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Biomedical subjects

M Nielsen

Publications and source records attributed to M Nielsen.

At least 217 records · Page 12Linked to original sources

Radial scars in women with breast cancer.

In 84 consecutive autopsies of women with a clinical diagnosis of invasive breast cancer, radial scars were found in the contralateral breast in 35 cases (42%) by an extensive histopathologic method. Four women had radial scars on the ipsilateral side in the breast tissue available from the primary surgical procedure or at autopsy. One woman had an invasive breast cancer with morphologic features compatible with but not diagnostic of transition from a radial scar. Of the six radial scars with carcinoma in situ occurring in three women, three were of ductal and three of lobular type. In the remaining cases only radial scars with a benign appearance were found except for two with atypical hyperplasia. The frequency of radial scars was significantly higher in women with fibrocystic disease (55%) compared to women without (24%). Contralateral primary invasive and in situ breast cancer occurred in 68%. No difference in the frequency of radial scars in women with and without breast cancer was found and radial scars were not associated with any specific type of breast cancer. Our findings do not indicate a higher malignant potential of radial scars than of fibrocystic disease. It is suggested that only radial scars containing high-risk epithelial changes such as atypical hyperplasia and carcinoma in situ are associated with an increased risk of subsequent breast cancer development.

Adult↗

Luteinizing hormone and progesterone concentrations in serum of heifers administered a short half-life prostaglandin (PGF(2alpha)) or long half-life prostaglandin analogue (fenprostalene) on days six or eleven of the estrous cycle.

Two trials were conducted to measure the progesterone (P(4)) decline and luteinizing hormone (LH) surge in serum subsequent to administration of a short half-life (short t (1 2 )) prostaglandin (PGF(2alpha)) or a long half-life (long t (1 2 )) prostaglandin analogue (fenprostalene) on Days 6 or 11 of the estrous cycle. Twenty-five crossbred Shorthorn and five Hereford heifers with a mean weight of 331.4 +/- 29.8 kg were used in both trials. The heifers were randomly allotted to receive either a short t (1 2 ) or long t (1 2 ) prostaglandin treatment on Day 6 or 11 of the estrous cycle. A crossover design for the main effect, treatment (type of prostaglandin), was conducted. Heifers that received PGF(2alpha) in Trial I were given fenprostalene in Trial II and vice versa. Stage of the estrous cycle (day) was the same for each heifer in both trials. Stage of estrous cycle was standardized to either Day 6 or 11 by administering Syncro-Mate B (SMB). Blood was collected every hour for 80 h post injection to quantify LH and P(4) concentrations. There were no significant differences (P > 0.05) between the short t (1 2 ) or long t (1 2 ) for either P(4) or LH profiles. In addition, no differences were detected between stages of the estrous cycle for the timing of the preovulatory surge of LH after prostaglandin administration.

Journal Article↗

Breast cancer and atypia among young and middle-aged women: a study of 110 medicolegal autopsies.

In 110 consecutive, medicolegal autopsies of young and middle-aged women (range 20-54 years) the breasts were examined by an extensive histopathologic method and by correlative specimen radiography. Malignancy was found in 22 women (20%) of which only one was known to have had clinical invasive breast cancer (IBC). At autopsy 2 women had IBC (2%), the remaining in situ carcinoma (in situ BC) of microfocal type (18%), i.e. 15 (14%) intraductal carcinomas (DCIS), 4 (3%) lobular carcinoma in situ (LCIS) and one (1%) both DCIS and LCIS. Forty-five per cent of the women with malignancy had multicentric and 41% had bilateral lesions. Forty-five per cent of all histologically confirmed malignant lesions were identified by specimen radiography. Adenosis, benign epithelial hyperplasia, papilloma and duct ectasia were positively associated with malignancy. In addition malignancy was significantly more frequent among women aged more than 40 years, with late age at first full-term pregnancy, with alcohol abuse and with steatosis or cirrhosis of the liver. The results suggest that clinically occult in situ BC are frequent in young and middle-aged women.

Adult↗

In situ molecular size of agonist dopamine D-2 binding sites in rat striatum.

Specific binding of [3H]N-propylnorapomorphine [( 3H]NPA) to 3,4-dihydroxyphenylethylamine (dopamine) D-2 receptors was investigated in rat striatum in vitro. For various dopamine receptor substances, the rank order of potency to inhibit [3H]NPA binding was spiroperidol greater than or equal to NPA greater than LY 171555 greater than SCH 23390 greater than SKF 38393. A single high-affinity binding site was found in membranes prepared in either Tris-citrate buffer or imidazole buffer; the affinity constants were 0.11 and 0.76 nM, respectively. The number of receptors (33 pmol/g wet weight) was independent of whether the membranes were prepared in Tris-citrate buffer or imidazole buffer and was similar to the number of receptors estimated by [3H]spiroperidol binding to dopamine receptors. Irradiation inactivation of frozen whole rat striata showed a monoexponential loss of [3H]NPA binding sites without a change in the binding affinity. The target size of the [3H]NPA binding site was 81,000 daltons, which shows that the functional molecular entity to bind the dopamine D-2 agonist was smaller than the molecular entity to bind the dopamine D-2 antagonist [3H]spiroperidol (target size, 137,000 daltons).

Animals↗

Binding of [3H]SKF 38393 to dopamine D-1 receptors in rat striatum in vitro; estimation of receptor molecular size by radiation inactivation.

[3H]SKF 38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine) binds with high affinity to 3,4-dihydroxyphenylethylamine (dopamine) D-1 receptors in rat striatum in vitro (KD = 7 and 14 nM in nonfrozen and frozen striatum, respectively). The number of binding sites (Bmax) was approximately 80.0 pmol/g of original tissue, a value similar to the Bmax for the dopamine D-1 antagonist SCH 23390. Nondisplaceable [3H]SKF 38393 binding was approximately 45% of total binding. Irradiation (0-4 Mrad) of frozen whole striata decreased the number of [3H]SKF 38393 binding sites monoexponentially without changing the binding affinity. The functional molecular mass for the agonist dopamine D-1 binding site was 132,800 daltons, which is higher than the functional molecular mass of the antagonist dopamine D-1 binding site (approximately 80,000 daltons).

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

Target size of dopamine D-1 receptors in rat corpus striatum estimated by binding of the benzazepine 3H-SCH 23390.

The binding characteristics of 3H-SCH 23390 in rat striatum prepared in potassium phosphate buffer are described. The amount of binding sites labeled by 3H-SCH 23390 decreased monoexponentially when exposed to increasing radiation dose. The molecular weight was determined to 78,000 daltons similar to the molecular mass of 3H-piflutixol binding to D-1 receptor previously reported, however lower than the molecular mass of dopamine D-1 agonist binding sites (Gredal & Nielsen 1987).

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

The enhancement of diazepam and muscimol binding by pentobarbital and (+)-etomidate: size of the molecular arrangement estimated by electron irradiation inactivation of rat cortex.

Synaptosomal membranes were prepared from frozen rat cortices irradiated by 10 MeV electrons and the enhancement of [3H]diazepam and [3H]muscimol binding by pentobarbital (PB) and (+)-etomidate was studied. The target sizes of the corresponding parts of the receptor complex were estimated from the decrease in the enhancement as a function of irradiation dose. Different radiation inactivation constants suggest different regulatory units for the enhancement by PB and (+)-etomidate. Target sizes for PB and (+)-etomidate enhancement of [3H]diazepam binding were 127 +/- 14 and 360 + 124 kDa, respectively.

Animals↗

In situ molecular sizes of the various types of 5-HT binding sites in the rat brain.

The radiation inactivation technique has been used to estimate the molecular weights of 5-HT binding sites in various regions of the rat brain. Using 3H-5-HT or 3H-8-OH-DPAT as the ligand, the same molecular weight of 55,000-60,000 daltons was calculated for the postsynaptic 5-HT1A and 5-HT1B sites in the hippocampus and cerebral cortex. Studies with 3H-ketanserin as the selective ligand indicated a molecular weight in the same range for the post-synaptic 5-HT2 binding site in the cerebral cortex. In contrast, a higher value (67,000 daltons) was found for the presynaptic 5-HT3 site selectively labelled by 3H-8-OH-DPAT in the striatum and cerebral cortex. The curvilinear pattern of the radiation-induced inactivation of 5-HT1A and 5-HT1B binding sites suggested that both sites belong to complex polymeric structures. In contrast, the 5-HT2 and 5-HT3 sites may correspond to less cooperative structures since simple monoexponential inactivation curves were observed upon irradiation.

Animals↗

Calcium discriminates two [3H]kainate binding sites with different molecular target sizes in rat cortex.

Binding of [3H]kainate to the kainate subtype of excitatory amino acid receptors revealed two binding sites. The high-affinity site (Kd = 3.5 nM) was sensitive to calcium ions and has a molecular target size as determined by high-energy radiation inactivation analysis of 76,600 daltons. The low-affinity site (Kd = 65 nM) was insensitive to calcium ions and has a molecular target size similar to the quisqualate-subtype of excitatory amino acid receptors. The change in binding parameters of the two sites with radiation dose strongly suggests that low affinity, calcium-insensitive [3H]kainate binding sites are equivalent to quisqualate sites.

Animals↗

Contralateral cancerous breast lesions in women with clinical invasive breast carcinoma.

Eighty-four consecutive autopsies of women with a clinical diagnosis of invasive breast carcinoma (BC) were examined by extensive histopathologic methods for malignant changes of the contralateral breast. Sixty-eight percent of the women were found to have primary contralateral BC, of which 33% were invasive and 35% in situ lesions. Another 16% had metastases to the breast. Only two women had had treatment for their contralateral BC. In eight cases a malignant lesion was diagnosed or suspected clinically, but in the remaining cases, the malignancies were identified only by histopathologic examination. No clinical data or histologic characteristics of the first BC had any predictive value for the risk of contralateral BC. In the contralateral breast, a significant coincidence was found between fibrocystic disease and the occurrence of primary malignant BC. The majority of the BC on both sides were of ductal type. Seventy-nine percent of the invasive contralateral BC were tumefacient, and 71% had axillary lymph node metastases. The mean survival time was comparable for women with and without contralateral primaries, but a significantly higher proportion of women with contralateral invasive BC died of disseminated BC. The frequency of contralateral malignancies is thus much higher than previously reported. The consequence of these findings may implicate a reevaluation of the treatment and control schedule regarding the contralateral breast in women with invasive BC.

Adult↗