cascade were detected. CONCLUSION: We demonstrate for the first time a screening analysis of mRNA expression patterns in circulating monocytes of multiple injured patients indicating that only very few genes appeared to be influenced by the traumatic event. So far, no correlation to the severity of trauma or MOF could be detected.

Adult↗

Improvements for multipurpose bacteriological identification tables to suit the diagnosis of Vibrio cholerae.

The aim of the study was to reduce to key tests the 4 extensive polyvalent diagnostic biochemical tables most widely used in Croatia and to adapt them for the demonstration of Vibrio cholerae and its differentiation from the 3 Vibrios (V. alvinolyticus, V. mentschikovii, V. fluvialis) important in differential diagnosis. The fourth table has now been adapted to differentiate among all 12 Vibrio species known to be human pathogens (V. mimicus, V. cincinatiensis, V. holisae, V. damsela, V. furnisi, V. parahaemolyticus, V. vulnificus, V. carchariae). Using the inductive Learning by Logic Minimization Method (ILLM), we analyzed 2 tables (i.e. identification matrices) that were a part of bioMérieux's commercial packaged polyvalent identification systems widely used in Croatia (API 20E and ATB 32E), as well as 2 compilation tables by M. T. Kelly et al. The tables contained 27, 32, 59 and 8 tests, respectively. Cutting these solely to the key tests involved rationalizing them from 59 to the 5 necessary to differentiate Vibrio cholerae from 3 related Vibrios. Further rationalizations were from 32 to 2 and from 27 to the 3 necessary to differentiate Vibrio cholerae from 2 related Vibrios. By reducing the table of 8 tests to 7, and adding 4 new ones to these we achieved an optimization permitting mutual differentiation of all 12 known human Vibrio pathogens. Use of the selective TCBS plating medium was the only precondition for making these tables effective.

Bacteriological Techniques↗

Bed utilization performances of Slovenian and Croatian acute hospitals systems.

With Barber-Johnson-Yates scattergrams (BJYS), the performances of Slovenian and Croatian acute hospital system were explored by taking turnover interval as a predictor variable, length of stay as a dependent variable, and by looking at the variables of bed throughput and percentage of bed emptiness on installed network. The growing influences on the Slovenian hospital system of a cost-containment policy and of the past war on the Croatian hospital system are the best illustrations of the informatics potential inherent in BJYS presentations for the exploratory data analysis (EDA) used to identify systematic relations between variables in a setting of not complete a priori expectations of these relations.

Bed Occupancy↗

Programmed cell death: will it become a factor in cancer prevention?

Among the factors triggering programmed cell death (PCD) are a number of known carcinogens, and several consequences of DNA abnormalities characteristic of cancer have been shown capable of eliciting the PCD response. So although elimination of a potentially malignant cell is likely to be a rare consequence of PCD it could turn out to be important for cancer development. A brief survey is given of the most well-known triggering factors, the molecular mechanisms of the pathways involved and the emerging experimental and clinical data relating capacity of PCD to cancer initiation and progression. It is suggested that future cancer prevention will have to consider also those factors which may abrogate normal PCD.

Animals↗

[Encephalopathy in AIDS--increased formation of beta-chemokines in monocytes after HIV-1 virus infection: mechanisms of CNS involvement].

The characteristic trait of the family of lentiviruses (Retroviridae) which includes the human immune deficiency virus (HIV), is the tendency to cause a subacute neurologic disease in their animal host. The neuraxis can be inflicted at all its levels. In the advanced stage of HIV disease, more than 60 percent of patients suffer from a clinically evident neurological dysfunction. Neuropathologic changes are demonstrated in 75 - 90 percent of them at autopsy. HIV enters the CNS during the early phase of infection. HIV replicates predominantly in the nervous tissue macrophages which serve also as intrathecal reservoirs of infection. HIV isolated from the CNS is usually macrophagotropic. Neural cells are not susceptible to a productive HIV infection, contrasting with the permissivity of activated astroglial cells. The neuropathological picture of the brain involvement is typical by the giant multinuclear cells, i.e. fused monocytes/macrophages, then neuronal loss and changes in the white matter. The clinical manifestations of CNS involvement (AIDS encephalopathy) in HIV disease are variable protean, frequently associated with dementia. The pathogenesis of the neurological disease remains elusive. The cells supporting the HIV replication in the CNS (microglia, monocytes, astroglia) do not play a major role in dementia development. The neurotoxicity of viral glycoproteins, virus-induced cytokines and neurotoxin produced by CNS macrophages infected with particularly efficiently replicating HIV strains are being intensively studied. Dementia is associated with an increased virus load in the brain in the advanced stage of HIV disease. Neurotoxicity associated with HIV-infected microglial cells and macrophages activity remain to be considered, for the time being, as the most likely pathogenetic mechanism of neural dysfunction and injury. Our investigations have demonstrated that HIV infection of macrophages stimulate considerably the synthesis of MIP-1-alpha, MIP-1-beta RANTES chemokines (subgroup CC). These substances by their chemoattractant and activating properties may participate in the pathogenesis of HIV/AIDS encephalopathy, contributing to leukocytosis and inflammation, increasing thus the population of HIV-susceptible cells, facilitating their infection and enhancing finally the intrathecal spread of virus. (Tab. 2, Ref. 22.)

AIDS Dementia Complex↗

Clinical and immunological changes in AIDS patients following adoptive therapy with activated autologous CD8 T cells and interleukin-2 infusion.

OBJECTIVES: (1) To determine the safety and feasibility of repetitive reinfusions of activated autologous CD8 cells followed by low-dose continuous interleukin (IL)-2 infusion in patients with AIDS. (2) To study the relationships between clinical responses, surface marker phenotypic distributions and cytokine expression patterns of both cultured CD8 cells and lymphocytes in the peripheral blood compartment. DESIGN: Six adult patients with Centers for Disease Control and Prevention group IV HIV-1 disease ranging from mild to severe, were studied. All patients were receiving zidovudine prior to and during the study period, and had initial CD4 and CD8 cell counts > 50 and 200 x 10(6)/l, respectively. METHODS: Autologous CD8 T cells (10(8)-10(10)) were reinfused five times after ex vivo culture and stimulation with phytohemagglutinin and recombinant (r) IL-2. The fifth such infusion was followed by 5 days of rIL-2 infusion. Phenotypes and cytokine expression patterns of the expanded cells were determined as well as serum levels of immune mediators throughout the study. RESULTS: Patients showed stable CD4 and CD8 cell counts, p24 antigenemia, and minimal toxicity over the 24-week protocol study. Clinical improvement was observed in lymphadenopathy (six out of six), oral hairy leukoplakia (three out of four), and Kaposi's sarcoma (KS; two out of two) in the patients studied. In vivo induction of detectable levels of bioactive acid-stable interferon (IFN)-alpha, but not of other cytokines studied, upon activated CD8 cell reinfusion was associated consistently with improvement of oral hairy leukoplakia. However, partial regression of KS was observed after the CD8 cell infusion cycles and without IFN-alpha induction. In one of the two patients studied, KS regression was associated with decreased IL-1 alpha serum levels. In the other patient, who had failed previous IFN-alpha therapy, KS regression was observed after a decline in reinfused CD8 cell-associated gene expression of tumor necrosis factor (TNF)-beta. Both IL-1 alpha and TNF-beta are growth factors for KS cells. CONCLUSIONS: These observations demonstrate the feasibility and safety of ex vivo CD8 cell activation, expansion, and reinfusion, and rIL-2 infusion in AIDS patients. The findings in this Phase I trial suggest potential clinical efficacy and encourage Phase II trials. The correlations obtained between clinical and immunological states could contribute to an understanding of the relationship between CD8 T-cell function and HIV-1-associated disease progression.

Acquired Immunodeficiency Syndrome↗

Persistent viral infections in human carcinogenesis.

Several taxonomically distinct human pathogenic viruses capable of upholding persistent infections have been recognized as important carcinogens. Jointly they are characterized by going into decade-long interactions with host cells and/or tissues. Tumours arise after a long latent period in a few infected individuals. The cellular changes necessary for malignancy are only in part directly or indirectly caused by virus-cell interactions. Cofactors are assumed to be involved. The different routes to malignancy reflect the distinct strategies of each virus in its interaction with the host, which for the upkeep of chronic infections requires a tight control of both virus and cell multiplication and the extent to which an immune response is provoked. The size of the virus-cancer problem and the possibility of prevention makes virology one of the most promising areas of cancer prevention on a global scale. A much wider use of the vaccination against hepatitis B, especially in children, is warranted in developed countries.

Chronic Disease↗

[Inhibition of human immunodeficiency virus replication by azidothymidine (Azitidín Lachema) in cultured cells].

The inhibitory effect of the Czecho-Slovakia azidothymidine (AZT) preparation Azitidin (Lachema) on HIV 1 infection was studied in vitro. Its efficacy was compared with that of the approved AZT preparation Retrovir (Burroughs-Wellcome Co.). HIV 1 infected MT4 cells were cultivated in media containing different concentrations of Azitidin or Retrovir. Complete inhibition of virus production (reverse transcriptase activity) and of the cytopathic effect of HIV 1 was seen at the concentration of 0.1 microM of either preparation. Complete inhibition of viral antigen induction was recorded at the concentration of 1 microM. In the light of the obtained results we can conclude that Azitidin inhibits HIV 1 replication in vitro and its efficacy is fully comparable to that of Retrovir. (Tab. 4, Fig. 2, Ref. 17.)

Cell Line↗

Recombinant interferon-alpha 2 inhibits HIV replication in chronically infected promonocytic cells.

Promonocytic cells U937 with previously established HIV-1 persistent infection, were treated with increasing doses of the recombinant INF-alpha 2. This resulted in a significant decrease of virion-associated reverse transcriptase levels in medium of the cultures studied, most pronounced by the highest interferon doses, but depending on this cytokine presence. In spite of the marked restrictive effect of the interferon on the infectious virus production the synthesis, of viral structural proteins by the U937 cells, as detected by immunofluorescence, was not affected. The therapeutic index of interferon was considerably high.

Cell Line↗

Bacterially expressed core and envelope proteins of human immunodeficiency virus type-1 (HIV-1): comparative evaluation in detection of type-specific antibodies.

Recombinant proteins derived from immunodominant conserved domains of HIV-1 env and gag genes were synthesized in E. coli. An immunoblot system using total cell lysates was employed for the analysis of recombinant bacterial clones. Together 427 serum samples obtained from asymptomatic anti-HIV seropositive individuals, AIDS patients, healthy donors and persons suffering from various conditions were comparatively evaluated for the presence of HIV-1 antibodies using recombinant peptides and commercially available western blot (WB) and ELISA assays. The recombinant antigen product of plasmid pEX41 was found to be superior, with respect to sensitivity and specificity, to the viral gp41 which represents a diagnostically important constituent of the WB.

AIDS Serodiagnosis↗

Virus neutralizing antibodies at different stages of the HIV disease: increased levels after azidothymidine treatment.

Specific HIV-1 neutralizing activity was measured in single serum samples obtained from 52 individuals suffering from different stage of HIV disease, as well as in serum samples collected during a four years follow up of other 13 HIV-1 seropositive persons, from whose seven developed AIDS. Three of these persons were treated with azidothymidine. In the former group of single serum specimens, the specific neutralizing antibody positivity rate was 81 per cent in symptomless persons, 92 per cent in patients with ARC and 43 per cent in patients with AIDS. From 13 HIV-1 infected individuals, prospectively investigated from 1986 to 1990, six remained asymptomatic and no significant fluctuation of specific virus neutralizing antibody levels was noted. During this time period, remaining seven patients developed AIDS. In the sera of AIDS patients, specific neutralizing activity was either not detected or its titres were rather low before the appearance of clinical disease. Three AIDS patients were administered azidothymidine. Specific neutralizing antibody titres increased significantly one month after the beginning of azidothymidine administration and persisted at relatively high levels over several months of follow up.

AIDS-Related Complex↗