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Biomedical subjects

A Norgren

Publications and source records attributed to A Norgren.

At least 19 recordsLinked to original sources

Steroid hormone receptors in pelvic muscles and ligaments in women.

Using monoclonal antibody assay techniques estrogen receptors (ER) and progesterone receptors (PgR) were quantitated in female pelvic floor muscles, urogenital ligaments and uterus (myometrium). Receptors were detected in all these structures. In addition qualitative assessment showed distinct nuclear staining in the same structures. ER and PgR were not found in the musculus rectus abdominis with either method. The findings provide a rationale for estrogen treatment in women with urogenital disorders.

Adult

Estrogen and progesterone receptor analyses in more than 4,000 human breast cancer samples. A study with special reference to age at diagnosis and stability of analyses. Southern Swedish Breast Cancer Study Group.

Estrogen (ER) and progesterone receptors (PgR) were measured in the same laboratory in more than 4,000 breast cancer biopsy samples obtained from 15 different hospitals during ten years. ER was measured with isoelectric focusing and PgR with the dextran-coated charcoal method and Scatchard analysis. The distribution pattern for both ER and PgR was during this time period and for the different hospitals rather similar indicating a good stability of the analytical methods. ER concentration was positively correlated with patient age, with a higher percentage of positive samples and higher concentrations in patients greater than or equal to 50 years of age compared with patients less than 50 years. PgR concentration increased with age for patients under 50 years, but a considerable reduction of PgR concentration and of the proportion of positive samples was seen in patients between 50 and 59 years of age. Above this age the PgR concentration again increased with increasing age. The PgR/ER ratio and the proportion of ER- PgR+ samples were higher in patients under 50 years compared to older patients. ER and PgR values decreased during tamoxifen treatment, during pregnancy and after preoperative radiotherapy. Wet weight, DNA and protein were compared as reference parameters for the expression of ER and PgR concentrations. Strong correlations were obtained suggesting that similar information can be obtained with either of these reference parameters.

Adult

Prognostic value of steroid receptor concentration and flow cytometrical DNA measurements in stage I-II endometrial carcinoma.

In order to make a more individualized therapy possible in endometrial cancer we investigated the prognostic ability of steroid receptor concentration and the DNA content in individual cells as measured by flow cytometry. We found that although the steroid receptor concentration was a prognostic parameter, the DNA content proved to be a better parameter than all other known prognostic parameters in endometrial carcinomas stage I-II. Thus it was possible to divide the tumors into three groups; 1) diploid tumors with a relapse rate of 6%, 2) aneuploid tumors with a high estradiol receptor concentration and without myometrial invasion of more than the inner third, and with a relapse rate of 18%, 3) aneuploid tumors, poorly differentiated with a low estradiol receptor concentration or myometrial invasion and with a relapse rate of 44%.

Adult

Prognostic significance of estrogen and progesterone receptors in stage II breast cancer.

Estrogen (ER) and progesterone receptors (PgR) were evaluated in samples from primary tumors in 539 patients with stage II breast cancer participating in a randomized multicenter controlled clinical trial on adjuvant therapy. At the cut-off points of 10 fmol ER/mg protein and 30 fmol PgR/mg protein, no significant difference in recurrence-free survival (RFS) existed between premenopausal patients with receptor-positive and negative tumors, respectively. After recurrence, premenopausal patients with receptor-positive tumors had a significant longer survival than patients with receptor-negative tumors. In postmenopausal patients not treated with adjuvant tamoxifen, no correlations between RFS and receptor status were found. Patients with ER+ tumors survived longer than patients with ER-tumors. In postmenopausal patients treated with adjuvant tamoxifen, highly significant differences in RFS and in survival were observed when receptor-positive patients were compared with receptor-negative patients. No differences in survival after recurrence were registered among these patients.

Breast Neoplasms

A sequential extraction method for RNA from rabbit liver.

When naphthalene-1,5-disulfonate (NDS) and phenol-cresol were used for extraction of rRNA from rabbit liver approximately 80% of the extractable RNA was recovered. By subsequent treatment of the resulting insoluble interface with 4-aminosalicylate and triisopropylnaphthalenesulfonate (PAS-TIPNS) the remaining RNA was extracted. Subcellular fractionation and polyacrylamide gel electrophoresis or sucrose density gradient analysis showed that this last fraction contrained 28s RNA from membrane-bound polysomes. Applying the sequential extraction method for isolation of poly(A)-containing mRNA showed that only a minor part of that RNA was extracted with NDS while the rest was recovered by PAS-TIPNS treatment of the interface. Thus, a purification of poly(A)-containing mRNA was possible when the sequential extraction method was used.

Aminosalicylic Acids

Hybridization of polyuridylic acid to human DNA immobilized onto nitrocellulose filters.

The level of deoxyadenylate (da) regions in human DNA was estimated from formation of poly(U)-poly(da) triplexes on nitrocellulose filters that were RNAase resistant. The (dA) rich sequences were determined following mild ribonuclease treatment of the poly(U)-DNA hybrids (5 mug/ml at 25 degreesC for 30 min), where as exhaustive ribonuclease treatment (5 mug/ml at 25 degrees C for 6 hr) estimated the more (dA) pure sequences. The level of (dA) rich regions was 0.39% of the DNA and for the more (dA) pure regions it was 0.07%. The (dA) regions were widely distributed throughout human DNA regardless of base composition or sequence repetition. However, a concentration of (dA) regions into main band CsC1 gradient fractions of DNA and into repeated DNA was observed.

Adenine Nucleotides

5-year survival rate in endometrial carcinoma stage I-II related to steroid receptor concentration, degree of differentiation, age and myometrial invasion.

Three hundred and twenty-seven patients with endometrial carcinoma stage I-II were all followed for at least 5 years. The estradiol receptor concentrations were measured in 298 tumors. In 272 cases the progesterone receptor concentrations were measured as well. Both receptors were significant prognostic factors measured as 5 year survival rate. In a Cox regression test stage, degree of differentiation, myometrial invasion and age remained as independent significant factors. Progesterone receptor concentrations were almost significant in a two-sided test including all degrees of differentiation but were significant (p = 0.04) when only poorly differentiated tumors were included. Thus PgR concentrations were used only on poorly differentiated tumors. The patients could be divided into a high risk group (deep myometrial invasion), an intermediate risk group (poorly differentiated carcinomas without deep myometrial invasion but with a low progesterone receptor concentration) and a low risk group (the remaining) with 5 year survival rated of 61%, 80% and 96% respectively.

Adult

Spontaneous endometrial hyperplasia. The prognostic significance of steroid receptor concentration. A two year follow-up of patients treated with abrasio only.

The steroid receptor concentrations were measured in 63 patients. The patients were part of a prospective randomized study and were treated with abrasio only. With respect to Cystic Glandular Hyperplasia (43 patients) 16 out of 25 with PgR values less than 10,000 (fmol/mg DNA) were normalized compared to only 4/14 with higher PgR conc (p = 0.03). No limit could be identified regarding patients with Adenomatous Hyperplasia and Atypical Hyperplasia (29 patients). Consequently patients with CGH and a high PgR concentration are recommended for high dose gestagen therapy.

DNA

Endometrial hyperplasia: a prospective randomized study of histopathology, tissue steroid receptors and plasma steroids after abrasio, with or without high dose gestagen treatment.

274 patients with spontaneous endometrial hyperplasias were randomized into two groups: one treated with only abrasio, and another with additional 500 mg medroxyprogesterone acetate (MPA) twice weekly for 3 months. Total disappearance of all types of hyperplasias was seen following MPA treatment, whereas with only abrasio about 60% were removed suggesting that MPA does not have to be generally given to eliminate endometrial hyperplasias. Quantitative determinations of tissue steroid receptors and plasma steroids do not seem to be useful for the selection of patients in need of gestagen treatment.

Androstenedione

Menopausal status and cut off levels of steroid receptor ligand binding assays in breast cancer.

494 tubuloductal breast carcinomas obtained at operation were assayed for ER and PgR with short-term ligand incubation and isoelectric focusing. Plasma FSH and E2 concentrations available from 156 of the patients showed strictly premenopausal endocrine conditions in patients 45 years or younger; strictly postmenopausal conditions were found at 55 years or older. ER concentrations were significantly lower in biopsies from premenopausal compared with those from postmenopausal patients. ER concentrations assayed in intervening perimenopausal age period were not statistically different from the premenopausal period. An arbitrarily chosen cut off level to differentiate receptor low from receptor high tumours divided premenopausal assays into two equal parts; those from postmenopausal patients were cut at the second lower percentile. Arbitrary cut off levels ignorant of menopausal status should be replaced by fractionation of low and high receptor tumours on a percentile or quartile basis. Clinically, subgroups or subpopulations of patients should be identified with regard to endocrine and/or receptor status and evaluated separately.

Adult

Increased recovery of estrogen receptor in crude homogenates of breast cancer biopsies. A preliminary report.

Crude homogenates and cytosols of 31 breast cancer biopsies were analyzed for estrogen receptor, using the ER-EIA monoclonal assay (ABBOTT Laboratories). The recovery of the receptor was significantly higher in all homogenates than in their corresponding cytosols, in six of which the receptor was below the level of detection. The range of the ratio between homogenate and cytosol concentrations was 0.9-8.1 for 25 positive biopsies. If the recent hypothesis of nuclear localization of the receptor is accepted, the values obtained with crude homogenates would more correctly reflect the true concentration of the receptor in the cells.

Biopsy

Prognostic value of flow cytometrical DNA measurements in stage I-II endometrial carcinoma: correlations with steroid receptor concentration, tumor myometrial invasion, and degree of differentiation.

The prognostic value of flow cytometric DNA measurements of individual tumor cells was studied in 166 patients with endometrial carcinoma stage I-II. Follow-up time was 1-46 months and 110 patients were followed for more than 2 years. Three different ways of estimating DNA ploidy were evaluated, and the use of normal endometria in defining diploidy was considered the best. DNA-ploidy had a much more marked prognostic value in terms of 2-year recurrence-free survival than other known prognostic parameters, such as degree of differentiation, range of myometrial invasion and estradiol and progesterone receptor concentrations. The proliferative activity as determined by DNA flow cytometrical analysis was not correlated with prognosis.

Aneuploidy

Permanent alterations induced in plasma prolactin and estrogen receptor concentration in benign and malignant tissue of women who started oral contraceptive use at an early age.

In 65 young women undergoing curettage for benign uterine disorders a significant relationship was found between early oral contraceptive use (starting age less than 25 years) and a high ratio of ln plasma prolactin versus ln estrogen receptor concentration of the uterine mucosae (p less than 0.047, Mann-Whitneys U-test). Year of birth, age at menarche, age at first full term pregnancy, parity, menstrual cycle phase and duration of oral contraceptive use could not explain the results. Because similar results have previously been found for breast cancer patients using plasma prolactin and breast tumour estrogen receptor concentration, the findings indicate that early oral contraceptive use permanently alters plasma prolactin levels and estrogen receptor concentration, both in benign uterine tissue and in malignant breast tumours.

Adult

Relapse of endometrial carcinoma related to steroid receptor concentration, staging, histologic grading and myometrial invasion.

Estradiol and progesterone receptor concentrations were positively correlated to the stage of the disease and to the grade of the tumors, but not to myometrial invasion. Myometrial invasion of more than the inner third and degree of differentiation are both important prognostic factors. By combining low estradiol receptor concentration and the degree of myometrial invasion in poorly differentiated adenocarcinomas, stage I-II, it was possible to identify a group of patients containing a high percentage of relapses. This group consisted of 60% of all patients with poorly differentiated carcinoma stage I-II, who had a relapse rate of almost 50%, and were thus suitable for aggressive initial treatment.

Adult

Observations on wet weight, protein and DNA as reference for steroid receptors in malignant mammary tumours.

Estradiol and progesterone receptors were recorded together with DNA and soluble protein per unit wet weight for 235 breast cancer samples. Receptor concentration values per wet weight showed the greatest range of variation. Receptor expressed per unit wet weight, DNA or protein showed good correlation (rs greater than 0.90). In selected cases different information on receptor concentration levels may be obtained depending on the reference parameter used. An overrepresentation was found of tumours with low receptor concentrations or receptors below the level of detection in a subgroup with a low DNA content, indicating the possibility of false low receptor values in this group. High ER and PgR contents were significantly related to high level of tissue DNA. Low or high content of protein was not associated directly with low or high receptor levels. In this respect DNA is superior to wet weight and protein as reference standards for receptor concentration. Further, DNA offers the additional possibility of a rough correction for non-epithelial components of the tumours. A critical dilution of receptors, as shown by low DNA content in some homogenates, was not apparent but cannot be excluded.

Biopsy