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Biomedical subjects

J Zijlstra

Publications and source records attributed to J Zijlstra.

At least 19 recordsLinked to original sources
PubMed2005

An oral carcinogenicity and toxicity study of senna (Tinnevelly senna fruits) in the rat.

Senna (Tinnevelly senna fruits), a known laxative derived from plants, was administered by gavage to Sprague-Dawley (Crl:CD (SD) BR) rats once daily at dose levels of 0, 25, 100 and 300 mg/kg/day for up to 104 consecutive weeks. Based upon clinical signs related to the laxation effect of senna, the highest dose (300 mg/kg/day) was considered to be a maximum tolerated dose. Sixty animals per sex were assigned to the control and dose groups. Assessments included clinical chemistry, hematology, full histology (control and high-dose groups; in addition, low and mid dose: intestinal tract, adrenals, liver, kidneys, brain and gross lesions) and toxicokinetics. The primary treatment-related clinical observation was mucoid feces seen at 300 mg/kg/day. When compared to controls, animals administered 300 mg/kg/day had slightly reduced body weights, increased water consumption and notable changes in electrolytes in serum (increases in potassium and chloride) and urine (decreases in sodium, potassium and chloride). The changes in electrolytes are most likely physiologic adaptations to the laxative effect of senna. At necropsy, dark discoloration of the kidneys was observed in animals in all treated groups. Histological changes were seen in the kidneys of animals from all treated groups and included slight to moderate tubular basophilia and tubular pigment deposits. In addition, for all treated groups, minimal to slight hyperplasia was evident in the colon and cecum. These histological changes, together with the changes seen in the evaluation of clinical chemistry and urine parameters, have been shown to be reversible in a previous 13-week rat study of senna. No treatment-related neoplastic changes were observed in any of the examined organs. Based upon these data, it is concluded that senna is not carcinogenic even after daily administration for 2 years at dosages of up to 300 mg/kg/day in Sprague-Dawley rats.

Administration, Oral↗
PubMed2004

Mechanical ventilation of healthy rats suppresses peripheral immune function.

This study was designed to investigate the possible effect of injurious mechanical ventilation on peripheral immune function of healthy rats. Three ventilation strategies were compared: 1) low peak inspiratory pressure (PIP)/positive end-expiratory pressure (PEEP); 2) high PIP/PEEP; and 3) high PIP/zero PEEP (ZEEP). As a reference group, healthy, nonventilated, sham-operated, anaesthetised rats were used. After 4 h, rats were sacrificed and macrophage inflammatory protein (MIP)-2 levels in lung and plasma were determined. Peripheral immune function was determined by measurement of splenic natural killer (NK) activity, mitogen-induced splenocyte proliferation and in vitro cytokine production. All immune measurements in the low PIP/PEEP group did not differ from the immune measurements in the reference group. High PIP strategies, irrespective of applied PEEP, enhanced MIP-2 levels in lung and plasma. NK cell activity, mitogen-induced splenocyte proliferation and MIP-2 and interleukin (IL)-10 production significantly decreased after high PIP/PEEP ventilation. In the high PIP/ZEEP-ventilated group, the decrease in splenocyte proliferation, MIP-2 and IL-10 production and NK cell activity was more pronounced and interferon-gamma production was also significantly lower than in the low PIP/PEEP group. These data show that high positive inspiratory pressure ventilation induces an inflammatory response in the lung, whereas at the same time the peripheral immune response is downregulated. Ventilator-induced peripheral immune suppression may contribute to poor outcome in acute respiratory distress syndrome patients.

Animals↗
PubMed2003

Acute renal failure due to non-Hodgkin lymphoma infiltration of the kidneys detected by ultrasonography and confirmed by positron emission tomography.

Acute renal failure (ARF) as a consequence of non-Hodgkin lymphoma infiltration of the kidneys (LIK) is an uncommon complication of non-Hodgkin lymphoma. In literature, ARF due to LIK is reported in progressive disease. A case of non-oliguric acute renal failure secondary to relapse of large B cell non-Hodgkin lymphoma primarily localized in the mediastinum is reported. LIK of both kidneys was diagnosed by ultrasonography, computer tomography scan and 18-fluorodeoxyglucose positron emission tomography. No other causes for renal failure were found. The prognosis of renal involvement in relapsed non-Hodgkin lymphoma is poor, as is demonstrated by our case.

Acute Kidney Injury↗
PubMed2001

Neonatal dexamethasone treatment induces long-lasting changes in T-cell receptor vbeta repertoire in rats.

Glucocorticoids are frequently administered for the prevention of chronic lung disease in infants with respiratory distress syndrome. However, neonatal treatment may have consequences for immune functioning in the long-term. Here we demonstrate that neonatal glucocorticoid treatment has long-lasting effects on mRNA expression of several Vbeta genes within the CD4 and CD8 T cell subset in rats. Changes in the peripheral T cell Vbeta repertoire may be a consequence of altered intrathymic selection events in which corticosterone plays an important role. Indeed, here we show that neonatal glucocorticoid treatment affects corticosterone production by thymic epithelial cells during neonatal life. In conclusion, changes in T cell Vbeta repertoire after neonatal glucocorticoid treatment may contribute to altered immune reactivity in later life.

Age Factors↗
PubMed1998

Role of endogenous pro-enkephalin A-derived peptides in human T cell proliferation and monocyte IL-6 production.

In this paper, we describe that met-enkephalin and/or enkephalin-containing intermediary peptides of the prohormone pro-enkephalin A are produced and secreted by human peripheral blood T cells and monocytes. The peptides are produced after stimulation with the mitogenic monoclonal antibodies anti-CD2.1/2.2 and anti-CD28. In monocytes, enkephalin synthesis was induced by stimulation with lipopolysaccharide. We demonstrate here that these immune cell-derived enkephalins play an important regulatory role in the immune response. By using an anti-sense oligonucleotide strategy we could block the production of enkephalins. Blockade of the production of met-enkephalin and enkephalin-containing intermediary peptides resulted in enhancement of the proliferative T cell response and inhibition of monocyte IL-6 secretion. In vitro reconstitution of the anti-sense treated cultures with synthetic met-enkephalin or the delta-type specific opioid receptor agonist deltorphin could reverse inhibition of monocyte IL-6 production, suggesting that endogenous enkephalins act via membrane opioid receptors. In contrast, addition of met-enkephalin or deltorphin to the anti-sense treated T cell cultures did not have any effect on T cell proliferation.

Antibodies, Monoclonal↗
PubMed1997

Beta 2-adrenergic activation enhances interleukin-8 production by human monocytes.

Interleukin-8 (IL-8) is an important cytokine in inflammatory processes by functioning as a chemoattractant and as an activator of oxygen metabolism. In the present study we demonstrate that beta 2-adrenergic agonists potentiate the lipopolysaccharide (LPS) and IL-1 induced production of IL-8 by human monocytes. In addition, beta 2-adrenergic activation enhances IL-8 release and mRNA expression for IL-8 in the human monocytic cell line U937. beta 2-adrenergic activation of these cells also results in enhanced production of the anti-inflammatory cytokine IL-10. However, IL-10 is not involved in the regulation of IL-8 production. The effect of the beta 2-adrenergic agonist on IL-8 production is presumably mediated via increased cAMP formation, since it can be mimicked by the cAMP analogue dibutyryl-cAMP (db-cAMP). We conclude that enhancement of IL-8 production is one of the pathways via which beta 2-adrenergic agonists such as catecholamines can influence inflammatory responses.

Adjuvants, Immunologic↗
PubMed1995

Increased dexamethasone sensitivity of neonatal leukocytes: different mechanisms of glucocorticoid inhibition of T cell proliferation in adult and neonatal cells.

Glucocorticoids (GC) are known to inhibit the proliferative response of leukocytes after mitogenic activation. Until now, the effects of GC on the immune system have been studied predominantly in adults. However, GC are frequently administered to human fetuses and newborns for the prevention and treatment of respiratory distress syndrome. The immune system of human newborns is still a functionally immature system. Therefore, we wondered whether the immaturity is also reflected by altered responses to hormonal signals such as glucocorticoids. We studied the effects of the GC dexamethasone (DEX) on the proliferation of peripheral blood mononuclear cells and T cells in vitro after stimulation with phytohemagglutinin, anti-CD3, anti-CD3/anti-CD28 or anti-CD2/anti-CD28. Our data demonstrate that neonatal cells are much more sensitive to inhibition of the proliferative response by DEX than adult cells (ED50 1 +/- 0.8 nM vs. 221 +/- 135 nM). This difference in sensitivity is not related to differences in affinity and capacity of binding of [3H] DEX. Moreover, we show that the mechanisms of GC inhibition differ between adult and neonatal cells. In adult cells, addition of interleukin (IL)-2 does not restore DEX inhibition of the proliferative response. In contrast, the proliferative response of neonatal cells can be restored completely by the addition of IL-2. These data suggest that the primary target of GC in neonatal cells is inhibition of IL-2 production. In adult cells, other mechanisms are responsible for inhibition of T cell proliferation.

Adult↗
PubMed1993

Pulsed-field gel electrophoresis and radiation hybrid mapping analyses enable the ordering of eleven DNA loci in Xq22.

The Xq22 region of the human X chromosome encompasses the loci of several genes and random DNA markers whose relative positions have not been determined. By a combination of PFGE mapping and the analysis of a selected panel of X chromosome radiation hybrid cell lines, we have constructed physical maps of Xq22 that order a total of 11 polymorphic and nonpolymorphic DNA markers. Ten of these probes have been linked physically into three separate clusters, spanning nearly 6 Mb of DNA in total. The DXS94, DXS147, DXS211, DXS17, and DXS87 loci are all present on a 2.7-Mb MluI fragment; PLP, DXS54, DXS24, and DXS83 are present on MluI fragments spanning over 1.6 Mb; and DXS178 is present on a 1.5-Mb MluI fragment. Mapping with additional enzymes has allowed the further ordering of these loci with respect to each other. Together with these data, analysis of a small set of radiation hybrids has suggested the following over-all order of loci within Xq22: centromere-DXS178-DXS94-DXS147-DXS211-DXS17++ +-DXS87- PLP-DXS54-DXS24-DXS83-COL4A5-telomere. The ordering of these random DNA markers, genes, and disease loci, including the genes responsible for Pelizaeus-Merzbacher disease and Alport syndrome, indicates DNA markers that could be of further use clinically for these diseases. Furthermore, this map should form a basis for the refinement of additional disease-associated loci in this region.

Animals↗
PubMed1991

A genotypic mutation system measuring mutations in restriction recognition sequences.

The RFLP/PCR approach (restriction fragment length polymorphism/polymerase chain reaction) to genotypic mutation analysis described here measures mutations in restriction recognition sequences. Wild-type DNA is restricted before the resistant, mutated sequences are amplified by PCR and cloned. We tested the capacity of this experimental design to isolate a few copies of a mutated sequence of the human c-Ha-ras1 gene from a large excess of wild-type DNA. For this purpose we constructed a 272 bp fragment with 2 mutations in the PvuII recognition sequence 1727-1732 and studied the rescue by RFLP/PCR of a few copies of this 'PvuII mutant standard'. Following amplification with Taq-polymerase and cloning into lambda gt10, plaques containing wild-type sequence, PvuII mutant standard or Taq-polymerase induced bp changes were quantitated by hybridization with specific oligonucleotide probes. Our results indicate that 10 PvuII mutant standard copies can be rescued from 10(8) to 10(9) wild-type sequences. Taq polymerase errors originating from unrestricted, residual wild-type DNA were sequence dependent and consisted mostly of transversions originating at G.C bp. In contrast to a doubly mutated 'standard' the capacity to rescue single bp mutations by RFLP/PCR is limited by Taq-polymerase errors. Therefore, we assessed the capacity of our protocol to isolate a G to T transversion mutation at base pair 1698 of the MspI-site 1695-1698 of the c-Ha-ras1 gene from excess wild-type ras1 DNA. We found that 100 copies of the mutated ras1 fragment could be readily rescued from 10(8) copies of wild-type DNA.

Base Sequence↗
PubMed1991

Technetium-99m carboxymethylcellulose: a newly developed fibre marker for gastric emptying studies.

We report a study of technetium-99m-labelled carboxymethyl-cellulose (99mTc-CMC) as a newly developed non-digestible marker of the solid phase of gastric contents. The radiosynthesis is simple and shows a high labelling efficiency. In vitro and in vivo experiments demonstrated stability of the marker in the gastrointestinal tract during the process of gastric emptying. The gastric half-emptying time in ten healthy volunteers of both sexes was 105 +/- 17 min (mean +/- SD). This rate of gastric emptying is similar to that of non-digestible solid-phase markers such as in vivo labelled 99mTc-chicken liver or radio-iodinated cellulose. In comparison with digestible solid-phase markers such as 99mTc-labelled pancake or 99mTc-cooked egg, gastric emptying of 99mTc-CMC occurred more slowly, confirming the expected behaviour of a non-digestible solid-phase marker. We conclude that 99mTc-CMC has the advantage of a simple and rapid labelling procedure and may be useful for clinical studies of gastric emptying.

Adult↗
PubMed1990

A decreased functional capacity of CD4+ T cells underlies the impaired DTH reactivity in old mice.

The data presented in this paper show that the in vivo delayed-type-hypersensitivity (DTH) reaction to both H-2 and non-H-2 alloantigens declines with increasing age. It is also shown that cells generated in vitro are capable to transfer DTH to young naive syngeneic recipients. Using this in vitro system it could be demonstrated that cells from old CBA/Rij mice induced lower DTH responses than cells from young CBA/Rij mice. Depletion experiments with the effector T cell population showed that the DTH effector phase is mediated by CD4+ T cells. Lower responses in old mice were not due to increased CD8+ suppressor T cell activity, since after removal of the CD8+ T cells old CD4+ cells were still less effective in the generation of DTH effector T cells than young CD4+ cells. Addition of IL-2 containing supernatant to in vitro cultures did not improve the subsequent DTH response. From these data it can be concluded that the reduced DTH responses in old mice are not solely due to CD8+ suppressor cell activity and/or lack of IL-2, but that rather intrinsic defects of the CD4+ T cell population appear to play a major role in the impaired DTH reactivity during ageing.

Aging↗
PubMed1988

Generation of high-rate ovalbumin-specific antibody-secreting cells in cultures of human peripheral blood B cells obtained from non-immunized blood donors.

When human peripheral blood B cells are cultured for 6 days with the T cell-dependent peptide antigen ovalbumin (OA) in the presence of antigen-presenting cells and helper T cells, plaque-forming cells (PFC) are generated. These OA-induced PFC differ from the conventional high-rate antibody-secreting PFC formed after stimulation of B cells with recall antigens (e.g. tetanus toxoid) in that they secrete antibody at a very low level. Previous studies have shown that OA-induced PFC are B lymphocytes in an early activation state rather than cells that have differentiated into plasmablasts. The apparent arrest in the maturation of OA-induced PFC in an early activation phase can be overcome by simultaneous stimulation with interleukin 2 (IL-2) and gamma interferon (IFN-gamma). The isotype of the OA-specific antibodies secreted, however, are only of the IgM class, demonstrating that an isotype switch does not occur.

Antibody-Producing Cells↗
PubMed1988

Ovalbumin-specific human B-cell activation and maturation. The absence of final maturation is due to the incapacity of ovalbumin-activated T cells to produce maturation factors.

By means of a panel of monoclonal antibodies it is demonstrated that, in cultures of human peripheral blood mononuclear cells (PBMC) with the T-cell-dependent (TD) antigen ovalbumin (OA), responding B cells are activated from the resting state. The differentiation of the activated B cells to high rate-secreting plasma blasts, however, is arrested in an early activation phase, in which they can be detected as low rate-secreting plaque-forming cells. The arrest does not occur when stimulation with OA occurs in the presence of antigen-nonspecific activation and maturation factors, which are provided in the culture by the anamnestic response to the TD antigen tetanus toxoid.

Adjuvants, Immunologic↗
PubMed1987

Modulation of the immune response by POMC-derived peptides. I. Influence on proliferation of human lymphocytes.

The POMC-derived peptides beta-endorphin and ACTH are capable of modulating an immune response in physiological concentrations. These neuropeptides can either enhance or inhibit the proliferative response of human peripheral blood lymphocytes after stimulation with the mitogen concanavalin A. The modulatory action of the peptides is not only dependent on the concentration but appears to be donor dependent. The response pattern observed is not determined by a selective affinity for certain amino acid sites on the molecules with "enhancing" or "inhibiting" activities, since fragments of beta-endorphin and ACTH also produce a differential donor-dependent response pattern.

Adrenocorticotropic Hormone↗
PubMed1985

Analysis of the antigen-induced in vitro differentiation of human peripheral blood B cells: stimulation with ovalbumin induces the transition from the resting state into the excited state.

Human peripheral blood B lymphocytes, when cultured for 6 days with ovalbumin in the presence of T cells and monocytes, can differentiate into plaque-forming cells (PFC) secreting small amounts of antigen-specific IgM. Phenotype analysis using Ig-isotype and B-cell specific monoclonal antibodies revealed that the PFC precursor is a sIgM+ IgD+IgG- B lymphocyte. The PFC itself also carries the B-cell specific membrane antigens B1 and BA-1; it expresses only IgM on its surface. When apart from the antigen a Concanavalin A-induced, T-cell derived growth factor preparation was added to the cultures, we observed the disappearance of sIgM from the membrane. Furthermore, it was demonstrated by means of density gradient centrifugation that the differentiation of the PFC-precursor into a PFC is accompanied by a decrease in cellular density. Finally, it was shown using hydroxyurea as an inhibitor of DNA-synthesis, that the PFC-precursor passes several cycles of cell division during the process of differentiation into a PFC.

Antibody-Producing Cells↗