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Biomedical subjects

C Olive

Publications and source records attributed to C Olive.

At least 19 recordsLinked to original sources
PubMed2006

Enhanced protection against Streptococcus pyogenes infection by intranasal vaccination with a dual antigen component M protein/SfbI lipid core peptide vaccine formulation.

We investigated the efficacy of a synthetic Streptococcus pyogenes vaccine targeting two virulence factors using the Lipid Core Peptide (LCP) delivery system. BALB/c mice were immunised intranasally with LCPs containing peptides encompassing T-cell and B-cell epitopes of the conserved C-repeat region of the M protein (J8) or the fibronectin-binding repeats region (FNBR) of SfbI, or a combination formulation containing peptides representing both antigens. LCPs were co-administered with the TLR2/6 agonist MALP-2 as mucosal adjuvant. Humoral and cellular immune responses stimulated at systemic and mucosal levels were strongest in mice immunised with the dual antigen formulation. Mice were completely protected following a respiratory challenge with a lethal dose of a heterologous S. pyogenes strain, whereas there was 70% and 90% survival in mice immunised with LCP-J8 and LCP-FNBR, respectively. This is the first report demonstrating the elicitation of better protective immunity by a dual antigen component S. pyogenes vaccine.

Adhesins, Bacterial↗
PubMed2001

[Community-acquired Acinetobacter baumannii pneumonia].

We report two cases of community-acquired Acinetobacter baumannii pneumonia. Although most infections occur in hospitalized patients, a few cases of community-acquired pneumonia have been described. This disease occurs predominantly in men, and is often associated with underlying conditions such as cigarette smoking, alcohol abuse, diabetes mellitus, and chronic pulmonary diseases. Community-acquired Acinetobacter baumannii pneumonia cases are generally reported from tropical areas, especially during wet season. Microbiological identification in blood or sputum can be difficult because of frequent misinterpretation and possible confusion with Staphylococcus or Haemophilus infuenzae or neisseriae. Early antibiotherapy is required because of the fulminant clinical course, with approximatively 50% fatality rate.

Acinetobacter Infections↗
PubMed2001

Technological advances in antigen delivery and synthetic peptide vaccine developmental strategies.

Significant advances have been made in the field of peptide chemistry, especially in the design of synthetic peptide immunogens which has led to new concepts and strategies for human vaccine development. This article reviews some of these technological advances and approaches to vaccine design including the multiple antigenic peptide system, the lipid polylysine core peptide system, the polymerization of peptides into multivalent immunogens and self adjuvanting synthetic peptide-based immunogens.

Animals↗
PubMed1999

Apoptosis and expression of cytotoxic T lymphocyte effector molecules in renal allografts.

Cytotoxic T lymphocyte (CTL) mediated apoptosis is thought to play a major role in the rejection of renal allografts following transplantation, however, the CTL effector mechanism that is primarily responsible for immunological rejection is unknown. The two major effector pathways of CTL killing which lead to apoptosis involve the Fas/Fas ligand (Fas L) lytic pathway, and the perforin/granzyme degranulation pathway. The expression of CTL effector molecules which influence these pathways include Fas, Fas L and TiA-1 (cytotoxic granule protein). This study has investigated apoptosis by in situ terminal deoxytransferase-catalysed DNA nick end labelling (TUNEL), and the expression of CTL effector molecules by immunohistochemistry, in renal allograft biopsies obtained from patients following kidney transplantation. Renal biopsies were classified into three histological groups; acute cellular rejection, chronic rejection, or no rejection. The extent of T-cell infiltration of renal tissues was assessed by immunohistochemical staining with an anti-CD3 monoclonal antibody. Numerous TUNEL positive cells were detected in all transplant biopsies examined; these consisted mainly of renal tubular cells and infiltrating cells, with some TUNEL positive cells also detected in the glomeruli. In the case of normal kidney tissue, renal cells also stained positive for TUNEL but there was no lymphocytic infiltration. There was significantly more T-cell infiltration observed in acute rejection biopsies compared to the no rejection biopsies. In the case of Fas L expression, there was little expression in all three biopsy groups, apart from one case of chronic rejection. Conversely, although there were no significant differences in TiA-1 expression between the three biopsy groups, TiA-1 expression was more prominent in acute rejection biopsies. Furthermore, Fas expression was significantly decreased in acute rejection biopsies when compared to those of chronic and no rejection in which Fas was predominantly localized in the renal tubular cells. These results indicate that the mechanism of CTL killing leading to the rejection of renal allografts may be different in acute and chronic rejection. Moreover, our data indicate the potential for cytotoxic granule-based CTL killing in acute renal allograft rejection but not in chronic rejection.

Adult↗
PubMed1999

Expression of apoptotic regulatory molecules in renal cell carcinoma: elevated expression of Fas ligand.

Renal cell carcinoma (RCC) is the most common renal neoplasm. Despite being infiltrated by tumour infiltrating lymphocytes (TIL), these TIL are unable to control tumour growth in vivo, suggesting that the cytotoxic capacity of TIL against RCC is impaired, or that the tumour cells are resistant to killing and therefore escape detection by the immune system. It is postulated that the expression of apoptotic regulatory molecules in RCC favours tumour cell survival. The present study has therefore determined the expression of Fas (APO-1/CD95), Fas ligand (Fas L) and bcl-2 in these tumours. The expression of Fas, Fas L and bcl-2 mRNA transcripts was determined in RCC, normal kidney and peripheral blood by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), following RNA extraction and cDNA synthesis from tissues and cell samples. Transcript levels were measured by densitometry after Southern blot hybridization of PCR products with internal radio-labelled oligonucleotide probes; a densitometry score was assigned to each hybridizing DNA band and expressed as a ratio of the glyceraldehyde-3-phosphate dehydrogenase content. In peripheral blood, the expression of Fas L and bcl-2 transcripts was similar between patients and normal healthy individuals; however, Fas transcript expression was significantly down-regulated in the patients' versus normal peripheral blood (P = 0.026). Most interestingly, significantly up-regulated Fas L expression was observed in RCC compared to normal kidney (P = 0.041). In contrast, bcl-2 transcripts were well represented in normal kidney but markedly decreased in RCC (P = 0.021). The expression of Fas transcripts in normal kidney and RCC was variable. These data demonstrate elevated expression of Fas L transcripts in RCC, but the functional relevance of this remains to be investigated.

Adult↗
PubMed1999

Emergence and spread in French hospitals of methicillin-resistant Staphylococcus aureus with increasing susceptibility to gentamicin and other antibiotics.

Oxacillin (methicillin) resistance in methicillin-resistant Staphylococcus aureus (MRSA) is associated with an increased incidence of resistance to other antibiotics, which has increased since it was first reported in 1969. In 1992 a new phenotype of MRSA arose in France; this was characterized by a heterogeneous expression of resistance to oxacillin and susceptibility to various antibiotics, including gentamicin but also tetracycline, minocycline, lincomycin, pristinamycin, co-trimoxazole, rifampin, and fusidic acid. In French hospitals a longitudinal nationwide surveillance of antibiotic resistance in S. aureus has allowed for the detection of changes in antibiotic susceptibility profiles. Seven French clinical laboratories (six from the mainland and one from the West Indies) reported the results of susceptibility testing of 57,347 S. aureus strains isolated in their institutes between 1992 and 1998. Over a 7-year period the incidence of isolation of gentamicin-susceptible MRSA (GS-MRSA) strains has steadily increased to represent, in 1998, 46.8 to 94.4% of the MRSA strains, irrespective of the overall incidence of MRSA. Two predominant types recognized by pulsed-field gel electrophoresis (PFGE) accounted for the majority of the GS-MRSA in different mainland hospitals, both differing from the predominant type observed in the French West Indies. Some GS-MRSA and gentamicin-resistant MRSA (GR-MRSA) strains had closely related PFGE profiles, and hybridization studies confirmed the lack in GS-MRSA of the aac6'-aph2" gene, which confers resistance to all aminoglycosides, with conservation of the ant4' gene, which confers resistance to kanamycin, tobramycin, and amikacin. Thus, it is likely that certain GS-MRSA strains could have emerged from GR-MRSA strains by excision or deletion of the aac6'-aph2" gene.

Cross Infection↗
PubMed1998

Expression of cytokine mRNA transcripts in renal cell carcinoma.

Renal cell carcinoma (RCC) is a solid tumour of the kidney and is the most common renal neoplasm. Despite the presence of tumour infiltrating lymphocytes (TIL) in RCC, these tumours continue to progress in vivo suggesting a poor host immune response to the tumour, and the suppression of TIL effector function. Cytokines are key molecules that modulate the function of T cells. The possibility is investigated that the local production of cytokines in RCC contributes to immunosuppression of TIL. The expression of pro-inflammatory (IFN-gamma/IL-2) and immunosuppressive (IL-10/TGF-beta) cytokine mRNA transcripts was determined in RCC, normal kidney and peripheral blood of RCC patients using a semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) with cytokine-specific primers. Following Southern blot hybridization of the PCR products with internal radiolabelled oligonucleotide probes, cytokine transcript levels were measured by densitometry and expressed relative to the glyceraldehyde-3-phosphate dehydrogenase densitometry score. With the exception of IL-10, there were no differences in expression of cytokine mRNA transcripts between the peripheral blood of patients and normal healthy individuals. It was found that TGF-beta transcripts were well represented in normal kidney and RCC. In contrast, the expression of IFN-gamma transcripts, while low in the majority of samples, was significantly increased in RCC when compared to normal kidney (P=0.05). The IL-2 and IL-10 transcripts showed a more variable expression in normal kidney and RCC, with no significant differences in expression between the sample groups. The data demonstrating pro-inflammatory and immunosuppressive cytokine expression in RCC do not support a prominent immunosuppressive cytokine profile in these tumours.

Adult↗
PubMed1998

T cell engraftment in lymphoid tissues of human peripheral blood lymphocyte reconstituted SCID mice with or without prior activation of cells.

The reconstitution of severe combined immunodeficiency (SCID) mice with human PBL (Hu-PBL-SCID) was assessed using fresh unstimulated PBL and anti-CD3-stimulated PBL. Mice were reconstituted with PBL by intraperitoneal injection of 1-2.5 x 107 PBL in PBS; controls received PBS. Successful engraftment of human PBL in SCID mice was determined by measurement of human IgG in mouse sera, polymerase chain reaction (PCR) detection of human-specific HLA-DRbeta DNA in SCID periphery, and immunohistochemical staining of mouse tissues (spleen, lymph nodes, thymus, liver and lung) with antibodies specific for human CD45 and CD3. Human IgG was detected 1 week after reconstitution in sera of all animals that received at least 1 x 107 PBL and continued to increase for 8 weeks. Human-specific HLA-DRbeta DNA was detected in the majority of mice 3 weeks after reconstitution but not in controls. Moreover, immunohistochemical analysis of Hu-PBL-SCID mouse tissues revealed the presence of human CD45+ cells in all tissues examined. CD3+ T cell engraftment was observed in lymphoid tissues irrespective of whether PBL had been activated prior to transfer or not.

Animals↗
PubMed1997

Characterisation of gamma delta T cells in renal cell carcinoma patients by polymerase chain reaction analysis of T cell receptor transcripts.

Renal cell carcinomas (RCC) contain tumour infiltrating lymphocytes (TIL) but these are essentially immunosuppressed in that they do not generate effective antitumour immune responses in vivo. These TIL comprise predominantly alpha beta T cells, although gamma delta T cells are also present. The repertoire of gamma delta T cells in RCC, however, has not been fully investigated. To identify the gamma delta T cell populations infiltrating RCC, this study has characterised the gamma delta T cell receptor (TCR) repertoire expression in these tumours and compared this to autologous normal kidney and autologous peripheral blood. A semi-quantitative reverse transcriptase/polymerase chain reaction technique was used for amplification of rearranged TCR V-C mRNA transcripts. Primers specific for the four human TCR V gamma and six V delta subfamilies were used, each in conjunction with a primer specific for either the C gamma or C delta region. The specificity of the PCR products was confirmed by Southern blotting and hybridisation with an internal C region probe. A densitometry score was assigned to each DNA band and the level of V gene expression was determined as ratio of C delta gene expression. The gamma delta TCR expression in each sample was determined as a ratio of C delta: glyceraldehyde phosphate dehydrogenase densitometry score. This demonstrated that TCR C delta gene expression was significantly higher in RCC compared to normal kidney (P < 0.019), suggesting a selective infiltration of gamma delta T cells into the tumour. Furthermore, we observed differences in the TCR V gamma and V delta repertoires between RCC and peripheral blood. V gamma l expression was significantly decreased (P < 0.043) whereas there was an over-representation of V gamma 4 transcripts (P < 0.028) in RCC compared to blood. A significant reduction in expression of both V delta 1 (P < 0.028) and V delta 3 (P < 0.051) was also observed within kidney tumour compared to peripheral blood. These findings show that expression of the gamma delta TCR repertoire in RCC differs from that in peripheral blood and normal kidney.

Carcinoma, Renal Cell↗
PubMed1997

Modulation of experimental allergic encephalomyelitis in mice by immunization with a peptide specific for the gamma delta T cell receptor.

This study investigated the role of gamma delta T cells in experimental allergic encephalomyelitis (EAE), a chronic inflammatory disease of the central nervous system (CNS) that resembles multiple sclerosis. The strategy was to assess the effect on EAE of TCR peptide immunization directed against V gamma 6 T cells, shown recently to predominate in the CNS of mice during the early stages of EAE. The data show that TCR peptide immunization specific for V gamma 6 chains does not induce protection against EAE, since the incidence of EAE in TCR treated animals was similar to control mice, and therefore does not affect disease susceptibility per se, but rather alters the development of the disease. Specifically, there was a delay in the onset of EAE and a reduction in disease severity in TCR treated animals, although the effects were not highly significant. These findings suggest a role for gamma delta T cells in the development of EAE; however, further studies are necessary to confirm the specificity of TCR peptide immunization.

Analysis of Variance↗
PubMed1997

Expression of the mucosal gamma delta T cell receptor V region repertoire in patients with IgA nephropathy.

IgA nephropathy (IgAN) is characterized by the deposition of IgA in the glomerular mesangium and often leads to progressive renal dysfunction and kidney failure. We have previously shown that the mesangial IgA is likely to derive from the bone marrow plasma cells, and suggested that a primary abnormality within the mucosal immune system may underly the pathogenesis of IgAN. This study has analyzed the T cell receptor (TCR) variable (V) region expression by gamma delta T cells in the intestinal mucosa of patients with IgAN. The V gamma and V delta usage of TCR transcripts was determined using a semiquantitative reverse transcriptase-PCR protocol. Primers specific for the four human V gamma and six V delta subfamilies were used each with a constant (C) gamma or C delta specific primer, and the PCR-amplified TCR transcripts were detected by Southern blotting and oligonucleotide hybridization. gamma delta TCR V region expression was determined in gut biopsies and peripheral blood of 11 patients with IgAN, and the TCR V gamma and V delta repertoires were compared to those in gut and peripheral blood of 11 control individuals. gamma delta T cells in normal blood predominantly expressed V gamma 2 (V gamma 9 gene) and V delta 2 gene segments whereas those in normal gut mainly expressed V gamma 3 and V delta 3. In IgAN patients, V delta 2 was also the predominant V delta gene utilized by peripheral blood gamma delta T cells, however, we observed a predominance of V gamma 3 and reduced V gamma 2 usage by these cells. gamma delta T cells in the gut of IgAN patients mainly used V gamma 3 and V delta 1. While the gamma and delta TCR V region repertoires did not differ significantly between the peripheral blood of patients and controls, there were significant differences in V gamma and V delta repertoire expression between IgAN and control gut biopsies. V gamma 3 gene expression was significantly decreased in IgAN gut compared to control gut (P = 0.023). In addition, there was a significant decrease in V delta 3 gene expression in IgAN gut compared to control gut (P = 0.043). These findings indicate that a subpopulation of gamma delta T cells, which represent the majority of gamma delta T cells in normal gut mucosa, are significantly diminished in the gut of patients with IgAN. This suggests that a "hole" in the mucosal gamma delta T cell repertoire may play a fundamental role in contributing to the pathogenesis of IgAN.

Adult↗
PubMed1997

[Pubic osteitis caused by Salmonella indiana. Apropos of a case].

INTRODUCTION: The authors report the case of a pubic osteomyelitis caused by a salmonella indiana bacterium in a 12 year old child. CLINICAL CASE: A post traumatic left side pubic pain in a 12 year old child was associated to feverish and inflammatory syndrome, without any predisposing factor. Salmonella Indiana bacterium was found in fecal samples. Radiographs showed an asymetry of the iliopubic branches and an irregularity of the upper left border of the pubic branch. Bone scan showed a public hyperfixation and CT revealed a left-sided pubic osteolysis. The bacteriological examination of the osseous biopsy confirmed the presence of Salmonella Indiana bacterium. Recovery was obtained within 5 months with intravenous antibiotherapy. DISCUSSION: Since 1987, an increase of minor salmonella infections and particularly of Salmonella Indiana bacterium can be observed in metropolitan France (250 isolated in 1991). This increase is not experienced in Martinique. The contamination mode is yet unknown and the osseous localization is secondary to bacteriema. The patient had no predisposition excepted a chronic digestive carrier. This localization is unfrequent in children. The diagnostic has been achieved by bacteriological samples and osseous biopsy. The treatment based was on third generation cephalosporins and on quinolones.

Anti-Bacterial Agents↗
PubMed1996

Expression of the T cell receptor delta-chain repertoire in mouse lymph node.

Despite the potential for extensive diversity of gamma delta TCR, especially for delta-chains, expression of the gamma delta TCR repertoire in various mouse epithelial tissues is highly restricted. This implies that the recognition of antigen by gamma delta T cells may also be limited. To date, however, few studies have examined gamma delta TCR diversity in peripheral lymphoid tissue. This report presents the V delta usage and junctional region sequences of TCR delta-chain transcripts derived from the lymph nodes of normal (PL/J x SJ/L) F1 mice. Rearranged TCR V delta-C delta transcripts were amplified by PCR for TCR delta-chain cDNA using oligonucleotide primers specific for the murine V delta 1 to V delta 7 genes and the C delta region. Following cloning of the polymerase chain reaction-amplified TCR delta cDNA, the extent of junctional diversity was assessed by nucleotide sequencing of the V-D-J junctions of individual TCR cDNA clones. With the exception of V delta 3, all V delta genes were expressed in mouse lymph node. Furthermore, predominant usage of J delta 1 was found in cDNA clones expressing V delta 2, V delta 4, V delta 5, V delta 6 and V delta 7 gene segments but despite this there was extensive junctional diversity of delta-chains primarily due to the usage of multiple D delta segments and N-nucleotide sequence addition. In contrast, the V delta 1 cDNA clones had limited heterogeneity consisting mostly of V delta 1 directly spliced to C delta gene rearrangements. These results show that the expressed murine peripheral TCR delta-chain repertoire is extremely diverse indicating that gamma delta T cells may potentially recognize a large number of antigens, and play an important role in contributing to host immune responses.

Animals↗
PubMed1996

Experimental human Plasmodium falciparum infections: longitudinal analysis of lymphocyte responses with particular reference to gamma delta T cells.

The kinetics of the gamma delta T-cell response was analysed in the context of the overall haematological response in subjects experimentally infected with sporozoites of Plasmodium falciparum. Numbers of gamma delta and alpha beta T cells and NK cells declined markedly during infection to reach minimum values 12-13 days post-infection when the patients were ill. This decline commenced from the beginning of the erythrocytic cycle and well before parasites could be detected microscopically and clinical symptoms developed. Platelet numbers also declined. In vivo activation of gamma delta T cells was evident with sequential up-regulation of the activation markers CD69 and HLA-DR. gamma delta T cell numbers were highest after treatment with the majority being CD4-CD8-, HLA-DR+ and showing reduced CD45RA expression. Contrary to some published observations gamma delta T-cell percentages remained within the normal range. Little evidence of upregulation of activation or memory markers was observed in the alpha beta T-cell population. In vitro proliferative responses to malaria antigen which involve gamma delta T cells were lost as the infection progressed and the lymphocyte count declined but these could be restored with the addition of exogenous IL-2 to cultures. The authors findings are consistent with a protective and/or immunomodulatory role for gamma delta T cells in malaria.

Adult↗
PubMed1995

Gamma delta T cell receptor variable region usage during the development of experimental allergic encephalomyelitis.

The molecular diversity of gamma delta T cells has not previously been investigated in experimental allergic encephalomyelitis (EAE). This study characterised the gamma delta T cell receptor (TCR) variable (V) region repertoires of T cells infiltrating the brains of EAE mice during development of the disease. TCR gamma- and delta-specific cDNAs were synthesised from total RNA prepared from brain samples and transcription of rearranged V genes was assessed by polymerase chain reaction amplification of TCR V-C transcripts and Southern blot analysis. In the early stages of EAE, the TCR gamma-chain repertoire consisted of V gamma 1-3 and V gamma 6 transcripts and, similarly, a few V delta transcripts that used primarily V delta 1, V delta 4 and V delta 5 gene segments were detected. During the progression of EAE, however, most V gamma and V delta TCR transcripts were observed in the brain. These results indicate that in the course of murine EAE there is an initial infiltration into the brain of a restricted population of gamma delta T cells followed by a heterogeneous gamma delta TCR repertoire as the disease develops. Moreover, the data suggest that gamma delta T cells may play a role in the pathogenesis of demyelinating autoimmune disease.

Amino Acid Sequence↗