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Biomedical subjects

M Nielsen

Publications and source records attributed to M Nielsen.

At least 181 records · Page 10Linked to original sources

Histologic changes and silicone concentrations in human breast tissue surrounding silicone breast prostheses.

Using a previously developed method for quantitative measurements of silicone concentrations in breast tissue, material from 86 biopsies from 67 breasts in 55 patients who had silicone implants was examined. In the 49 breast with unruptured prostheses, there was a positive relation between the concentrations and inflammatory reactions, the only exception being the amount of plasma cells, which showed a negative relation. It is concluded that silicone prostheses provoke an inflammatory response not only because they act as foreign bodies, but also because of silicone seepage through intact membranes.

Breast↗

The effect of dose rate on X-radiation-induced mutant frequency and the nature of DNA lesions in mouse lymphoma L5178Y cells.

The induction of mutants at the heterozygous tk locus by X radiation was found to be dose-rate dependent in L5178Y-R16 (LY-R16) cells, but very little dose-rate dependence was observed in the case of strain L5178Y-S1 (LY-S1), which is deficient in the repair of DNA double-strand breaks. Induction of mutants by X radiation at the hemizygous hprt locus was dose-rate independent for both strains. These results are in agreement with the hypothesis that the majority of X-radiation-induced TK-/- mutants harbor multilocus deletions caused by the interaction of damaged DNA sites. Repair of DNA lesions during low-dose-rate X irradiation would be expected to reduce the probability of lesion interaction. The results suggest that in contrast to the TK-/- mutants, the majority of mutations at the hprt locus in these strains of L5178Y cells are caused by single lesions subject to dose-rate-independent repair. The vast majority of the TK-/- mutants of strain LY-R16 showed loss of the entire active tk allele, whether the mutants arose spontaneously or were induced by high-dose-rate or low-dose-rate X irradiation. The proportion of TK-/- mutants with multilocus deletions (in which the products of both the tk gene and the closely linked gk gene were inactivated) was higher in the repair-deficient strain LY-S1 than in strain LY-R16. However, even though the mutant frequency decreased with dose rate, the proportion of mutants showing inactivation of both the tk and gk genes increased with a decrease in dose rate. The reason for these apparently conflicting results concerning the effect of DNA repair on the induction of extended lesions is under investigation.

Animals↗

[Silicone breast implants].

A brief review of the use of silicone breast implants, their structure, methods of implantation and complications is presented. Acute complications are rare, being mainly infection and hematoma. Long-term complications, on the contrary, are common, consisting mainly of capsular contracture around the prosthesis with subsequent pain and deformation of the breast. More rarely silicone granulomas form, and prosthesis rupture or herniation occurs. The importance of silicone leakage for these complications is discussed separately as well as the treatment of and prevention of capsular contracture and demonstration of silicone in tissue. A critical attitude towards the use of silicone breast implants, when these are used for purely cosmetic purposes, is recommended at present. New improved types of silicone breast implants are currently being tested clinically.

Breast↗

The N-methyl-D-aspartate receptor channel complex and the sigma site have different target sizes.

Radiation inactivation technique has been used to measure the molecular sizes of the N-methyl-D-aspartate (NMDA) receptor and the sigma recognition site. Target size analysis of [3H]MK-801 (dizocilpine maleate) binding to the NMDA receptor channel complex in rat cortical membranes has given a molecular size of 128,000 +/- 9,000 Da. This is in contrast to the target size of the sigma site in the same tissue as labelled by [3H]DTG (ditolylguanidine), giving a value of 36,000 +/- 2,900 Da. These studies have provided evidence for a clear difference in the molecular sizes of these two recognition sites.

Animals↗

Determination of the molecular size of the 5-HT3 receptor binding site by radiation inactivation.

The radiation inactivation technique has been used to estimate the molecular size of the 5-HT3 receptor binding site labelled by [3H]zacopride, in comparison with that of the 5-HT1A receptor binding site labelled by [3H]8-OH-DPAT, in rat cortical membranes. The calculated molecular weight of the 5-HT3 site: 35.4 +/- 2.2 kDa (mean +/- S.E.M., n = 4) was significantly less than that of the 5-HT1A site: 62.9 +/- 1.8 kDa (mean +/- S.E.M., n = 4) and of other 5-HT1 and 5-HT2 receptors of the G-protein coupled family. These data further support that the 5-HT3 receptor is not coupled to G-proteins in the rat brain.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Non-NMDA glutamate receptor antagonist 3H-CNOX binds with equal affinity to two agonist states of quisqualate receptors.

Binding of 3H-CNQX to rat cortical membranes is saturable and reversible. Apparently, 3H-CNQX binds to a single site with KD = 39 nM. However, studies using AMPA as inhibitor revealed a biphasic inhibition of 3H-CNQX binding. The results suggest that CNQX binds with the same affinity to two different sites. The molecular target size of 3H-CNQX binding (51.8 +/- 3.4 kD) is equivalent to the size of the high affinity 3H-AMPA binding sites, but different from the high affinity 3H-kainate binding sites. A monoexponential decay curve for the high energy radiation inactivation analysis of 3H-CNQX binding indicates that the two 3H-CNQX binding sites have the same molecular weight and therefore might be two different conformations of the same receptor. The standard excitatory amino acids quisqualate, AMPA and kainate have a different rank order of potency as binding inhibitors at the two conformations of the quisqualate receptor.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Molecular target size analyses of the NMDA-receptor complex in rat cortex.

The molecular weights of different subunits of the NMDA-receptor complex were determined by high-energy radiation inactivation analyses of the binding of [3H]L-glutamate, [3H](3-(+/-)-2-(carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine (TCP) and [3H]glycine to rat cortical membranes. The molecular target sizes of [3H]L-glutamate binding (the recognition site), [3H]TCP binding (the ionophore) and [3H]glycine (a modulatory unit) were similar: 121,000, 118,000 and 115,000 Da, respectively. These results suggest that the three subunits are on the same protein. The molecular weight of [3H]CPP binding was 209,000 Da. This suggests that in order to bind [3H]CPP (a competitive antagonist) with high affinity an additional macromolecule may be associated to the agonist site.

Animals↗

Behavior of mother rats in conflict tests sensitive to antianxiety agents.

Previous studies of freezing and open-field activity have demonstrated that lactating rats are less fearful or less anxious than nonpregnant ones. The purpose of this investigation was to observe the behavior of mother rats in conflict tests, which are frequently used in studies on the neurobiology of anxiety. In the punished drinking test, in which licking from a water spout is punished by electric shocks, mothers (observed on Day 1 postpartum following 24 hr of water deprivation) were found to drink more than virgins. Mothers (Day 1 postpartum) also consumed more food than controls in an unfamiliar open field. In contrast, no difference between mothers (Day 5 postpartum) and virgins was present in the exploration of an electrified shock probe. The largest maternal anticonflict effects in the drinking and feeding tests were recorded when the females were tested with their pups. Increased punished drinking was also observed in virgin rats treated with the anxiolytic benzodiazepine midazolam. Water-deprived virgins and mothers did not differ in the shock titration test, a result suggesting that diminished pain reactivity was unlikely to account for the increased punished drinking in mothers. Moreover, females in late pregnancy, which are hypoalgesic (Gintzler, 1980), did not lick more than virgins in the punished drinking test. Following 24 hr of water deprivation, unpunished drinking was higher in lactating females than in virgins, so the increased acceptance of punishment by mothers might have been due to their being more thirsty than virgins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Autopsy studies of the occurrence of cancerous, atypical and benign epithelial lesions in the female breast.

The main purpose of the present thesis has been to estimate the frequency of malignant, premalignant and benign morphological changes in the female breast and evaluate their possible interrelationship. The method used was a conventional but detailed and systematic examination, both macroscopically and histologically of all available breast tissue. Consequently autopsi material has been the natural basis of the studies. Three groups of women have been examined: 1. A consecutive series of 110 younger women, mean age 39 years, undergoing medicolegal autopsy at the Institute of Forensic Medicine in Copenhagen, Denmark, from October 1983 to July 1984. 2. A consecutive series of 83 unselected, elderly women, mean age 67 years, undergoing autopsy at a large community hospital in Esbjerg, Jutland, Denmark, from November 1976 to May 1977. 3. A consecutive series of 84 women, mean age 74 years, dying with a known diagnosis of breast cancer and undergoing autopsy at two community hospitals in the Copenhagen area, (Glostrup and Frederiksberg), Denmark, from November 1982 to December 1984. The main results were: 1. In younger women clinically occult in situ breast cancer lesions occurred with surprisingly high frequency, 18%, a result which may influence the planning of future screening programs. 2. In elderly women, dying from a number of various reasons, invasive breast carcinomas were found with a frequency corresponding to the life-long risk of Danish women having this disease diagnosed clinically, 8%. Occult in situ carcinomas were found in 18%. 3. In women dying with a clinical diagnosis of breast cancer, the frequency of malignant histological changes in the opposite breast (metastases, invasive and in situ breast carcinomas) was unexpectedly high, 80%, a result which should be taken into consideration during clinical follow-up after treatment for breast cancer.

Autopsy↗