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Biomedical subjects

J L Herrmann

Publications and source records attributed to J L Herrmann.

At least 19 recordsLinked to original sources
PubMed2006

[The role of human dendritic cells in tuberculosis: protector or non-protector?].

INTRODUCTION: Mycobacterium tuberculosis, the cause of tuberculosis remains a pathogenic organism capable of infecting a large number of individuals and of resisting the immune response of the infected host. The main constituents of this response are the antigen presenting cells such as dendritic cells, macrophages and T lymphocytes. BACKGROUND: Comparative study of the interactions between M. tuberculosis and the antigen presenting cells has shown that dendritic cells do not permit intracellular growth of M. tuberculosis, unlike that seen in macrophages. A hostile intracellular compartment creates a bacteriostatic environment. M. tuberculosis is internalised by binding to a C-type lectin receptor (DC-SIGN). VIEWPOINT: This receptor recognises polysaccharide compounds on the surface of M. tuberculosis. This sugar-lectin bond may compensate for the bond between bacterial compounds and Toll receptors, partially inhibiting the protective inflammatory reaction or compensating for an excessive inflammatory reaction. CONCLUSIONS: This bond encourages both the persistence of quiescent bacteria in the dendritic cells and the reciprocal adaptation of the host and the bacteria over the course of time.

Antigen-Presenting Cells↗
PubMed2004

Evaluation of the automated phoenix system for potential routine use in the clinical microbiology laboratory.

A comparative study was designed to evaluate the identification (ID) and antimicrobial susceptibility testing (AST) performances of the BD Phoenix Automated Microbiology System (Becton Dickinson Diagnostic Systems [BD], Pont de Claix, France). A total of 305 single clinical isolates were collected, and comparisons were made with routine manual methods in use in our microbiology laboratories. The percentages of correct IDs were 93.3, 89.4, 91.8, and 85.7% for enterobacteria, nonfermenting gram-negative bacilli, staphylococci, and streptococci-enterococci, respectively. The median ID time was 3 h, and the median time for AST was 10 h 30 min. AST results showed variable percentages of errors for the different antibiotics. None of the enterobacteria and 0.3% of Pseudomonas aeruginosa isolates showed a very major error (VME). Only one strain of Staphylococcus aureus showed a VME with oxacillin. We demonstrate here the efficiency of the Phoenix system, which can be used for the majority of strains encountered in a university-based laboratory, for ID and AST.

Anti-Bacterial Agents↗
PubMed2003

Rapid diagnosis of extrapulmonary tuberculosis by PCR: impact of sample preparation and DNA extraction.

In cases of suspected extrapulmonary tuberculosis, rapid and accurate laboratory diagnosis is of prime importance, since traditional techniques of detecting acid-fast bacilli have limitations. The major difficulty with mycobacteria is achieving optimal cell lysis. Buffers used in commercial kits do not allow this complete lysis in a number of clinical specimens. A comparison of two sample preparation methods, pretreatment with proteinase K (PK-Roche) and complete DNA purification (cetyltrimethylammonium bromide [CTAB]-Roche), was conducted on 144 extrapulmonary specimens collected from 120 patients to evaluate the impact on the Cobas-Amplicor method. Thirty patients were diagnosed with tuberculosis, with 15 patients culture positive for Mycobacterium tuberculosis. Amplification and detection of the amplicons were impaired by a high number of inhibitory specimens (39 to 52%). CTAB-Roche allowed the detection of more culture-positive specimens by PCR than PK-Roche. Comparison with the final diagnoses of tuberculosis confirmed that CTAB-Roche produced the best sensitivity (53.8%) compared to culture (43.3%), PK-Roche (16%), and smear (13%). However, the specificity of the PCR assay with CTAB-Roche-extracted material was always lower (78.8%) than those with culture (100%) and PK-Roche (96.5%). False-positive specimens were lung biopsy material, lymph node biopsy material and aspirate, or bone marrow aspirate, mainly from immunocompromised patients. Despite the efficiency of complete DNA extraction for the rapid diagnosis by PCR of extrapulmonary tuberculosis, the false-positive results challenge our understanding of PCR results.

Abscess↗
PubMed2001

Lipoprotein access to MHC class I presentation during infection of murine macrophages with live mycobacteria.

Following uptake by macrophages, live mycobacteria initially reside within an immature phagosome that resists acidification and retains access to recycling endosomes. Glycolipids are exported from the mycobacterial phagosome and become available for immune recognition by CD1-restricted T cells. The aim of this study was to explore the possibility that lipoproteins might similarly escape from the phagosome and act as immune targets in cells infected with live mycobacteria. We have focused on a 19-kDa lipoprotein from Mycobacterium tuberculosis that was previously shown to be recognized by CD8(+) T cells. The 19-kDa Ag was found to traffic separately from live mycobacteria within infected macrophages by a pathway that was dependent on acylation of the protein. When expressed as a recombinant protein in rapid-growing mycobacteria, the 19-kDa Ag was able to deliver peptides for recognition by MHC class I-restricted T cells by a TAP-independent mechanism. Entry into the class I pathway was rapid, dependent on acylation, and could be blocked by killing the mycobacteria by heating before infection. Although the pattern of 19-kDa trafficking was similar with different mycobacterial species, preliminary experiments suggest that class I presentation is more efficient during infection with rapid-growing mycobacteria than with the slow-growing bacillus Calmette-Guérin vaccine strain.

Animals↗
PubMed2001

Multicenter evaluation of a pathogenic mycobacterium screening probe.

The introduction of nucleic acid amplification assays into the clinical laboratory has reduced the time needed to diagnose diseases caused by members of the Mycobacterium tuberculosis complex (MTBC). However, several mycobacterial species other than those of the MTBC are known to cause disease, especially in immunocompromised individuals. A screening assay has been developed for the detection of the major pathogenic mycobacterial species. The assay utilizes pan-genus primers to amplify mycobacterial DNA and a screening probe (KY493) that detects all major pathogenic mycobacteria. A multicenter European study was conducted to assess the performance of the screening probe in the clinical laboratory. The screening probe was evaluated against individual probes specific for M. tuberculosis, M. avium, and M. intracellulare, a genus-specific probe with broader species coverage, and culture. The screening probe had a sensitivity equivalent to that of the species-specific probes; all specimens positive with any of the species-specific probes were also positive with the screening probes. Compared to culture, the sensitivity of the screening probe was 89% (154 of 173) for all culture-positive specimens tested. This value was 89.6% for the genus-specific probe. The screening probe was more specific than the genus-specific probe. Specificity was 93.9% (661 of 704) compared to culture results alone. The comparable specificity value for the genus-specific probe was 84.8%. When clinical data were taken into consideration, the sensitivity of the screening assay was similar to that of culture (81% versus 76.2%) but the positive predictive value of the test was lower (76.2% versus 100% for culture). However, the screening probe was more sensitive than smear and may be a useful tool in the rapid diagnosis of mycobacterial disease.

DNA Probes↗
PubMed2001

Diagnostic value of a nested polymerase chain reaction assay on peripheral blood mononuclear cells from patients with pulmonary and extra-pulmonary tuberculosis.

SETTING: Saint Louis Hospital, Paris, France. OBJECTIVE: To determine the clinical relevance of detection of Mycobacterium tuberculosis DNA by nested polymerase chain reaction (PCR) in peripheral blood mononuclear cells (PBMCs) in the rapid diagnosis of tuberculosis. DESIGN: Single-centre prospective case study of 90 hospitalised patients and 50 healthy subjects or blood donors from 1 January to 30 June 1998. RESULTS: Twenty-three patients were diagnosed with tuberculosis (26.7%); 20 tuberculosis patients were culture-positive, with seven smear-positive for acid-fast bacilli. Sensitivity of smear, culture and nested PCR was 30.4 (7/23), 87 (20/23) and 30.4% (7/23), respectively. The specificity of smear and culture was 100%, and the specificity of the nested PCR was 96% in the healthy subjects. However, the specificity decreased to 83.6% in the hospitalised patients, with 11 nested PCR-positive patients without a diagnosis of tuberculosis. The sensitivity of the nested PCR was low in pulmonary tuberculosis (22.2%), but increased in pulmonary/extra-pulmonary tuberculosis (50%), extra-pulmonary tuberculosis (33%), and disseminated tuberculosis (33%). CONCLUSION: The use of a nested PCR assay on PBMC may pose problems for the rapid diagnosis of tuberculosis with regard to low sensitivity and specificity. However, further studies are needed to confirm this technique as an alternative test for the diagnosis of paucibacillary forms of tuberculosis.

Adult↗
PubMed2000

Analysis of post-translational modification of mycobacterial proteins using a cassette expression system.

A recombinant expression system was developed to analyse sequence determinants involved in O-glycosylation of proteins in mycobacteria. By expressing peptide sequences corresponding to known glycosylation sites within a chimeric lipoprotein construct, amino acids flanking modified threonine residues were found to have an important influence on glycosylation. The expression system was used to screen mycobacterial sequences selected using a neural network (NetOglyc) trained on eukaryotic O-glycoproteins. Evidence of glycosylation was obtained for eight of 11 proteins tested. The results suggest that sites involved in O-glycosylation of mycobacterial and eukaryotic proteins share similar structural features.

Alkaline Phosphatase↗
PubMed2000

Kinetics of circulating antibodies, immune complex and specific antibody-secreting cells in tuberculosis patients during 6 months of antimicrobial therapy.

OBJECTIVE: During the follow-up of a group of patients with active tuberculosis, the predictive potential of several antibody-based assays was evaluated in monitoring treatment efficacy. DESIGN: Eleven patients with bacteriologically documented pulmonary tuberculosis and two patients with tuberculosis pleurisy were studied over a period of 6 months, from the day before treatment to its completion. The kinetics of the humoral response to Mycobacterium tuberculosis was determined by the number of specific circulating antibody secreting cells (ASC) (ELISPOT assay), as well as the titres of specific circulating antibody and specific antibody present in circulating immune complexes (quantitative ELISA). RESULTS: Follow-up ELISPOT assays, performed after initiation of tuberculosis therapy showed a rapid increase of ASC, during the first week, followed by rapid 3-10 fold decline of ASC in 12 of 13 patients tested. This decline occurred more rapidly than the mycobacterial culture conversion. In contrast, follow-up of ELISA assays did not give relevant information in assessing the outcome of treatment. CONCLUSION: In comparison with direct detection of tubercle bacilli in sputum samples, the rapid clearance of specific circulating ASC occurring early on after the onset of therapy could suggest a potential usefulness of ELISPOT in monitoring therapeutic response.

Adult↗
PubMed2000

Mycobacteriosis in the compromised host.

The studies of rare genetic defects, the preliminary results of population-based studies, being validated by the experimental immunocompromised animal models and the current observations accumulated in immunocompromised patients with mycobacterial diseases provide us with insights into the importance of the macrophage activation pathway in controlling human infection with pathogenic and non pathogenic intracellular multiplying mycobacteria. Initial cytokine production by infected macrophages and/or dendritic cells could be crucial in the overall regulation of self cure, acquired protection or immunopathological sequelae expressing the disease. Knowledge of molecular and genetic cross-talks between phagocytic and specialized antigen presenting cells and different mycobacterial products associated with persistence or replication of the intracellular bacteria, could provide further informations on the global immune regulation of the early host responses to infection and the following events. It seems likely that the development of mycobacterial infections in humans will turn out to be as much dependent on the genetic make up of the host as or the virulence of the bacteria.

Acquired Immunodeficiency Syndrome↗
PubMed2000

E1A-mediated paclitaxel sensitization in HER-2/neu-overexpressing ovarian cancer SKOV3.ip1 through apoptosis involving the caspase-3 pathway.

HER-2/neu-overexpressing breast cancer cells are more resistant to the chemotherapeutic agent paclitaxel (Taxol) than low-HER-2/neu-expressing breast cancer cells, and the adenoviral type 5 EIA can down-regulate HER-2/neu overexpression. Therefore, in this study, we asked (a) whether EIA might sensitize response to paclitaxel in human HER-2/neu-overexpressing ovarian cancer cells, and, if so, what is the mechanism responsible; and (b) whether this enhanced chemosensitivity would translate into a therapeutic effect in an ovarian cancer xenograft model. Consequently, we demonstrated that: (a) adenovirus type 5 E1A could enhance the sensitivity of paclitaxel in paclitaxel-resistant HER-2/neu-overexpressing human ovarian cancer cells in vitro by inducing apoptosis, (b) this induction was heavily dependent on activation of the caspase-3 pathway, and (c) nude mice bearing i.p. HER-2/neu-overexpressing human ovarian cancer cells and treated with both paclitaxel and E1A gene therapy survived significantly longer than did mice treated only with paclitaxel or E1A gene therapy. Thus, we concluded that the E1A gene enhanced both the in vitro and in vivo sensitivity of paclitaxel in paclitaxel-resistant HER-2/ neu-overexpressing ovarian cancer SKOV3.ipl cells. Because a Phase I clinical trial using E1A gene targeted to HER-2/neu down-regulation has recently been completed, the current study also provided a scientific basis to further develop a novel therapy that combines paclitaxel and E1A gene therapy and its testing in a Phase II trial.

Adenovirus E1A Proteins↗
PubMed1998

Prostate carcinoma cell death resulting from inhibition of proteasome activity is independent of functional Bcl-2 and p53.

The ATP/ubiquitin-dependent 26S proteasome is a central regulator of cell cycle progression and stress responses. While investigating the application of peptide aldehyde proteasome inhibitors to block signal-induced IkappaBalpha degradation in human LNCaP prostate carcinoma cells, we observed that persistent inhibition of proteasomal activity signals a potent cell death program. Biochemically, this program included substantial upregulation of PAR-4 (prostate apoptosis response-4), a putative pro-apoptotic effector protein and stabilization of c-jun protein, a potent pro-death effector in certain cells. We also observed modest downregulation of bcl-XL, a pro-survival effector protein. However, in contrast to some recent reports stable, high level, expression of functional bcl-2 protein in prostate carcinoma cells failed to signal protection against cell death induction by proteasome inhibitors. Also in disagreement to a recent report, no evidence was found for activation of the JNK stress kinase pathway. A role for p53, a protein regulated by the proteasome pathway, was ruled out, since comparable cell death induction by proteasome inhibitors occurred in PC-3 cells that do not express functional p53 protein. These data signify that the ubiquitin/proteasome pathway represents a potential therapeutic target for prostate cancers irrespective of bcl-2 expression or p53 mutations.

Aldehydes↗
PubMed1998

Pulmonary Mycobacterium avium complex disease without dissemination in HIV-infected patients.

Pulmonary disease due to Mycobacterium avium complex (MAC) without evidence of dissemination is uncommon in HIV-infected patients. Five cases were observed over a 2-year period. All patients had AIDS and the median CD4 cell count at the time of presentation was 90 x 10(6)/L. Radiographic patterns included unilobar alveolar infiltrates or diffuse alveolar densities. All patients had a favorable clinical response to antimycobacterial chemotherapy with a median follow-up period of 10 months. MAC should be considered in HIV-infected patients with positive respiratory samples for acid-fast bacilli and pulmonary infiltrates. Patients with such findings in whom presumptive therapy for tuberculosis has failed should receive broad-spectrum antimycobacterial chemotherapy until final identification is available.

AIDS-Related Opportunistic Infections↗
PubMed1998

[Stenting for iatrogenic coronary dissection treatment].

Catheter-induced coronary dissection is rare but has a significant mortality and morbidity. The ideal management of acute coronary occlusion, whatever the cause, is the prompt restoration of the vessel patency to limit the extent and duration of ischemia. In the setting of dissection during angiography the usual approach to myocardial salvage has been emergency aortocoronary bypass surgery preceded by insertion of an intra-aortic balloon. The main disadvantages of this approach is the delay in performing emergency surgery, mainly in centers without surgical back-up on site. The authors present a case of an elderly woman with left circumflex artery dissection caused by the catheter during coronary angiography. This problem was successfully managed using an intracoronary stent. This technique has potential advantages in terms of the speed of reperfusion and availability in centers performing diagnostic angiography without surgical back-up on site.

Aged↗