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A H Mulder

Publications and source records attributed to A H Mulder.

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

Repeated and chronic morphine administration causes differential long-lasting changes in dopaminergic neurotransmission in rat striatum without changing its delta- and kappa-opioid receptor regulation.

Repeated, once daily morphine treatment (14 days) as well as chronic morphine administration (6 days) caused a rebound reduction in the electrically evoked release of [3H]dopamine from superfused rat striatal slices 1 day after the last subcutaneous injection. Interestingly, whereas [3H]dopamine release remained significantly reduced for at least 3 weeks following morphine withdrawal in chronically treated (tolerant/dependent) rats, neurotransmitter release from dopaminergic nerve terminals gradually increased above control values following cessation of repeated morphine administration. Postsynaptically, dopamine D1 receptor-stimulated adenylate cyclase appeared to be sensitized 1-3 days but was unchanged 3 weeks after chronic morphine treatment. In contrast, such an enhanced postsynaptic dopamine D1 receptor efficacy did not occur 1-3 days following repeated morphine administration, but appeared to develop slowly resulting in a profound increase of dopamine-sensitive adenylate cyclase 3 weeks after the last injection. The inhibitory effect of dynorphin A-(1-13) on [3H]dopamine release, as well as that of [Met5]enkephalin on dopamine D1 receptor-stimulated adenylate cyclase appeared to be unchanged subsequent to repeated or chronic morphine treatment. These data indicate that, long after cessation of drug treatment, chronic morphine treatment causes a reduction whereas repeated morphine administration gradually induces an enhancement of opioid receptor-regulated dopaminergic neurotransmission due to local adaptive changes within the rat striatum. Such distinct long-lasting alterations of dopaminergic neurotransmission induced by different temporal patterns of morphine administration in projection areas of mesencephalic dopaminergic neurons may be related to the enduring effects of drug abuse such as behavioural sensitization and drug craving.

Adenylyl Cyclases↗
PubMed1994

Detection of genetic changes in Barrett's adenocarcinoma and Barrett's esophagus by DNA in situ hybridization and immunohistochemistry.

We have investigated the occurrence of chromosomal DNA and cell cycle-related protein changes in Barrett's epithelium and adenocarcinoma. The presence of numerical chromosomal aberrations was studied by applying nonisotopic in situ hybridization (ISH) with (peri-)centromeric DNA probes, specific for chromosomes 7, 8, 17, and Y, to routinely processed tissue sections of five cases (4 male, 1 female) of Barrett's adenocarcinoma and adjacent Barrett's epithelium. Cell cycle-related protein expression was studied by immunohistochemistry (IHC) for p53 protein and the Ki-67 antigen (Mib-1) in subsequent sections. P53 protein overexpression was found in 3 of the 5 tumors. Overrepresentation of chromosome 8 and loss of chromosome 17 were found in 2 adenocarcinomas, both also negative for p53 protein overexpression. Y-loss, mostly clonal, was detected in 3 of the 4 male adenocarcinomas and 2 cases of adjacent Barrett's epithelium. One tumor had both areas of overrepresentation and loss of the Y chromosome. All Barrett's adenocarcinomas appeared to contain aneuploid cell populations. No relation was found between cell proliferation characteristics and chromosomal aberrations. We conclude that ISH with chromosome specific DNA probes can be applied for the assessment of potentially important numerical chromosome changes in Barrett's esophagus. Further, the combination of IHC and ISH is useful for evaluation of specific genetic events.

Adenocarcinoma↗
PubMed1994

Dopamine displays an identical apparent affinity towards functional dopamine D1 and D2 receptors in rat striatal slices: possible implications for the regulatory role of D2 receptors.

In this study we examined the selectivity of dopamine (DA) for rat striatal DA D1 and D2 receptors. In a Krebs-HEPES buffer, the Ki values of DA for D1 binding sites (labelled with [3H]SCH23390) and D2 binding sites (labelled with [3H]spiroperidol) in striatal membranes amounted to about 30 and 0.3 microM, respectively. However, the EC50s of DA (3 microM) and the DA releasing drug amphetamine (1 microM) were identical considering D1 receptor-stimulated and D2 receptor-inhibited adenylate cyclase activity in superfused striatal slices. Moreover, these EC50 values were also obtained studying DA- and amphetamine-induced D2 receptor activation, resulting in inhibition of the electrically evoked release of [14C]acetylcholine from the slices. Therefore, with regard to the apparent affinity of exogenous and endogenous DA for D1 and D2 receptors in rat striatal slices, the ligand-receptor binding data appeared to be misleading. Thus, our data show that in rat striatal slices DA has an identical apparent affinity towards functional D1 and D2 receptors, which is particularly intriguing in view of the very high receptor selectivity of synthetic D1 and D2 receptor agonists for these functional receptors in superfused brain slices as predicted on the basis of binding assays. This may have important implications for our understanding of central DA neurotransmission. For instance, since the inhibitory effect of opioid and muscarinic receptor activation on adenylate cyclase activity has been shown to be inversely related to the degree of DA D2 receptor activation, the degree of activation of D1 and D2 receptors by released DA is suggested to act as a functional gate allowing distinct neurotransmitters to play a role in striatal neurotransmission.

Acetylcholine↗
PubMed1994

Somatostatin analogue scintigraphy in granulomatous diseases.

Normal as well as activated lymphocytes and macrophages have previously been shown by radioreceptor analysis to express somatostatin receptors (SS-R). The somatostatin (SS) analogue [111In-DTPA-D-Phe1]octreotide (111In-octreotide) is already used successfully in the visualization of a variety of neuro-endocrine tumours and malignant lymphomas. In the present study 20 consecutive patients were investigated, 12 with sarcoidosis, one with both sarcoidosis and aspergillosis, four with tuberculosis and three with Wegener's granulomatosis. For in vivo SS-R imaging, total-body scintigraphy was performed 24 and 48 h after the administration of 111In-octreotide. Granuloma localizations could be visualized in all patients studied; additional sites were found in nine patients with sarcoidosis and in two patients with tuberculosis. In vitro autoradiography of fresh tissue biopsies, using the SS analogue [125I-Tyr3]octreotide, showed binding at sites that were microscopically identified as granulomatous inflammation. These observations demonstrate the expression of SS-R by human granulomas. This scintigraphy procedure may contribute to a more precise staging and evaluation of granulomatous diseases, but more importantly it may be a sensitive indicator of the efficacy of glucocorticoid and/or immunosuppressive therapy.

Adult↗
PubMed1994

Anti-neutrophil cytoplasmic antibodies (ANCA) in sera from patients with inflammatory bowel disease (IBD). Relation to disease pattern and disease activity.

Anti-neutrophil cytoplasmic antibodies producing a perinuclear fluorescence pattern on ethanol-fixed granulocytes (p-ANCA) were found in 33 of 67 patients (49%) with ulcerative colitis (UC) but also in 14 of 35 patients (40%) with Crohn's disease (CD). In the latter condition p-ANCA were equally present in subgroups with colonic, ileocolonic, or ileal involvement only. Titers of p-ANCA were higher in patients with UC compared to CD patients, in particular when comparing patients with active disease. In contrast to findings in CD, patients with active UC had higher titers of p-ANCA than patients with inactive UC. Although p-ANCA were incidentally directed to lactoferrin, both in UC and CD, and to proteinase-3 and myeloperoxidase in UC only, the antigenic nature of p-ANCA could not be identified in most of the cases. We conclude that, within the spectrum of inflammatory bowel disease, the presence of p-ANCA is not specific for UC. When titers of p-ANCA are taken into account, the presence of high-titered p-ANCA, however, suggests active UC.

Adolescent↗
PubMed1994

Neutrophil activation in vitro and in vivo in Wegener's granulomatosis.

The mechanisms underlying glomerular capillary wall injury in Wegener's granulomatosis (WG) are not well understood. Anti-neutrophil cytoplasmic antibodies (ANCA), present in sera from patients with WG, are known to stimulate respiratory burst and degranulation of primed polymorphonuclear neutrophils (PMN) in vitro. Experimental studies have shown that oxygen radical production and lysosomal enzymes are important mediators of glomerular capillary wall injury. In the present study we investigated the presence of activated PMN and the extracellular localization of lysosomal enzymes in 28 consecutive renal biopsies from patients with WG. The presence of activated PMN within the renal biopsies was compared with the capacity of ANCA, isolated from simultaneously drawn serum samples, to activate primed PMN obtained from a normal donor. Both parameters were also related to renal function. Renal biopsies were obtained from newly diagnosed WG patients before therapy had started. Activation of PMN in the biopsies was assessed by measuring hydrogen peroxide production in situ. The number of activated PMN in the biopsy correlated with the extent of impairment of renal function. Proteinase 3, myeloperoxidase, and elastase, all targets of ANCA, were localized extracellularly in renal tissue and were also found within tubular epithelial cells. All ANCA positive samples were capable of activating primed PMN. The amount of activation correlated with the ANCA titer in those samples. No correlation, however, was found between the in vitro capacity of ANCA-positive IgG fractions to activate primed PMN and the number of activated PMN present in the renal biopsy. We conclude that activated PMN producing toxic oxygen metabolites and releasing lysosomal enzymes, are present in renal biopsies from patients with WG. The amount of activated PMN present within the kidney, and not the capacity of the corresponding ANCA to activate PMN, correlates with renal tissue damage as assessed by serum creatinine levels.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Arteritis of both carotid arteries in a patient with focal, crescentic glomerulonephritis and anti-neutrophil cytoplasmic autoantibodies.

We report a 32-yr-old woman who suffered a stroke as a consequence of arteritis of both internal carotid arteries confirmed by selective carotid arteriography. Laryngeal inflammation and kidney biopsy proven focal crescentic glomerulonephritis were also present in this patient. Anti-neutrophil cytoplasmic autoantibodies with specificity for proteinase 3 were detected in high titre during the active phase of the disease. This overlap syndrome with features indicating both Takayasu's arteritis and Wegener's granulomatosis suggests a common pathogenesis for these diseases.

Adult↗
PubMed1994

Activation of granulocytes by anti-neutrophil cytoplasmic antibodies (ANCA): a Fc gamma RII-dependent process.

ANCA have been demonstrated to induce the respiratory burst in primed neutrophils. In this study we have extended the investigations on neutrophil activation by ANCA directed against proteinase 3 (PR3), myeloperoxidase (MPO) and lactoferrin (LF), and we have analysed the underlying mechanisms. All three ANCA antigens were expressed on the cell surface of primed neutrophils. Superoxide production assayed by both cytochrome c reduction and oxidation of dihydrorhodamine 123, was induced by heterologous polyclonal anti-MPO and anti-LF antibodies, and ANCA-positive plasma samples. Induction of superoxide production was dose-dependent. F(ab')2 fragments did not induce the respiratory burst. Blockade of Fc receptors by specific MoAbs showed that anti-Fc gamma RII antibodies were able to turn off the ANCA-induced respiratory burst, whereas anti-Fc gamma RIII antibodies did not. Plasma samples that induced the respiratory burst did not differ from samples that did not induce superoxide production with respect to ANCA titre, but had higher levels of the IgG3 subclass of ANCA. Levels of the other subclasses of ANCA were comparable between those samples. We conclude that ANCA-induced activation of primed neutrophils is Fc gamma RII-dependent, and appears to be facilitated by antibodies of the IgG3 subclass.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Anti-neutrophil cytoplasmic antibodies (ANCA) in inflammatory bowel disease: characterization and clinical correlates.

ANCA were detected by indirect immunofluorescence in 34 out of 67 patients with ulcerative colitis (UC, 51%) and in 14 out of 35 patients with Crohn's disease (CD, 40%). All but one ANCA-positive sera produced a perinuclear pattern of fluorescence (P-ANCA) on ethanol-fixed neutrophils. On paraformaldehyde-fixed neutrophils 76% of P-ANCA-positive sera in UC and 50% of P-ANCA-positive sera in CD produced cytoplasmic fluorescence, indicating that, indeed, cytoplasmic antigens are recognized by a considerable number of these sera. By Western blot analysis using whole neutrophil extract as a substrate 46% of sera from patients with UC and 32% of sera from patients with CD showed reactivity with either lactoferrin, polypeptides occurring as a doublet of 66/67 kD mol. wt, or polypeptides occurring as a doublet of 63/54 kD mol. wt, respectively. Identical patterns of reactivity have been observed among P-ANCA-positive sera from patients with autoimmune liver disease and rheumatoid arthritis. These data suggest that ANCA of restricted specificities are not specific for inflammatory bowel disease (IBD), but are present in diverse conditions characterized by chronic idiopathic inflammation.

Adolescent↗
PubMed1994

Dysplasia and aneuploidy as markers of malignant degeneration in Barrett's oesophagus. The Rotterdam Oesophageal Tumour Study Group.

The role of dysplasia and aneuploidy as markers in columnar epithelium for malignant degeneration in Barrett's oesophagus was compared in a case control study comprising 38 patients with benign Barrett's oesophagus and 50 patients with Barrett's oesophagus associated with adenocarcinoma. Tissue specimens of columnar epithelium were reviewed for the presence of specialised columnar epithelium and the grade of dysplasia. Ploidy was determined using the method for formalin fixed paraffin wax embedded tissue described by Hedley. There was no significant difference in the frequency of specialised columnar epithelium between both groups. Dysplasia was found more often in columnar epithelium associated with adenocarcinoma compared with benign Barrett's oesophagus (p < 0.001). Multivariate analysis using logistic regression showed an increased risk of malignancy in Barrett's oesophagus in case of dysplasia (odds ratio 9.4, p = 0.003 for mild dysplasia and 33.1, p < 0.001 for moderate or severe dysplasia). Ploidy was not statistically significantly correlated with dysplasia. Aneuploidy or increased G2/tetraploidy proved to be an independent risk factor for younger patients (age < 65 years: odds ratio 44.7, p = 0.003). In conclusion, dysplasia and aneuploidy or increased G2/tetraploidy in columnar epithelium are independent risk factors for malignant degeneration. Patients with these risk factors should be offered a more intensive screening programme.

Adult↗
PubMed1994

A case of lymphoblastic lymphoma with aberrant morphologic feature.

We report a case of 33-year-old Japanese female who had B-cell lymphoblastic lymphoma with Burkitt's lymphoma (BL)-like morphologic feature. Both breasts were involved and the resected tissue showed starry sky macrophages and a proliferation of lymphoblasts containing lipid droplets. The nucleus of the lymphoblast was oval or indented. The neoplastic cells examined expressed TdT, CD10, CD14, CD38, and WH14 (a marker of pre-B cell leukemia/lymphomas). Southern blotting analysis showed a rearrangement of the immunoglobulin heavy chain gene and germline configurations of T-cell receptor gene and c-myc 3rd exon gene. The immunophenotype and genotype of this neoplasm were different from those of previously reported BLs, but identical to those of B-cell lymphoblastic lymphoma. This case, therefore, was regarded as B-cell type lymphoblastic lymphoma containing lipid droplets.

Adult↗
PubMed1994

Anti-neutrophil cytoplasmic antibodies: a new class of autoantibodies in glomerulonephritis, vasculitis and other inflammatory disorders.

Anti-neutrophil cytoplasmic antibodies (ANCA) constitute a new group of antibodies that are directed against myeloid proteins. Several antigens recognized by ANCA have been described. Antibodies directed to proteinase 3, myeloperoxidase and/or elastase are closely associated with necrotizing systemic vasculitis and/or necrotizing and crescentic glomerulonephritis. Changes in levels of anti-proteinase 3 in generally reflect disease activity in Wegener's granulomatosis. The diagnostic significance of other or still unknown specificities has not yet been definitely established. Recent data from in vitro and in vivo models suggest a role for ANCA in the pathogenesis of systemic vasculitides and/or necrotising and crescentic glomerulonephritis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Chronic activation of mu- and kappa-opioid receptors in cultured catecholaminergic neurons from rat brain causes neuronal supersensitivity without receptor desensitization.

The effects of chronic activation of mu- and kappa-opioid receptors on the release of [3H]dopamine from cultured ventral mesencephalic neurons and that of [3H]noradrenaline from cultured locus ceruleus neurons were studied. It was found that a 4-day exposure of cultured mesencephalic neurons to the kappa-agonist U69,593 (5 alpha, 7 alpha, 8 beta)-(-)-N-methyl-N-[7(1-pyrrolidinyl)-1-oxaspiro(4,5)-dec-8-yl] benzeneacetamide; 1 microM] increased markedly 25 mM K(+)-induced dopamine release upon opioid withdrawal by about 70%, with no change in the release-inhibitory effects of U69,593 (EC50, 3-6 nM; maximal inhibition about 50%). Moreover, 1.2 mM Ca++ (in the continuous presence of K+) and 100 microM N-methyl-D-aspartic acid receptor-mediated dopamine release also was potentiated to a similar extent after chronic kappa receptor activation. Similarly, 4-day treatment of cultured locus ceruleus neurons with morphine (1 microM) caused an enhanced release of [3H]noradrenaline induced by K+, Ca++ or N-methyl-D-aspartic acid upon opioid withdrawal by 55 to 150%. In addition, the release-inhibitory effect of the mu-selective agonist [D-Ala2,MePhe4,Gly-ol5]-enkephalin on the K(+)-induced [3H]noradrenaline release remained unaffected (EC50, 10-12 nM; maximal effect, 80-90%). Interestingly, chronic activation of autoreceptors on cultured mesencephalic neurons by the dopamine D-2 receptor-selective agonist LY171,555 [(trans)-(-)-(4aR)-4, 4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo[3,4g]quinoline; 1 microM] or those of cultured locus ceruleus neurons by the alpha-2 adrenoceptor-selective agonist clonidine (1 microM) did not affect K(+)-induced neurotransmitter release upon agonist withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Long-lasting reciprocal changes in striatal dopamine and acetylcholine release upon morphine withdrawal.

In superfused rat striatal slices, the electrically evoked release of [3H]dopamine was reduced by about 30% and that of [14C]acetylcholine was enhanced by about 25% no less than 3 weeks after morphine withdrawal in rats chronically treated with the opiate for 6 days. The lasting nature of the reduced dopamine release at the level of dopaminergic nerve terminals and the concomittant enhanced excitability of neurons tonically inhibited by released dopamine, such as cholinergic interneurons, could play an important role in the maintenance of opiate dependence.

Acetylcholine↗
PubMed1993

Adaptive changes in the number of Gs- and Gi-proteins underlie adenylyl cyclase sensitization in morphine-treated rat striatal neurons.

In the present study we investigated the possible role of changes in the number of membrane-bound G-proteins in the sensitization of dopamine D1 receptor-stimulated adenylyl cyclase, observed in primary cultures of rat striatal neurons chronically exposed to morphine. Whereas exposure of these neurons to 10 microM morphine for 7 days caused a profound increase in cyclic AMP production, induced by the dopamine D1 receptor agonist SKF 38393 (1 microM), Scatchard analysis of [125I]SCH 23982 binding to membrane preparations revealed that neither the Bmax nor the Kd values of dopamine D1 receptor binding sites were affected. Interestingly, immunoblotting experiments revealed an increase (of more than 50%) in the number of stimulatory G-proteins (G alpha s) in neurons displaying an enhanced adenylyl cyclase activity. In morphine-treated neurons, the number of inhibitory G-proteins (G alpha i) appeared to be slightly reduced (by about 16%). Moreover, the observation that cholera toxin (0.1 nM)-stimulated cyclic AMP production, unlike that induced by forskolin (1 microM), was enhanced in morphine-treated neurons, indicates a causal relationship between the reciprocal changes in G-protein number and the increase of dopamine D1 receptor-stimulated adenylyl cyclase activity. The possible role of these changes in G-protein number in the development of morphine tolerance and dependence is discussed.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗