Biomedical subjects
Publications and source records attributed to C J de Groot.
Chronic hypertension occurs in 5% of pregnancies and can threaten the life of the mother and the fetus. Chronic hypertension should be evaluated before pregnancy; special attention should be paid to the existence of organ damage and the presence of an acceptable incentive for treatment. The risk of complications of chronic hypertension in pregnancy should be discussed with the couple before pregnancy.
In this study, the release of recombinant human interleukin-2 (rhIL-2) from methacrylated dextran (dex-MA) and (lactate-)hydroxyethyl methacrylated dextran (dex-(lactate-)HEMA) hydrogels with varying crosslink density was investigated. Hydrogels derived from dex-MA are stable under physiological conditions (pH 7 and 37 degrees C), whereas dex-HEMA and dex-lactate-HEMA hydrogels degrade due to the presence of hydrolytically sensitive esters in the crosslinks of the gels. The protein release profiles both the non-degradable and degradable dextran-based hydrogels showed that with increasing crosslink density of the gel, the release of rhIL-2 decreases. From dex-MA hydrogels with an initial water content above 70%, the rhIL-2 release followed Fickian diffusion, whereas from gels with an initial water content of 70% or lower the protein was fully entrapped in the hydrogel meshes. In contrast with non-degradable dex-MA hydrogels, degradable dex-lactate-HEMA gels with comparable network characteristics (degree of methacrylate substitution and initial water content) showed an almost zero-order, degradation controlled release of rhIL-2 in a time period of 5-15 days. This paper demonstrates that the release of rhIL-2 from non-degradable dex-MA and degradable dex-lactate-HEMA gels can be modulated by the crosslink density and/or the degradation characteristics of the hydrogel. Importantly, rhIL-2 was mainly released as monomer from the hydrogels and with good retention of its biological activity.
Experimental autoimmune encephalomyelitis (EAE) induced by immunization of mice with epitopes of the proteolipid protein (PLP), a major myelin constituent, forms a useful model for the study of multiple sclerosis (MS). In addition, MS patients display PLP-specific T- and B-cell responses, suggesting that PLP reactivity is relevant to pathogenesis.Here, the generation and characterization of a panel of mouse monoclonal antibodies (Mab) against PLP139-151, the prominent encephalitogenic sequence in SJL/J mice is described. Five Mab were generated by conventional immunization of an SJL/J mouse and hybridoma generation. These Mab reacted well with the PLP139-151 peptide in ELISA and belonged to the IgG2a and IgG2b subclasses, consistent with CD4+ T helper 1-cell-supported antibody formation. The Mab also efficiently detected PLP peptide-BSA conjugates in Western blot, confirming their multi-assay applicability. The Mab were subsequently used to determine the occurrence of demyelination in brains of MS patients and marmoset monkeys with EAE. Immunohistochemistry on both paraffin and frozen sections demonstrated a homogeneous expression of PLP139-151 in normal myelin, and a complete absence in lesions containing demyelinated areas, confirming that the Mab can be used as a general myelin marker. In active demyelinating MS lesions, the Mab visualized the peptide in the cytoplasm of macrophages containing phagocytosed myelin. In conclusion, this panel of Mab against the encephalitogenic PLP139-151 epitope forms a useful tool for further study of autoantigen expression, demyelination/remyelination and the staging of lesional activity in MS patients, as well as in EAE models in distinct animal species.
Cell cultures have become an integral part of the daily routine in most biological research laboratories. Because they are very dynamic and highly accessible, cell cultures permit direct experimental manipulations where cause-effect relations can be more definitely assayed. We have developed cultures of microglial cells from rapid autopsies (range 3-10 hours) of nondemented elderly patients and Alzheimer's disease patients. Cultures were derived from the subcortical white matter, corpus callosum, and frontal, temporal, and occipital cortex. The adherent microglial cells were immunoreactive for CD68, CD45, CD11c, and major histocompatibility complex (MHC) class II markers, and were not immunoreactive for astrocyte or oligodendrocyte markers. In addition, some functional characteristics of the isolated microglial cells were also studied. Upon stimulation with lipopolysaccharide (LPS), microglial cells secreted pro- and antiinflammatory mediators, i.e., interleukin- (IL)-6, prostaglandin E2 (PGE2), and IL-10, indicating the functional capacity of cultured microglia.
Although the pathophysiology of pre-eclampsia is unknown, several studies have indicated that abnormal placentation early in pregnancy might play a key role. It has recently been suggested that this abnormal placentation may result in transfusion of fetal cells (feto-maternal transfusion) in women with pre-eclampsia. In the present study, fetal nucleated red blood cells were isolated from 20 women with pre-eclampsia and 20 controls using a very efficient magnetic activated cell sorting (MACS) protocol. The number of male cells was determined using two-color fluorescence in situ hybridization (FISH) for X and Y chromosomes. Significantly more XY cells could be detected in women with pre-eclampsia (0.61+/-1.2 XY cells/ml blood) compared to women with uncomplicated pregnancies (0.02+/-0.04 XY cells/ml blood) (Mann-Whitney U-test, p<0.001). These results suggest that fetal cell trafficking is enhanced in women with pre-eclampsia, and this finding may contribute to the understanding of the pathophysiology of the disease.
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UNLABELLED: A prospective cohort study of breastfeeding practice (0-4 mo) was carried out in well-baby clinics. The cohort included 4438 newborns brought to a clinic for the first time between 1 April and 1 July 1998. The odds ratios of demographic and gestational variables connected with the start and duration of breastfeeding were measured. The frequency of the reasons why breastfeeding was interrupted was determined. At birth 71% of the infants included in this study were exclusively breastfed. After 4 mo the percentage had dropped to 21%. Breast milk was replaced directly by formula (23%) or by a mixture of breast milk and formula (77%). Exclusive breastfeeding was given irrespective of the mother's cultural background. Higher education appeared to be the most decisive factor for the initiation of exclusive breastfeeding; higher parity was found to be the most decisive factor for continuation. In 46% of cases the infant's health and behaviour caused mothers to stop exclusive breastfeeding; in 38% the reasons were mother related; in 17% both mother- and infant-related motives were mentioned. CONCLUSION: Mothers' perception of hunger and crying colics were the main infant-related reasons for cessation of breastfeeding, whereas physical problems, return to work, doubt about the sufficiency of breast milk and the feeling of being restricted by breastfeeding were the main mother-related reasons. The decision to abandon exclusive breastfeeding was made primarily by mothers (71%). In The Netherlands more babies are breastfed at birth than was the case 10 y ago, but the duration of the breastfeeding period has become shorter.
Various lines of evidence suggest a close relationship between heat shock proteins (hsp) and several autoimmune diseases such as arthritis, diabetes and multiple sclerosis. While enhanced expression of hsp in autoimmune diseases is often regarded as a non-specific bystander effect of the inflammatory process, surprisingly little is known on hsp regulation by inflammatory mediators such as cytokines. In this study cytokine-induced expression of hsp60, hsp27 and alphaB-crystallin was studied in cultures of primary human adult astrocytes at the mRNA as well as at the protein level. We show differential hsp expression patterns in response to pro-inflammatory and immunoregulatory cytokines. Hsp60 expression was found to be enhanced in response to cytokines as diverse as IL-1beta, TNF-alpha, IL-4, IL-6 and IL-10. Upregulation of hsp27, however, was primarily induced by immunoregulatory cytokines like IL-4, IL-6 and TGF-beta whereas alphaB-crystallin expression was found to be enhanced by the pro-inflammatory cytokine TNF-alpha only. None of the cytokines studied was able to enhance expression of all three hsp simultaneously. These results show that in human astrocytes induced expression of hsp27 and alphaB-crystallin is dependent on the presence of a defined set of stimuli, while induced expression of hsp60 is a much less selective event. This highly differential pattern of hsp expression in response to inflammatory mediators known to play an important role in the pathogenesis of autoimmune diseases indicates that hsp responses are specific rather than non-specific bystander responses.
Dextran-based hydrogels were obtained by polymerization of aqueous solutions of methacrylated dextran (dex-MA) or lactate-hydroxyethyl methacrylate-derivatized dextran (dex-lactate-HEMA). Both nondegradable dex-MA and degradable dex-lactate-HEMA disk-shaped hydrogels, varying in initial water content and degree of substitution (DS, the number of methacrylate groups per 100 glucose units), were implanted subcutaneously in rats. The tissue reaction was evaluated over a period of 6 weeks. The initial foreign-body reaction to the dex-MA hydrogels was characterized by infiltration of granulocytes and macrophages and the formation of fibrin, and exudate, as well as new blood vessels. This reaction depended on the initial water content as well as on the DS of the hydrogel and decreased within 10 days. The mildest tissue response was observed for the gel with the highest water content and intermediate DS. At day 21 all dex-MA hydrogels were surrounded by a fibrous capsule and no toxic effects on the surrounding tissue were found. No signs of degradation were observed. The initial foreign-body reaction to the degradable dex-lactate-HEMA hydrogels was less severe compared with the dex-MA gels. In general, the size of the dex-lactate-HEMA hydrogels increased progressively with time and finally the gels completely dissolved. Degradation of the dex-lactate-HEMA hydrogels was associated with infiltration of macrophages and the formation of giant cells, both of which phagocytosed pieces of the hydrogel. A good correlation between the in vitro and the in vivo degradation time was found. This suggests that extra-cellular degradation is not caused by enzymes but depends only on hydrolysis of the ester and/or carbonate bonds present in the crosslinks of the hydrogels. After 21 days, the degradable hydrogels, as such, could not be retrieved, but accumulation of macrophages and giant cells was observed, both of which contained particles of the gels intracellularly. As for the dex-MA hydrogels, no toxic effects on the surrounding tissue were found. The results presented in this study demonstrate that dextran-based hydrogels can be considered as biocompatible materials, making these hydrogels attractive systems for drug delivery purposes.
This study assessed the reliability, validity, and responsiveness of a new pain measure for children aged 1 to 4 years that was developed from the Children's Hospital of Ontario Pain Scale and its Neonatal Infant Pain Scale. Pain in 311 children, aged 1 to 4 years, was measured by two observers at fixed intervals after adenotonsillectomy (n = 114), adenotomy (n = 109), or insertion of ventilation tubes (grommets) (n = 88) until discharge using a dichotomous pain scale of 9 behavioral and physiological categories. The scale proved to be strongly homogeneous. The interobserver agreement was substantial for 7 items. On these final 7 items, the ability to distinguish between patients with differing degrees of pain and the sensitivity to detect changes over time within each patient were substantial. The resulting Pain Observation Scale for Young Children is reliable and easy to use for assessment of short- and longer-lasting pain after ear, nose, and throat surgery and may be used for assessing pain with other conditions.
Eicosanoids play an important role in the pathogenesis of preeclampsia. The major eicosanoid metabolite reported to be secreted by endothelial cells, the vasodilator prostacyclin, is generally reduced in preeclampsia. By contrast, it was shown previously that prostacyclin secretion by cultured human umbilical vein endothelial (HUVE) cells is increased significantly after exposure to blood from preeclamptic women. In the current study, eicosanoid profiles in conditioned media from HUVE cells incubated with pregnancy plasma were analyzed by high-performance liquid chromatography, thin layer chromatography and quantitative radio- and enzyme immunoassays. More prostaglandin F2alpha, prostacyclin and 8-isoprostane were secreted after exposure to plasma from preeclamptic women than plasma from matched, normal pregnant patients. Predominant secretion of the vasoconstrictor prostaglandin F2alpha by HUVE cell cultures and a stimulatory effect of preeclampsia plasma on eicosanoid biosynthesis underscore the importance of bioactive lipids in the vasospasm associated with clinical preeclampsia.
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During the past decade a new hypothesis has been formulated that explains many of the disparate findings associated with the pregnancy syndrome preeclampsia. With an increased awareness of the physiological significance of vascular endothelial cell function, the seemingly unrelated signs of hypertension, proteinuria, edema, and hypercoagulability have converged to provide clinical evidence of a unifying pathophysiological mechanism: systemic, maternal endothelial cell dysfunction. Investigators have attempted to test this hypothesis through two approaches. The first approach involves the identification of in vivo markers of vascular endothelial cell injury in women with clinically evident preeclampsia. The second approach focuses on the ability of circulating factors derived from the serum or plasma of patients afflicted with preeclampsia to perturb endothelial cell function in vitro. In this review we summarize the increasingly compelling evidence that maternal vascular endothelial cells are a critical target for toxic humoral activities that precipitate the multifaceted preeclampsia syndrome.
OBJECTIVE: To determine the effect of brief early exposure to cows' milk on atopy in the first 2 years of life. DESIGN: Double blind, placebo controlled, randomised feeding intervention trial (Bokaal study). SETTING: Dutch midwifery practices. PARTICIPANTS: 1533 breast fed neonates. INTERVENTION: Exposure to cows' milk protein (n = 758) or a protein free placebo (n = 775) during the first 3 days of life. MAIN OUTCOME MEASURES: Clinical atopic disease and any positive radioallergosorbent (RAST) tests at 1 year of age. RESULTS: Atopic disease in the first year was found in 10.0% (cows' milk) v 9.3% (placebo) of the children, with a relative risk of 1.07; in the second year, atopic disease was found in 9.6% v 10.2%, respectively, with a relative risk of 0.94. Per protocol analysis showed similar results. Any RAST positive test was found in 9.4% (cows' milk) v 7.9% (placebo) of children, with a relative risk of 1.19. Stratified analysis for high family risk of allergy showed a doubled incidence of atopic disease but no effect from the intervention. CONCLUSION: Early and brief exposure to cows' milk in breast fed children does not increase the risk of atopic disease in the first 2 years.
OBJECTIVE: To analyse the correlation of specific risk factors and measles complications in children admitted to a Philippine university medical centre. DESIGN: Retrospective cross-sectional study. SETTING: Department of Pediatrics, De La Salle University Medical Center at Dasmarinas, a suburb of Manila, the Philippines. METHOD: Information was collected on patients under 16 admitted for measles from January 1993 to May 1996, using a data collection form. RESULTS: Of the 180 patients included in this study, 8 (4%) died during the hospital stay, and 172 left the hospital in good condition. 61 Patients (34%) had complicated measles (pneumonia, gastroenteritis, and (or) encephalitis). Age under 2 years and stay in the service ward (as opposed to the private ward) were significantly related to complicated measles. No significant relation was found for the presence of associated illnesses or malnutrition. CONCLUSION: More severe complications were seen at an early age than in industrialised countries where the frequency appears to increase with age. Malnutrition possibly contributes less to severity of the disease than environmental factors such as hygiene and social class.
In clinical practice walking independently has always been considered a major milestone in development. Nevertheless, little attention has been paid to the quality of movement expressed in the first attempts at walking free. Even when children achieve walking within a normal time range, some of them show features that are deviant. Early walking is difficult to judge, but at the same time may provide a sensitive means for detecting possible developmental impairments. The main aim of this paper is to provide a standardized clinical instrument for the qualitative assessment of early walking in a structured free field situation and to compare preterm and fullterm infants. All subjects were assessed 14 days after being able to walk 5 meters independently. The study group consisted of 52 children, of whom 33 were born prematurely (further distinguished in terms of being small- or appropriate-for-gestational age), and 19 were born fullterm. Judgments of walking performance were made in terms of optimal, near-optimal, near-poor, or poor. After correction for age, the preterm group was still later in the onset of walking, but more importantly, showed a qualitatively different pattern of locomotion. Those who were the youngest and small-for-gestational age were overrepresented in the near-poor and poor categories of walking.
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