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Biomedical subjects

A H Mulder

Publications and source records attributed to A H Mulder.

At least 109 records · Page 6Linked to original sources
PubMed1992

Prognostic relevance of DNA flow cytometry in oligodendroglioma.

In a retrospective study of 85 cases, the prognostic value of DNA flow cytometry in oligodendrogliomas was evaluated. Paraffin-embedded material was processed for flow cytometry, and the survival rates of the patients with DNA diploid, aneuploid, and tetraploid tumors were compared using analysis of variance. In addition, the mitotic index was correlated with the results of flow cytometry. Finally, the results of flow cytometry, histopathologic grading, and counting mitoses were tested for dependency. Thirty-one percent of the tumors were diploid, 39% were tetraploid, and 31% were aneuploid. The results of the DNA flow cytometry did not correlate with the survival times (P = 0.798) or with tumor degree. In contrast, the number of mitoses (P less than 0.05), and the grades of the grading system of Smith (P less than 0.003) had relevance for the prognosis. No correlation between flow cytometry, histopathologic grading, and mitotic index was found. It is concluded that flow cytometry has no value in predicting the biologic behavior of oligodendrogliomas, whereas the number of mitoses is a valuable prognostic parameter and thus is considered to be incorporated into the grading system for oligodendrogliomas.

Adolescent↗
PubMed1992

Differential ontogeny of functional dopamine and muscarinic receptors mediating presynaptic inhibition of neurotransmitter release and postsynaptic regulation of adenylate cyclase activity in rat striatum.

To study the ontogeny of functional striatal dopamine (DA) D2 and muscarinic receptors we determined the first appearance of the inhibitory effects of activation of autoreceptors on neurotransmitter release and that of postsynaptic receptors on adenylate cyclase activity in striatal slices of rat foetuses and pups. On embryonic day 17 (E17), activation of D2 receptors with LY 171555 (1 microM) resulted in a 50% inhibition of the electrically evoked release of [3H]DA from superfused striata, indicating that D2 autoreceptors are functional at that time. Stimulation of adenylate cyclase activity with the Da D1 agonist SK&F 38393 could also be determined in the striatum on E17. In contrast, inhibition of D1-stimulated adenylate cyclase activity through activation of postsynaptic D2 receptors did not occur until postnatal day 14 (P14), whereas activation of postsynaptic muscarinic receptors with oxotremorine (1 microM) resulted in 30% inhibition already on E17. Endogenous activation of muscarinic receptors with physostigmine (1 microM) was ineffective in the prenatal period, but its inhibitory effect on D1-stimulated adenylate cyclase increased strongly between P7 and P21. Inhibition of striatal [3H]acetylcholine (ACh) release by activation of muscarinic receptors could not be determined until P7, because the release of the neurotransmitter was not measurable before that day. But on P7, oxotremorine and physostigmine (as well as the D2 receptor agonist LY 171555) reduced the electrically evoked release of [3H]ACh from striatal slices. Taken together, these data show that there is a marked time difference between the coupling of D2 receptors and that of the D1 and muscarinic receptors to adenylate cyclase in the developing striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1992

Prognostic factors in bladder carcinoma: histologic parameters and expression of a cell cycle-related nuclear antigen (Ki-67).

A total of 316 biopsies from patients with bladder carcinoma who entered a trial of the genito-urinary group of the European Organization for Research and Treatment of Cancer (EORTC) were reviewed. The histological data were subsequently correlated with the clinical course. A strong correlation between the number of mitoses and the time of first recurrence, muscle invasion, and death was noted. Next the expression of Ki-67 in frozen sections from 49 transitional cell carcinomas (TCCs) and the DNA content of the tumour cells were determined. The frequency of Ki-67-positive tumour cells increased with tumour grade and stage. Grade II TCCs and superficially infiltrating TCCs showed a wide range of Ki-67 scores. There was a significant difference in Ki-67 score between non-infiltrating (Ta) and superficially infiltrating (T1) grade II TCCs. All DNA-aneuploid carcinomas but also 15 out of 36 DNA-diploid tumours contained more than 10 per cent Ki-67-positive cells. Only some of these tumours were DNA-aneuploid or -tetraploid. The results indicate that the number of Ki-67-positive cells in grade II tumours may be a useful aid in separating grade II TCCs with a favourable prognosis from those with a poor clinical outcome.

Antigens, Neoplasm↗
PubMed1992

Opioid receptor-mediated inhibition of 3H-dopamine and 14C-acetylcholine release from rat nucleus accumbens slices. A study on the possible involvement of K+ channels and adenylate cyclase.

The release of 14C-ACh from rat nucleus accumbens slices, induced by 15 mM [K+], was inhibited by the mu- and delta-opioid agonists DAMGO and DPDPE, respectively, whereas only the kappa agonist U50,488 reduced the release of 3H-DA. The opioid receptors involved appear to be localized on nerve terminals, since blockade of action potential propagation by 1 microM TTX did not diminish the inhibitory effects of DAMGO, DPDPE or U50,488. Enhancement of the potassium concentration in the superfusion medium to 56 mM with simultaneous reduction of the Ca2+ concentration from 1.2 mM to 0.12 mM induced a release similar to that caused by 15 mM K+ and 1.2 mM Ca+. Under this conditions, the inhibitory effects of both DAMGO and DPDPE on stimulated 14C-ACh release were reduced, whereas the inhibition of evoked 3H-DA release caused by U50,488 was not affected. Activation of mu- as well as delta-opioid receptors by DAMGO and DPDPE, respectively, inhibited forskolin-stimulated adenylate cyclase activity. However, increasing the intracellular cAMP levels with 0.3 mM 8-bromo-cAMP affected neither the depolarization-induced release of 14C-ACh or 3H-DA from accumbens slices nor the inhibitory effects of opioid receptor activation thereon. The results indicate that the mechanism by which functional mu and delta receptors presynaptically inhibit the depolarization-induced 14C-ACh release from nucleus accumbens slices is likely to involve an increase of potassium channel conductance. In contrast, activation of kappa-opioid receptors, which inhibits depolarization-evoked 3H-DA release, apparently does not result in a hyperpolarization of (dopaminergic) nerve terminals. In none of these inhibitory effects presynaptic adenylate cyclase appears to be involved.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1992

Antineutrophil cytoplasmic antibodies: a still-growing class of autoantibodies in inflammatory disorders.

Antineutrophil cytoplasmic antibodies (ANCA) have been described as sensitive and specific markers for active Wegener's granulomatosis (WG). ANCA in WG produce a characteristic cytoplasmic staining pattern of neutrophils (c-ANCA) and are directed against proteinase 3 (Pr3), a serine protease from the azurophilic granules. c-ANCA, more or less equivalent to anti-Pr3, occur in more than 90% of patients with extended WG, in 75% of patients with limited WG without renal involvement, and in some 40% to 50% of patients with vasculitic overlap syndromes suggestive of WG such as microscopic polyarteritis. The presence of c-ANCA is highly specific for those diseases (greater than 98%). Changes of levels of c-ANCA precede disease activity and may be used as guidelines for treatment. Antibodies producing a perinuclear staining of ethanol-fixed neutrophils (p-ANCA) occur in a wide range of diseases. They are directed against different cytoplasmic constituents of neutrophils. Among those, antibodies to myeloperoxidase are found in patients with idiopathic crescentic glomerulonephritis, the Churg-Strauss syndrome, polyarteritis nodosa with visceral involvement, and vasculitic overlap syndromes. Their specificity for this group of necrotizing vasculitides is high (94% to 99%), although they may occur in patients with hydralazine-induced glomerulonephritis, anti-glomerular basement membrane disease, and possibly in some patients with idiopathic systemic lupus erythematosus. Antibodies to leukocyte elastase are incidentally found in patients with vasculitic disorders, whereas lactoferrin antibodies are detected in patients with primary sclerosing cholangitis with or without ulcerative colitis and in rheumatoid arthritis. Their diagnostic significance awaits further studies. p-ANCA of undefined specificity may distinguish ulcerative colitis (sensitivity of 75%) from Crohn's disease (sensitivity of 20%). p-ANCA also occur in autoimmune liver diseases: in 75% of patients with chronic active hepatitis, in 60% to 85% of those with primary sclerosing cholangitis, and in about 30% of patients with primary biliary cirrhosis. Finally, p-ANCA are detected in chronic arthritides and in some 5% of healthy controls. Assessment of their diagnostic value has to await further characterization of the antigens involved, allowing the development of antigen-specific assays.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1992

Differential effects of chronic agonist administration on mu-opioid receptor- and muscarinic receptor-regulated adenylate cyclase in rat striatal neurons.

In cultured rat striatal neurons exposed to 10 microM morphine or oxotremorine for 24 hours, we observed an increased (about 30%) dopamine D1 receptor-stimulated cyclic AMP production, whereas no desensitization of mu-opioid receptor or muscarinic cholinergic receptor was found. However, whereas upregulation of dopamine D1 receptor-stimulated adenylate cyclase activity upon 7 days morphine exposure was at least as pronounced as observed after 24 hours of exposure to the opioid, this adaptive phenomenon was virtually absent following one week of oxotremorine treatment. This reduced adenylate cyclase sensitization upon 7 days oxotremorine exposure appeared to coincide with desensitization of muscarinic cholinergic receptors. A possible role of the resistance of mu receptors to desensitization and the (resulting) upregulation of the neuronal adenylate cyclase system upon chronic receptor activation in the development of opiate tolerance and dependence is suggested.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Outcome of surgical treatment of adenocarcinoma in Barrett's oesophagus.

A retrospective study was performed of an 11 year period (1978-88) to analyse the survival of 112 patients (85 men and 27 women, mean age 63 years) with adenocarcinoma in a columnar lined (Barrett's) oesophagus in respect of surgical treatment, tumour staging, and histological grading. Presenting symptoms were dysphagia (60%) and pain (25%). Only six patients were previously known to have a columnar lined oesophagus. Eighty five patients (76%) underwent partial resection of the oesophagus and cardia. Postoperative mortality was 6%. After resection (n = 85), the 5 year survival was 24%. Survival was significantly better for patients without regional lymph node metastases (stage 0, I, IIA (n = 61): 5 year survival 30%) and even better if the tumour was restricted to the submucosa (stage 0, I (n = 12): 5 year survival 63%). Survival was not influenced by the histological grade of the tumour. Staging based on infiltration of the oesophageal wall and lymph node spread is valuable in determining the prognosis for patients with adenocarcinoma in Barrett's oesophagus.

Adenocarcinoma↗
PubMed1992

Renal insufficiency due to bilateral primary renal lymphoma.

Diffusely enlarged nonhydronephrotic kidneys on ultrasound and computer-tomographic examination in a case of progressive preterminal renal insufficiency were very suggestive of extensive lymphomatous infiltration. Diffuse infiltration of the kidney by centrocytic/centroblastic non-Hodgkin lymphoma was confirmed upon renal biopsy. No other localizations of lymphoma could be found. After four courses of CHOP chemotherapy there was a complete remission of this primary renal non-Hodgkin lymphoma, with complete recovery of renal function.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Opioid receptor antagonists discriminate between presynaptic mu and delta receptors and the adenylate cyclase-coupled opioid receptor complex in the brain.

The present study addressed the question as to whether or not' interacting mu and delta opioid receptors, which may constitute an opioid receptor complex-inhibitory coupled to adenylate cyclase in rat neostriatum, display different antagonistic properties than the classical (noncomplexed) mu and delta receptors. In concentrations that antagonized the presynaptic inhibitory effect of [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO) on [3H]norepinephrine release from rat neocortical slices, the cyclic somatostatin-related mu opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 did not affect the inhibition of dopamine-sensitive adenylate cyclase caused by DAMGO in neostriatal slices. The delta opioid receptor antagonist naltrindole appeared to be about 200-fold more effective as an antagonist against inhibitory effect of [D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6 on [14C]acetylcholine release from neostriatal slices than against the inhibitory effect of DAMGO on [3H]norepinephrine release from neocortical slices, in agreement with the involvement of presynaptic delta and mu receptors, respectively. However, regarding the inhibitory effect of DAMGO and [D-Ser2(O-tert-butyl),Leu5] enkephalyl-Thr6 on adenylate cyclase activity in neostriatal slices, naltrindole not only displayed a very low affinity but also only 10-fold delta-selectivity. In striking contrast to D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 and naltrindole, naloxone did not discriminate between the neurotransmitter release-and adenylate cyclase-inhibitory effects of DAMGO and [D-Ser2(O-tert-butyl), Leu5]enkephalyl-Thr6.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1991

Cyclic somatostatin analogues as potent antagonists at mu-, but not delta- and kappa-opioid receptors mediating presynaptic inhibition of neurotransmitter release in the brain.

The opioid receptor antagonist properties of four conformationally constrained cyclic octapeptide analogues of somatostatin were investigated using in vitro functional paradigms of mu-, delta- and kappa-opioid receptors in the rat brain. The analogues examined were D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), D-Tic-CTOP (TCTOP) and D-Tic-CTAP (TCTAP). Activation of mu-receptors by the enkephalin analogue Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAGO) inhibited the (electrically evoked) release of [3H]noradrenaline (NA) from superfused cortical slices and this inhibitory effect was antagonized in a competitive fashion by all of the octapeptides tested (pA2 values: CTOP and CTAP 7.9-8.0, TCTOP and TCTAP 8.7-8.8). Selective activation of kappa-opioid receptors by the cyclohexylbenzeneaceamide U69593 (0.02 microM) inhibited (by 40-45%) the release of [3H]dopamine (DA) from striatal slices, whereas selective activation of delta-opioid receptors by [D-Ser2(O-t-butyl),Leu5]enkephalyl-Thr6 (DSTBULET; 0.1 microM) caused an inhibition (by 38-46%) of striatal [14C]acetylcholine (ACh) release. However, these inhibitory effects were not affected by any of the octapeptides in concentrations that caused full antagonism of the inhibitory effect (55-65%) of 0.1 microM DAGO on cortical [3H]NA release. Thus, the cyclic octapeptide somatostatin analogues CTOP, CTAP, TCTOP and TCTAP are potent and highly selective antagonists at the mu-opioid receptors mediating presynaptic inhibition of NA release in the brain. The mu-receptor affinity of the most potent of these antagonists, TCTOP and TCTAP, appears to be similar to that of naloxone but these antagonists have a much greater selectivity than the latter.

Amino Acid Sequence↗
PubMed1991

Effect of chronic prenatal morphine treatment of mu-opioid receptor-regulated adenylate cyclase activity and neurotransmitter release in rat brain slices.

Timed-pregnant rats received a semisynthetic diet with or without morphine (0.5-1 mg/g) for 2 weeks. After 21 days of gestation the morphine-dependent dams were decapitated and the foetal brains were dissected. Chronic morphine administration caused a profound increase of adenylate cyclase activity stimulated by postsynaptic D1 dopamine receptors in striatal slices. The relative inhibitory effect of [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO) on D1-stimulated cyclic AMP (cAMP) production was unaffected. In contrast, cAMP production induced via direct activation of the catalytic unit of adenylate cyclase with forskolin was not changed upon long-term morphine treatment, although DAGO strongly inhibited the effect of forskolin. The electrically evoked release of [3H]noradrenaline (NA) from superfused neocortical slices was strongly enhanced upon morphine treatment, whereas release induced by the calcium ionophore A23187, bypassing voltage-sensitive calcium channels, was unchanged. Again, the inhibitory effect of the mu receptor agonist DAGO was unaffected in neocortical slices from morphine-treated rats. It is suggested that tolerance to morphine may be caused by the fact that the opiate is acting against up-regulated signal transduction mechanisms, rather than by desensitization of central mu-opioid receptors. The pre- and postsynaptic changes may include an enhanced expression and/or biochemical modification of D1 receptors, Gs proteins and calcium channels in central neurons on which mu-opioid receptors are present. At the same time, these adaptive changes may underlie morphine withdrawal phenomena.

Adaptation, Physiological↗
PubMed1991

mu-Opioid receptor-regulated adenylate cyclase activity in primary cultures of rat striatal neurons upon chronic morphine exposure.

Rat striatal neurons cultured in serum-free, hormone-supplemented medium, were exposed to 10 microM morphine for several hours or days before intracellular cyclic AMP production was measured. Dopamine D1 receptor- and beta-adrenoceptor-stimulated cyclic AMP production were profoundly increased upon morphine exposure (up to 150% of control). In contrast, cyclic AMP production induced by direct activation of the catalytic unit of adenylate cyclase with forskolin remained unaffected. Interestingly, the relative inhibitory effect of the mu-opioid receptor agonist [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO) on dopamine D1 receptor-stimulated cyclic AMP production was unchanged after exposure to morphine. On the other hand, unlike mu-opioid receptors chronically exposed to morphine, beta-adrenoceptors mediating activation of adenylate cyclase were rapidly desensitized upon prolonged exposure of the neurons to isoprenaline. It is suggested that tolerance to morphine may be caused by the fact that morphine is acting against up-regulated signal transduction mechanisms rather than by mu receptor desensitization. Moreover, this enhanced effector system function may be involved in opioid dependence. The adaptive changes following morphine treatment appear to be independent of possible alterations at the level of dopaminergic or noradrenergic nerve terminals which are not present in primary cultures of rat striatum.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Beta-endorphin: a highly selective endogenous opioid agonist for presynaptic mu opioid receptors.

In the presence of physiological cations (in Krebs-4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid buffer) at 37 degrees C the Ki value's of beta-endorphin for mu- and delta-opioid receptor binding sites in rat neocortical membranes, labeled with [3H][D-Ala2,MePhe4,Gly- ol5]enkephalin (DAMGO) and [3H][D-Ala2-D-Leu5]enkephalin (in the presence of unlabeled DAMGO), respectively, amounted to about 9 and 22 nM. Surprisingly, a very different selectivity pattern for the endogenous opioid peptide was found when the affinity of beta-endorphin for functional presynaptic opioid receptors was examined. Thus, beta-endorphin strongly inhibited the electrically evoked release of [3H]NE from rat neocortical slices with an IC50 value of about 0.5 nM, whereas [14C] acetylcholine release from neostriatal slices was inhibited with an IC50 value of about 100 nM. On the other hand, the electrically evoked release of [3H]dopamine from striatal slices was not affected by beta-endorphin. The inhibitory effects of DAMGO and beta-endorphin on [3H]NE release from neocortical slices were equally well antagonized by naloxone. Moreover, 10 nM of the highly selective mu-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen- Thr-NH2 antagonized competitively the inhibitory effect of beta-endorphin on [3H]NE release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

[Non-Hodgkin lymphoma in patients with an HIV-infection].

In the period 1985-1990, 111 patients with AIDS were treated in the University Hospital Rotterdam-Dijkzigt. In 8 out of 111 patients malignant non-Hodgkin lymphoma developed. The unusual and bizarre representation is highlighted by several clinical histories and a review of literature. HIV-related non-Hodgkin lymphoma is characterized by widespread extranodal disease, often at unusual sites, and high grade B-cell malignancy. The therapeutic outcome and survival in these cases has been disappointing. Prognosis is better for patients without a prior AIDS diagnosis, higher total CD4 cell counts, good performance score and absence of an extranodal site of disease. Treatment should be tailored to individual patients based upon a variety of prognostic features.

Adult↗
PubMed1991

Beta-adrenoceptor-sensitive adenylate cyclase is inhibited by activation of mu-opioid receptors in rat striatal neurons.

The beta-adrenoceptor-sensitive adenylate cyclase in primary cultures of rat striatal neurons was inhibited by opioids, unlike that in rat striatal slices. Isoprenaline (1 microM)-stimulated cyclic AMP production was dose dependently inhibited by the mu-opioid receptor agonist. [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAGO, EC50 = 0.02 microM, 36% inhibition), and only slightly reduced by relatively high concentrations of the delta-opioid receptor agonist, [D-penicillamine2, D-penicillamine5]enkephalin (DPDPE, 1 microM). The highly selective and potent delta-opioid receptor agonist. [D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6 (DSTBULET), and the kappa-opioid receptor agonist, U50-488, were ineffective in concentrations up to 3 microM. Naloxone reversed equally well the inhibitory effects of DPDPE and of DAGO, indicating the involvement of functional mu-opioid receptors. The isoprenaline (1 microM)-stimulated adenylate cyclase activity in cultured glial cells, which exceeded that in neurons about 10-fold, was not affected by opioids. Therefore, opioids were ineffective in rat brain slices probably due to the fact that cyclic AMP production induced by beta-adrenoceptor activation occurs primarily in the glial cells, where it is not subject to inhibition by opioids. These data indicate for the first time the existence of an interaction between functional mu-opioid receptors and beta-adrenoceptors on striatal neurons of the rat.

Adenylyl Cyclase Inhibitors↗