Search PubMed⌕ Search

Biomedical subjects

A H Mulder

Publications and source records attributed to A H Mulder.

At least 37 records · Page 2Linked to original sources
PubMed1998

Subtotal liver calcification due to epithelioid hemangioendothelioma.

A hepatic epithelioid hemangioendothelioma leading to almost complete calcification of the right and left liver lobes in a 75-year-old female is reported. Over a period of 16 years the liver progressively calcified, but its function remained normal by compensatory hypertrophy of the caudate lobe. Multiple partially calcified metastases were present in the lungs, peripancreatic region and along the left principal bronchus. Extreme liver calcification has only rarely been reported. The case presented here reflected slow tumor growth and subsequent long disease course. The vascular nature of the tumor was confirmed by immunohistochemical and ultrastructural analysis.

Aged↗
PubMed1998

IL-1/IL-3 gene therapy of non-small cell lung cancer (NSCLC) in rats using 'cracked' adenoproducer cells.

Cytokine gene therapy was studied in established L42 tumours in syngeneic rats. L42 is a transplantable non-immunogenic non-small cell lung cancer (NSCLC). Genes coding for human interleukin-1 alpha and for rat interleukin-3 beta were transferred by injecting producer cells of recombinant adenovirus vectors into the tumour in attempts to achieve high concentrations of the cytokines inside the tumor without systemic toxicity. Limited tumour growth delay was obtained with viable producer cells. For logistic reasons stocks of pooled frozen producer cells allowed intensive treatment of groups of tumour bearing rats. The cells were lysed by thawing before administration. Ten daily injections of such 'cracked' producer cells induced reproducible tumour responses. These were due to local release of cytokines, not to systemic effects. Growth retardation also occurred in contralateral tumours which were not injected. When rats carrying established tumours were vaccinated with lysates of tumours collected during treatment with 'cracked' producer cells, significant tumour growth retardation was obtained. We speculate that both cytokines, if produced at sufficiently high concentrations in tumours, induce inflammation which in turn initiates an immune response against tumours growing at a distant site. These findings seem to justify further exploration of IL-1 and IL-3 gene transfer for the treatment of cancers.

Adenoviridae↗
PubMed1998

Drug-induced reinstatement of heroin- and cocaine-seeking behaviour following long-term extinction is associated with expression of behavioural sensitization.

The present study was designed to evaluate the relationship between reinstatement of drug-seeking behaviour following long-term extinction of intravenous (i.v.) drug self-administration (an animal model for craving) and long-term behavioural sensitization. Rats were allowed to self-administer heroin (50 microg/kg per inj., 14 daily sessions), cocaine (500 microg/kg per inj., 10 daily sessions) or saline. Following a 3-week extinction period, reinstatement tests were performed to evaluate priming effects of amphetamine, cocaine and heroin on nonreinforced drug-seeking behaviour. In addition, the occurrence of long-term behavioural sensitization in rats with a history of heroin or cocaine self-administration was determined. Heroin-seeking behaviour was reinstated by heroin (0.25 mg/kg), amphetamine (1.0 mg/kg) and cocaine (10 mg/kg). In addition, animals with a history of heroin self-administration displayed locomotor sensitization to both heroin and amphetamine. Cocaine-seeking behaviour was reinstated by cocaine and amphetamine, but not by heroin. Interestingly, locomotor sensitization to amphetamine, but not heroin, was observed in animals with a history of cocaine self-administration. In other words, the induction of drug-seeking behaviour following a prolonged drug-free period was found to be associated with the expression of long-term behavioural sensitization. These data provide experimental evidence for a role of behavioural sensitization in the incentive motivation underlying drug-seeking behaviour. If drug hyperresponsiveness would indeed be a crucial factor in drug-induced craving in human addicts, pharmacological readjustment of the neuroadaptations underlying drug sensitization may prevent relapse to drug use long after detoxification.

Animals↗
PubMed1998

Induction of mammary tumors in rats by single-dose gamma irradiation at different ages.

The effect of age at exposure on induction of mammary tumors was studied in female rats of the inbred WAG/Rij strain. Groups of 40 animals were exposed to a single total-body dose of 1 or 2 Gy of 137Cs gamma radiation at ages of 8, 12, 16, 22, 36 or 64 weeks and were observed for life. Mammary tumors, identified as nodules persisting and growing for 6 weeks, were resected and classified histologically as carcinoma or fibroadenoma. The age-specific incidence of mammary carcinoma was compared with that in a group of 120 unirradiated control rats, using lifetime statistical analysis with both parametric and nonparametric methods. The excess normalized risk of carcinoma was 0.9 for 1 Gy and 2.2 for 2 Gy in age groups 8-36 weeks, with no significant differences between the age groups. However, irradiation at 64 weeks yielded fewer carcinomas than in the controls, the excess normalized risk being -0.7 and -0.3 for 1 and 2 Gy, respectively. The occurrence of one or more fibroadenomas did not influence the incidence of carcinoma. The present data agree closely with the results reported previously for rats irradiated at age 8 or 17 weeks with a dose of 1.2 Gy. The reduced risk of radiation exposure at midlife is consistent with the available epidemiological data for exposed women. Although our findings have been obtained with a single total-body dose that is several orders of magnitude higher than the multiple doses delivered to the mammary gland during mammography, it is suggested that radiological screening for mammary cancer after the age of menopause will not increase the normal incidence of breast cancer.

Age Factors↗
PubMed1998

The influence of estrogen treatment on induction of mammary carcinoma in rats by single-dose gamma irradiation at different ages.

The effect of age at exposure on induction of mammary carcinoma was studied in female rats of the inbred WAG/Rij strain that were treated with estrogen. Groups of 40 animals were exposed to a single total-body dose of 1 or 2 Gy of 137Cs gamma radiation at age 8, 10, 12, 15, 22, 36 or 64 weeks. Hormone levels in the animals were increased by implantation of a pellet containing Estradiol-17beta 2 weeks prior to irradiation. Animals were killed when moribund. All mammary tumors were resected and classified histologically as carcinoma or fibroadenoma. The age-specific incidence of mammary carcinoma was compared with that in control groups of unirradiated estrogen-treated rats using lifetime statistical analysis with both parametric and nonparametric methods. The excess normalized risk of carcinoma was 7.7 for both 1 and 2 Gy in the age groups 8-15 weeks, with no significant differences between the age groups. However, in the age groups 22-64 weeks, the excess normalized risk decreased with increasing age at exposure. Irradiation at 64 weeks yielded fewer carcinomas than in the controls, with an excess normalized risk of -0.6 for both 1 and 2 Gy. The excess normalized risk was 10-80 in estrogen-treated controls compared to untreated rats. The present data agree with the results reported previously for estrogen-treated rats irradiated at ages 8 or 17 weeks with doses of 0.3 or 1.2 Gy. The reduced risk of radiation exposure at midlife observed in this study in hormone-treated rats has also been reported for animals not treated with estrogens. The present findings support the earlier conclusion that radiological screening for mammary cancer after the age of menopause will not increase the normal incidence of breast cancer. Estrogen treatment at midlife may increase the risk of breast cancer in women using replacement estrogens during and after menopause.

Age Factors↗
PubMed1997

Intermittent morphine administration induces a long-lasting synergistic effect of corticosterone on dopamine D1 receptor functioning in rat striatal GABA neurons.

Glucocorticoid receptor (GR)-mediated facilitation of striatal dopaminergic (DA) neurotransmission has been proposed to play a role in behavioral sensitization induced by intermittent exposure to drugs of abuse or stressors. Searching for possible common neuronal substrates acted upon by drugs of abuse and corticosterone, we addressed the question as to whether such a facilitatory effect is apparent (i.e., persists) in primary cultures of rat striatum subsequent to intermittent (prenatal) morphine administration. As previously observed in striatal slices of morphine-treated rats, intermittent morphine exposure in vivo caused a long-lasting increase in DA D1 receptor-stimulated adenylyl cyclase activity, that appeared to persist in primary cultures of rat striatal gamma-aminobutyric acid (GABA) neurons. Subsequent in vitro exposure of these striatal neurons to corticosterone or dexamethasone, simultaneously activating GR and mineralocorticoid receptors (MR), about doubled this adaptive effect of previous in vivo morphine administration. The selective MR agonist aldosterone was ineffective in this respect. Prior in vivo morphine treatment also enhanced the stimulatory in vitro effect of corticotropin releasing hormone (CRH) on adenylyl cyclase in cultured GABA neurons. However, the enhanced CRH receptor functioning was not potentiated by in vitro corticosterone exposure. Activation of GR by corticosterone did not facilitate the increase in D1 receptor efficacy induced by sustained activation of muscarinic receptors in cultured striatal neurons. These data indicate that previous intermittent morphine administration induces a long-lasting synergistic effect of corticosterone on enhanced striatal DA neurotransmission at the level of postsynaptic D1 receptors. Moreover, the induction of this neuroadaptation seems to display opioid receptor selectivity and its long-term expression may be confined to D1 receptors. Since exposure to drugs of abuse or stressors not only increase striatal DA release but also plasma corticosterone levels, we hypothesize that this adaptive phenomenon in DA-sensitive GABA neurons is involved in the expression of morphine-induced long-term behavioral sensitization to drugs of abuse and stressors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1997

Morphine-induced long-term sensitization to the locomotor effects of morphine and amphetamine depends on the temporal pattern of the pretreatment regimen.

The development of behavioural sensitization is thought to depend on the dose and temporal pattern of drug treatment. Previous studies have shown that two distinct morphine pretreatment regimens cause different long-term neuroadaptations in rat striatum. Therefore, in the present study the ability of these pretreatment regimens to induce long-term behavioural sensitization was investigated. One pretreatment regimen, termed "chronic", consisted of three daily injections, for 5 days, with escalating doses (10-50 mg/kg) of morphine, and the other, termed "intermittent", of 14 daily injections with morphine (10 mg/kg). Both intermittent and chronic morphine pretreatment caused sensitization to the locomotor effects of morphine, 3 weeks post-treatment, although the former induced a far greater level of sensitization. Moreover, 3 weeks post-treatment, intermittent, but not chronic, morphine pretreatment induced cross-sensitization to the locomotor stimulant effects of amphetamine. Behavioural sensitization following intermittent morphine pretreatment was clear-cut both 1 day and 3 weeks post-treatment, while after 9 weeks, the locomotor effects of morphine were still slightly augmented. It is concluded that intermittent morphine pretreatment is far more effective in inducing long-term behavioural sensitization than chronic morphine pretreatment.

Amphetamine↗
PubMed1997

Ethanol, like psychostimulants and morphine, causes long-lasting hyperreactivity of dopamine and acetylcholine neurons of rat nucleus accumbens: possible role in behavioural sensitization.

Repeated treatment of rats with ethanol (1 g/kg, once daily for 15 days) enhanced the locomotor effect of morphine, 3 weeks post-treatment. This ethanol-induced long-term behavioural sensitization to morphine was associated with an increase in the electrically evoked release of [3H]dopamine (DA) and [14C]acetylcholine (ACh) from nucleus accumbens slices. A similar enhanced responsiveness of accumbal dopaminergic and cholinergic neurons to depolarization was apparent 3 weeks after repeated morphine, amphetamine or cocaine administration. Prior ethanol exposure also caused a long-term enhancement of electrically evoked release of [3H]DA and [14C]ACh from slices of the caudate-putamen. Unlike the locomotor effect of morphine, that of amphetamine was not enhanced in ethanol-pretreated rats. These data indicate that ethanol administration may cause long-term behavioural sensitization associated with adaptive changes in dopaminergic and cholinergic neurons of rat nucleus accumbens and caudate-putamen. Furthermore, an enhanced reactivity of nucleus accumbens dopaminergic nerve terminals and dopamine-sensitive cholinergic neurons appears to be a common long-term neuroadaptive effect of distinct types of addictive drugs. However, since repeated ethanol exposure did not cause a long-term increase in the locomotor effect of amphetamine, these neuroadaptations may not always be sufficient to cause long-lasting behavioural (cross-)sensitization.

Acetylcholine↗
PubMed1997

Syndrome of inappropriate ADH secretion attributed to the serotonin re-uptake inhibitors, venlafaxine and paroxetine.

We report on 2 patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) which developed a few weeks after they had started treatment with venlafaxine and paroxetine, respectively. Due to the temporal relationship and the exclusion of other potential causes, a causal relationship between the use of the antidepressants and SIADH seems likely. Diagnostic criteria for SIADH and the role of drugs, especially serotonin re-uptake inhibitors, are discussed.

Aged↗
PubMed1997

Delayed occurrence of enhanced striatal preprodynorphin gene expression in behaviorally sensitized rats: differential long-term effects of intermittent and chronic morphine administration.

Protracted changes in basal "steady-state" opioid peptide gene expression in the brain may represent adaptations underlying the behavioral effects of drugs of abuse, observed long after drug exposure. Here, we have studied the long-term effects of two distinct regimens of morphine administration ("intermittent" vs "chronic" morphine treatment) on behavioral sensitization and "steady-state" striatal preprodynorphin and preproenkephalin gene expression in rats. Opioid peptide gene expression was investigated using in situ hybridization at three rostrocaudal levels (rostral, intermediate and caudal) of the caudate-putamen and the nucleus accumbens. Behavioral studies showed that the intermittent morphine treatment resulted in a significantly greater enhancement of morphine-induced locomotion than the chronic morphine treatment three weeks after cessation of opiate exposure. The intermittent morphine treatment resulted in an initial decrease of preprodynorphin gene expression of about 5-10% in the caudate-putamen and the nucleus accumbens at the rostral and intermediate levels one day after the last morphine administration. In contrast, a protracted increase of preprodynorphin gene expression of about 20% throughout the caudate-putamen and of about 6% in intermediate sections of the nucleus accumbens was observed 21 days after cessation of intermittent morphine treatment. Although the chronic morphine treatment induced a decrease of preprodynorphin messenger RNA levels one day after the last administration, no significant changes were observed three weeks after cessation of chronic morphine treatment. No long-term changes were observed in preproenkephalin gene expression after either morphine treatment. Since the intermittent morphine administration induced long-term behavioral sensitization much more effectively than the chronic morphine treatment, we tentatively suggest that the protracted increase of preprodynorphin gene expression may play a facilitative role in the long-term character of opiate-induced behavioral sensitization.

Animals↗
PubMed1997

Kappa1- and kappa2-opioid receptors mediating presynaptic inhibition of dopamine and acetylcholine release in rat neostriatum.

1. The effects of selective opioid receptor agonists and antagonists on N-methyl-D-aspartate (NMDA, 10 microM)-induced release of [3H]-dopamine and [14C]-acetylcholine (ACh) from superfused neostriatal slices were studied to investigate the possible occurrence of functional kappa-opioid receptor subtypes in rat brain. 2. The kappa receptor agonists (-)-ethylketocyclazocine ((-)-EKC), U69593 and the endogenous opioid peptide dynorphin A1-13 caused a naloxone-reversible inhibition of NMDA-induced [3H]-dopamine release, with pD2 values of about 9, 8.5 and 8.2, respectively, whereas both the mu agonist Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAMGO) and the delta agonist D-Pen2-D-Pen5-enkephalin (DPDPE) were ineffective in this respect. The inhibitory effect of submaximally effective concentrations of dynorphin A1-13, U69593 and (-)-EKC on NMDA-induced [3H]-dopamine release were not changed by the delta1/delta2-opioid receptor antagonist naltrindole (up to a concentration of 1 microM, but reversed by the kappa receptor antagonist nor-binaltorphimine (nor-BNI), with an IC50) as low as 0.02 nM, indicating the involvement of U69593-sensitive kappa1-opioid receptors. 3. NMDA-induced [14C]-ACh release was reduced in a naloxone-reversible manner by DPDPE (pD2 about 7.2), dynorphin A1-13 (pD2 6.7) and EKC (pD2 6.2), but not by U69593 and DAMGO. The inhibitory effect of a submaximally effective concentration of DPDPE, unlike those of dynorphin A1-13 and (-)-EKC, on NMDA-induced [14C]-ACh release was antagonized by naltrindole with an IC50 of 1 nM, indicating the involvement of delta-opioid receptors in the inhibitory effect of DPDPE. On the other hand, the inhibitory effects of dynorphin A1-13 and (-)-EKC on [14C]-ACh release were readily antagonized by nor-BNI with an IC50 of about 3 nM. A 100 fold higher concentration of nor-BNI also antagonized the inhibitory effect of DPDPE, indicating the involvement of U69593-insensitive kappa2-opioid receptors in the inhibitory effects of dynorphin A1-13 and (-)-EKC. 4. Although naloxone benzoylhydrazone (NalBzoH), displaying high affinity towards the putative kappa3-opioid receptor, antagonized the inhibitory effects of dynorphin A1-13 and (-)-EKC on [3H]-dopamine and [14C]-ACh release as well as that of U69593 on [3H]-dopamine release, it displayed a low apparent affinity (IC50 about 100 nM) in each case. 5. In conclusion, whereas activation of kappa1-opioid receptors causes presynaptic inhibition of NMDA-induced dopamine release, kappa2 receptor activation results in inhibition of ACh release in rat neostriatum. As such, this study is the first to provide unequivocal in vitro evidence for the existence of functionally distinct kappa-opioid receptor subtypes in the brain.

Acetylcholine↗
PubMed1996

Treatment of relapsing experimental autoimmune encephalomyelitis with largely MHC-matched allogeneic bone marrow transplantation.

BUF rats suffering from severe relapsing experimental autoimmune encephalomyelitis (R-EAE), a model for multiple sclerosis, were treated with intensive cytoreductive therapy and grafting of allogeneic bone marrow (BM). BN.1B rats were used as EAE-resistant, largely MHC-matched donors, resembling human BMT from HLA-identical siblings. The treatment induces complete remission and low recurrence rates of R-EAE. Evidence is provided that the efficacy of the treatment depends on a high degree of lymphoablation: a minority of rats had host-type residual activated T lymphocytes in the CNS after treatment. Furthermore, complete replacement of host-type BM by donor-type hemopoietic cells is essential, as higher relapse rates were observed in animals with incomplete reconstitution by donor cells than in completely reconstituted rats. Overall, our results indicate that patients with severe MS might benefit from treatment with HLA-matched allogeneic BM.

Animals↗
PubMed1996

Mifepristone prevents the expression of long-term behavioural sensitization to amphetamine.

Three weeks following intermittent amphetamine exposure (2.5 mg/kg/day for 5 days), rats showed an enhanced locomotor response to an amphetamine challenge. Mifepristone (20 mg/kg) given 45 min prior to the challenge completely prevented the expression of amphetamine hyperresponsiveness. The glucocorticoid antagonist did not affect the locomotor response to amphetamine in drug-naive rats. These data demonstrate for the first time that glucocorticoid receptor antagonist treatment may prevent long-term hyperreactivity to drugs of abuse in individuals with a drug history.

Amphetamine↗
PubMed1996

Both bone marrow- and non-bone marrow-associated factors determine susceptibility to experimental autoimmune encephalomyelitis of BUF and WAG rats.

To determine the feasibility of treatment with allogeneic bone marrow for experimental autoimmune encephalomyelitis, we investigated the susceptibility to experimental autoimmune encephalomyelitis of bone marrow chimeras using BUF, (WAG X BUF)F1 (high responder), and WAG (low responder) rats. In contrast to previous studies in which other rat strains were used, the response was largely determined by the genotype of the grafted bone marrow, but the influence of a non-bone marrow-associated factor was evident. The latter factor was identified as a low corticosterone response in BUF rats and a high corticosterone response in WAG rats. After adrenalectomy, a significant proportion of WAG rats developed clinical experimental autoimmune encephalomyelitis. The bone marrow-associated factor of resistance appeared to be the activity of cyclophosphamide-sensitive suppressor cells. The latter cells were found to interfere with the formation of inflammatory foci in the central nervous system, while corticosterone primarily prevents the clinical expression of lesions.

Animals↗
PubMed1996

Abnormal glomerular basement membrane in idiopathic multicentric osteolysis.

The primary cause of nephropathy in idiopathic multicentric osteolysis is as yet unknown. We report a young girl with idiopathic multicentric osteolysis and nephropathy. An abnormal glomerular basement membrane was the only abnormality found in a renal biopsy taken 2 years before the development of end-stage renal failure. We believe that this biopsy finding represents or is related to the unknown primary lesion causing nephropathy in idiopathic multicentric osteolysis.

Basement Membrane↗
PubMed1996

Morphine-induced increase in D-1 receptor regulated signal transduction in rat striatal neurons and its facilitation by glucocorticoid receptor activation: possible role in behavioral sensitization.

One month (but not 1-3 days) after intermittent morphine administration, the hyperresponsiveness of rats toward the locomotor effects of morphine and amphetamine was associated with an increase in dopamine (DA) D-1 receptor-stimulated adenylyl cyclase activity and enhanced steady state levels of preprodynorphin gene expression in slices of the caudate/putamen and nucleus accumbens. Such an enduring increase in postsynaptic D-1 receptor efficacy also occurred in cultured gamma-aminobutyric acid (GABA) neurons of the striatum obtained from rats prenatally treated with morphine. Interestingly, in vitro glucocorticoid receptor activation in these cultured striatal neurons by corticosterone potentiated this neuroadaptive effect of prior in vivo morphine exposure. Since activation of glucocorticoid receptors by corticosterone did not affect D-1 receptor functioning in cultured neurons of saline-pretreated rats, prior intermittent exposure to morphine (somehow) appears to induce a long-lasting state of corticosterone hyperresponsiveness in striatal neurons. Therefore, DA-sensitive striatal GABA neurons may represent common neuronal substrates acted upon by morphine and corticosterone. We hypothesize that the delayed occurrence of these long-lasting morphine-induced neuroadaptive effects in GABA/dynorphin neurons of the striatum is involved in the enduring nature of behavioral sensitization to drugs of abuse and cross-sensitization to stressors.

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