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Biomedical subjects

M de Boer

Publications and source records attributed to M de Boer.

At least 37 records · Page 2Linked to original sources
PubMed1999

Hypermobility and peripartum pelvic pain syndrome in pregnant South African women.

OBJECTIVE: To determine the incidence and correlation of joint hypermobility (HM) and peripartum pelvic pain (PPPP) in an homogeneous pregnant South African population. STUDY DESIGN: A cross-sectional study among Cape Coloured pregnant women. Joint mobility was measured by Beighton score; PPPP with a specially developed PPPP score. RESULTS: Using the Beighton scores with a cut-off point of HM > or = 5/9, only 4.9% of the 509 pregnant women were hypermobile. Hyperextension of the elbow was the largest contributor to HM (35.4%). No correlation of HM with the incidence of PPPP was established. Only 20 very mild cases of PPPP were recorded. Back pain increased significantly during pregnancy to a mean of 38%. Right handedness occurred in 95.9%. No significant relation was found between HM and the non-dominant side. CONCLUSION: Hypermobility in pregnant Cape Coloured women was surprisingly low (4.9%) with a decrease with age, but no increase during pregnancy. Peripartum pelvic pain is virtually absent and has no correlation with joint laxity. Back pain increased during pregnancy to a mean of 38%. Right handedness was high (96%) in comparison with the world-wide figure of 85%. No correlation was found between the dominant body side and hypermobility.

Adolescent↗
PubMed1999

Prolonged skin graft survival by administration of anti-CD80 monoclonal antibody with cyclosporin A.

Costimulation via the B7/CD28 pathway is an important signal for the activation of T cells. Maximal inhibition of T-cell activation and the induction of alloantigen-specific nonresponsiveness in vitro was achieved using anti-CD80 monoclonal antibody (mAb) in combination with cyclosporin A (CsA). Based on this knowledge, the efficacy of the prophylactic treatment of anti-CD80 mAb and CsA on allogeneic skin graft survival was tested in a preclinical rhesus monkey model. No side effects have been observed. Administration of anti-CD80 mAb resulted in high mAb serum levels that decreased to undetectable values around day 7. At the same time, the anti-mouse antibody response started to develop. The anti-CD80 mAb bound to peripheral blood mononuclear cells and was detectable in lymph node and grafted skin during the treatment period. The skin graft survival time of untreated or suboptimally CsA-treated rhesus monkeys was 10 days. Treatment with CsA (blood levels of 100-160 ng/ml) in combination with anti-CD80 mAb (0.5 mg/kg) resulted in a significantly increased skin graft survival time to 14 days. Eventually, skin grafts in all rhesus monkeys were rejected, which coincided with an increase in helper and cytotoxic T-cell frequency and induction of an antibody response directed against the donor antigens. Therefore, treatment of anti-CD80 mAb in combination with CsA has significant immunosuppressive potency, but was unable to induce donor-specific nonresponsiveness in skin graft recipients.

Adjuvants, Immunologic↗
PubMed1999

A highly sensitive assay for detection and quantitation of human cytomegalovirus DNA in serum and plasma by PCR and electrochemiluminescence.

We describe a diagnostic PCR assay (D-PCR) and a quantitative PCR assay (Q-PCR) for the detection of human cytomegalovirus (CMV) in plasma and serum. In the D-PCR, DNA was purified from plasma or serum together with internal control (IC) DNA, which monitored both DNA extraction efficiency and PCR efficiency. DNA was subjected to PCR with a single primer pair, and the amount of PCR products was determined by electrochemiluminescence (ECL) in the QPCR System 5000 (Perkin-Elmer) after hybridization with Tris (2,2'-bipyridine) ruthenium (II) chelate-labeled probes. The lower limit of sensitivity of the D-PCR was reached at about 25 CMV particles/ml. Even with extremely low DNA inputs (four molecules of IC DNA/200 microl of plasma), very high yields (near 100%) were reached. DNA extracted from specimens that were CMV positive by the D-PCR was subsequently used in the Q-PCR, which was similar to the D-PCR. The viral load was calculated directly from the ratio of CMV and IC signals obtained by ECL. The Q-PCR assay is quantitative in the range of 100 to 150,000 copies of CMV/ml, independent of the anticoagulant. Interassay variation, intra-assay variation, and interspecimen variation were about 25%, suggesting that the Q-PCR will reliably detect fourfold differences in viral load. Comparison of paired serum and plasma specimens from CMV-infected individuals showed that serum CMV loads were frequently more than 10-fold lower than plasma CMV loads.

Anticoagulants↗
PubMed1999

Shedding of soluble receptor for tumor necrosis factor alpha induced by M. leprae or LPS from human mononuclear cells.

Cell surface expression and release of the tumor necrosis factor receptor (TNFR type I) was analyzed after stimulation of peripheral blood mononuclear cells (PBMC) with Mycobacterium leprae (M. leprae) or lipopolysaccharide (LPS). A transient spontaneous expression of TNFR type I on the surface of PBMC was observed. Two hr after activation with LPS, a significant reduction of TNFR type I expression was detected: Release of TNFR type I by M. leprae or LPS-stimulated PBMC was evaluated with an enzyme-linked immunoabsorbent assay. This release occurred relatively later (20 to 40 hr) than the secretion of TNF alpha which reached high levels between 8 to 20 hr after activation. Thalidomide, a potent drug for the treatment of erythema nodosum leprosum episodes by inhibiting TNF alpha production, had no influence on the TNFR type I expression. Similar results were obtained with pentoxifylline. It is concluded that the release of TNFR type I by M. leprae or LPS-stimulated PBMC may counteract the pro-inflammatory activities of TNF alpha, by reducing the systemic toxicity of this cytokine in leprosy.

Cells, Cultured↗
PubMed1998

Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus).

Accessory molecules and cytokines are involved in the immunopathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) in rodent models, and are potential targets for immunotherapy. Evaluation of such experimental therapies requires appropriate animal models. Therefore, we analysed the expression of selected accessory molecules and cytokines in the brain of marmoset monkeys (Callithrix jacchus) with acute EAE, a newly described non-human primate model for MS. All animals experienced active disease clinically and histopathologically with strong resemblance to MS. Perivascular infiltrates of mononuclear cells showed abundant expression of CD40. CD40 was expressed on macrophages, indicating that T cell priming and macrophage effector functions may result from local CD40-CD40L interactions. CD40 ligand (CD40L) and B7-2 (CD86) were also expressed, but to a lower extent, while B7-1 (CD80) expression was limited. Both pro-inflammatory and anti-inflammatory cytokines were produced within individual lesions during active disease (IFN-alpha, IFN-gamma, TNF-alpha, IL-1alpha, IL-1beta, IL-2, IL-4, IL-10 and IL-12). This suggests that relative levels rather than sequential expression of Th1- and Th2-type cytokines determine disease activity. These findings demonstrate the value of EAE in marmoset monkeys as a model to assess the role of accessory molecules and cytokines in multiple sclerosis, and to evaluate targeted intervention.

Acid Phosphatase↗
PubMed1998

Somatic triple mosaicism in a carrier of X-linked chronic granulomatous disease.

The X-linked form of chronic granulomatous disease (CGD) is caused by mutations in the CYBB gene, which encodes the 91-kD subunit of the flavocytochrome b558, a component of the superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytic leukocytes. Mutations in this gene are very heterogeneous and often unique for one family. Here we report on a family with two patients (brothers), one with a 3-kb deletion comprising exon 5 and the other with a 3.5-kb deletion comprising exons 6 and 7 of the CYBB gene. Sequence analysis of polymerase chain reaction (PCR)-amplified genomic DNA proved these deletions to be overlapping for 35 bp. Analysis by restriction fragment length polymorphism of genomic DNA from the mother's leukocytes showed her to be a carrier of both deletions in addition to the normal CYBB sequence. This triple somatic mosaicism was confirmed with PCR-amplified genomic and complementary DNA. The presence of the normal CYBB gene in the mother was also proven by the finding of normal superoxide-generating neutrophils in addition to cells lacking this ability. Triple X syndrome was excluded. These findings suggest that the mutations are the result of an event in early embryogenesis of the mother, possibly involving a mechanism like sister chromatid exchange.

Adolescent↗
PubMed1998

Docetaxel (Taxotere): an active agent in metastatic urothelial cancer; results of a phase II study in non-chemotherapy-pretreated patients.

The semisynthetic taxoid docetaxel was investigated in a phase II study in non-chemotherapy pretreated patients with metastatic urothelial cell cancer. Thirty patients (median age 61, range 45-72) were treated with docetaxel 100 mg m(-2) administered as a 1-h infusion every 3 weeks. Of 29 evaluable patients, four achieved a complete response and five a partial response, for an overall response rate of 31%. The median duration of response was 6 months (range 4-51+). A total of 104 cycles were administered. The median number of cycles given was three (range 1-9). Toxic effects of docetaxel mainly consisted of neutropenia, which, however, rarely caused infectious complications (5%). Fluid retention or neuropathy necessitated treatment cessation in two patients. We conclude that docetaxel is an effective agent in urothelial cell cancer, and should be further tested in combination chemotherapy.

Aged↗
PubMed1998

The effect of immunotoxins directed against CD80 and CD86 on primary T-cell alloresponses.

Activation of primary resting T cells requires costimulation which can be delivered by the B7 molecules (CD80 and CD86) expressed on activated antigen-presenting cells (APC). In the present study, we examined in vitro effects of immunotoxins (ITs) composed of gelonin conjugated to mAbs against CD80 or CD86 (alphaCD80-IT and alphaCD86-IT). The specificity of both ITs was demonstrated using CD80 and CD86 transfected cell lines. In primary mixed lymphocyte cultures (MLCs), it was found that the average inhibitory capacity of alphaCD86-IT (72%) and alphaCD80-IT (30%) was significantly higher than alphaCD86 (54%) and alphaCD80 (11%). In reculture MLC experiments it was found that peripheral blood mononuclear cells pretreated with alphaCD86/alphaCD80 regained full stimulatory capacity whereas alphaCD86-IT/alphaCD80-IT pretreatment induced >95% loss of stimulatory capacity. Our results therefore demonstrate that these alphaB7-ITs functionally block B7-CD28 costimulatory signaling and eliminate activated APC.

Antigen-Antibody Reactions↗
PubMed1998

[Dentes natales].

As an introduction, this article describes the circumstances under which dental anatomy was taught to first year students at Utrecht University on November 26, 1945, as this led to the observation of a dens natalis. Relevant literature is discussed concerning the significance of the dens natalis for the child's future and for the family. Investigations into the frequency of the phenomenon are mentioned. Variations of the phenomenon are discussed in two cases. An overview of feeding and eating difficulties and measures to be taken concludes the article.

Child, Preschool↗
PubMed1997

Risk factors for HIV-1 transmission from HIV-seropositive male blood donors to their regular female partners in northern Thailand.

OBJECTIVE: To describe risks for HIV transmission from male blood donors to their regular female sex partners in Chiang Mai, Thailand. DESIGN: Cross-sectional study. METHODS: From March 1992 through September 1995, 405 HIV-seropositive male blood donors (index cases) and their regular female partners were enrolled in the study. Women with risk factors for HIV infection other than sexual contact with the index male were excluded. Couples were interviewed and examined; specimens were collected for laboratory analysis. RESULTS: Overall, 46% of the 405 women enrolled were HIV-positive. Ninety-eight per cent of male index cases had a history of sex with a female prostitute; 1.5% reported always using condoms with their regular partner. History of sexually transmitted disease (STD) and swollen inguinal lymph nodes in the female partner were associated with an increased risk of HIV infection in the female. History in the female of genital herpes [odds ratio (OR), 3.46; 95% confidence interval (CI), 1.50-8.78], gonorrhea or chlamydia infection (OR, 2.71; 95% CI, 1.39-5.53), and stable relationship of longer than 24 months (OR, 2.28; 95% CI, 1.02-5.09) were associated with an increased risk of HIV infection in the female. Consistent condom use in the past 2 years (OR, 0.10; 95% CI, 0.01-0.79) was associated with a decreased risk of HIV infection in the female. CONCLUSIONS: Married women in northern Thailand who appear otherwise to be at low risk for HIV infection may be exposed to this virus by their husbands. High rates of sex with commercial sex workers among men and low use of condoms within stable relationships may be important factors promoting the transmission of HIV in married couples. Programs to increase the regular use of condoms among married couples could be an important public health intervention to prevent transmission of HIV and other types of STD in northern Thailand.

Adolescent↗
PubMed1997

Leukocyte adhesion deficiency type 1 (LAD-1)/variant. A novel immunodeficiency syndrome characterized by dysfunctional beta2 integrins.

Leukocyte adhesion deficiency (LAD) is characterized by the inability of leukocytes, in particular neutrophilic granulocytes, to emigrate from the bloodstream towards sites of inflammation. Infectious foci are nonpurulent and may eventually become necrotic because of abnormal wound healing. LAD-1 is characterized by the absence of the beta2 integrins (CD11/CD18) on leukocytes. When expression is completely absent, patients often die within the first year. However, low levels of beta2 expression may result in a milder clinical picture of recurrent infection, which offers a better prognosis. In this paper, we describe the in vivo and in vitro findings on a patient with clinical features of a mild LAD-1 disorder, i.e., suffering from bacterial infections without apparent pus formation in the presence of a striking granulocytosis, showing no delayed-type hypersensitivity reaction upon skin testing, no specific antibody generation, but normal in vitro T cell proliferation responses after immunization. Expression levels of CD11/CD18 proteins were completely normal, but leukocyte activation did not result in CD11/ CD18 activation and high-avidity ligand-binding. In vitro chemotaxis and endothelial transmigration of the neutrophils as well as leukocyte aggregation responses were almost absent. On the other hand, beta1 and beta3 integrin-mediated adhesion functions were completely normal. During follow-up, a bleeding tendency related to decreased beta3 activation became clinically apparent, different from previously described cellular adhesion molecule variants. Therefore, this is the first well-documented case of a clinical combined immunodeficiency syndrome that results from nonfunctional CD11/CD18 molecules, and thus designated LAD-1/ variant.

Antigens, CD↗
PubMed1997

Human dendritic cells require exogenous interleukin-12-inducing factors to direct the development of naive T-helper cells toward the Th1 phenotype.

Dendritic cells (DC) are important initiators of specific primary immune responses because they are the only APC that can efficiently activate naive Th cells. DC have the capacity to produce interleukin-12 (IL-12), a cytokine that plays a pivotal role in the development of Th1-mediated cellular immune responses. The present study focuses on the conditions under which human DC produce bioactive IL-12 p70 and, consequently, direct the development of naive T helper (Th) cells toward the Th1 phenotype. Bacteria or bacterial compounds such as Staphylococcus aureus Cowan strain I (SAC) or lipopolysaccharide (LPS) induced substantial IL-12 levels in DC, which could be further upregulated by interferon-gamma (IFN-gamma), whereas induction of IL-12 production via CD40 ligation required IFN-gamma as an obligatory, complementary signal. Also, activated naive Th cells were poor inducers of IL-12 production, unless exogenous IFN-gamma was present, whereas activated memory Th cells were effective inducers of IL-12 production and did not require exogenous IFN-gamma. Next, the cytokine profiles of matured Th cells that were primed by DC under different conditions were examined. DC promoted the development of naive Th cells into memory Th0 cells that produced both the type 1 cytokine IFN-gamma and the type 2 cytokine IL-4. In contrast, after activation with SAC, DC efficiently directed the development of Th1 cells through the release of IL-12. An APC-independent Th cell maturation model, using either recombinant IL-12 or supernatants of SAC-activated DC and neutralizing anti-IL-12 antibodies, confirmed that DC-derived IL-12 was the major Th1 skewing factor. Together, these data indicate that the contact between DC and naive Th cells during the initiation of specific immune responses does not result in the efficient induction of IL-12 production and that, consequently, exogenous IL-12-inducing factors are required to promote primary Th1-mediated cellular immune responses.

Cell Differentiation↗
PubMed1997

B7-blocking agents, alone or in combination with cyclosporin A, induce antigen-specific anergy of human memory T cells.

T cell anergy refers to a functional state in which the cells are alive but unable to produce IL-2 after appropriate triggering. Lack of CD28 costimulation through CD80 and CD86 molecules on APC might play a causative role in anergy induction, as previously shown with T cell clones. We now developed a model of anergy induction in cultures of freshly isolated memory T cells. Addition of either CTLA-4Ig or blocking anti-CD80 and anti-CD86 mAbs, in combination with cyclosporin A, to cultures of PBMC with soluble Ag consistently resulted in Ag-specific unresponsiveness, as evidenced upon antigenic rechallenge. In most experiments, the presence of cyclosporin A was not required, and blocking the B7-CD28 interaction during antigenic stimulation was sufficient to induce unresponsiveness. Unresponsiveness was apparent at the level of T cell proliferation as well as at the level of IL-2 and IFN-gamma production, and T cell responses to unrelated Ags were intact. Induction of unresponsiveness correlated with lack of T cell proliferation in the induction culture and could largely be prevented by supplementing the induction cultures with rIL-2, indicating that lack of IL-2 was responsible for this altered functional state. Unresponsive T cells did not suppress the proliferation of autologous T cells in response to original or third-party Ags. On the other hand, culture with IL-2 and Ag could reverse established T cell unresponsiveness, pointing to anergy rather than deletion as the underlying mechanism. Anergy induction in freshly isolated memory T cells opens perspectives for treatment of autoimmune and allergic diseases.

Abatacept↗
PubMed1997

[Chronic granulomatous disease (CGD): dysfunction of the neutrophil granulocyte NADPH-oxidase enzyme system].

Dysfunction of NADPH oxidase results in chronic granulomatous disease (CGD), a syndrome characterized by severe bacterial and fungal infections. Phagocytes of the patients are unable to kill ingested microorganisms which leads to the formation of granulomas and abscesses. Predominant pathogens are the catalase-positive bacteriae (Staphylococcus aureus) and some fungi (Aspergillus species). Infections of these patients should be treated by antimicrobial agents, which penetrate cells and kill pathogens inside. The aim of this study was to give a short description of the structure and function of the NADPH oxidase enzyme and to summarize the results obtained during the diagnostic of 10 patients with chronic granulomatous disease. Characterization of the disease was confirmed by mutation analyses.

Common Variable Immunodeficiency↗
PubMed1997

Confirmation of self-report of HIV testing among a cohort of pregnant women.

Early identification of pregnant women infected with the human immunodeficiency virus (HIV) is becoming increasingly important in light of recent findings that interventions during and shortly after pregnancy can reduce the rates of vertical transmission. The ability of patients to accurately self-report previous HIV testing and test results is important in clinical settings. Over a one-year period, 283 women attending a hospital-affiliated obstetrical clinic reported previous HIV testing (44% of the total women approached), and 105 women (37% of the women reporting previous testing) reported being previously tested at that hospital. Self-reported data on previous HIV testing at the hospital were compared with information maintained in a centralized computerized database by the hospital laboratory. Only 41.9% of the women who reported previous HIV testing at the hospital had their reports confirmed. Women whose HIV testing reports were confirmed were found to be similar to those women whose reports were not confirmed with regard to age, educational level, gestational age, parity, reason(s) for seeking HIV testing, and knowledge of testing, transmission and acquired immunodeficiency syndrome (AIDS). These data suggest that, when HIV status is of concern, health care professionals should continue to encourage testing in the absence of laboratory documentation of recent HIV antibody testing.

Adult↗
PubMed1997

B7-1 (CD80) as target for immunotoxin therapy for Hodgkin's disease.

In this preclinical study, the potential applicability of an anti-B7-1 immunotoxin (IT) for the treatment of Hodgkin's disease (HD) was investigated. Immunohistochemical analysis demonstrated strong expression of B7-1 on Hodgkin and Reed-Sternberg (R-S) cells and clear expression on dendritic cells, macrophages and some B-cells in tissues, but not on other tissue cells. Flow cytometric analysis demonstrated that B7-1 was expressed on a few monocytes, but not on CD34+ cells from bone marrow, resting T- or B-cells from peripheral blood or epithelial and endothelial cell lines. An anti-B7-1 immunotoxin containing the anti-B7-1 monoclonal antibody (MAb) B7-24 and saporin as toxin moiety was constructed and showed an affinity similar to that shown by the native MAb. It exhibited strong cytotoxicity against the B7-1+ B-cell line Raji (IC50 10(-11) M), R-S cell lines HDLM2, KM/H2 and L428 and also against a B7-1-transfected epithelial cell line, A431, whose parental line lacks expression of B7-1. In clonogenic assays with Raji cells or KM/H2 cells, a 3- or 4-log kill, respectively, was observed. No cytotoxicity was found against the B7-1- epithelial and endothelial cell lines or against haematopoietic progenitor cells. In conclusion, an anti-B7-1 immunotoxin was developed that had good cytotoxicity against R-S cell lines and that may be used in the elimination of R-S cells in vivo. A concomitant elimination of activated antigen-presenting cells may avoid development of antitoxin and anti-mouse Ig responses and allow repeated administration.

Antibodies, Monoclonal↗