Search PubMed⌕ Search

Biomedical subjects

T Thorsen

Publications and source records attributed to T Thorsen.

At least 55 records · Page 3Linked to original sources
PubMed1989

Estrogen receptor in breast cancer; its relation to mean nuclear area, age and lymph node status.

A study of 378 patients with infiltrating breast carcinoma using linear logistic regression and ANOVA analysis demonstrated a different relation between age at operation and estrogen-receptor (ER) concentration in the lymph-node negative and the lymph-node positive groups. Tumours from patients between 51 and 70 years old had lower median ER concentration in the lymph-node negative group than in the lymph-node positive group. In the group older than 70 years, however, tumours from lymph-node negative patients had higher median ER concentrations than those from the lymph-node positive patients. Patients 50 years and younger had similar median ER concentrations in both lymph-node groups. Low mean nuclear area (MNA) of the tumour cells was associated with high frequency of tumours able to produce ER. No such association was found for age. Independent of age and lymph-node status tumours with low MNA also had high ER concentration. These findings suggest that tumours from different lymph-node/age groups may have different biological properties. The relationship between ER and nuclear size point to a key function of the nucleus, both as regards the ability to produce ER and its level of production.

Age Factors↗
PubMed1987

Progesterone-binding cyst protein in human breast tumor cytosol.

Breast tumor cytosol has been analyzed for the presence of a progesterone-binding protein (PBCP), commonly present in benign breast cysts in huge concentrations. In 377 primary carcinoma investigated PBCP was present in measurable quantities in 60.7% using "rocket" immunoelectrophoresis. Concentrations of PBCP ranged from 0 to 12.4% of total cytosol protein with an average of 4.0 micrograms/mg cytosol protein. The distribution of PBCP values seems to suggest two tumor populations, one of which is lacking in PBCP and the other showing a lognormal distribution. In malignant tumors PBCP levels were negatively correlated (P = 0.024) to estrogen receptor but not to (P = 0.38) progestin receptor levels. There was a highly significant (P less than 0.001) positive correlation to cytosol albumin concentration which suggests an extracellular localization of PBCP possibly caused by restricted lymphatic drainage of tumor tissue. In benign breast tumors, mainly fibroadenomas, both PBCP incidence (81%) and average concentration (13.5 micrograms/mg protein) was higher than in malignant tumors. A positive correlation to sex-hormone receptor levels were observed indicating that PBCP production could be under hormonal control in this type of tumor development. In 71 metastatic tumors examined PBCP incidence was far less than in primary tumors (P less than 0.001) and the levels seen were also considerably lower. PBCP holds promise as a marker of tumors in an early stage of development and/or with a low metastatic potential.

Adult↗
PubMed1987

Alterations in the metabolism of oestrogens during treatment with aminoglutethimide in breast cancer patients. Preliminary findings.

In this small study, the effect of aminoglutethimide on the disposition of oestrogens in women with advanced breast cancer was investigated using bolus injections of 4-[14C]-oestradiol and 6,7-[3H]-oestrone sulphate, alone or in combination. No alterations in oestrogen disposition were seen after short term (6 hours) aminoglutethimide administration. During long term (3 weeks to 8 months) aminoglutethimide treatment mean 4-[14C]-oestradiol clearance was not changed. 14C-Oestrone sulphate AUC was reduced by 43% at a low dose of aminoglutethimide (125 mg twice daily) and by 65% at a high dose (250 mg 4 times daily) with hydrocortisone acetate 25 mg twice daily. The oestrone sulphate terminal elimination rate constant (lambda z) was concurrently increased (mean of 46 and 79%, respectively, with the 2 dosage regimens). A possible increase in oestrone sulphate clearance during long term treatment was tested for by injecting 6,7-[3H]-oestrone sulphate. These studies revealed a marked increase (mean 104%) in oestrone sulphate clearance in patients receiving the high dose aminoglutethimide schedule. Following injection of 4-[14C]-oestradiol plus 6,7-[3H]-oestrone sulphate, the fraction of 4-[14C]-oestradiol metabolised to oestrone sulphate was found to be reduced in all patients (mean 13%). A mean increase of 80% in the urinary excretion of 14C-oestriol was observed after 4-[14C]-oestradiol administration. Our results, although preliminary, suggest that aminoglutethimide is a potent inducer of aminoglutethimide metabolism, thereby producing a significant reduction in plasma bioavailability of oestrone sulphate. These effects may have a role in the action of aminoglutethimide, a finding which warrants further investigation.

Aged↗
PubMed1987

Transmission and scanning electron microscopy of N2 microbubble-activated human platelets in vitro.

When N2 microbubbles are stirred in platelet-rich plasma, they cause a fall in the number of free platelets. Changes in the platelets ultrastructure during this interaction between gas bubbles and platelets have been studied by transmission and scanning electron microscopy. Platelets, and aggregates of platelets, adhere to the surface of the N2 microbubbles. This adhesion induces ultrastructural changes (shape change, pseudopod formation, granule centralization, fusion, and disappearance) that are similar to "classical" agonists like ADP, collagen, and thrombin. These ultrastructural studies further strengthen our previous contention that N2 microbubbles activate platelets in a way similar to these physiologic agonists, and show that the previously reported fall in the number of free platelets is due to platelet aggregation. Platelet aggregates are also present in the interstices between gas bubbles. Fixed N2 microbubbles have been demonstrated, and these can be broken like cracked eggs by means of the electron beam in the electron microscope. Possible mechanisms for activation of the platelets by the gas bubbles are: through ADP released from some few platelets; by diffusion of gas after bubble-platelet interaction; and through certain fractions of the plasma proteins and lipids in the bubble surface that may act as binding sites for the platelets and promote adhesion and spreading of the platelets over the surface.

Blood Platelets↗
PubMed1986

An epidemic of cirrhosis in Danish women revisited.

Between 1944 and 1947 the mortality statistics for the Danish population show an epidemic increase of liver diseases: subacute necrosis and cirrhosis. The epidemic only affected female mortality rates. Mortality due to cirrhosis remained at a higher rate for women than men until 1970 as a result of an excess mortality in the cohort of women who in 1945 were over the age of 45. Up to 1981 this group showed an excess of 4,000 fatalities. A reevaluation of medico-statistical data shows that the disease cannot be explained by the epidemic hepatitis occurring in 1942-1944 or by increased consumption of alcohol. Possible causes could be pharmaceutical products or additives, perhaps hormone preparations.

Adult↗
PubMed1986

Effects of platelet antagonists on the reduction in platelet density caused by microbubbles in vitro.

Platelet-rich plasma (PRP) was stirred and incubated at 37 degrees C with N2 microbubbles in vitro in the presence and absence of platelet antagonists. The N2 microbubbles acted as a platelet agonist, like "classical" agonists such as ADP, collagen, and thrombin, causing an agonist-induced aggregation requiring extracellular Ca2+. This aggregation is abolished by 2-ethylamineglycolether (N',N',N',N') tetraacetate (chelator of extracellular Ca2+), and 2-deoxy-D-glucose plus antimycin A (inhibitors of glycolysis and electron transport, and thereby of ATP production). Furthermore, this aggregation could be depressed pharmacologically by several antagonists of the aggregation induced by "classical" platelet agonists. The greatest inhibition of microbubble-induced aggregation was obtained by substances that increase the intracellular levels of cyclic AMP. Medications that are in common clinical use, such as theophylline, seem promising in this respect. The prostaglandin-thromboxane pathway did not seem to be involved in the N2 microbubble-induced platelet aggregation in vitro, since acetylsalicylic acid and indomethacin were without effect, nor did the 3',5'-cyclic guanosine monophosphate pathway seem to be linked to this aggregation mechanism.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Aminoglutethimide as an inducer of microsomal enzymes. Part 2: Endocrine aspects.

Using a [4-14C]estradiol bolus injection technique possible effects of AG administration on estrogen metabolism were studied in seven patients. No alterations in steroid disposition were seen after a short term AG treatment. Chronic AG administration produced no change in mean estradiol clearance value. Chronic AG treatment as a low- or high-dose drug schedule produced a consistent reduction in estrone sulfate production rate (mean reductions 24 and 42%) as well as an increased estrone sulfate elimination rate constant (mean increase 30 and 69%). Urinary estriol secretion rate was consistently increased during chronic treatment (mean increase 95%) with no difference between low- and high dose drug schedules. These findings are consistent with AG being a potent enzyme inducer stimulating estrogen metabolism, and this mechanism may be an important part of AG mechanism of action by reducing estrone sulfate bioavailability.

Aminoglutethimide↗
PubMed1986

A method for production of N2 microbubbles in platelet-rich plasma in an aggregometer-like apparatus, and effect on the platelet density in vitro.

The mechanisms involved in the interactions between microgasbubbles and platelets are not clear. The platelet aggregatory response to agonist-induced, receptor-mediated stimuli has been studied extensively. As a direct in vitro approach to elucidate the interaction between gas bubbles and platelets, N2 microbubbles were used as a platelet agonist in an experimental apparatus similar to an ordinary aggregometer. N2 microbubbles of varying number and size were produced in platelet-rich plasma (PRP) and incubated at 37 degrees C. The gas-liquid interface of the gas bubbles consists of plasma proteins and lipids. In stirred PRP a considerable decrease occurred in the platelet density, which could not be attributed to formation of citrate complexes with calcium and/or the corresponding reduction in the concentration of free calcium. Gas bubbles with a diameter in the range of 40-120 micron caused the greatest reduction in the platelet density. The platelet movements in PRP and the curvature of the N2 microbubble surface seemed more important for the interaction than the total gas bubble surface available for contact.

Analysis of Variance↗
PubMed1983

Relationship of cyclic AMP binding capacity and estrogen receptor to hormone sensitivity in human breast cancer.

Estrogen receptor (ER) and total binding capacity for cyclic AMP (cAR) were measured in cytosols from human mammary tumors. Patients with advanced, evaluable breast cancer were biopsied before the start of endocrine treatment, and ER and cAR measurements were performed. All patients included in this study were ER positive. Sixteen of 30 patients (53%) had an objective response to endocrine treatment. When ER and cAR were expressed as a ratio and this ratio was related to treatment response, it was found that all objective responders had ratio values above 2.5 X 10(-3). Nine of 14 nonresponders had ER/cAR ratios below this value. In our limited series of patients a threshold limit of 2.5 X 10(-3) would have correctly predicted the response to endocrine treatment in 25 of 30 patients (83%). In patients with ER values below 100 fmol/mg protein and PgR negative or unknown, cAR might strengthen the predictive value of steroid receptor measurements.

Adult↗
PubMed1983

The changing pattern of recurrence in oestrogen positive and negative breast cancer with nodal spread, related to efferent vascular invasion.

In a series of 50 cases of node-positive breast carcinoma, 11 of 26 of those with efferent vascular invasion (EVI) in the axillary nodes at the time of operation were dead 3 years later, in contrast to 1 of 24 EVI-negative. Recurrence within the 1st year was more common in the cases with an oestrogen receptor (ER) negative primary, but by the 3rd year this trend had reversed, and there were more recurrences in the ER-positive. While recurrence and death came earlier in EVI + ER - cases, the EVI + ER + followed soon after. Next came recurrence and death in the EVI - ER +, while there have been no deaths to date in the EVI - ER -. A model is proposed to explain the timing of recurrence in these different groups.

Aged↗
PubMed1983

Sinophobic growth in oestrogen receptor-negative metastatic breast cancer.

The mode of growth of tumour cells from primary breast carcinoma in the axillary nodes is shown to be related to the oestrogen receptor (ER) status of the primary tumour. ER-positive primaries are described as tending to show sinophilic growth, the tumour cells spreading along the nodal sinuses; while the ER-negative are sinophobic, spreading more diffusely in the lymphoid tissue.

Axilla↗
PubMed1982

Blood hormone levels related to stages and grades of prostatic cancer.

Human follicle stimulating hormone (FSH), human luteinizing hormone (LH), human prolactin, testosterone, estradiol, and sex hormone binding globulin (SHBG) were measured in the blood of 100 consecutive new patients with prostatic carcinoma. According to the VACURG classification, 14% of the patients were in Stage I, 25% in Stage II, 25% in Stage III, and 36% in Stage IV. Within each stage the tumors were further subdivided into either highly, moderately, or poorly differentiated carcinomas. Thus the whole group consisted of 12 categories (stages and grades) of prostatic carcinoma. No specific hormonal pattern emerged which could distinguish any particular category or group of categories. We, therefore, conclude that single hormone measurements are of no practical value for diagnostic purposes related to staging and grading of prostatic carcinoma.

Aged↗
PubMed1982

Oestrogen and progesterone receptor content and the distribution of histological grade in breast cancer.

Histological grading of 160 primary infiltrating breast carcinomas showed that both oestrogen and progesterone receptor status are strongly related to grade, tumours that are receptor positive tending to be of lower grade than the receptor negative. The nuclear factors used in grading were those that determined this association. In addition the absence/presence of both receptors was reflected in the grade present, beyond the correlation expected on the basis of either receptor alone.

Adult↗
PubMed1982

Concentration of endogenous oestradiol as related to oestradiol receptor sites in breast tumor cytosol.

Biopsies or mastectomy specimens from 69 malignant and 17 non-malignant human breast tumours have been examined with respect to cytoplasmic oestradiol receptors and endogenous oestradiol concentration. Of the malignant tumours, 45 (65%) had significant oestradiol receptor concentrations (136.7 fmol/mg protein +/- 38.3 S.E.M.). Oestradiol values in the cytosol were not correlated to receptor levels. Cytosol oestradiol concentrations in the receptor-negative tumours were normally distributed about a mean value of 7.4 fmol/mg protein +/- 0.9 (S.E.M.). Oestradiol levels were similar to the median concentration of receptor found in tumours from younger women, and consequently may influence receptor measurements in such tumours. In receptor-positive cytosols a much wider range (less than 1 to 69.7 fmol/mg protein) and a non-symmetrical distribution of oestradiol values were found which closely corresponded to the range of occupied receptor concentrations previously measured in tumour cytosol. When tumours having undetectable oestradiol values were excluded, receptor-positive cytosols had significantly higher oestradiol concentrations than those found in receptor-negative tumours (P less than 0.01). No significant difference in cytosol oestradiol concentration was found in receptor-positive and negative pre- and postmenopausal women. This would indicate that factors other than plasma levels influence tissue availability of oestradiol.

Adenofibroma↗
PubMed1982

Association of plasminogen activator activity and steroid receptors in human breast cancer.

Plasminogen activating activity (PAA) has been determined in 105 human breast cancer cytosols with a colorimetric assay. PAA has been related to steroid receptors in the same cytosols. A strong positive correlation between PAA and progesterone receptor levels was found (Spearmans coefficient of rank correlation, R - 0.74, P less than 0.001). PAA discriminates between progesterone receptor-positive and -negative tumours, irrespective of oestradiol receptor content. It is suggested that PAA is a marker of functional oestradiol receptor and that fibrinolytic activity may be a causative factor in the low metastatic potential of progesterone receptor-positive tumours.

Breast Neoplasms↗