K. Nagy | Semmelweis University (original) (raw)

Papers by K. Nagy

International Journal of Cancer, 1983

HTLV-producing T-cell lines induce cell fusion when co-certain whether ATL patients produce neutr... more HTLV-producing T-cell lines induce cell fusion when co-certain whether ATL patients produce neutralizing cultivated with a wide variety of indicator cells, suggest-antisera reacting with HTLV envelope glycoproteins. ing that HTLV envelope antigens interact with the mem-Our first approach has been to develop a simple test of branes of many cell types-Serum antibodies from T-HTLV envelope biological activity based on cell memcell lymphoma-leukemia (ATL) patients inhibited the formation of syncytia, and sera from British, American and brane fusion. Since the discovery of XC cell fusion by J~~~~~~ ATL patients inhibited cell fusion induced by ecotropic murine leukemia viruses (Klement et al., American and Japanese HTLV isolates equally well. NO 1969), the envelope glYcoProteins of several strains of serological cross-inhibition of syncytium induction was animal C-type retrovirus have been found to induce found between HTLV and bovine leukosis virus, Moloney syncytia in certain indicator cells co-cultivated with murine leukemia virus and simian sarcoma-associated vi-virus-producing cells (Weiss et al., 1982). Syncytial asrus. A simple syncytium inhibition test in microtiter says have been described for simian sarcoma-associplater has been developd to provide a rapid lcreen for ated virus (Rangan et al., 1972), feline leukemia virus (Rangan et al., 1973), Mason-Pfizer monkey virus antibodies presumed to be specific to HTLV envelope glycoproteins.

Clinical Immunology, 1999

Antibodies to solid phase C1q (C1qAb) were determined in 295 serum samples from 132 HIV-infected ... more Antibodies to solid phase C1q (C1qAb) were determined in 295 serum samples from 132 HIV-infected subjects and in sera from 140 HIV-seronegative healthy individuals as control. An ELISA method applied for the determination of C1qAb in other diseases was used. In part of these sera, other autoantibodies (antibodies reacting with 60-kDa human heat shock protein (hsp60) or mycobacterial hsp65; IgA and IgG class antibodies against the Fab and F(ab)2 moieties of IgG) as well as complement-mediated antibody-dependent enhancement/neutralization (C-ADE) were also determined. Increased amount of C1qAb was found in HIV-infected subjects as compared with HIV-seronegative controls (P ‫؍‬ 0.0138). In 17 of 132 (13.0%) seropositive individuals but only in 7/140 (5.0%) samples from the controls, the amount of C1qAb exceeded the upper limit (95th percentile) of the normal values (P ‫؍‬ 0.031). The amount of C1qAb significantly decreased during a follow-up period of 65 months. C1qAb levels were found to strongly correlate to hsp60/65 autoantibodies but did not correlate or only weakly correlated to the amount of anti-Fab or anti-F(ab) 2 autoantibodies measured in the same serum samples. Anti-C1q antibodies recognized the solid phase hsp60/65. Three predicted epitope regions of M. paratuberculosis hsp65 were able to bind efficiently C1q antibodies. An inverse correlation was found between C1qAb and C-ADE, neutralization was more frequent in the sera with detectable C1qAb, whereas sera without C1qAb more likely enhanced HIV infection in vitro.

Acta Microbiologica et Immunologica Hungarica, 2009

For the molecular detection of Treponema pallidum authors introduced and used a nested PCR amplif... more For the molecular detection of Treponema pallidum authors introduced and used a nested PCR amplifying a conservative portion of the gene coding for the Tp 47 kDa membrane protein. PCR verified the presence of T. pallidum specific DNA in 5.7 per cent of syphilis seronegative 105 MSM belonging to HIV risk group. Treponema DNA was also detected in HIV infected, syphilis seronegative cases. Specificity of the method was demonstrated in rabbit inoculation test and also in clinically positive syphilis cases.

American Journal of Infection Control, 2014

Background: Extended-spectrum b-lactamase (ESBL)-producing Klebsiella species cause worldwide pro... more Background: Extended-spectrum b-lactamase (ESBL)-producing Klebsiella species cause worldwide problems in neonatal intensive care units (NICUs). This study aimed to determine possible risk factors for infection or colonization with ESBL-producing Klebsiella pneumoniae (ESBLKp) during an outbreak in the NICU. Methods: A retrospective cohort study was conducted among neonates admitted to the NICU of a teaching hospital in Riyadh, Saudi Arabia, during an outbreak of ESBLKp from April to July 2008. The incidence density ratio was calculated to determine possible predictors of ESBLKp colonization or infection. Results: During 2,265 person-days of follow-up of 118 neonates, 4 became infected, and 8 were colonized with ESBLKp. Univariate analyzes revealed that, among 14 neonates who were treated with vancomycin, 9 (64.3%) developed infection or colonization with ESBLKp, whereas, among 104 neonates who were not treated with vancomycin, 3 (2.9%) were affected, with an incidence density ratio of 4.22 (95% confidence interval: 1.47-5.15). Parenteral feeding and mechanical ventilation were found to be marginally significant risk factors. Conclusion: Treatment with vancomycin appears to be a risk factor for infection or colonization with ESBLKp in the NICU setting.

Acta Microbiologica Et Immunologica Hungarica, 2010

Mutations in the HIV-1 pol gene associated with resistance to antiretroviral drugs in therapy-naï... more Mutations in the HIV-1 pol gene associated with resistance to antiretroviral drugs in therapy-naïve Hungarian individuals transmitted as primary infection by their foreign sexual partners originated from African, Asian and other European countries had been analyzed. Drug resistance genotyping of HIV RT and PR genes were performed where mutations of 72 codons - among them 64 specific resistance codons representing 6 nucleoside reverse transcriptase inhibitor (NRTIs), 2 non-nucleoside reverse transcriptase inhibitor (NNRTIs) and 6 proteinase inhibitor (PRIs) drugs - had been analyzed by Truegene HIV-1 Genotyping kit and OpenGene Sequencing System. Viral variants harboring resistance mutations in the po l gene were detected in 14% of the subjects. The highest rate of resistance to a single class of inhibitors was detected towards PR inhibitors (12%), followed by NRTI (8%) and NNRTI (5%). On the contrary, 25% of viruses transmitted by homosexual activity contained mutations led to resistance to NNRT. Viruses from 11 percent of cases were resistant to 2 classes of inhibitors, and 7 percent to three classes of inhibitors. Based upon sequence data non-B subtypes and CRFs were detected in more than 71% of cases. HIV-1 C (10.7%), HIV-F1 (7.2%) and HIV-1 G (3.6%) were detected as the more frequent subtypes. Among the HIV-1 recombinant viruses CRF02_AG variants were found more frequently (28.5%) followed by CRF06_cpx (17.8%) indicating penetration of non-B subtypes and recombinant African variants into Hungary, which raises serious clinical and public health consequences.

Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, 1999

Journal of investigational allergology & clinical immunology, 2001

Impaired cell-mediated immune reactivity to polyclonal mitogens was determined in HIV-negative ho... more Impaired cell-mediated immune reactivity to polyclonal mitogens was determined in HIV-negative homosexual men (HIV-MSM). Results were compared to those we reported in a complex clinical and immunological investigation in the same risk groups 15 years ago, before the onset of the AIDS epidemic in Hungary. Cellular immune reactivity to polyclonal mitogens was studied in 74 HIV-infected or HIV-uninfected homosexual men and heterosexual controls. Lymphocytes in whole-blood cultures were stimulated with various doses of phytohaemagglutinin (PHA), concanavalin-A (Con-A), and pokeweed mitogen (PWM) in a blast transformation assay. A significant difference (p = .0002) in lymphocyte proliferation between HIV-MSM vs. heterosexuals using PWM in both concentrations was found. Proliferative capacity was similar in HIV- MSM and HIV infected males with CD4+ > 500/microl. Con-A and PHA showed a less expressed proliferative response. Decreased lymphocyte reactivity to PWM, similar to the one in e...

Acta microbiologica Hungarica, 1983

The effect of glutaurine (gamma-L-glutamyl-taurine, Litoralon) on the take and development of hep... more The effect of glutaurine (gamma-L-glutamyl-taurine, Litoralon) on the take and development of hepatoma and acute leukaemia induced by MC29/L avian oncorna-virus has been investigated in turkey poults. Glutaurine significantly decreased the incidence of hepatoma, but had no significant effect on the lethality of MC29/L infected birds. The number of primitive myeloid cells was lower in the peripheral blood of glutaurine treated birds than in the untreated controls. Reverse transcriptase determinations in turkey fibroblast cell cultures indicated that glutaurine delays MC29/L virus expression.

Acta Astronautica, 1984

... Hungary and IRINA KONSTANTINOVA,t MARINA RYKOVA, IRINA MOZGOVAYA, OLGA GUSeVA and VALERn KOZH... more ... Hungary and IRINA KONSTANTINOVA,t MARINA RYKOVA, IRINA MOZGOVAYA, OLGA GUSeVA and VALERn KOZHARINOV Institute of Biomedical Problems ... 4. DISCU,~SION In earlier spaceflight experiments, aboard bio-satellites of the Cosmos series[7], in Skylab-3 mission ...

Microbial Pathogenesis, 2009

Cytotoxin genes in 128 Austrian (AT) MSSA, 48 MRSA, 94 Hungarian (HU) MSSA, 110 MRSA and 67 Maced... more Cytotoxin genes in 128 Austrian (AT) MSSA, 48 MRSA, 94 Hungarian (HU) MSSA, 110 MRSA and 67 Macedonian (MK) MSSA, 81 MRSA strains were examined. The presence of alfa-haemolysin gene (hla) was more common in HU MSSA strains compared to AT and MK (99%, 86%, 72%: p < 0.001). AT and MK MRSA harboured hlb genes more frequently compared to HU (60%, 62%, 33%: p < 0.001). HU and MK MRSA strains carried gamma-haemolysin gene (hlg) in higher percentage in contrast to AT (88%, 83%, 69%: p ¼ 0.01). Haemolysin gamma-variant gene (hlgv) was more prevalent in HU MSSA compared to AT and MK (84%, 56%, 69%: p < 0.001). Panton-Valentine leukocidin genes were found only in AT, HU, MK MSSA and MK MRSA in 2.3%, 4%, 1.5% (p ¼ 0.53) and 1% (p ¼ 0.38), respectively. The 3-gene combination pattern comprising of hla, hlg and hld genes showed increased prevalence among AT MSSA compared to HU (27%, 11%: p < 0.001). The 4-gene pattern composed of hla, hlg, hlgv and hld genes was significantly characteristic for HU MRSA in contrast to AT and MK MRSA (56%, 12.5%, 27%: p < 0.001). Frequency of certain cytotoxin genes and combinations differed significantly in Staphylococcus aureus strains according to geographical origin and methicillin-resistance.

JAIDS Journal of Acquired Immune Deficiency Syndromes, 1999

Human herpesvirus type 6 variant A (HHV-6A) has been isolated from patients with AIDS and lymphop... more Human herpesvirus type 6 variant A (HHV-6A) has been isolated from patients with AIDS and lymphoproliferative disorders. It has little or no cross-immunity with variant B (HHV-6B). Through saliva, HHV-6B infects almost all children by 2 years of age. The mode of ...

International Journal of Antimicrobial Agents, 2007

European Journal of Clinical Microbiology & Infectious Diseases, 2012

The purpose of this study was to investigate the impact of fluoroquinolone resistance on the exis... more The purpose of this study was to investigate the impact of fluoroquinolone resistance on the existence and dynamic of MRSA clones. Resistance to ciprofloxacin was induced in strains of community-acquired (CA) MRSA from various sequence types and the fitness cost suffered by mutant derivatives measured in a propagation assay. In addition, the fitness of fluoroquinolone resistant health care-associated (HA) MRSA isolates from major clones prevalent in Hungary were compared with each other and with those of the CA-MRSA derivatives. The genetic background of fluoroquinolone resistance and fitness cost in CA-MRSA was investigated. The fitness cost observed in the CA-MRSA derivatives proved diverse; the derivatives of the ST30-MRSA-IV strain suffered significantly greater fitness cost than those of the ST8-MRSA-IV and ST80-MRSA-IV isolates. Strains from the New York-Japan (ST5-MRSA-II), South German (ST228-MRSA-I) and EMRSA-15 (ST22-MRSA-IV) HA-MRSA clones proved more viable than CA-MRSA derivatives with similar MIC values to ciprofloxacin and HA-MRSA strains from the Hungarian/Brazilian clone (ST239-MRSA-III). Our strains from the New York-Japan, South-German and EMRSA-15 clones seem to have a competitive edge over the tested CA-MRSA isolates in the health care setting. The greater fitness observed in our New York-Japan and South-German strains could account for the replacement by them of the Hungarian/Brazilian clone in Hungary about ten years ago. Alterations in relevant genes were detected. The Ser80 → Phe mutation in the grlA gene may have seriously compromised viability. Surprisingly silent nucleotide substitutions in the grlB gene seemed to impact fitness in derivatives of the ST30-MRSA-IV isolate.

European Journal of Clinical Microbiology & Infectious Diseases, 2011

The purposes of this study were to quantify the impact of Staphylococcus haemolyticus in the epid... more The purposes of this study were to quantify the impact of Staphylococcus haemolyticus in the epidemiology of the blood stream infection (BSI) and to characterize the rates and quantitative levels of resistance to antistaphylococcal drugs. During an eight-year period, 2967 BSIs of the patients hospitalized in different clinical departments of the Semmelweis University, Budapest, Hungary were analyzed. 184 were caused by S. haemolyticus amounting to 6% of all infections. The antibacterial resistance of S. haemolyticus isolates was investigated by the broth microdilution method, vancomycin agar screen, population analysis profile and PCR for mecA, vanA and vanB genes detection. Epidemiological investigation was processed by determining of phenotypic antibiotic resistance patterns and PFGE profiles.

Current Medicinal Chemistry, 2013

Polymyxins are polypeptide antibiotics, with a primary effect of membrane damaging due to their s... more Polymyxins are polypeptide antibiotics, with a primary effect of membrane damaging due to their selective binding to the lipopolysaccharide of Gram-negative bacteria. Their nephro-and neurotoxic side effects limited their use, however, in the last decade the emergence of multidrug-resistant Gram-negative bacteria led to the reintroduction of polymyxins into clinical practice. This review provides an overview about the history and the latest developments of polymyxins. We describe the antimicrobial effects, pharmacodynamics, pharmacokinetics and different routes of administration. We highlight natural classic polymyxins, namely polymyxin B and E, the non-classic agents polymyxin M, S and T. Novel polymyxin chemical structure derivatives will be listed including NAB739, NAB740, NAB741 and NAB7061, that can have important therapeutical role in the future.

Clinical Microbiology and Infection, 2007

Numerous clinical studies have indicated, based on mortality rates, that methicillin-resistant St... more Numerous clinical studies have indicated, based on mortality rates, that methicillin-resistant Staphylococcus aureus (MRSA) strains are more virulent than methicillin-susceptible S. aureus (MSSA) strains. In contrast, quantitative laboratory examinations of the presence and magnitude of pathogenic mechanisms and virulence factors in strains of MRSA and MSSA have generated conflicting data. The most important reason for these conflicting results is probably the heterogeneic nature of the resistant population. A comparison of selected and congenic MRSA and MSSA sub-populations of the same strain is required to resolve this issue.

British Journal of Dermatology, 2000

1 Hann SK, Im S, Bong HW et al. Treatment of stable vitiligo with autologous epidermal grafting a... more 1 Hann SK, Im S, Bong HW et al. Treatment of stable vitiligo with autologous epidermal grafting and PUVA. J Am Acad Dermatol 1995; 32: 943±8. 2 Kim HY, Kang KY. Epidermal grafts for treatment of stable and progressive vitiligo. J Am Acad Dermatol 1999; 40: 412±7. 3 Jones SK, Darville JM. Transmission of virus particles by cryotherapy and multi-use caustic pencils: a problem to dermatologists? Br J Dermatol 1989; 121: 481±6. 4 Charles CR, Sire DJ. Transmission of papovavirus by cryotherapy applicator. JAMA 1971; 218: 1435.

Brazilian Journal of Medical and Biological Research, 2001

IFN-g mRNA expression was evaluated in nonstimulated peripheral blood mononuclear cells (PBMC) of... more IFN-g mRNA expression was evaluated in nonstimulated peripheral blood mononuclear cells (PBMC) of HIV-infected and seronegative individuals using quantitative competitive and semiquantitative RT-PCR and the sensitivity of these methods was compared. A significant correlation was found between quantitative competitive and semiquantitative RT-PCR in samples of both HIV-seronegative (P = 0.004) and HIV-infected individuals (P = 0.0004). PBMC from HIV-infected individuals presented a remarkable increase of IFN-g mRNA expression, as determined by both types of RT-PCR methods. Semiquantitative RT-PCR even without an internal standard is also acceptable for measuring cytokine mRNA expression, but less reliable if small amounts are quantified. Moreover, we found that increased IFN-g mRNA expression is independent of CD4+ cell count in AIDS-free HIV-infected patients.

Acta Microbiologica et Immunologica Hungarica, 2009

Recently, a PCR-derived method for serotyping Streptococcus pneumoniae has been devised to substi... more Recently, a PCR-derived method for serotyping Streptococcus pneumoniae has been devised to substitute the conventional antiserum phenotypic method. The method initially used a multiplex PCR reaction, dividing the isolates into 6 different groups based on the detected PCR gel pattern. In order to optimise and refine this crucial step, the Taguchi technique was employed, which can evaluate the individual effect of six parameters (in this case: primers, MgCl2, nucleotide mix, polymerase and buffer), with only 18 experiments; varying the parameter levels in an orthogonal matrix which suppresses the interactions between them. With this method, clear and sharp bands were observed in 5 experiments out of the 18, while the PCR did not work reliably in the remaining cases. In addition, the PCR-based technique could be rendered more economic by the 10-fold lowering of the quantities of two primers. The modified reaction yielded identical results to those obtained with the original method. Furthermore, we have designed serotype-specific primers for 11 new serotypes. The most important ones are those that can distinguish the very closely related, but equally important serotypes 6A and 6B.

Acta Microbiologica et Immunologica Hungarica, 2010

Mutations in the HIV-1 pol gene associated with resistance to antiretroviral drugs in therapy-naï... more Mutations in the HIV-1 pol gene associated with resistance to antiretroviral drugs in therapy-naïve Hungarian individuals transmitted as primary infection by their foreign sexual partners originated from African, Asian and other European countries had been analyzed. Drug resistance genotyping of HIV RT and PR genes were performed where mutations of 72 codons - among them 64 specific resistance codons representing 6 nucleoside reverse transcriptase inhibitor (NRTIs), 2 non-nucleoside reverse transcriptase inhibitor (NNRTIs) and 6 proteinase inhibitor (PRIs) drugs - had been analyzed by Truegene HIV-1 Genotyping kit and OpenGene Sequencing System. Viral variants harboring resistance mutations in the po l gene were detected in 14% of the subjects. The highest rate of resistance to a single class of inhibitors was detected towards PR inhibitors (12%), followed by NRTI (8%) and NNRTI (5%). On the contrary, 25% of viruses transmitted by homosexual activity contained mutations led to resistance to NNRT. Viruses from 11 percent of cases were resistant to 2 classes of inhibitors, and 7 percent to three classes of inhibitors. Based upon sequence data non-B subtypes and CRFs were detected in more than 71% of cases. HIV-1 C (10.7%), HIV-F1 (7.2%) and HIV-1 G (3.6%) were detected as the more frequent subtypes. Among the HIV-1 recombinant viruses CRF02_AG variants were found more frequently (28.5%) followed by CRF06_cpx (17.8%) indicating penetration of non-B subtypes and recombinant African variants into Hungary, which raises serious clinical and public health consequences.

International Journal of Cancer, 1983

HTLV-producing T-cell lines induce cell fusion when co-certain whether ATL patients produce neutr... more HTLV-producing T-cell lines induce cell fusion when co-certain whether ATL patients produce neutralizing cultivated with a wide variety of indicator cells, suggest-antisera reacting with HTLV envelope glycoproteins. ing that HTLV envelope antigens interact with the mem-Our first approach has been to develop a simple test of branes of many cell types-Serum antibodies from T-HTLV envelope biological activity based on cell memcell lymphoma-leukemia (ATL) patients inhibited the formation of syncytia, and sera from British, American and brane fusion. Since the discovery of XC cell fusion by J~~~~~~ ATL patients inhibited cell fusion induced by ecotropic murine leukemia viruses (Klement et al., American and Japanese HTLV isolates equally well. NO 1969), the envelope glYcoProteins of several strains of serological cross-inhibition of syncytium induction was animal C-type retrovirus have been found to induce found between HTLV and bovine leukosis virus, Moloney syncytia in certain indicator cells co-cultivated with murine leukemia virus and simian sarcoma-associated vi-virus-producing cells (Weiss et al., 1982). Syncytial asrus. A simple syncytium inhibition test in microtiter says have been described for simian sarcoma-associplater has been developd to provide a rapid lcreen for ated virus (Rangan et al., 1972), feline leukemia virus (Rangan et al., 1973), Mason-Pfizer monkey virus antibodies presumed to be specific to HTLV envelope glycoproteins.

Clinical Immunology, 1999

Antibodies to solid phase C1q (C1qAb) were determined in 295 serum samples from 132 HIV-infected ... more Antibodies to solid phase C1q (C1qAb) were determined in 295 serum samples from 132 HIV-infected subjects and in sera from 140 HIV-seronegative healthy individuals as control. An ELISA method applied for the determination of C1qAb in other diseases was used. In part of these sera, other autoantibodies (antibodies reacting with 60-kDa human heat shock protein (hsp60) or mycobacterial hsp65; IgA and IgG class antibodies against the Fab and F(ab)2 moieties of IgG) as well as complement-mediated antibody-dependent enhancement/neutralization (C-ADE) were also determined. Increased amount of C1qAb was found in HIV-infected subjects as compared with HIV-seronegative controls (P ‫؍‬ 0.0138). In 17 of 132 (13.0%) seropositive individuals but only in 7/140 (5.0%) samples from the controls, the amount of C1qAb exceeded the upper limit (95th percentile) of the normal values (P ‫؍‬ 0.031). The amount of C1qAb significantly decreased during a follow-up period of 65 months. C1qAb levels were found to strongly correlate to hsp60/65 autoantibodies but did not correlate or only weakly correlated to the amount of anti-Fab or anti-F(ab) 2 autoantibodies measured in the same serum samples. Anti-C1q antibodies recognized the solid phase hsp60/65. Three predicted epitope regions of M. paratuberculosis hsp65 were able to bind efficiently C1q antibodies. An inverse correlation was found between C1qAb and C-ADE, neutralization was more frequent in the sera with detectable C1qAb, whereas sera without C1qAb more likely enhanced HIV infection in vitro.

Acta Microbiologica et Immunologica Hungarica, 2009

For the molecular detection of Treponema pallidum authors introduced and used a nested PCR amplif... more For the molecular detection of Treponema pallidum authors introduced and used a nested PCR amplifying a conservative portion of the gene coding for the Tp 47 kDa membrane protein. PCR verified the presence of T. pallidum specific DNA in 5.7 per cent of syphilis seronegative 105 MSM belonging to HIV risk group. Treponema DNA was also detected in HIV infected, syphilis seronegative cases. Specificity of the method was demonstrated in rabbit inoculation test and also in clinically positive syphilis cases.

American Journal of Infection Control, 2014

Background: Extended-spectrum b-lactamase (ESBL)-producing Klebsiella species cause worldwide pro... more Background: Extended-spectrum b-lactamase (ESBL)-producing Klebsiella species cause worldwide problems in neonatal intensive care units (NICUs). This study aimed to determine possible risk factors for infection or colonization with ESBL-producing Klebsiella pneumoniae (ESBLKp) during an outbreak in the NICU. Methods: A retrospective cohort study was conducted among neonates admitted to the NICU of a teaching hospital in Riyadh, Saudi Arabia, during an outbreak of ESBLKp from April to July 2008. The incidence density ratio was calculated to determine possible predictors of ESBLKp colonization or infection. Results: During 2,265 person-days of follow-up of 118 neonates, 4 became infected, and 8 were colonized with ESBLKp. Univariate analyzes revealed that, among 14 neonates who were treated with vancomycin, 9 (64.3%) developed infection or colonization with ESBLKp, whereas, among 104 neonates who were not treated with vancomycin, 3 (2.9%) were affected, with an incidence density ratio of 4.22 (95% confidence interval: 1.47-5.15). Parenteral feeding and mechanical ventilation were found to be marginally significant risk factors. Conclusion: Treatment with vancomycin appears to be a risk factor for infection or colonization with ESBLKp in the NICU setting.

Acta Microbiologica Et Immunologica Hungarica, 2010

Mutations in the HIV-1 pol gene associated with resistance to antiretroviral drugs in therapy-naï... more Mutations in the HIV-1 pol gene associated with resistance to antiretroviral drugs in therapy-naïve Hungarian individuals transmitted as primary infection by their foreign sexual partners originated from African, Asian and other European countries had been analyzed. Drug resistance genotyping of HIV RT and PR genes were performed where mutations of 72 codons - among them 64 specific resistance codons representing 6 nucleoside reverse transcriptase inhibitor (NRTIs), 2 non-nucleoside reverse transcriptase inhibitor (NNRTIs) and 6 proteinase inhibitor (PRIs) drugs - had been analyzed by Truegene HIV-1 Genotyping kit and OpenGene Sequencing System. Viral variants harboring resistance mutations in the po l gene were detected in 14% of the subjects. The highest rate of resistance to a single class of inhibitors was detected towards PR inhibitors (12%), followed by NRTI (8%) and NNRTI (5%). On the contrary, 25% of viruses transmitted by homosexual activity contained mutations led to resistance to NNRT. Viruses from 11 percent of cases were resistant to 2 classes of inhibitors, and 7 percent to three classes of inhibitors. Based upon sequence data non-B subtypes and CRFs were detected in more than 71% of cases. HIV-1 C (10.7%), HIV-F1 (7.2%) and HIV-1 G (3.6%) were detected as the more frequent subtypes. Among the HIV-1 recombinant viruses CRF02_AG variants were found more frequently (28.5%) followed by CRF06_cpx (17.8%) indicating penetration of non-B subtypes and recombinant African variants into Hungary, which raises serious clinical and public health consequences.

Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, 1999

Journal of investigational allergology & clinical immunology, 2001

Impaired cell-mediated immune reactivity to polyclonal mitogens was determined in HIV-negative ho... more Impaired cell-mediated immune reactivity to polyclonal mitogens was determined in HIV-negative homosexual men (HIV-MSM). Results were compared to those we reported in a complex clinical and immunological investigation in the same risk groups 15 years ago, before the onset of the AIDS epidemic in Hungary. Cellular immune reactivity to polyclonal mitogens was studied in 74 HIV-infected or HIV-uninfected homosexual men and heterosexual controls. Lymphocytes in whole-blood cultures were stimulated with various doses of phytohaemagglutinin (PHA), concanavalin-A (Con-A), and pokeweed mitogen (PWM) in a blast transformation assay. A significant difference (p = .0002) in lymphocyte proliferation between HIV-MSM vs. heterosexuals using PWM in both concentrations was found. Proliferative capacity was similar in HIV- MSM and HIV infected males with CD4+ > 500/microl. Con-A and PHA showed a less expressed proliferative response. Decreased lymphocyte reactivity to PWM, similar to the one in e...

Acta microbiologica Hungarica, 1983

The effect of glutaurine (gamma-L-glutamyl-taurine, Litoralon) on the take and development of hep... more The effect of glutaurine (gamma-L-glutamyl-taurine, Litoralon) on the take and development of hepatoma and acute leukaemia induced by MC29/L avian oncorna-virus has been investigated in turkey poults. Glutaurine significantly decreased the incidence of hepatoma, but had no significant effect on the lethality of MC29/L infected birds. The number of primitive myeloid cells was lower in the peripheral blood of glutaurine treated birds than in the untreated controls. Reverse transcriptase determinations in turkey fibroblast cell cultures indicated that glutaurine delays MC29/L virus expression.

Acta Astronautica, 1984

... Hungary and IRINA KONSTANTINOVA,t MARINA RYKOVA, IRINA MOZGOVAYA, OLGA GUSeVA and VALERn KOZH... more ... Hungary and IRINA KONSTANTINOVA,t MARINA RYKOVA, IRINA MOZGOVAYA, OLGA GUSeVA and VALERn KOZHARINOV Institute of Biomedical Problems ... 4. DISCU,~SION In earlier spaceflight experiments, aboard bio-satellites of the Cosmos series[7], in Skylab-3 mission ...

Microbial Pathogenesis, 2009

Cytotoxin genes in 128 Austrian (AT) MSSA, 48 MRSA, 94 Hungarian (HU) MSSA, 110 MRSA and 67 Maced... more Cytotoxin genes in 128 Austrian (AT) MSSA, 48 MRSA, 94 Hungarian (HU) MSSA, 110 MRSA and 67 Macedonian (MK) MSSA, 81 MRSA strains were examined. The presence of alfa-haemolysin gene (hla) was more common in HU MSSA strains compared to AT and MK (99%, 86%, 72%: p < 0.001). AT and MK MRSA harboured hlb genes more frequently compared to HU (60%, 62%, 33%: p < 0.001). HU and MK MRSA strains carried gamma-haemolysin gene (hlg) in higher percentage in contrast to AT (88%, 83%, 69%: p ¼ 0.01). Haemolysin gamma-variant gene (hlgv) was more prevalent in HU MSSA compared to AT and MK (84%, 56%, 69%: p < 0.001). Panton-Valentine leukocidin genes were found only in AT, HU, MK MSSA and MK MRSA in 2.3%, 4%, 1.5% (p ¼ 0.53) and 1% (p ¼ 0.38), respectively. The 3-gene combination pattern comprising of hla, hlg and hld genes showed increased prevalence among AT MSSA compared to HU (27%, 11%: p < 0.001). The 4-gene pattern composed of hla, hlg, hlgv and hld genes was significantly characteristic for HU MRSA in contrast to AT and MK MRSA (56%, 12.5%, 27%: p < 0.001). Frequency of certain cytotoxin genes and combinations differed significantly in Staphylococcus aureus strains according to geographical origin and methicillin-resistance.

JAIDS Journal of Acquired Immune Deficiency Syndromes, 1999

Human herpesvirus type 6 variant A (HHV-6A) has been isolated from patients with AIDS and lymphop... more Human herpesvirus type 6 variant A (HHV-6A) has been isolated from patients with AIDS and lymphoproliferative disorders. It has little or no cross-immunity with variant B (HHV-6B). Through saliva, HHV-6B infects almost all children by 2 years of age. The mode of ...

International Journal of Antimicrobial Agents, 2007

European Journal of Clinical Microbiology & Infectious Diseases, 2012

The purpose of this study was to investigate the impact of fluoroquinolone resistance on the exis... more The purpose of this study was to investigate the impact of fluoroquinolone resistance on the existence and dynamic of MRSA clones. Resistance to ciprofloxacin was induced in strains of community-acquired (CA) MRSA from various sequence types and the fitness cost suffered by mutant derivatives measured in a propagation assay. In addition, the fitness of fluoroquinolone resistant health care-associated (HA) MRSA isolates from major clones prevalent in Hungary were compared with each other and with those of the CA-MRSA derivatives. The genetic background of fluoroquinolone resistance and fitness cost in CA-MRSA was investigated. The fitness cost observed in the CA-MRSA derivatives proved diverse; the derivatives of the ST30-MRSA-IV strain suffered significantly greater fitness cost than those of the ST8-MRSA-IV and ST80-MRSA-IV isolates. Strains from the New York-Japan (ST5-MRSA-II), South German (ST228-MRSA-I) and EMRSA-15 (ST22-MRSA-IV) HA-MRSA clones proved more viable than CA-MRSA derivatives with similar MIC values to ciprofloxacin and HA-MRSA strains from the Hungarian/Brazilian clone (ST239-MRSA-III). Our strains from the New York-Japan, South-German and EMRSA-15 clones seem to have a competitive edge over the tested CA-MRSA isolates in the health care setting. The greater fitness observed in our New York-Japan and South-German strains could account for the replacement by them of the Hungarian/Brazilian clone in Hungary about ten years ago. Alterations in relevant genes were detected. The Ser80 → Phe mutation in the grlA gene may have seriously compromised viability. Surprisingly silent nucleotide substitutions in the grlB gene seemed to impact fitness in derivatives of the ST30-MRSA-IV isolate.

European Journal of Clinical Microbiology & Infectious Diseases, 2011

The purposes of this study were to quantify the impact of Staphylococcus haemolyticus in the epid... more The purposes of this study were to quantify the impact of Staphylococcus haemolyticus in the epidemiology of the blood stream infection (BSI) and to characterize the rates and quantitative levels of resistance to antistaphylococcal drugs. During an eight-year period, 2967 BSIs of the patients hospitalized in different clinical departments of the Semmelweis University, Budapest, Hungary were analyzed. 184 were caused by S. haemolyticus amounting to 6% of all infections. The antibacterial resistance of S. haemolyticus isolates was investigated by the broth microdilution method, vancomycin agar screen, population analysis profile and PCR for mecA, vanA and vanB genes detection. Epidemiological investigation was processed by determining of phenotypic antibiotic resistance patterns and PFGE profiles.

Current Medicinal Chemistry, 2013

Polymyxins are polypeptide antibiotics, with a primary effect of membrane damaging due to their s... more Polymyxins are polypeptide antibiotics, with a primary effect of membrane damaging due to their selective binding to the lipopolysaccharide of Gram-negative bacteria. Their nephro-and neurotoxic side effects limited their use, however, in the last decade the emergence of multidrug-resistant Gram-negative bacteria led to the reintroduction of polymyxins into clinical practice. This review provides an overview about the history and the latest developments of polymyxins. We describe the antimicrobial effects, pharmacodynamics, pharmacokinetics and different routes of administration. We highlight natural classic polymyxins, namely polymyxin B and E, the non-classic agents polymyxin M, S and T. Novel polymyxin chemical structure derivatives will be listed including NAB739, NAB740, NAB741 and NAB7061, that can have important therapeutical role in the future.

Clinical Microbiology and Infection, 2007

Numerous clinical studies have indicated, based on mortality rates, that methicillin-resistant St... more Numerous clinical studies have indicated, based on mortality rates, that methicillin-resistant Staphylococcus aureus (MRSA) strains are more virulent than methicillin-susceptible S. aureus (MSSA) strains. In contrast, quantitative laboratory examinations of the presence and magnitude of pathogenic mechanisms and virulence factors in strains of MRSA and MSSA have generated conflicting data. The most important reason for these conflicting results is probably the heterogeneic nature of the resistant population. A comparison of selected and congenic MRSA and MSSA sub-populations of the same strain is required to resolve this issue.

British Journal of Dermatology, 2000

1 Hann SK, Im S, Bong HW et al. Treatment of stable vitiligo with autologous epidermal grafting a... more 1 Hann SK, Im S, Bong HW et al. Treatment of stable vitiligo with autologous epidermal grafting and PUVA. J Am Acad Dermatol 1995; 32: 943±8. 2 Kim HY, Kang KY. Epidermal grafts for treatment of stable and progressive vitiligo. J Am Acad Dermatol 1999; 40: 412±7. 3 Jones SK, Darville JM. Transmission of virus particles by cryotherapy and multi-use caustic pencils: a problem to dermatologists? Br J Dermatol 1989; 121: 481±6. 4 Charles CR, Sire DJ. Transmission of papovavirus by cryotherapy applicator. JAMA 1971; 218: 1435.

Brazilian Journal of Medical and Biological Research, 2001

IFN-g mRNA expression was evaluated in nonstimulated peripheral blood mononuclear cells (PBMC) of... more IFN-g mRNA expression was evaluated in nonstimulated peripheral blood mononuclear cells (PBMC) of HIV-infected and seronegative individuals using quantitative competitive and semiquantitative RT-PCR and the sensitivity of these methods was compared. A significant correlation was found between quantitative competitive and semiquantitative RT-PCR in samples of both HIV-seronegative (P = 0.004) and HIV-infected individuals (P = 0.0004). PBMC from HIV-infected individuals presented a remarkable increase of IFN-g mRNA expression, as determined by both types of RT-PCR methods. Semiquantitative RT-PCR even without an internal standard is also acceptable for measuring cytokine mRNA expression, but less reliable if small amounts are quantified. Moreover, we found that increased IFN-g mRNA expression is independent of CD4+ cell count in AIDS-free HIV-infected patients.

Acta Microbiologica et Immunologica Hungarica, 2009

Recently, a PCR-derived method for serotyping Streptococcus pneumoniae has been devised to substi... more Recently, a PCR-derived method for serotyping Streptococcus pneumoniae has been devised to substitute the conventional antiserum phenotypic method. The method initially used a multiplex PCR reaction, dividing the isolates into 6 different groups based on the detected PCR gel pattern. In order to optimise and refine this crucial step, the Taguchi technique was employed, which can evaluate the individual effect of six parameters (in this case: primers, MgCl2, nucleotide mix, polymerase and buffer), with only 18 experiments; varying the parameter levels in an orthogonal matrix which suppresses the interactions between them. With this method, clear and sharp bands were observed in 5 experiments out of the 18, while the PCR did not work reliably in the remaining cases. In addition, the PCR-based technique could be rendered more economic by the 10-fold lowering of the quantities of two primers. The modified reaction yielded identical results to those obtained with the original method. Furthermore, we have designed serotype-specific primers for 11 new serotypes. The most important ones are those that can distinguish the very closely related, but equally important serotypes 6A and 6B.

Acta Microbiologica et Immunologica Hungarica, 2010

Mutations in the HIV-1 pol gene associated with resistance to antiretroviral drugs in therapy-naï... more Mutations in the HIV-1 pol gene associated with resistance to antiretroviral drugs in therapy-naïve Hungarian individuals transmitted as primary infection by their foreign sexual partners originated from African, Asian and other European countries had been analyzed. Drug resistance genotyping of HIV RT and PR genes were performed where mutations of 72 codons - among them 64 specific resistance codons representing 6 nucleoside reverse transcriptase inhibitor (NRTIs), 2 non-nucleoside reverse transcriptase inhibitor (NNRTIs) and 6 proteinase inhibitor (PRIs) drugs - had been analyzed by Truegene HIV-1 Genotyping kit and OpenGene Sequencing System. Viral variants harboring resistance mutations in the po l gene were detected in 14% of the subjects. The highest rate of resistance to a single class of inhibitors was detected towards PR inhibitors (12%), followed by NRTI (8%) and NNRTI (5%). On the contrary, 25% of viruses transmitted by homosexual activity contained mutations led to resistance to NNRT. Viruses from 11 percent of cases were resistant to 2 classes of inhibitors, and 7 percent to three classes of inhibitors. Based upon sequence data non-B subtypes and CRFs were detected in more than 71% of cases. HIV-1 C (10.7%), HIV-F1 (7.2%) and HIV-1 G (3.6%) were detected as the more frequent subtypes. Among the HIV-1 recombinant viruses CRF02_AG variants were found more frequently (28.5%) followed by CRF06_cpx (17.8%) indicating penetration of non-B subtypes and recombinant African variants into Hungary, which raises serious clinical and public health consequences.