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Biomedical subjects

M Nielsen

Publications and source records attributed to M Nielsen.

At least 199 records · Page 11Linked to original sources
PubMed1988

Stromal fibronectin staining pattern and metastasizing ability of human breast carcinoma.

The peripheral stromal fibronectin (FN) staining patterns of invasive breast carcinomas (IBC) from 77 women were compared to the aggressivity of the tumors, which in each case had been determined through a complete clinical follow-up and autopsy investigation. Polyclonal, monospecific rabbit antibody to human FN was applied on formalin-fixed, paraffin-embedded tissue sections using the peroxidase-antiperoxidase staining technique. An FN-positive staining reaction was defined as a constant, diffuse, or pericellular demarcation of FN-positive fibers surrounding tumor cells at the invasive border. In lack of such a staining pattern, FN-negative staining was recorded. The FN-positive staining reaction was significantly associated with a low metastatic potential and appeared in a multivarians analysis to be an excellent prognostic factor, which surpassed other known parameters, such as clinical stage, histological type or grade, and lymph node status. 27 out of 31 women, who died without evidence of metastatic spread, had FN-positive IBC (87%) in contrast to women with metastatic disease, where only 15 out of 46 had FN-positive tumors (33%). An extensive histopathological examination of the contralateral breast revealed in this latter group a high rate of second primaries (22/46), which might have been responsible for the metastatic spread. If these women with bilateral IBC were excluded, only three metastasizing tumors with a FN-positive staining pattern remained, suggesting that the prognostic value of the FN-staining pattern along the invasive border of IBC might be even higher than anticipated from this study.

Analysis of Variance↗
PubMed1988

Effect of nifedipine on the shuttlebox escape deficit induced by inescapable shock in the rat.

The behavioural effect of subchronic treatment with calcium channel antagonists (nifedipine, verapamil) and with imipramine was assessed in rats subjected to inescapable shock (IS). The effect of subchronic treatment with nifedipine and imipramine on specific [3H]nitrendipine ([3H]NDP) binding was investigated in frontal cortex of naive rats and in rats given IS then tested for shuttlebox escape. The rats showed a severe impairment in escape behaviour after IS. Imipramine and nifedipine significantly reduced FR1 and FR2 escape deficits. Verapamil had no effect. A small but significant increase in the number of [3H]NDP binding sites (Bmax) was seen in rats exposed to the shuttlebox escape test independent of a previous exposure to IS. Imipramine had no influence on Bmax in any of the groups. Nifedipine did not affect [3H]NDP binding in naive rats but decreased Bmax in rats subjected to IS and the shuttlebox escape test. The comparable ability of nifedipine and imipramine to reverse the shuttlebox escape deficit induced by IS argues for a possible antidepressant activity of nifedipine. The biochemical data indicate that cortical [3H]NDP binding sites are not correlated to performance in the shuttlebox escape test.

Animals↗
PubMed1988

High affinity of the naturally-occurring biflavonoid, amentoflavon, to brain benzodiazepine receptors in vitro.

In a search for pharmacologically-active ingredients in the plant extract Karmelitter Geist, we have isolated and identified a high-affinity benzodiazepine receptor ligand, amentoflavon. Amentoflavon binds in a mix-type competitive and non-competitive manner to brain benzodiazepine receptors with an IC50-value of 6 nM in vitro, comparable to the affinity of diazepam. Amentoflavon shows a GABA ratio of 1.4 at 0 degrees and increases 35S-TBPS binding by 12% (60 min incubation at 25 degrees), which indicates a partial agonistic effect on benzodiazepine receptors. The substance does not influence the binding of a variety of other brain receptor ligands. Amentoflavon does not inhibit 3H-flunitrazepam-binding to brain benzodiazepine receptors following i.v. administration in the mouse in vivo, and it is therefore not likely that amentoflavon is responsible for any pharmacological effect of Karmelitter Geist.

Animals↗
PubMed1988

The apparent target size of rat brain benzodiazepine receptor, acetylcholinesterase, and pyruvate kinase is highly influenced by experimental conditions.

Radiation inactivation is a method to determine the apparent target size of molecules. In this report we examined whether radiation inactivation of various enzymes and brain receptors is influenced by the preparation of samples preceding irradiation. The apparent target sizes of endogenous acetylcholinesterase and pyruvate kinase from rat brain and from rabbit muscle and benzodiazepine receptor from rat brain were investigated in some detail. In addition the target sizes of alcohol dehydrogenase (from yeast and horse liver), beta-galactosidase (from Escherichia coli), lactate dehydrogenase (endogenous from rat brain), and 5-HT2 receptors, acetylcholine muscarine receptors, and [35S] butyl bicyclophosphorothionate tertiary binding sites from rat brain were determined. The results show that apparent target sizes are highly influenced by the procedure applied for sample preparation before irradiation. The data indicate that irradiation of frozen whole tissue as opposed to lyophilized tissue or frozen tissue homogenates will estimate the smallest and most relevant functional target size of a receptor or an enzyme.

Acetylcholinesterase↗
PubMed1988

[3H]diazepam specific binding to rat cortex in vitro is enhanced by oleic, arachidonic and docosahexenoic acid isolated from pig brain.

Substances were found in purified fractions from pig brain that enhanced the specific binding of [3H]diazepam to membranes from rat brain in vitro. These substances were identified as oleic acid, arachidonic acid and docosahexenoic acid. Oleic acid (10(-5) - 10(-4)M) increased the affinity for agonists binding to the benzodiazepine receptor, whereas the binding of antagonists to this receptor was only slightly enhanced. The number of [3H]muscimol binding sites was increased, whereas binding of [3H]SR 95331, a GABA receptor antagonist, was unchanged. The effect of oleic acid was additional to the GABA-induced enhancement of [3H]diazepam binding.

Animals↗
PubMed1988

Axillary lymph node morphology in women with in situ breast carcinoma. An autopsy study.

Axillary lymph nodes in 184 female autopsy cases were studied using morphological criteria. Special attention was paid to the morphology in 34 women with in situ breast carcinoma (in situ BC) compared to the remaining women without malignant breast lesions, who served as controls. Sinus histiocytosis (SH) and diffuse cortical hyperplasia (DCH) were significantly more frequent among women with in situ BC compared to controls. No significant association was found between unilateral in situ BC and these lymph node patterns on the contralateral side. Germinal center and follicular hyperplasia (GCH/FH), lymphocyte depletion (LD), fibrosis, hyalinization, calcifications and lipomatosis were not associated with in situ BC. The results indicate that in situ BC provokes reactive morphological changes of the regional axillary lymph nodes similar to the changes associated with a good prognosis in women with invasive breast cancer (IBC).

Adult↗
PubMed1988

Chronic treatment with lithium chloride: reduced number of GABA receptors in frontal cortex of rat brain.

Chronic consumption of lithium leads to a significant decrease in GABA receptor binding in frontal cortex of rat brain with no change in the binding characteristics in the remaining part of the cortex and in the hippocampus. In conclusion, the effect of lithium on the muscimol receptor is brain region-specific and due to a change in the number of receptors rather than in the affinity constant.

Animals↗
PubMed1988

The growth pattern of in situ carcinoma in the female breast.

The histopathological growth pattern of in situ carcinoma in the female breast is divided into three forms: 1) microfocal, 2) diffuse, and 3) tumour forming. This classification is clearly correlated to our diagnostic findings and forms furthermore the basis for our planning of treatment, as the growth pattern is probably of prognostic relevance.

Breast Neoplasms↗
PubMed1988

Silicon in human breast tissue surrounding silicone gel prostheses. A scanning electron microscopy and energy dispersive X-ray investigation of normal, fibrocystic and peri-prosthetic breast tissue.

Implanted silicone breast prostheses leak silicone gel through the intact membrane. In order to determine the exact location and to achieve a semiquantitative estimation of the amount of silicone in the surrounding tissue, a method involving scanning electron microscopy (SEM) and energy dispersive analysis of X-rays (EDAX) was used. By this method we were able to demonstrate the presence of the element silicon (Si) (main component of silicone, a polymer with a general formula e.g. (CH3[Si(CH3)2O]n Si(CH3)3 along the inner border of vacuoles corresponding to the light microscopic localization of droplets and in macrophages. The tissue adjacent to the prostheses had a higher silicon content than the control tissue.

Breast↗
PubMed1987

Irradiation inactivation studies of the dopamine D1 receptor and dopamine-stimulated adenylate cyclase in rat striatum.

In frozen rat striatal tissue, exposed to 10 MeV electrons from a linear accelerator, the sizes of the dopamine (DA) D1 receptor and the DA-sensitive adenylate cyclase complex were determined using target size analysis. The number of D1 receptors (labelled by [3H]SCH 23390) declined monoexponentially with increasing radiation intensity, yielding a molecular weight (mol.wt.) of 80 kDa. Also the activity of the catalytic unit (C) of the adenylate cyclase (as measured by forskolin stimulation), decreased monoexponentially, however with a mol.wt. of 145 kDa. Both basal, DA- and fluoride (F-)-stimulated activity declined in a concave-downward fashion with a limiting mol.wt. of 134, 138 and 228 kDa, respectively. It was estimated that the basal and DA-stimulated activity originated from an enzyme complex with a mol.wt. of 325 kDa, a value close to the combined size of RGs and C. These data suggest that F- stimulation of the adenylate cyclase, which occurs by a Gs activation, does not cause dissociation of Gs into the alpha s and beta gamma subunits. Further, the DA-regulated adenylate cyclase apparently exists as a complex consisting of RGs and C; the mechanism of hormonal activation is a dissociation of C from this complex.

Adenylyl Cyclases↗
PubMed1987

Convulsant/barbiturate activity on the soluble gamma-aminobutyric acid-benzodiazepine receptor complex.

Cage convulsant t-butyl bicyclophosphoro[35S]thionate binding activity in rat brain membrane homogenates was solubilized with the zwitterionic detergent 3-[(3-cholamidopropyl)-dimethylammonio]propane sulfonate (Chaps) and shown to co-purify with the benzodiazepine--gamma-aminobutyric acid (GABA) receptor complex on gel filtration and affinity chromatography. Whereas convulsant binding activity, but not GABA and benzodiazepine receptor binding, was eliminated by solubilization in other detergents like sodium deoxycholate or Triton X-100, or by addition of Triton X-100 to the extracts solubilized in the zwitterionic detergent, convulsant activity was not irreversibly lost or selectively unstable, but could be restored by exchanging the protein back into the detergent Chaps. The GABA-benzodiazepine receptor activity solubilized in Chaps alone, containing convulsant activity, and a sample in Chaps supplemented with Triton X-100 and lacking convulsant activity, did not differ in size as measured by gel filtration column chromatography or by radiation inactivation target size analysis. This suggests that convulsant binding activity does not require any additional protein subunits or other macromolecules nor any unique aggregation state relative to GABA and benzodiazepine receptor binding, and that all three activities reside on the same protein complex. As in intact brain, the target size for convulsant binding activity was 3-5 times that of benzodiazepine binding activity, suggesting that an oligomeric protein structure of the receptor complex with intact strong subunit interactions present in the native membrane environment is needed for convulsant activity, and that this and other properties are more preserved in Chaps than in other detergents.

Animals↗
PubMed1987

Chronic treatment with antidepressants decreases the number of [3H]SCH 23390 binding sites in the rat striatum and limbic system.

Binding of [3H]SCH 23390 to dopamine D-1 receptors and of [3H]spiperone to D-2 sites was measured in identical membrane preparations of the striatum and limbic system of rats treated chronically (twice daily, for two weeks) with antidepressants. Chronic administration of imipramine, amitriptyline, mianserin, citalopram, bupropion, iprindole and electroconvulsive shocks, but not benztropine or cyproheptadine (non-antidepressants) decreased the number of [3H]SCH 23390 binding sites, while no change in the parameters of [3H]spiperone binding was observed. The serotonin2 receptor antagonist ketanserin when added to the incubation medium had no effect on [3H]SCH 23390 binding to D-1 sites. The results suggest that D-1 receptor subsensitivity is a component of the therapeutic effect of antidepressants.

Animals↗
PubMed1987

Binding of [3H]SCH 23390 to dopamine D-1 receptors in rat retina in vitro.

[3H]SCH 23390 binding was examined in membranes of rat retina. The binding was saturable with a dissociation constant of 0.2 nM and the maximum number of binding sites was 236 +/- 74 fmol/mg protein. The pharmacology of [3H]SCH 23390 binding indicated that the binding was specific for a dopamine D-1 receptor because the binding was preferentially inhibited by D-1-selective agonists and antagonists but not by dopamine D-2-selective agonists and antagonists. The same membrane preparations were used to characterize the dopamine D-2 receptor binding as measured with [3H]spiperone and the amount of binding sites was found to be similar to the amount of D-1 sites. It is concluded that [3H]SCH 23390 is a useful tool to examine dopamine D-1 receptors in the retina.

Animals↗