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Biomedical subjects

M Nielsen

Publications and source records attributed to M Nielsen.

At least 253 records · Page 14Linked to original sources

Differentiation between metaplastic carcinomas and sarcomas of the human female breast by fibronectin.

The distribution pattern of fibronectin in metaplastic carcinomas, stromal sarcomas, malignant cystosarcoma phyllodes tumours and histiocytic type lymphomas of the human female breast has been studied using the indirect immunoperoxidase technique on formalin fixed paraffin embedded tissue. Fibronectin was demonstrated as intensely stained strands between tumour cells forming an irregular network in metaplastic carcinomas and lymphomas. Stromal sarcomas and the malignant stromal component of the phyllodes tumours exhibited, in contrast, a uniform staining throughout tumour cells and stroma which was weaker than in adjacent normal-looking connective tissue. We suggest that the intense staining reaction of metaplastic carcinomas is due to the scirrhous reaction generally associated with invasive human breast carcinomas. The advantage of using fibronectin as a diagnostic tool in the differentiation of carcinoma/lymphoma versus sarcoma is the fact that the antigen is a stromal marker and its staining intensity is not influenced by the morphology or degree of differentiation of non-mesenchymal tumours.

Breast Neoplasms↗

In vivo demonstration of cytoplasmic fibronectin in human breast carcinomas.

The distribution pattern of fibronectin in 24 invasive human breast carcinomas has been studied using the indirect immunoperoxidase technique. A positive cytoplasmic staining reaction was observed in 16 tumours. Well-differentiated carcinomas showed weak or no staining, whereas all moderately or poorly differentiated carcinomas and one signet ring cell carcinoma contained fibronectin positive tumour cells with moderate or strong staining. The staining intensity was positively correlated to degree of anaplasia with the exception of two moderately differentiated duct carcinomas and the two medullary carcinomas, which were only slightly positive. Non-attached independently growing tumour cells stained more intensely than tumour cells in clusters. Pericellular fibronectin was found in only one carcinoma of medullary type. In normal ducts and glands it was seen at the stromal-epithelial junction corresponding to the basement membrane, around myoepithelial cells and along the luminal border. The results support the findings of several in vitro investigations that breast tumour cells synthesize fibronectin. It also suggests that cytoplasmic fibronectin expression might be an indicator of tissue differentiation in non-solidly growing invasive duct carcinomas of the human mammary gland.

Breast Neoplasms↗

An autopsy study of radial scar in the female breast.

In a study of breasts from 83 consecutive, unselected female autopsies, 23 women (28%) were found to have radial scars. The lesion was multicentric in 67% and bilateral in 43%. The frequency of radial scar was significantly increased among women with fibrocystic disease (43%) compared to women without this lesion (17%). No difference in the frequency of radial scar was registered between women with primary breast malignancy and women with either normal breasts or benign breast abnormalities. No radial scar demonstrated transition to invasive or in situ carcinoma. No evidence was found of any association between radial scar and breast carcinoma.

Adult↗

Uremic arterial disease in rabbits with special reference to the coronary arteries.

In rabbits with chronic renal failure of 9 months' duration, the distribution and morphological characteristics of uremic arterial disease were investigated, with special reference to the coronary arteries. All major systemic arteries were affected, large vessels more severely than smaller ones, and within each artery the changes were most pronounced in the proximal part of the vessel. The intimal lesions consisted primarily of smooth muscle cells without calcification or lipid accumulation. A reduction of the lumen exceeding 50% of the normal cross sectional area was not seen and mural thrombosis was not encountered. In the media, degenerative changes with increased amounts of proteoglycans and calcifications were prominent, but foci of increased cellularity were also seen. There was no evidence of lipid accumulation in the media either. Similar changes were found in the coronary arteries, but coronary angiography revealed no irregularities or stenosis. The calcified medial degenerative changes and intimal cellular lesions without lipid accumulation in non-cholesterol-fed rabbits distinguish uremic arterial disease from atherosclerosis.

Animals↗

Specific 3H-DMCM binding to a non-benzodiazepine binding site after silver ion treatment of rat brain membranes.

Specific binding of the BZ-receptor ligand 3H-DMCM to rat cortical membranes was dramatically enhanced by preincubation of the homogenate with 0.1 mM silver (Ag+) nitrate. The binding was completely inhibited by midazolam. Nevertheless, the pharmacological specificity of the Ag+-enhanced 3H-DMCM binding was different from that of BZ-receptors. Furthermore, the Bmax value, the regional distribution and the molecular target size determined by radiation inactivation analysis of the Ag+-enhanced binding site were different from those of BZ-receptors. The results indicate that Ag+-enhanced 3H-DMCM binding represent a high affinity metal complex formation between 3H-DMCM and an unknown brain specific protein of approximately 100,000 daltons molecular weight.

Animals↗

Size determination of binding polymers for [3H]imipramine and [3H]paroxetine in human platelet membranes.

Imipramine and paroxetine both inhibit the transport of serotonin in serotonergic neurons and in platelets; furthermore specific high affinity binding sites for [3H]imipramine and [3H]paroxetine are located in these two cell types, probably on the serotonin transport mechanism. However, previous studies indicated that the binding site for [3H]imipramine was different from the binding site for [3H]paroxetine. We now report that the polymers on which the two binding sites are located have different molecular weights.

Blood Platelets↗

Precancerous and cancerous breast lesions during lifetime and at autopsy. A study of 83 women.

Among 83 consecutive, unselected female autopsy cases, 6 had been treated for invasive breast carcinoma (IBC) during lifetime. At autopsy, of these six women, two had IBC in the contralateral breast, and another two had in situ carcinoma. Among the 77 women without previous clinical breast cancer, one case of IBC and 14 cases of in situ carcinoma were found at autopsy. Thus, the total occurrence of primary malignant breast lesion was as high as 25.4%. Assuming that all IBCs evolve from in situ forms and that in situ carcinomas do not undergo total regression, our results seem to indicate that about one third of all in situ carcinomas develop into IBC.

Adult↗

Distinct target size of dopamine D-1 and D-2 receptors in rat striatum.

Frozen rat striatal tissue was exposed to 10 MeV electrons from a linear accelerator. Based on the theory of target size analysis, the molecular weights of dopamine D-1 receptors (labelled by 3H-piflutixol) and dopamine D-2 receptors (labelled by 3H-spiroperidol) were 79,500 daltons and 136,700 daltons, respectively. The size of the dopamine-stimulated adenylate cyclase was 202,000 daltons. The estimated molecular sizes were deduced by reference to proteins with known molecular weights which were irradiated in parallel. The results showed that the molecular entities for 3H-piflutixol binding and 3H-spiroperidol binding were not identical. The present results do not allow conclusions as to whether D-1 and D-2 receptors are two distinct proteins in the membrane, or whether the receptors are located on the same protein. In the latter case the binding of 3H-spiroperidol needs the presence of a second molecule.

Adenylyl Cyclases↗

Barbiturate shift as a tool for determination of efficacy of benzodiazepine-receptor ligands.

The change in benzodiazepine(BZ)-receptor affinity for selected BZ receptor ligands, induced by pentobarbital at 30 degrees C in the presence of 200 mM NaCl (barbiturate shift) was investigated. The affinity for benzodiazepines (e.g. flunitrazepam) was increased approximately two-fold by the presence of pentobarbital (1 mM) whereas the affinity for convulsive BZ-receptor ligands (e.g. DMCM ) was reduced approximately two-fold. The affinity for BZ-receptor antagonists (e.g. Ro 15-1788) was unaltered by pentobarbital. The results obtained suggest that barbiturate shifts have predictive value in determining the pharmacological efficacies of BZ-receptor ligands. However, compounds such as CL 218.872 and ZK 93423 would not have been recognized as agonists, notwithstanding their clear agonistic profile in pharmacological tests.

Animals↗

A study of the contribution of hippocampal-accumbens-subpallidal projections to locomotor activity.

Locomotor activity recorded in an automated open-field apparatus was increased substantially by unilateral injections of carbachol, a cholinergic agonist, into the dentate gyrus of the hippocampus. Hyperactivity elicited in this way was reduced significantly when glutamate antagonists were injected into the ipsilateral nucleus accumbens. Injecting gamma-aminobutyric acid into the ipsilateral subpallidal region also reduced the hyperactivity from injections of carbachol into the dentate gyrus. When these compounds were injected into the contralateral accumbens and subpallidal region, respectively, there was little or no reduction in the carbachol-elicited locomotor activity. These observations suggest that neural pathways fom hippocampus to accumbens to subpallidal region may contribute to locomotor activity.

Animals↗

Neuropharmacological evidence to suggest that the nucleus accumbens and subpallidal region contribute to exploratory locomotion.

Rats showed a substantial increase in locomotor activity when novel objects were introduced into an open-field apparatus. This exploratory locomotion was reduced significantly when glutamic acid diethyl ester HCl, a glutamate antagonist, was injected bilaterally into the nucleus accumbens or when gamma-aminobutyric acid was injected bilaterally into the subpallidal region. These observations provide preliminary support for a contribution of the nucleus accumbens and subpallidal region to exploratory locomotion.

Animals↗