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Biomedical subjects

D De Groote

Publications and source records attributed to D De Groote.

80 records · Page 5Linked to original sources

Imbalance in cytokine production by whole blood related to presence of cytopathogenic HIV-1 strains in HIV-1-infected patients.

The possible association between the emergence of cytopathogenic HIV-1 variants and disturbance of the cytokine production in the course of HIV-1 infection was studied in 18 infected patients. The cytopathogenicity of the isolates was studied in a microassay based on the use of HIV-1-infectible Hela-CD4 cells carrying the bacterial LacZ gene under the control of the HIV-LTR (P4 cells). In addition, the production of cytokines by heparinized whole blood (HWB) obtained the same day from HIV-1(+) patients was measured. TNF-alpha was determined in a one-step procedure combining HWB culture in the presence of LPS+PHA for 24 h and detection of cytokines in the same wells. In separate experiments HWB was cultured in the presence of LPS+PHA for 48 h, then the supernatants were collected and stored until assayed by ELISa for IFN-gamma and IL-4. Higher TNF-alpha levels were found in activated HWB of patients with cytopathic strains (n = 9) than in patients with non-cytopathic strains (n = 9, p = 0.02) assessed with P4 cells. A defective production of type 1 cytokine (IFN-gamma) and no increased secretion of type 2 cytokines (IL-4) was observed in patients with cytopathic strains. IFN-gamma/IL-4 ratios were significantly lower in patients with cytopathic strains (n = 9) than in other patients (n = 9, p = 0.009). The results show that the disarray of cytokine production, as assessed with whole blood culture, is associated with the cytopathogenicity of HIV-1 isolates in HIV-1-infected individuals.

Acquired Immunodeficiency Syndrome↗

Cellular vaccines.

This project is devoted to the development of novel cellular vaccines designed to treat cancer patients. These cellular vaccines present and enhance immunogens, which will elicit a potent immune response. The goal is to achieve safe and effective immune reaction against the patient's own tumour. (1) Autologous cellular vaccines are prepared by processing circulating blood mononuclear cells outside of the patient's body (ex vivo) to differentiate them into antigen-presenting cells (APCs). Monocyte-derived APCs (MD-APCs) are then grown in the presence of exogenous target antigens (tumour cell debris, or apoptotic bodies) to become fully mature APCs. (2) Functionality for antigen presentation to T cells of ex vivo MD-APCs is evaluated in vivo. (3) Cellular vaccines are tested in selected rodent animal models. Efficiency and immune response are monitored in pertinent experimental systems for cancer. Pharmacological data are generated for clinical investigation. Tolerance and biologic effects are documented in primates. (4) The first clinical trials on cancer patients are taking place in 1998 on melanoma and prostate cancer to validate the concept. Specialized cell processors with dedicated software and standardized controls are being developed and used for the preparation of cellular vaccines. (5) The evaluation of new non-viral vectors and the validation of new non-viral transfection methods of mononuclear cells with marker genes is in progress and will lead to the ex vivo transfection of genes coding for immunostimulating cytokines or for tumour antigens in MD-APCs. Efficiency will be validated in vitro and in animal models. The ex vivo and animal model studies validate the clinical relevance of this new cellular immunotechnology. Clinical validation of individual autologous cellular vaccines in specific indications for which no treatment is presently available will allow the development of cellular and gene immunotherapy for other types of cancers.

Animals↗

[Central function of the thymus in the recognition of neuroendocrine functions by T lymphocytes during their development].

The dual physiological role of the thymus in T cell positive and negative selection appears prominent in the establishment of appropriate host immune defenses. However, the cellular and molecular mechanisms underlying those thymic functions begin only to be understood. On the basis of our previous investigations about the thymic expression of different neuroendocrine-related signals, we have advanced a model which transposes at the peptide level the intervention of this primary lymphoid organ in both T cell positive and negative selective processes. There is now ample evidence that the thymic subcapsular and medullary epithelium is the site for synthesis of neurohypophysial (NHP)-related peptides (reviewed in Geenen et al., 1992a). We have also demonstrated that the epithelial component of thymic "nurse" cells (TNC) synthesizes NHP-related peptides and expresses a neuroendocrine-like phenotype (Geenen et al., 1988a). This observation was a remarkable example of the intimate neuroendocrine-immune interactions that take place during T cell ontogeny. Further immunocytochemical analyses have confirmed that one dominant NHP-related epitope belongs to the oxytocin (OT) lineage of the NHP peptide superfamily (Robert et al., 1991, 1992). The intrathymic coexpression of this OT-like epitope with a neurophysin protein domain is a strong argument for a local synthetic process similar to the hypothalamo-NHP one. However, the absence of ir-OT in secretory granules of thymic epithelial cells (TEC), as well as of NHP-related peptides in the supernatant of TEC cultures questioned the application to the thymus of the classical neurosecretory model established for hypothalamic magnocellular neurons (Scharrer & Scharrer, 1944).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Helicobacters of possible zoonotic origin: a review.

Since the isolation of Helicobacter pylori, many new Helicobacter species have been identified from the gastrointestinal tract in humans and animals. In humans, a spiral organism different from H. pylori and provisionally named "Helicobacter heilmannii", has been associated with gastritis, gastric ulceration and to a lesser degree, gastric cancer. In addition Helicobacter cinaedi, Helicobacter fennelliae, Helicobacter pullorum and "Flexispira rappini" have been isolated from cases of enteric disease, bacteremia and pneumonic illness. In the biliary tract, the presence of Helicobacter bilis, Helicobacter pullorum and "Flexispira rappini" has been demonstrated. Morphological, epidemiological and genotypic data suggest the involvement of animal helicobacters in these infections. In this paper, a review of the literature addressing the current knowledge about epidemiology, diagnosis, pathogenesis and therapy of these infections is given.

Animals↗

[Personality disorders related to schizophrenia].

Personality disorders related to schizophrenia were described since Kraepelin's works. According to the DMS III-R those disorders are gathered into the A cluster of personality disorders consisting in: schizotypal, schizoid and paranoid personality disorders. Schizotypal and paranoid personalities are biologically linked to schizophrenia and support the concept of "schizophrenia spectrum". Until now such a link is not found between schizoid personality and schizophrenia. Future research in the field of those personality disorders will bring a better knowledge in the pathogenesis of schizophrenia.

Female↗

Stabilisation of functional tumor necrosis factor-alpha by its soluble TNF receptors.

Using two enzyme-linked immunosorbent assays (ELISA), one able to detect trimeric TNF-alpha, but not its monomeric form (T-ELISA), and the other able to detect trimeric plus monomeric TNF-alpha together (T+M-ELISA), the effect of two soluble TNF-alpha receptors (P55 and P75) on the dimethylsulphoxide (DMSO) induced conversion of TNF-alpha from a trimeric to a monomeric form was determined. When TNF-alpha was incubated in the presence of a 5% final concentration of DMSO, the level of trimer, as measured by the T-ELISA, dropped to between 25 and 50% of its initial concentration whereas no change in the level of TNF-alpha was observed with the T+M-ELISA. When the incubation was performed in the presence of P55 or P75, the reduction of trimeric TNF-alpha values in the presence of 5% DMSO decreased in proportion to the concentration of sTNF-R, whereas trimeric plus monomeric TNF-alpha values remained unaffected. These results suggest a shift of TNF-alpha from a trimeric to a monomeric form in the presence of DMSO, and that TNF-Rs play a major rôle in preventing this phenomena. This could have implications for therapeutic schedules.

Dimethyl Sulfoxide↗