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M Kantzanou

Publications and source records attributed to M Kantzanou.

9 recordsLinked to original sources

Evidence for lack of cross-genotype protection of CD4+ T cell responses during chronic hepatitis C virus infection.

CD4+ T lymphocyte responses are thought to play a major role in control of the hepatitis C virus (HCV). Few, however, have been mapped down to the level of peptide and HLA restriction. Furthermore, the ability of such T cells to respond to viruses which differ in genotype has not been addressed in detail. In most cases of persistent infection with HCV, CD4 proliferative responses are weak or absent. From a large cohort of persistently infected patients, we identified an individual with unusually robust and persistent responses in the face of chronic infection. We firstly mapped two peptide epitopes to regions of the nonstructural protein NS4 (aa1686-1705 and aa 1746-1765). However, in contrast to the genotype 1a derived antigens used for mapping, the infecting virus was identified as genotype 3a. Strikingly, the patient's CD4 response to these epitopes were specific only for the genotype 1a sequence, and did not recognize genotype 3a synthetic peptides. Serologic assays indicated that prior exposure to HCV of genotype 1 had occurred. This patient therefore maintains strong CD4 proliferative responses which are genotype specific and not cross-reactive. The apparent 'misdirection' of these nonprotective responses has important implications for the role of natural and vaccine induced CD4 responses in the face of variable viruses.

CD4-Positive T-Lymphocytes↗

The ica operon and biofilm production in coagulase-negative Staphylococci associated with carriage and disease in a neonatal intensive care unit.

Coagulase-negative staphylococci (CoNS) are a major cause of sepsis in the neonatal intensive care unit (NICU). We evaluated the hypothesis that the ica operon and biofilm production are associated with CoNS disease in this setting. CoNS associated with bacteremia or blood culture contamination and from the skin of infants with CoNS bacteremia or healthy controls were obtained during a prospective case-control study on a busy NICU. A total of 180 strains were identified, of which 122 (68%) were Staphylococcus epidermidis and the remainder were S. capitis (n = 29), S. haemolyticus (n = 11), S. hominis (n = 9), S. warneri (n = 8), and S. auricularis (n = 1). The presence of the genes icaA, icaB, icaC, and icaD was determined by PCR, and biofilm production was examined using qualitative (Congo red agar [CRA]) and quantitative (microtiter plate) techniques. There were no significant differences in the presence of the ica operon or CRA positivity among the four groups of strains. However, quantitative biofilm production was significantly greater in strains isolated from either the blood or the skin of neonates with S. epidermidis bacteremia. We conclude that the quantity of biofilm produced may be associated with the ability to cause CoNS infection. This conclusion suggests that the regulation of biofilm expression may play a central role in the disease process.

Bacteremia↗

Ex vivo analysis of phenotype and TCR usage in relation to CD45 isoform expression on cytomegalovirus-specific CD8+ T lymphocytes.

Human cytomegalovirus (CMV) is a ubiquitous pathogen which sets up a lifelong persistent infection and which can lead to significant disease in the immunosuppressed. The immunological mechanisms controlling CMV in the long term are not defined completely, but CD8+ T lymphocytes are thought to play an important role. Antiviral CD8+ T lymphocytes may exist in very large pools in healthy individuals. Although the detailed composition of these pools is not completely understood, there is known to be heterogeneity, in particular of CD45 isoform expression. We have therefore investigated the CD8+ T-lymphocyte response against CMV directly ex vivo using Class I tetramers combined with stains for a range of phenotypic markers followed by four-colour flow cytometric analysis. In particular, we examined expression of these phenotypic markers in relation to the expression of CD45 isoforms. We found that a spectrum of phenotypes exists stably, from CD45R0(high)/RA(low) through CD45RA(high)/R0(low), and that expression of other surface markers such as CD28 and CD62L, and also TCR usage, may vary in parallel with CD45 isoform expression. In some individuals, expansions of antigen-specific CD8+ T lymphocytes bearing specific TCR Vbeta chains were restricted to cells of particular CD45 isoforms. Immunity against CMV comprises a large population of CD8+ T lymphocytes with heterogeneous potential, a spectrum in which CD45 isoform expression may play a central role.

CD8-Positive T-Lymphocytes↗

Direct ex vivo measurement of CD8(+) T-lymphocyte responses to human parvovirus B19.

Parvovirus B19 is a common human pathogen which can cause severe syndromes, including aplastic anemia and fetal hydrops. The mapping of the first parvovirus B19-derived CD8(+) T-lymphocyte epitope is described. This HLA-B35-restricted peptide derives from the nonstructural (NS1) protein and is strongly immunogenic in B19 virus-seropositive donors.

CD8-Positive T-Lymphocytes↗

A multi-centre study of nosocomial methicillin-resistant Staphylococcus aureus in Greece. Greek MRSA Study Group.

All 105 non-replicate consecutive Staphylococcus aureus strains isolated in 1997 from seven Greek hospitals, were found to be susceptible to vancomycin, teicoplanin and chloramphenicol, but only five (8%) were susceptible to all 16 antibiotics tested. Forty-three (41%) isolates were methicillin-resistant, 58% homogeneously (homMRSA) and 42% heterogeneously (hetMRSA). Resistance of homMRSA strains to other antibiotics was generally high (88-100%), although only one strain was resistant to netilmicin. Resistance in hetMRSA (6-39%) or in MSSA (5-11%) was significantly lower. Consequently, the majority (76%) of homMRSA were multi-drug resistant, while the dominant phenotype of hetMRSA and MSSA was resistance to penicillin (50% and 76%, respectively). Comparison of these strains with isolates from 1994 showed higher resistance rates to erythromycin among MSSA, to erythromycin and amikacin among hetMRSA and to rifampicin among homMRSA strains.

Anti-Bacterial Agents↗

Reduced susceptibility to vancomycin of nosocomial isolates of methicillin-resistant Staphylococcus aureus.

The MICs of vancomycin for 56 random nosocomial Staphylococcus aureus isolates homogeneously resistant to methicillin (homMRSA), 16 heterogeneously resistant isolates (hetMRSA) and 25 susceptible isolates (MSSA) were determined by a standard broth microdilution method. Representative isolates were also tested by an agar incorporation method, the Etest and population analysis. Although always in the susceptible range, MICs of vancomycin for homMRSA were significantly higher than those for hetMRSA or MSSA. Moreover, a homMRSA strain belonging to one of the major Greek MRSA clones contained a sub-population of cells that could grow in the presence of vancomycin 8 mg/L at a frequency of 6.7 x 10(-8).

Anti-Bacterial Agents↗

Streptococcus agalactiae: a vaginal pathogen?

The significance of Streptococcus agalactiae as an aetiological agent in vaginitis was evaluated. A total of 6226 samples from women who presented with vaginal symptoms was examined. The presence of >10 leucocytes/high-power field (h.p.f.) was taken to be the criterion of active infection. S. agalactiae was isolated from 10.1% of these samples. The isolation rates of other common pathogens such as Candida spp., Gardnerella vaginalis and Trichomonas spp. were 54.1%, 27.2% and 4.2%, respectively, in the same group of patients. In contrast, the isolation rates of these micro-organisms in the group of patients who had no infection (<10 leucocytes/h.p.f.) were 4.2%, 38.3%, 33% and 0.5%, respectively. In the majority of samples from which S. agalactiae was isolated, it was the sole pathogen isolated (83%) and its presence was associated with an inflammatory response in 80% of patients. Furthermore, the relative risk of vaginal infection with S. agalactiae (2.38) in patients with purulent vaginal discharge was greater than that of Candida spp. infection (1.41) and lower than that of Trichomonas spp. infection (8.32). These data suggest that S. agalactiae in symptomatic women with microscopic evidence of inflammation should be considered a causative agent of vaginitis.

Adolescent↗

Studies of human antiviral CD8+ lymphocytes using class I peptide tetramers.

Understanding the interactions between a host and a pathogen relies crucially on quantitative measurements of immune responses. Until recently, measurements of the levels of cellular immune responses, i.e. those mediated by CD4+ and CD8+ T lymphocytes have depended largely on culture in vitro and subsequent measurement of specific functions (such as cytolysis). More recently, new technologies based around tetrameric class I peptide complexes (tetramers) have allowed immunologists to measure CD8+ T lymphocyte levels directly ex vivo and independently of function. Since CD8+ lymphocytes play a key role in a number of important human viral infections, these tools have yielded useful insights into the dynamics, phenotype and function of human antiviral lymphocyte populations. In this review we describe some of the basic aspects of the biology of virus-specific CD8+ lymphocytes, and the current methods available to detect them. The use of tetramers has, in just four years, transformed our understanding of the immune responses against HIV, HTLV-1, HBV, HCV, CMV and EBV, and holds promise in a number of areas where quantitative analysis of the antiviral response in terms of both number and function is critical.

Animals↗