Search PubMed⌕ Search

Biomedical subjects

J M Vossen

Publications and source records attributed to J M Vossen.

At least 73 records · Page 4Linked to original sources
PubMed1994

Persistence of host-type hematopoiesis after allogeneic bone marrow transplantation for leukemia is significantly related to the recipient's age and/or the conditioning regimen, but it is not associated with an increased risk of relapse.

We investigated the chimerism pattern within flow-sorted peripheral blood- or bone marrow-derived cell populations after allogeneic bone marrow transplantation (BMT) for the treatment of leukemia in children. This study was performed to define the identity of persistent host-type cells, to identify prognostic variables for the persistence of host-type hematopoiesis, and to determine the prognostic significance of the chimerism pattern on the duration of the leukemia-free interval, the overall survival, and the leukemia-free survival. The patients received either HLA-identical non-T-cell-depleted (n = 46) or HLA nonidentical T-cell-depleted (n = 7) BMT. In the peripheral blood, the children showed either stable mixed chimerism (SMC; ie, persistent host-type hematopoiesis; n = 14), (transient) mixed T-lymphoid chimerism (MTLC; n = 9), or complete chimerism (CC; n = 30). In the bone marrow, only donor-type cells were found in children with either CC (n = 8) or MTLC (n = 2), and a mixture of donor- and recipient-type cells was found in children with SMC (n = 7). The persistence of host-type hematopoiesis (SMC) was significantly related to a lower age of the recipient, the type of conditioning regimen, a lower total body irradiation dose, T-cell depletion of the bone marrow graft, and the use of cyclosporine A for acute graft-versus-host disease prophylaxis. No significant differences were found between patients with (SMC) or without (CC/MTLC) persistent host-type hematopoiesis with respect to the duration of the leukemia-free interval, the overall survival, or the leukemia-free survival. We conclude that ablation of host-type hematopoiesis is not compulsory for long-term leukemia-free survival after allogeneic BMT for various hematologic malignancies.

Adolescent↗
PubMed1994

[Immunodeficiency in The Netherlands: clinical and immunological survey, 1970-1983. Interfacultaire werkgroep Immunodeficiëntie].

OBJECTIVE: Inventory of patients with immunodeficiency in the Netherlands. DESIGN: Retrospective over the period 1970-1983. SETTING: Dutch Working Group on Immunodeficiency, University Children's Hospital, 'Het Wilhelmina Kinderziekenhuis', Utrecht. METHOD: A questionnaire with specific information on immunodeficient patients was completed by clinical members of the Working Group i.e. paediatricians and internists. Diagnosis of the immunodeficiency was according to WHO recommendations. RESULTS: The data of 336 patients could be included and analysed. Defects in humoral immunity were the most common (62.9%), followed by combined defects (18.75%), T cell defects (7.4%), phagocytic disorders (6.8%) and complement component deficiencies (2.7%). Sixty-two patients (15.5%) died, notably those with combined T and B cell defects, selective T cell defects and those with immunodeficiency based on DNA repair defects. Autoimmunity was relatively frequent in immunodeficiency (7.7%) as was cancer (2.7%). CONCLUSION: Results were similar to those of other European countries.

Antibody Formation↗
PubMed1994

Usage of TCRAV and TCRBV gene families in human fetal and adult TCR rearrangements.

We have investigated fetal and adult T-cell receptor (TCR) A and B V-gene repertoires both by fluorescence-activated cell sorter (FACS) analysis with the available TCR V region-specific mAbs and by the polymerase chain reaction (PCR) with TCR V gene family-specific oligonucleotides. Among the low number of CD3+ T cells, most of the TCR V regions tested for could be detected by FACS analysis in liver, bone marrow, and spleen derived from a 14-week-old fetus and two 15-week-old fetuses. Similarly, the PCR analysis showed that the majority of the TCRAV and TCRBV families were expressed in the peripheral organs of the 13-week-old fetus, although an apparent absence of particular TCR V families was found in liver and bone marrow. This was most probably the consequence of the low number of CD3+ T cells in these organs. In 17-week-old fetal thymi the level of expression of some TCRAV and TCRBV gene families, in particular those that contain a single member, was lower compared to post-partum thymi and adult peripheral blood mononuclear cells. The combined data of FACS and PCR analysis demonstrate that TCR V genes belonging to the majority of TCR V gene families can be used in TCR alpha and beta chain rearrangements during early human fetal life. Our data also suggest that the expression levels of some of the single member TCR V gene families may be influenced by the developmental stage.

Animals↗
PubMed1994

Prevalence of penicillin-resistant viridans streptococci in healthy children and in patients with malignant haematological disorders.

The prevalence of penicillin-resistant viridans streptococci was studied in healthy children and in paediatric and adult patients with leukaemia to determine whether the frequent presence of penicillin-resistant streptococci in the oral cavity of children with leukaemia is the result of antibiotic therapy. Twenty of the oral swabs from 50 healthy children who had not received antibiotics in the three months prior to sampling yielded viridans streptococci that could be cultured on blood agar containing 2 micrograms/ml benzyl-penicillin. In 11 of the 20 cases the streptococci were resistant to penicillin (MIC > or = 4 micrograms/ml). This prevalence is significantly higher than that found in adult leukaemia patients (40% vs. < or = 5%) but is about the same as that found in paediatric patients with leukaemia. The high prevalence of penicillin-resistant streptococci in the paediatric age group should be considered when selecting therapy and prophylaxis, especially when the risk of infection with one of these cocci is enhanced.

Adolescent↗
PubMed1994

Effects of the neuroleptanalgesic fentanyl-fluanisone (Hypnorm) on spike-wave discharges in epileptic rats.

Effects of fentanyl-fluanisone (Hypnorm), a combination often used as a neuroleptanalgesic and anaesthetic, were investigated on spike-wave discharges of epileptic WAG/Rij rats. Fentanyl-fluanisone has stimulating effects on the amount of spike-wave discharges, but not in a dose-dependent manner. A low dose of 0.01 mg/kg fentanyl with 0.5 mg/kg fluanisone causes a large increase in epileptic activity. This effect is larger than with a middle dose of 0.1 mg/kg fentanyl and 5 mg/kg fluanisone and much larger than with a high dose of 0.2 mg/kg fentanyl with 10 mg/kg fluanisone. The last two doses cause a prolonged anaesthetic state in rats. The frequency of the spikes in the spike-wave discharges was decreased by the mixture of fentanyl-fluanisone; this decrease was dose-dependent. Administration of fentanyl alone in the same doses as in the combination abolishes spike-wave activity during the anaesthetic phase but causes a moderate increase after this phase. It also causes a lowering in spike frequency, which is of the same order as with fentanyl-fluanisone. The mechanisms of action of fentanyl are not completely clear, but the opposite effects of mu- and kappa-opioid receptors on spike-wave discharges may play a role in this biphasic effect. Fluanisone alone in the same doses as in the mixture induces a large dose-dependent increase in spike-wave activity, with only a small effect on spike frequency. This might be caused by the antagonistic action of this drug at dopamine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The WAG/Rij rat model for nonconvulsive absence epilepsy: involvement of nonNMDA receptors.

The involvement of AMPA and kainate receptors in nonconvulsive epilepsy was studied by intracerebroventricular injections of AMPA, GDEE, kainic acid and kynurenic acid in WAG/Rij rats. The WAG/Rij rat strain is recognized as an animal model for human absence epilepsy. EEG registrations showed that AMPA (0.1 pmol/5 microliters; 1 pmol/5 microliters; 10 pmol/5 microliters) dose-dependently increased the nonconvulsive absence epilepsy while GDEE (0.2 mumol/5 microliters; 1 mumol/5 microliters; 5 umol/5 microliters) caused a dose-dependent decrease. All effects of GDEE could be blocked by an inactive AMPA dosage. Kainic acid (0.01 nmol/5 microliters; 0.1 nmol/5 microliters; 0.15 nmol/5 microliters) had no effects on the nonconvulsive epilepsy but induced convulsions in the two highest dosages. Kynurenic acid (50 nmol/5 microliters; 100 nmol/5 microliters; 500 nmol/5 microliters) decreased dose-dependently the incidence of nonconvulsive epilepsy. The effect of kynurenic acid could be blocked by a nonconvulsive dosage of kainic acid. These results show that the AMPA and kainate receptor appear to be involved in nonconvulsive epilepsy. Furthermore, blockage of these two receptor subtypes led to an antiepileptic effect without inducing behavioural alterations. Therefore, selective AMPA and kainate receptor antagonists might be potent anti-epileptics.

Animals↗
PubMed1994

Interactions between NMDA and nonNMDA receptors in nonconvulsive epilepsy in the WAG/Rij inbred strain.

The interaction between NMDA and nonNMDA receptors was studied in nonconvulsive epilepsy in WAG/Rij rats. Compounds acting on NMDA (NMDA, APH) and nonNMDA (AMPA, GDEE, kainic acid, kynurenic acid) receptors were coinjected intracerebroventricularly. The WAG/Rij rat strain may be an animal model for human nonconvulsive absence epilepsy. The effects on the epilepsy, EEG and behaviour were measured. It appeared that the epilepsy increase, induced by the nonNMDA receptor agonist AMPA, and in a less obvious way, kainic acid, was blocked by the NMDA receptor antagonist APH. The effects of NMDA were completely blocked by the nonNMDA receptor antagonists GDEE and kynurenic acid. These results suggest that there is an interaction between NMDA and nonNMDA receptors. It might be that nonNMDAergic compounds act via activation or inactivation of NMDA receptors and that this latter receptor subtype is the trigger for an epileptic seizure.

Animals↗
PubMed1994

Bone marrow transplantation for autosomal recessive osteopetrosis. A report from the Working Party on Inborn Errors of the European Bone Marrow Transplantation Group.

The outcomes of 69 patients who received allogeneic bone marrow grafts for autosomal recessive osteopetrosis in the period between 1976 and 1994 were analyzed retrospectively. Four patients received bone marrow transplants (BMT) without prior myeloablative conditioning; transient osteoclast function was demonstrated in one of them. Sixty-five patients received myeloablative pretreatment. Recipients of a genotypically human leukocyte antigen (HLA)-identical BMT had an actuarial probability for 5-year survival, with osteoclast function, of 79%; recipients of a phenotypically HLA-identical bone marrow graft from a related or unrelated donor, or one HLA-mismatched graft from a related donor, had an actuarial probability for 5-year survival, with osteoclast function, of 38%; patients who received a graft from an HLA-haplotype mismatched related donor had a probability for 5-year survival of only 13%. The main problems in haplotype-nonidentical BMT were graft failure and BMT-related complications such as sepsis, bleeding, and interstitial pneumonia. Osteoclast function developed in all patients with full engraftment. Recovery of osteoclast function was associated with severe hypercalcemia in 24% of the patients with engraftment, especially those older than 2 years of age. At the time of BMT, severe visual impairment was present in 35% of the patients; of the 15 patients who had visual impairment at the time that a successful BMT was performed, two had improvement after BMT (13%). Within the total group, one patient had neurodegeneration. Engraftment of healthy donor cells had no influence on the progression of that abnormality and BMT thus had no beneficial effect on this phenotype of osteopetrosis. In general, however, early BMT remains the only curative treatment for autosomal recessive osteopetrosis.

Actuarial Analysis↗
PubMed1994

Non-random employment of V beta 6 and J beta gene elements and conserved amino acid usage profiles in CDR3 regions of human fetal and adult TCR beta chain rearrangements.

We have studied the usage of V beta 6, D beta, and J beta elements, and the composition of the CDR3 regions of human fetal TCR beta chain rearrangements in a 17 week old fetal thymus and in fetal liver, bone marrow, spleen, and cord blood at 11 and 13 weeks of gestation. These fetal sequences were compared with TCR beta chain rearrangements obtained from post-partum thymus, adult spleen, and adult peripheral blood mononuclear cells. Both fetal and adult TCR V beta 6 rearrangements exhibited a non-random usage of V beta and J beta elements. Up to 90% of the sequences obtained at 11 weeks of gestation used J beta 2 elements, most notably J beta 2.1. In the 13 and 17 week old fetal and in the adult tissues, J beta 1 elements were used in approximately 30% of the rearrangements while, within the J beta 2 rearrangements, J beta 2.1 and J beta 2.7 were used most frequently. Both fetal and adult TCR beta chain CDR3 regions showed non-random usage of amino acids. However, the early fetal repertoire was further limited due to the relative absence of N-regions in up to 60% of the 11 and 13 week old TCR beta chain rearrangements, resulting in smaller antigen binding sites. In fetal and adult TCR beta chain rearrangements the distribution patterns of the length of N-regions and the usage profiles of J beta elements were similar in hematopoietic and peripheral organs, suggesting no apparent preference for particular TCR beta chain rearrangements.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Ten years after acquiring an HIV-1 infection: a study in a cohort of eleven neonates infected by aliquots from a single plasma donation.

We present data from a 10-year follow-up study of 11 children who had been infected in the neonatal period by small aliquots of plasma from a single donation. Three of the children died within the first 2.5 years of life, 5 other children died between 6.2 and 11 years after infection and 3 are alive at present. The latter children are classified as P1B (asymptomatic), P2A (non-specific findings) and P2B (neurological changes). All infected children showed progressive decline of cellular immunity. Immunoglobulin levels in serum were increased in the majority of children for prolonged periods and homogeneous immunoglobulin components were present. The severity of the disease was related neither to the clinical condition of the infants in the neonatal period nor to the volume of transfused plasma, the interval between freezing and thawing of the plasma, gestational age at birth and age at transfusion. Coinciding infections with other viruses had no impact on disease progression during the follow-up period of 10 years.

Blood Donors↗
PubMed1994

Autosomal recessive osteopetrosis: variability of findings at diagnosis and during the natural course.

OBJECTIVE: To determine the variability and the natural course of children suffering from autosomal recessive osteopetrosis to allow optimal counseling and decision making with respect to therapeutic intervention. DESIGN: Retrospective and longitudinal evaluation of clinical symptoms and natural course with emphasis on survival and sensoneurologic and hematologic findings. SETTING: Two large referral-based pediatric bone marrow transplantation units in Europe. PATIENTS: Thirty-three patients with autosomal recessive osteopetrosis admitted to units in Paris and Leiden between 1972 and 1988 were analyzed until last follow-up or the time at which bone marrow transplantation was performed. The great number of patients and unprecedented amount of data make this report one of the single largest clinical studies on autosomal recessive osteopetrosis. MAIN RESULTS: Ocular involvement occurring at a median age of 2 months was the symptom at initial examination in half of the patients. A striking variability between patients was found. Retinal degeneration was present in three patients and associated generalized neurodegeneration was present in two. The probability of survival until the age of 6 years was about 30% for the group as a whole. The cumulative risk of developing visual or hematologic impairment in the first year of life was about 75% and leveled off afterward. Patients with early hematologic impairment, ie, before 3 months of age, especially when combined with early visual impairment, had a very poor prognosis regarding life expectancy. CONCLUSIONS: Autosomal recessive osteopetrosis seems to be a variable disorder with a poor prognosis, especially in children with early visual and hematologic impairment. Allogenic bone marrow transplantation remains the only curative approach.

Bone Marrow Transplantation↗
PubMed1993

Immunoglobulin levels and monoclonal gammopathies in children after bone marrow transplantation.

Bone marrow graft recipients suffer profound immunodeficiency during at least 3 months after transplantation. B-cell reconstitution following allogeneic bone marrow transplantation (BMT) in children was studied longitudinally by quantification of Ig (sub)class levels in serum and by investigation of numbers and characteristics of homogeneous Ig components (H-Ig); ie, monoclonal gammopathies (MG). For the latter purpose, a sensitive immunoblotting technique capable of detecting H-Ig of a concentration as low as 0.5 microgram/mL was used. Sera of 40 children grafted for a variety of diseases were investigated and followed up for 5 years. It was found that Ig (sub)classes reached normal levels from 3 months after BMT onward. The sequential increase of the different Ig isotypes was in accordance with that seen in normal ontogeny. This was especially clear following BMT for severe congenital immunodeficiency. H-Ig appeared from as early as 6 weeks after BMT in increasing numbers, beginning within IgM, IgG3, and IgG1, and afterward within other isotypes. After an initial increase of serum Ig levels, "overshooting" occurred accompanied by high frequency of H-Ig. H-Ig were still present at 5 years after BMT, when Ig levels normalized. Our data indicate that B-cell reconstitution after allogeneic BMT recapitulates normal ontogeny but in a clonally dysregulated fashion; that is, with overexpression of some clones and underexpression of others.

Adolescent↗
PubMed1993

Interferon-gamma prevents graft-versus-host disease after allogeneic bone marrow transplantation in mice.

Lethally irradiated C3H/Law mice were injected (i.v.) with C57BL/Rij allogeneic bone marrow cells to induce a delayed type graft-vs-host disease (GVHD). Signs of GVHD first became apparent in the third week after transplantation. The disease resulted in a mortality rate of 70% at 80 days. Treatment with IFN-gamma twice weekly, for a period of 6 wk, starting at the time of bone marrow transplantation (BMT), completely prevented overt GVHD, as evidenced by a lack of diarrhea and no mortality during the follow-up period of 100 days after BMT. Also, the histologic GVHD lesions in the gastrointestinal tract were almost completely abrogated by the IFN-gamma treatment. All long term survivors were proven to be chimeras. During the induction phase of GVHD, the number of Con A-induced, IFN-gamma-producing cells in the spleen was significantly reduced in the IFN-gamma-treated mice as compared with control mice. These results suggest that the normally enhanced production of endogenous IFN-gamma in the spleen at the time of hematopoietic reconstitution after BMT is down-regulated by exogenously administered IFN-gamma. This cytokine-mediated strategy to prevent GVHD might be an alternative to the current strategy of in vitro depletion of T cells for allogeneic BMT.

Animals↗
PubMed1993

Mixed T-lymphoid chimerism after allogeneic bone marrow transplantation for hematologic malignancies of children is not correlated with relapse.

We performed polymerase chain reaction-variable number of tandem repeats analysis of flow-sorted peripheral blood T-, B-, natural killer-, and myeloid cell populations (van Leeuwen et al, Br J Haematol 79:218, 1991) in 32 children following allogeneic bone marrow transplantation (BMT) for leukemia to evaluate the relationship between mixed lymphoid chimerism and leukemia relapse. Five patients showed a stable mixed chimerism pattern characterized by the presence of both recipient as well as donor type cells in all cell populations up to 1 year posttransplantation. Five others showed transient mixed chimerism in the T-lymphoid cell lineage. In one patient, host T cells persisted until leukemia relapse. The remaining 21 patients showed a complete chimerism throughout the period of investigation. Twenty-five of these patients were classified according to the presence (n = 10) or absence (n = 15) of recipient type T cells. Statistical analysis did not show significant differences in the distribution of a number of clinical variables between the two groups, nor in the actuarial survival (P = .11) and leukemia-free interval (P = .97). Therefore, these results suggest that persistence of recipient type T lymphoid cells after allogeneic BMT for hematologic malignancies is not correlated with leukemia relapse. In addition, we observed that persistence of host cells within the original leukemia cell lineage and at the correct maturational stage was predictive for leukemia relapse in one case.

Adolescent↗
PubMed1993

Thalamic multiple-unit activity underlying spike-wave discharges in anesthetized rats.

In epilept WAG/Rij rats, multiple unit activity coinciding with the occurrence of spike-wave discharges was recorded under neurolept anesthesia. Recordings were made in the frontal cortex and in various nuclei of the thalamus, in specific nuclei such as the ventroposterolateral, the ventroposteromedial and the ventrolateral nuclei, as well as in non-specific nuclei such as the mediodorsal nucleus, the reticular thalamic nucleus, the interanteromedial nucleus and the intralaminar nuclei (the central medial nucleus, the centrolateral nucleus and the paracentral nucleus). Rhythmic unit firing concurrent with the spike component of the cortical spike-wave discharge was observed in deep layers of the cortex and in the following thalamic nuclei: in specific nuclei, the mediodorsal and the reticular thalamic nucleus. The activity in the specific nuclei and the mediodorsal nucleus shortly preceded the peak of the spike component. The burst in the reticular thalamic nucleus occurred later than in the specific nuclei. A wave-concurrent firing pattern was observed in the centrolateral nucleus and the paracentral nucleus. Cells in the central medial nucleus and interanteromedial nucleus did not fire in a phase-locked manner. Neurons in the latter nucleus, however, were generally tonically activated during the occurrence of spike-wave discharges. It is suggested that those thalamic nucleic thought to be involved in the production of cortical spindles, and that also fire concurrently with the spike component of the spike-wave discharges, are mediated in the genesis of the latter activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1993

Contribution to scientific research in paediatrics in The Netherlands: evaluation according to subspeciality over a 10-year period.

The board of the Dutch Paediatric Association requested a survey of the scientific research performed in all academic and non-academic paediatric hospitals, authorized to train medical doctors in paediatrics in the Netherlands. Contributions to the international and the Dutch scientific literature, in the form of regular publications, chapters in books, contributions to proceedings and Ph.D. theses were counted over two 5-year periods, i.e. 1981-1985 and 1986-1990. The quality of publications in the international journals was assessed using the average impact factor of the journals over the 10-year period. The number of publications in the international literature doubled during the observation period 1986-1990 compared to the period 1981-1985. Nevertheless, the quality of the publications remained the same. Metabolism, oncology/haematology, immunology/infectious diseases and cardiology are the subspecializations in which scientific research takes place in four or more academic paediatric hospitals. In total, 84 Ph.D. theses were produced in which a paediatrician was either the project leader (mostly a professor in paediatrics) or the investigator-in-charge. Insight into structure and major research efforts of paediatric hospitals in other countries of Europe may lead to exchange of views and, maybe, profitable co-operation.

Netherlands↗
PubMed1993

Context conditioning: positive reinforcing effects of various food-related stimuli.

Rats were subjected to context preference tests to investigate the degree to which various manipulations involving food stimuli can be used to appetitively condition contextual cues. One manipulation consisted of placing hungry rats in a context that contained food that they could consume. A second one involved exposure to a context containing food that could only be seen and smelled, without consumption being possible. A third type of manipulation consisted of exposing animals to a context after the consumption of a small meal in the home cage. Finally, hungry, control subjects were merely exposed to a context containing an empty food tray. Preference for the context was only enhanced after the first type of manipulation, indicating that the actual consummatory act constitutes the major source of reinforcement in the present procedure. Olfactory and visual food cues, as well as postingestional aftereffects in isolation, did not function as reinforces.

Animals↗