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Biomedical subjects

B Vandekerckhove

Publications and source records attributed to B Vandekerckhove.

At least 19 recordsLinked to original sources

The safety and efficacy of a powered toothbrush on soft tissues in patients with implant-supported fixed prostheses.

The safety, efficacy and acceptability of an oscillating/rotating powered toothbrush was assessed in patients rehabilitated with fixed prostheses on implants. One hundred consecutive patients (aged 18-80; mean 56.3; 51 females), who met the inclusion/exclusion criteria and who participated in a regular annual recall scheme, were enrolled. They were instructed on how to use the powered toothbrush, as well as on classical interdental plaque control. The electric toothbrush had to be used twice daily for 2 min. The following periodontal parameters were measured at baseline and at 3 months, 6 months and 12 months: presence/absence of gingival and/or mucosal ulceration/desquamation; sulcus bleeding index; probing pocket depth; periodontal pocket-bleeding index and gingival recession. At 3 months and at the end of the study, patients completed a questionnaire concerning the overall acceptability and convenience of the powered toothbrush, as compared with their habitual manual toothbrush. A total of 80 patients completed the study. No dropouts were related to the use of the powered toothbrush. All parameters improved over the course of the study. The mean overall pocket depth decreased from 3.3 mm at baseline to 3.0 mm at 12 months, while the mean decrease in recession was 0.1 mm at 12 months. During the 1-year observation, there was a slight gain in periodontal attachment level. Gingival ulcerations were not observed at any point in the study. High scores for convenience and comfort of the powered toothbrush were reported, and the majority (95%) said that they would continue to use it for habitual oral hygiene. It is concluded that the powered toothbrush investigated is effective, safe and comfortable for patients rehabilitated by means of oral implant-supported prostheses.

Adolescent↗

The immediate rehabilitation by means of a ready-made final fixed prosthesis in the edentulous mandible: a 1-year follow-up study on 50 consecutive patients.

Although a two-stage procedure with symphyseal oral implants can lead to a long-term (15 years) 99% cumulative survival rate, a one-stage approach with immediate loading via prefabricated elements seems to offer a short-term acceptable outcome with significantly lower costs. A series of 50 consecutive patients, not eliminated for any systemic or smoking condition, received at the department of periodontology three implants in the symphyseal area, connected by a very rigid horse shoe-shaped titanium bar. A final screw retained prosthetic framework was placed on top of it at the department of prosthetic dentistry within 2 days after surgery (44) or after a delay, due to purely external factors, of up to 10 days (6). Forty-five patients were followed for 1 year. In one patient, all three implants failed and another four patients were lost to follow-up. The cumulative failure rates for implants and prostheses at 1 year were, respectively, 7.3% and 5%. The mean marginal bone loss at 1 year was 1.08 mm (SD: 1.62; range -5.68 to +2.55). This study shows that stable marginal bone levels can be maintained around immediately loaded implants in the lower jaw in an average patient population for at least 1 year. The survival rate is, however, lower than for a staged approach.

Aged↗

Arthroscopic partial lateral meniscectomy long-term results in athletes.

This is a retrospective case-control study of arthroscopic partial meniscectomy for isolated lesions of the lateral meniscus, performed between 1990 and 1995. Thirty-one knees were evaluated after an average follow-up of 8 years: 48.4% had excellent/good IKDC-scores and 64.5% excellent/good Lysholm scores. The Tegner activity score dropped from 7.2 (competitive sports) to 5.7 (recreational sports). Fairbank changes were noted in 92.9% of the radiographs. Deterioration of results after arthroscopic partial lateral meniscectomy is obvious. The extent of the resection is a significant factor.

Adult↗

[The role of periodontal diseases in bad breath].

The majority of bad breath originates within the oral cavity. However, it is also possible that it is caused by other extra-oral sources. Ear-nose-and-throat causes and systemic diseases, such as diabetes mellitus, uremia, liver failure, pulmonary carcinoma, bronchiectasis, are the most frequent problems. In 65-85% of the cases of bad breath, we find the cause in the parodontium and/or tongue. Components from tongue coating and periodontal pockets circulate through the saliva in the whole oral cavity and also reach the tonsils.

Diagnosis, Differential↗

Both CD34+38+ and CD34+38- cells home specifically to the bone marrow of NOD/LtSZ scid/scid mice but show different kinetics in expansion.

Human hemopoietic stem cells (HSC) have been shown to engraft, differentiate, and proliferate in the hemopoietic tissues of sublethally irradiated NOD/LtSZ scid/scid (NOD/SCID) mice. We used this model to study homing, survival, and expansion of human HSC populations from different sources or phenotype. We observed that CD34+ cells homed specifically to bone marrow (BM) and spleen, but by 3 days after injection, survived only in the BM. These BM-homed CD34+ cells proliferated intensively and gave rise to a 12-fold, 5.5-fold, and 4-fold expansion in 3 days for umbilical cord blood, adult mobilized peripheral blood, and adult BM-derived cells, respectively. By injection of purified subpopulations, it was demonstrated that both CD34+38+ and CD34+38- umbilical cord blood HSC homed to the BM and expanded. Importantly, kinetics of expansion were different: CD34+38+ cells started to increase in cell number from day 3 onwards, and by 4 wk after injection, virtually all CD34+ cells had disappeared. In contrast, CD34+38- cells remained quiescent during the first week and started to expand intensively from the third week on. In this paper, we have shown that homing, survival, and expansion of stem cells are three independent phenomena important in the early phase of BM engraftment and that kinetics of engraftment differ between CD34+38+ and CD34+38- cells.

ADP-ribosyl Cyclase↗

Human T lymphopoiesis. In vitro and in vivo study models.

Successive steps in T lymphocyte differentiation and T potential of human stem cells (HSC) can be tested in the following models: (a) the infusion of cells in NOD-SCID mice, (b) the injection of cells in renconstituted SCID/hu mice, (c) the differentiation of cells in fetal thymus organ culture (FTOC), and (d) on thymic stromal layers. Using mixed human-murine FTOC, we showed (a) TCR alpha beta, TCR gamma delta lymphocytes, NK cells, and dendritic cells complete their differentiation, (b) IL-7R alpha signaling and IL-7 are essential, (c) a detailed phenotypic and functional analysis of discrete successive steps of positively selected thymocytes, (d) an efficient transduction of genes in HSC with persistent gene expression throughout the T-lymphocyte differentiation, and (e) adaptation to submerging high oxygen culture increases the test sensitivity to a clonal assay. Other approaches are the in vivo SCID/hu reconstitution model. With this method small fragments of human fetal liver and thymus are implanted under the kidney capsule of an adult SCID mouse with result in an impressive human thymus organ, six months after transplantation. We use this model to study thymus T-cell developmental kinetics, development of gene-marked precursor cells and thymic homing of precursor cells.

Adult↗

Thymic repopulation by CD34(+) human cord blood cells after expansion in stroma-free culture.

Thymic repopulation by transplanted hematopoietic progenitor cells (HPC) is likely to be important for long-term immune reconstitution and for successful gene therapy of diseases affecting the T-cell lineage. However, the T-cell progenitor potential of HPC, cultured in vitro for cell number expansion and gene transfer remains largely unknown. Here, we cultured highly purified human umbilical cord blood (CB) CD34(+)CD38(-) or CD34(+)CD38(+) cells for up to 5 weeks in stroma-free cultures supplemented with various combinations of the cytokines thrombopoietin (TPO), stem cell factor (SCF), flt3/flk-2 ligand (FL), interleukin-3 (IL-3), and IL-6 and investigated thymus-repopulating ability of expanded cells in vitro and in vivo. After up to 5 weeks of culture in IL-3 + SCF + IL-6 or TPO + FL + SCF supplemented medium, the progeny of CD34(+)CD38(-) CB cells generated T cells and natural killer cells in the thymus. Limiting dilution experiments demonstrated increase in the number of T-cell progenitors during culture. After 3 weeks of culture, gene marked CD34(+)CD38(-) CB cells injected in the human thymus fragment transplanted in severe combined immunodeficient (SCID) mice (SCID-hu) generated thymocytes expressing the retroviral encoded marker gene GFP in vivo. Thus, our results show that the progeny of CD34(+)CD38(-) CB cells cultured for extensive periods, harbor thymus-repopulating cells that retain T-cell progenitor potential after expansion and gene transfer.

Animals↗

In vitro intrathymic differentiation kinetics of human fetal liver CD34+CD38- progenitors reveals a phenotypically defined dendritic/T-NK precursor split.

Human CD34+CD38- hematopoietic precursor cells from fetal liver are able to develop into T, NK, and dendritic cells in a hybrid human/mouse fetal thymic organ culture (FTOC). In this report, we pay particular attention to the early events in differentiation of these precursor cells. We show that the CD34+CD38- precursor cells, which are CD4-CD7-cyCD3-HLA-DR-/++ (cy, cytoplasmatic), differentiate into a CD4+ population that remained CD7-cyCD3-HLA-DR++ and a CD4- population that expressed CD7 and cyCD3. The CD4+CD7-cyCD3- cells differentiate into phenotypically and functionally mature dendritic cells, but do not differentiate into T or NK cells. The CD4-CD7+cyCD3+ population later differentiates into a CD4+CD7+cyCD3+HLA-DR- population, which has no potential to differentiate into dendritic cells but is able to differentiate into NK cells and gammadelta and alphabeta T lymphocytes. These findings support the notion that the T/NK split occurs downstream of the NK/dendritic split.

ADP-ribosyl Cyclase↗

The analgesic effect of preoperative administration of propacetamol, tenoxicam or a mixture of both in arthroscopic, outpatient knee surgery.

A prospective, randomized, double-blind, placebo-controlled, comparative study was undertaken to assess the efficacy of the preemptive use of propacetamol, tenoxicam or the combination of both in arthroscopic, outpatient surgery of the knee. One hundred patients aged 18 to 65 years, ASA 1-2, scheduled for arthroscopy were randomized to receive propacetamol 30 mg/kg i.v. (repeated after 6 hours), tenoxicam 0.5 mg/kg i.v. (max. 40 mg), the combination of both or placebo one hour prior to a standard anesthetic. There were no differences with regard to total dose opioid consumption, sedation scores and side effects in the four groups.

Acetaminophen↗

Passive particle agglutination test for screening of Treponema Pallidum antibodies in blood bank routine.

In most laboratories and blood banks, the TP.PA test has replaced the TPHA test for the screening of Treponema pallidum antibodies. In this study we show that the 1:20 serum dilution should be used to discriminate between negative and positive samples instead of the recommended 1:40 dilution, thus increasing sensitivity without a significant loss of specificity.

Antibodies, Bacterial↗

Abnormal thymocyte development and generation of autoreactive T cells in mixed and cortical thymomas.

To gain insight into the pathogenesis of thymoma-associated myasthenia gravis, thymocyte maturation was investigated in mixed and cortical thymomas by three-color flow cytometry. Although we detected cells at all recognizable stages, we noted an unusual increased percentage of early CD4+/CD3- thymocytes--especially in mixed thymoma--and a pronounced decreased percentage of mature CD4+/CD3+ cells in cortical thymomas as well. The percentage of CD3+/CD69+ cells that arose after positive selection was reduced in both thymoma subtypes compared with control thymuses, which suggests differences in the rate or efficiency of positive selection particularly in mixed thymomas. Mature T cells in 10 of 11 thymomas were not activated in situ as shown by the absence of CD25 expression. After stimulation with recombinant human acetylcholine receptor alpha-subunit fragments, thymocytes from 8 of 11 thymomas of both subtypes proliferated more strongly than those from controls, regardless of whether the donors were myasthenic. Responses of residual thymus cells to tetanus toxoid correlated well with those of autologous blood T cells, whereas those from the thymomas clearly did not--implying minimal colonization of thymomas by mature recirculating T cells. In conclusion, our results show that cortical and mixed thymomas exhibited differences in thymocyte maturation. Nevertheless, both thymoma subtypes seem to contribute to the pathogenesis of paraneoplastic myasthenia gravis by generating naive but potentially autoaggressive T cells; in some thymomas, these cells may then be actively immunized inside the tumor.

Autoantigens↗

Human thymocytes become lineage committed at an early postselection CD69+ stage, before the onset of functional maturation.

Mature functional CD4 or CD8 single positive (SP) thymocytes differentiate from immature CD4+ 8+ double positive (DP) precursors through a process of positive selection and terminal differentiation. To study CD4/CD8 lineage commitment, human postselection CD69+ thymocytes were separated into distinct subpopulations based on the differential expression of CD27, CD1, and CD45RA/RO. We demonstrate that these CD69+ subpopulations represent transitional stages of a common differentiation pathway during which CD69+ thymocytes that are initially CD27- CD1+ CD45RA- will sequentially up-regulate CD27, down-regulate CD1, and eventually acquire CD45RA upon maturation. Examination of CD4 and CD8 expression on these CD69+ subsets identified an early postselection CD69+ CD27- CD4SP population that gives rise to both CD4SP and CD8SP mature T cells when cultured in mouse thymus organs. In addition, a CD4+ 8+ DP population was identified that is CD69+ and CD27+, which only gives rise to CD8SP progeny upon culture. Although these results suggest that development of CD4SP and CD8SP cells may proceed through distinct intermediates, examination of active biosynthesis of CD4 and CD8 by the various subsets demonstrated that cells that have selectively terminated CD4 synthesis are already present in the CD27- CD4SP and CD27+ DP populations before culture. These data support a model of thymocyte differentiation whereby the decision of thymocytes to differentiate into one or the other lineage occurs concomitantly with, or very soon after, acquisition of CD69 and before the cells acquire CD27, down-regulate CD1, or acquire functional properties.

Animals↗

Phenotypic and functional maturation of TCR gammadelta cells in the human thymus.

In contrast to thymic differentiation of TCR alphabeta cells, differentiation stages of TCR gammadelta cells are largely unknown. This report shows that CD1, a known marker of immature TCR alphabeta thymocytes, was expressed on some postnatal TCR gammadelta thymocytes. Only CD1+ TCR gammadelta thymocytes expressed recombination-activating gene-1 mRNA, and they were shown to differentiate into CD1- TCR gammadelta thymocytes. Functionally, sorted CD1- TCR gammadelta thymocytes proliferated in the presence of immobilized anti-CD3 Ab plus exogenous rIL-2 or rIL-15. Interestingly, in contrast to CD1- TCR alphabeta cells, CD1- TCR gammadelta thymocytes also proliferated extensively when cultured with exogenous rIL-2 or rIL-15 alone. FACS analysis as well as reverse transcription-PCR analysis showed that only CD1- TCR gammadelta thymocytes expressed IL-2Rbeta protein and mRNA. The differential expression of maturation markers, such as CD27, CD45RO, and CD45RA, as a function of expression of CD1 was similar in TCR gammadelta and TCR alphabeta thymocytes. An important exception is the expression of CD4 and CD8. Whereas TCR alphabeta thymocytes are mainly CD4-CD8 double positive at the immature CD1+ stage and CD4 or CD8 single positive at the mature CD1- stage, CD1(bright) TCR gammadelta thymocytes all expressed CD4, but only some of them expressed CD8. Some CD1- TCR gammadelta thymocytes also expressed CD8, but were negative for CD4. Collectively, our data clearly show that CD1 is a useful marker to distinguish immature human TCR gammadelta thymocytes from functional mature gammadelta cells based on recombination-activating gene-1 expression, in vitro differentiation, and phenotypic and functional characteristics.

Antigens, CD1↗

MHC class II molecules are required for initiation of positive selection but not during terminal differentiation of human CD4 single positive thymocytes.

Positive selection of T cell precursors is an MHC dependent, multistep process by which functionally mature CD4+8- helper and CD4-8+ cytotoxic single positive (SP) T cells are generated from immature CD4+8+ double positive (DP) thymocytes. We investigated the requirement for TCR/MHC class II interactions during different stages of positive selection of human CD4 SP thymocytes. We show that sorted CD69- CD4+8+ DP preselection thymocytes cultured in fetal thymus lobes of normal mice were subject to positive selection and differentiated to CD3(high) CD69+, mature CD8 SP, and CD4 SP cells. When cultured in thymus lobes from MHC class II-deficient mice, these precursors failed to develop into mature CD4 SP T cells, indicating that in the hybrid cultures, murine MHC class II molecules are required for the development of mature human CD4 SP T cells. We have previously identified CD4 SP intermediate thymocytes that have received at least some of the signals involved in positive selection, since these cells are CD69+, CD3/TCR(high), and CD8beta- but that are still phenotypically and functionally immature. Here we demonstrate that in contrast to preselection thymocytes, these CD4 SP intermediate thymocytes can give rise to phenotypically mature and functionally CD4 SP progeny both in normal and in MHC class II-deficient thymus lobes. These results suggest that TCR/MHC interactions are required for the initial stages of positive selection, but are not essential during terminal differentiation to functionally mature CD4 SP T cells.

Animals↗

Interleukin-7 is a critical growth factor in early human T-cell development.

Highly purified human CD34+ fetal liver stem cells differentiate to mature T cells when seeded in vitro into isolated fetal thymic lobes of severe combined immunodeficient (SCID) mice followed by fetal thymus organ culture (FTOC). Here, this chimeric human-mouse FTOC was used to address the role of interleukin-7 (IL-7) and of the alpha chain of the IL-7 receptor (IL-7R alpha) in early human T-cell development. We report that addition of either the monoclonal antibody (MoAb) M25, which neutralizes both human and mouse IL-7, or the MoAb M21, which recognizes and blocks exclusively the human high-affinity alpha-chain of the IL-7R, results in a profound reduction in human thymic cellularity. Analysis of lymphoid subpopulations indicates that a highly reduced number of cells undergo maturation from CD34+ precursor cells toward CD4+CD3-CD1+ progenitor cells and subsequently toward CD4+CD8+ thymocytes. Our results reveal a critical role for IL-7 during early human thymocyte development, and may explain the absence or highly reduced levels of T cells in patients with X-linked SCID. The molecular defect in these patients has been shown to be a mutation in the gamma chain of the IL-2R. Although this gamma chain is not only present in the IL-2R, but also forms an essential part of other cytokine receptors, including IL-4, IL-7, IL-9, IL-13, and IL-15, the T-cell defect in these patients can be explained by the fact that IL-7 is not able to transduce its signal by the molecular defect of the common gamma (gamma c) chain and that IL-7 is indispensable for T-cell development.

Animals↗

Differentiation to T helper cells in the thymus. Gradual acquisition of T helper cell function by CD3+CD4+ cells.

We investigated at which point during thymocyte differentiation functions were acquired that are characteristic for mature Th cells. Differentiation from CD3+CD69-, CD4+CD8+ double-positive (DP) cells to terminally differentiated CD3+, CD4+CD8- single-positive (SP) cells was broken down into six discrete stages that were purified by four-color sorting: CD69-CD3+DP (stage 0), CD69+CD27-DP (stage 1), CD69+CD27-CD4+SP (stage 2), CD27+CD1+CD4+SP (stage 3), CD1-CD45RO+CD4+SP (stage 4), and CD1-CD45RO-CD4+SP cells (stage 5). Phenotypically, these stages seem to describe consecutive steps in differentiation from immature stage 0 to the terminally matured stage 5. Functionally, the capacity to proliferate on IL-2 after stimulation was absent in CD69- stage 0 cells, but was acquired gradually during stages 1 to 4. Clonal expandability and the capacity to respond to stimulation with the production of cytokines were acquired later and rather abruptly by CD1- stage 4 and 5 cells. Activation markers such as CD69 expression and in vivo IL-2 gene transcription came up simultaneously at the DP stage and peaked at stage 3 to 4. These data suggest that functional maturation of Th cells occurs over an extended period in differentiation, stages 1 to 4, and coincides with a gradual increase in activation markers. After completion of functional differentiation, at stage 5, in vivo IL-2 mRNA transcription and CD69 expression are down-regulated, and the cells become functionally resting naive T cells expressing CD45RA+.

Antigens, CD↗

Characterization of distinct stages during the differentiation of human CD69+CD3+ thymocytes and identification of thymic emigrants.

During thymocyte development, CD69 expression is induced at an early stage of positive selection. To examine the differentiation of human CD69+CD3+ thymocytes, discrete phenotypes were defined by the relative expression of CD69, CD27, CD1, and CD45RA/RO: CD3+CD69- thymocytes were CD27-CD1+CD45RA-/RO+ (phenotype I), whereas the CD3+ CD69+ population could be subdivided into CD27-CD1+CD45RA-/RA+ (phenotype II), CD27+CD1+CD45RA-/RO+ (phenotype III), CD27+CD1-CD45RA-/dull/RO+ (phenotype IV), and CD27+CD1-CD45RA+/ROdull (phenotype V) thymocytes. Phenotype I thymocytes were CD4+CD8 alpha beta + double positive (DP). Phenotype II thymocytes contained DP and CD4+CD8 alpha dullCD8 beta- cells, whereas phenotype III thymocytes were DP and mostly CD4dullCD8 alpha beta+, indicating that CD27 on DP cells may be a marker for CD8-committed cells. Results obtained with SCID-hu mice, transplanted with human fetal thymus and liver, showed that immature human CD69-CD3+ thymocytes were corticosteroid-sensitive, whereas essentially all CD69+CD3+ cells were resistant. During differentiation of one cohort of corticosteroid-resistant CD69+CD3+ thymocytes, phenotype II and III thymocytes, disappeared within a week, whereas the percentage of phenotype IV and especially V thymocytes increased, suggesting that the latter represent the end stages in differentiation. Recent thymic emigrants in SCID-hu mice were identified as CD69-CD27+CD1-CD45RA-/dull/RO+ or CD45RA+/ROdull cells. Because phenotype IV and phenotype V thymocytes rapidly lose CD69 expression in cell culture, these thymocytes are probably the cells that are exported from the thymus. In conclusion, after the acquisition of CD69, thymocyte differentiation appears to continue in an ordered pattern, and cells that eventually leave the thymus are CD69-CD1-CD45RA+ or CD45RA-/dull.

Animals↗