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Biomedical subjects

C J de Groot

Publications and source records attributed to C J de Groot.

At least 37 records · Page 2Linked to original sources
PubMed1996

Biochemical evidence of impaired trophoblastic invasion of decidual stroma in women destined to have preeclampsia.

OBJECTIVE: Reduced trophoblastic migration into the decidua during the first half of pregnancy is a fundamental abnormality in preeclampsia. CA 125 and insulin-like growth factor binding protein-1 are major endometrial proteins whose primary sources are decidual epithelial and stromal cells, respectively. We hypothesized that reduced trophoblastic invasion in pregnancies destined for preeclampsia would affect the maternal vascular deportation of these decidual proteins. STUDY DESIGN: CA 125 and insulin-like growth factor binding protein-1 concentrations were analyzed by radioimmunoassays of plasma from preeclamptic and matched control patients in a longitudinal, nested case-control study. RESULTS: CA 125 concentrations did not differ with respect to pregnancy outcome or trimester. Midtrimester plasma insulin-like growth factor binding protein-1 concentrations were significantly lower in women who later had preeclampsia compared with normal pregnant controls. CONCLUSION: These findings provide biochemical evidence that abnormalities of trophoblastic invasion affect the maternal vascular deportation of a decidual stromal protein. Lower circulating concentrations of insulin-like growth factor binding protein-1 in women destined to have preeclampsia were observed 12 to 26 weeks before the onset of clinical signs of this syndrome.

Adult↗
PubMed1996

The use of rhG-CSF in chronic autoimmune neutropenia: reversal of autoimmune phenomena, a case history.

An 8-year-old boy had been suffering from chronic autoimmune neutropenia for more than 5 years. The neutropenia proved to be resistant to high-dose steroids and intravenous (either low-or high-dose) immunoglobulin (Ig) therapy. The chronic autoimmune thrombocytopenia and recurrent phases of autoimmune haemolytic anaemia did, however, respond to high-dose prednisone. Other signs of immune dysregulation in this patient consisted of insulin-dependent diabetes mellitus type I (IDDM) and an acquired hypogammaglobulinaemia, most compatible with common variable immunodeficiency (CVI). Prior to rhG-CSF therapy the child had suffered for more than 2 years from recurrent life-threatening bacterial infections. Anti-neutrophil autoantibodies had pan-Fc gamma RIII (CD116, NA1/NA2) specificity. The neutropenia as well as the antineutrophil autoantibodies disappeared when subcutaneous rhG-CSF therapy was started. Upon tapering rhG-CSF, anti-Fc gamma RIII antibodies reappeared together with an absolute neutropenia. Renewed administration resulted again in the normalization of symptoms. Soluble Fc gamma RIII (sFc gamma RIII) antigen levels in plasma increased dramatically during rhG-CSF treatment. These high levels of sFc gamma RIII together with increased numbers as well as decreased apoptotic reactions of neutrophils apparently result in adsorption of the autoantibodies in vivo, contributing to the normalization of autoimmune-mediated neutropenia upon rhG-CSF treatment. Long-term administration of rhG-CSF represents as alternative in the treatment of autoimmune neutropenia.

Autoimmune Diseases↗
PubMed1995

Uptake and tissue distribution of dietary and aqueous cadmium by carp (Cyprinus carpio).

The aim of this study was to assess whether contaminated prey can be a major source of Cd for fish. For this purpose, the uptake and tissue distribution of dietary and aqueous cadmium by the carp (Cyprinus carpio) was studied. The fish were exposed to either Cd-contaminated food or Cd-contaminated water for 4 weeks in laboratory experiments. When exposed to contaminated food, the fish were kept in clean water and fed contaminated chironomid larvae, equilibrated with 99 micrograms Cd. liter-1. During exposure to contaminated water (nominal 100 micrograms Cd. liter-1; actual 80 micrograms Cd. liter-1) the fish were fed uncontaminated food. The Cd accumulation in the tissues of fish fed contaminated larvae was, in decreasing order, gut > kidney > liver = gill > muscle. In the water experiment this order was gut > gill > kidney > liver > muscle. In almost all tissues the Cd uptake was similar for both routes; only the gill had accumulated more Cd from Cd-contaminated water than from Cd-contaminated food. Considering the ongoing discussion of the importance of Cd transfer from contaminated food to predators, these findings suggest that uptake of Cd from Cd-contaminated prey by fish plays an important role in contaminated waters.

Analysis of Variance↗
PubMed1995

Plasma from preeclamptic women increases human endothelial cell prostacyclin production without changes in cellular enzyme activity or mass.

OBJECTIVE: We investigated differences in prostacyclin production by endothelial cells exposed to plasma from either preeclamptic women or normal pregnant women. STUDY DESIGN: A case-control study of matched preeclamptic and normal pregnancies was used to compare prostacyclin synthesis by human umbilical vein endothelial cells incubated with pregnancy plasma for 24 hours. Prostacyclin concentrations in conditioned media were measured by radioimmunoassay of its stable metabolite (6-keto-prostaglandin F1 alpha). Human umbilical vein endothelial cell lysates were used to determine concentrations of the enzymes cyclooxygenase and prostacyclin synthase. RESULTS: Prostacyclin production by human umbilical vein endothelial cells incubated with plasma from preeclamptic women was significantly greater than that by cells exposed to normal pregnancy plasma. Differences in prostacyclin production under the two experimental conditions could be explained neither by differences in enzyme mass nor activities of cyclooxygenase and prostacyclin synthase. CONCLUSION: The stimulatory effect of preeclampsia plasma on prostacyclin biosynthesis in human umbilical vein endothelial cells appears to be manifested at a step(s) proximal to the activation of cyclooxygenase. Possible mechanisms are increased phospholipase A2, lipoprotein, or lipid peroxide activities in preeclampsia.

Case-Control Studies↗
PubMed1995

Plasma type II phospholipase A2 levels are elevated in severe preeclampsia.

OBJECTIVE: Our purpose was to compare plasma concentrations of type II phospholipase A2 in normal and preeclamptic pregnancies and to determine whether plasma from preeclamptic patients increases endothelial cell secretion of type II phospholipase A2. STUDY DESIGN: We compared the plasma levels of type II phospholipase A2 in 23 patients with normal pregnancies and 25 patients with strictly defined preeclampsia. Plasma samples were collected throughout pregnancy and stored at -80 degrees C. Patients with preeclampsia were matched closely as possible with controls for maternal age, race, gestational age at blood sampling, and parity. Plasma levels of type II phospholipase A2 were measured by enzyme immunoassay. To investigate endothelial cell type II phospholipase A2 production, we measured levels of prostacyclin and type II phospholipase A2 in conditioned media from cultured human umbilical vein endothelial cells exposed to plasma from preeclamptic and normal pregnant patients. RESULTS: The mean plasma type II phospholipase A2 level in the mild preeclampsia group (6.1 +/- 3.0 ng/ml, n = 6) was not different from that in control patients (6.0 +/- 3.2 ng/ml, n = 23). However, the mean type II phospholipase A2 level in patients with severe preeclampsia (19.9 +/- 12.3 ng/ml, n = 19) was significantly higher when compared with the other two groups (p < 0.001). Prostacyclin concentrations in conditioned media of endothelial cells exposed to plasma from patients with preeclampsia were elevated compared with cells incubated with control plasma (8.6 +/- 1.7 vs 4.0 +/- 5.0 ng/ml, p < 0.05). However, the concentration of type II phospholipase A2 in conditioned medium was not significantly different (1.6 +/- 0.3 vs. 1.8 +/- 1.0 ng/ml, p = 0.40). CONCLUSIONS: Plasma concentrations of type II phospholipase A2 are elevated in preeclampsia and correlate well with the severity of disease. Plasma from preeclamptic women increased secretion of prostacyclin, but not type II phospholipase A2 by endothelial cells in culture.

Case-Control Studies↗
PubMed1995

Human endothelial cell morphology and autacoid expression.

Human umbilical vein endothelial (HUVE) cells plated on plastic or gelatin-coated dishes grow as a "cobblestone" monolayer. By contrast, endothelial cells cultured on a complex matrix (e.g., Matrigel) form three-dimensional, capillary-like structures. In the current study, we verified the capillary phenotype of the latter structures and asked whether the morphological changes induced by extracellular matrix also affect human endothelial gene expression and function in vitro. Concentrations of cellular fibronectin, prostacyclin, and endothelin-1 were measured in the conditioned media by enzyme-linked immunosorbent and radioimmunoassays. Steady-state concentrations of HUVE mRNA were estimated by reverse transcription-polymerase chain reaction and quantified by Northern analyses to assess fibronectin and endothelin-1 gene expression. We found that the subjacent extracellular matrix affects the morphology, proliferation, and differentiation of HUVE cells in vitro. Cells cultured on gelatin were more mitotically active, expressed significantly less cellular fibronectin, made similar amounts of prostacyclin, and secreted significantly more endothelin-1 compared with the same cells grown on a Matrigel substrate.

Autacoids↗
PubMed1994

Aldehyde dehydrogenase involvement in a variant of the brown Norway rat acute myelocytic leukaemia (BNML) that acquired cyclophosphamide resistance in vivo.

The development of drug resistance is an important factor contributing to failure of chemotherapy in cancer patients. Cyclophosphamide (CP) is a cytostatic drug widely used in the treatment of haematological malignancies and solid tumours. Because CP requires bioactivation to become cytotoxic, an in vivo approach was chosen to generate a subline of the Brown Norway rat acute myelocytic leukaemia (BNML/CPR) highly resistant to CP to serve as a model to investigate the molecular mechanism(s) of cyclophosphamide resistance. The role of the CP-detoxifying enzyme aldehyde dehydrogenase (ALDH) in the molecular mechanism of CP resistance in this subline of the BNML has been investigated. Compared to the parent BNML cell line, the BNML/CPR cell line displayed an approximately 6-fold higher level of ALDH enzyme activity. Pretreatment of leukaemic rats with the ALDH inhibitor disulfiram resulted in a restoration of CP sensitivity of animals carrying the BNML/CPR cells. Furthermore, in vitro incubation of BNML/CPR cells with disulfiram prior to incubation with the activated CP derivative mafosfamide resulted in an extra 2-3 log cell kill as indicated by the survival time of rats which were injected with disulfiram pretreated BNML/CPR cells compared to non-pretreated BNML/CPR cells. Data on the glutathione S-transferases (GSTs) isozyme profiles of cytoplasmic liver and spleen extracts of BNML- and BNML/CPR-carrying leukaemic rats indicated that the total GST enzyme amount was lower in BNML/CPR cells than in parent BNML cells. Furthermore, the BNML/CPR subline proved to be sensitive to phosphoramide mustard, both in vivo and in vitro.

Aldehyde Dehydrogenase↗
PubMed1994

Plasma cellular fibronectin as a measure of endothelial involvement in preeclampsia and intrauterine growth retardation.

OBJECTIVE: Our purpose was to determine the presence and degree of endothelial injury, by measuring plasma concentrations of cellular fibronectin, in pregnancies complicated by preeclampsia or intrauterine growth retardation. STUDY DESIGN: A matched, nested, case-control study design was used. Plasma was collected prospectively from pregnant women throughout gestation. At least 12 weeks after delivery women with preeclampsia, both preeclampsia and intrauterine growth retardation, or intrauterine growth retardation alone were identified. Normal controls were matched to these patients by age, race, and gestational age. Stored plasma, which had been obtained in the third trimester, was assayed for cellular fibronectin by means of a sensitive and specific enzyme immunoassay. After an appropriate transformation of the data results were compared with one-way analysis of variance with Fisher's post hoc test. RESULTS: Patients with preeclampsia (n = 18) had higher plasma cellular fibronectin concentrations than did control patients (n = 68) with median values of 2.8 and 1.4 micrograms/ml, respectively (p < 0.001, using transformed data). Patients with intrauterine growth retardation alone (n = 10) had 2.3 micrograms/ml cellular fibronectin, significantly higher than values of controls (p < 0.02 using transformed data) and significantly lower than those of patients with preeclampsia (p < 0.05 using transformed data). CONCLUSION: Pregnancies complicated by preeclampsia had significantly higher plasma cellular fibronectin concentrations than did pregnancies with intrauterine growth retardation alone, which in turn had significantly higher plasma cellular fibronectin concentrations than did control pregnancies. We speculate that endothelial involvement in intrauterine growth retardation is confined to the uteroplacental circulation, whereas it is systemic in preeclampsia.

Adult↗
PubMed1994

Effect of K+ channel blockers on the clinical course and histological features of experimental allergic encephalomyelitis.

INTRODUCTION: Beneficial clinical effects of 4-aminopyridine (4-AP) in multiple sclerosis (MS) have been reported. The use of 4-AP in MS is based upon its ability to facilitate conduction in axons blocked by demyelination. This improvement is due to blocking of potassium (K+) channels in these fibres. Because K+ channels also play an important role in immune mechanisms successful treatment with K+ channel blockers in neuroimmunological diseases may have several causes. Therefore it seems important to study effects of K+ channel blockers in animal models of autoimmune disease. MATERIAL & METHODS: We studied the effects of 4-AP and quinidine on actively induced acute experimental allergic encephalomyelitis (EAE) in Lewis rats. RESULTS: There was no effect on the incidence of the disease. The severity of the disease was also unchanged although the disease duration was slightly diminished in the treated groups. Immunohistological comparison between the animals of different groups showed no differences. CONCLUSION: We conclude that 4-AP and quinidine are not capable of significantly changing the clinical course of EAE.

4-Aminopyridine↗
PubMed1993

The significance of in-situ Ia antigen expression in the pathogenesis of autoimmune central nervous system disease.

Major histocompatibility class II antigen (Ia) expression is thought to play an important role in the pathogenesis of autoimmune central nervous system (CNS) disease. It has been suggested that Ia expression within the CNS might be sufficient to induce experimental allergic encephalomyelitis (EAE). The expression of Ia antigen in the CNS was studied during the natural course of both acute and chronic relapsing EAE. We found that Ia expression in the CNS starts at a relatively late stage in the course of EAE and persists after the disappearance of the clinical signs. In order to further evaluate the functional significance of Ia expression on glial cells we also studied the effect of intraventricular administration of interferon-gamma. This caused widespread Ia expression within the CNS but no signs of autoimmune CNS disease. Based on these results and data from the literature, the role of local Ia expression in the CNS is reconsidered. In certain circumstances Ia expression may contribute to suppressive rather than enhancing effects on the immune response.

Acute Disease↗
PubMed1993

Evaluation of plasma insulin-like growth factor-binding protein-3 as a potential predictor of preeclampsia.

OBJECTIVE: Elevated growth factor activity in women with preeclampsia is caused by an acid- and heat-labile protein complex with a native molecular mass of 150,000. The major plasma insulin-like growth factor-binding protein-3 has identical molecular characteristics. We hypothesized that increased endothelial cell release or decreased proteolytic degradation of insulin-like growth factor-binding protein-3 in preeclampsia would result in higher circulating levels of insulin-like growth factors and hence in increased mitogenic activity. STUDY DESIGN: Plasma insulin-like growth factor-binding protein-3 concentrations were determined by iodine-125 insulin-like growth factor-II radioligand blots of nonreducing gels in 16 normal and 16 preeclamptic patients collected from a prospective, case-control study. Enzyme-linked immunosorbent assays also were performed with a specific anti-insulin-like growth factor-binding protein-3 antiserum. RESULTS: Insulin-like growth factor-binding protein-3 concentrations were not different between women with normal versus preeclamptic pregnancies (p = 0.23). Enzyme-linked immunosorbent assays confirmed these results in a subset of patients. CONCLUSIONS: The findings indicate that insulin-like growth factor-binding protein-3 concentrations do not account for the elevated mitogenic activity observed in plasma from women with preeclampsia and are not a useful screening test for preeclampsia risk.

Adult↗
PubMed1993

Influence of treatment on the maturation of the somesthetic pathway in infants with primary congenital hypothyroidism during the first year of life.

To assess the influence of treatment on the development of the somesthetic pathway in infants with congenital hypothyroidism receiving early treatment, median nerve somatosensory evoked potentials were measured during the 1st y of life. Twenty-nine infants were studied with six to seven somatosensory evoked potential tests per infant. The cervical latency (N13) divided by arm length and the first (N19) and second (N32) cephalic latencies as well as N13-N32 latency were measured. At diagnosis, all components showed a small but significant delay, which was not related to thyroxine (T4) levels before treatment. During treatment, T4 ranged from 50 to 290 nmol/L. At 12 mo, the cervical latency divided by arm length had normalized, whereas N19 and N13-N32 were more abnormal than at diagnosis. For N19, these abnormalities were related to a slow initial rise of T4 (< or = 100 nmol/L after 1 wk of treatment) and the initial N19 values. Abnormal N13-N32 values were associated with high T4 values during treatment (> 200 nmol/L) and the type of congenital hypothyroidism (partial or total deficiency in T4 production). Induction of therapy with l-triiodothyronine rather than l-thyroxine and the occurrence of low T4 values (< 100 nmol/L) after the 4th wk of therapy had no such effect. Our data suggest that, for normal CNS development, euthyroidism should be reached as soon as possible by adequate induction therapy. Thereafter, T4 supplementation should be strictly dosed, keeping the serum T4 values within narrow limits around the mean normal for age, because overtreatment, like initial undertreatment, may lead to CNS abnormalities at the end of the first year.

Central Nervous System↗
PubMed1993

New insights into the etiology of pre-eclampsia.

Pre-eclampsia is a pregnancy-specific syndrome of unknown etiology, defined by clinical findings of elevated blood pressure combined with proteinuria and oedema. The decidual portion of the spiral arteries of women who later develop pre-eclampsia does not undergo the normal pregnancy-induced remodelling that converts these vessels to high volume-low resistance conduits. We have postulated that this failure leads to vascular spasm, restricted blood flow, placental ischaemia and the release of toxic substances that enter the maternal circulation, resulting in multi-organ disease. The complex and interwoven pathways of endocrine, paracrine and autocrine factors appear to result in a vicious cycle of endothelial cell dysfunction, which is expressed clinically as pre-eclampsia.

Endothelins↗
PubMed1993

Retrovirus-mediated transfer and expression of marker genes in the BN rat acute myelocytic leukemia model for the study of minimal residual disease (MRD).

To study minimal residual disease (MRD) in leukemia, we transferred the Escherichia coli genes encoding beta-galactosidase (lacZ) and neomycin resistance (neo(r)) into the subline LT12 of the Brown Norway rat acute myelocytic leukemia (BNML), employing the retroviral BAG vector. In this way leukemic cells were genetically marked. Ten independent cell lines were characterized during in vitro growth as well as during two subsequent in vivo passages for expression of neo(r) for which the neomycin analogue G418 was used, and for lacZ expression for which the substrate 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) was used. Out of 10 lines, four revealed permanent high expression of lacZ in all cells. In four other lines greatly varying lacZ expression between the individual cells from these lines was observed. In the remaining two lines lacZ expression was gradually lost. In contrast, neo(r) expression was gradually lost in eight out of the 10 lines, particularly rapidly during in vivo passaging. In the remaining two lines neo(r) expression was retained. The genetic modification did not alter the in vitro leukemogenicity of the cells. Long term in vivo expression of neo(r) and lacZ was followed in two selected lines up to 12 subsequent passages, i.e. one from the group of homogeneous high lacZ expression and one from the group of heterogeneous lacZ expression. In both lines lacZ expression was retained whereas neo(r) expression was rapidly lost after the third passage. The feasibility of using genetically marked leukemic cells for studies of minimal residual disease (MRD) was explored by injecting rats with leukemic cells, treating them with chemotherapy at full blown leukemia development to reduce the tumor load, mimicking the induction of a state of MRD and studying lacZ expression at relapse. LacZ expression was evident in 100% of the cells whereas neo(r) expression was lost in a considerable fraction. These results indicate that the viral vector BAG can be used to mark leukemia cells genetically although a selection of clones with the desired stability of long-term expression is required.

Acetyltransferases↗
PubMed1992

Determination of the origin and nature of brain macrophages and microglial cells in mouse central nervous system, using non-radioactive in situ hybridization and immunoperoxidase techniques.

The origin and nature of brain macrophages and microglial cells in the mouse central nervous system (CNS) were investigated. First, the expression and localization of determinants recognized by the different monoclonal antibodies (mAbs) MOMA-1, Mac-1-alpha, and F4/80 (raised against cells of the mononuclear phagocyte system) were immunohistochemically studied in the developing and adult mouse brain. In order to clarify the origin of brain macrophages and microglial cells, we used bacteriophage lambda transgenic mice as donors for bone marrow transplantations in recipient mice of different ages. During ontogeny, numerous MOMA-1-, Mac-1-alpha-, and F4/80-positive blood monocyte-derived brain macrophages (amoeboid microglia) infiltrated the CNS parenchyma. These brain macrophages gradually disappeared from the brain parenchyma at postnatal day 7 (P7). From P17 on, Mac-1-alpha- and F4/80-positive cells were detected within the brain parenchyma with the morphology of resting microglial cells. Transitional forms between brain macrophages and "resting" microglia were not observed in the developing brain. Combined non-radioactive in situ hybridization and immunohistochemistry revealed many MOMA-1-positive bone marrow-derived brain macrophages that were located in the leptomeninges, the ventricles, and occasionally the blood vessel walls. These results show that brain macrophages are of bone marrow origin. Many "resting" microglial cells were detected in the brain, mainly in the white matter. It appeared that about 10% of these cells displayed the transgenic signal. This result indicates that the majority of "resting" microglial cells are of local, presumably neuroectodermal, origin.

Animals↗
PubMed1992

Circulating concentrations of fetal fibronectin do not reflect reduced trophoblastic invasion in preeclamptic pregnancies.

This prospective, nested, case-control study investigated whether maternal plasma fetal fibronectin reflects reduced trophoblastic invasion at 16 to 20 weeks in women who later have preeclampsia. Concentrations of fetal fibronectin were 8.7 +/- 2.6 micrograms/ml in women with preeclampsia and 8.1 +/- 2.5 micrograms/ml in matched controls (p greater than 0.5). These results are discussed.

Case-Control Studies↗