In February 1999, an outbreak of listeriosis caused by Listeria monocytogenes serotype 3a occurred in Finland. All isolates were identical. The outbreak strain was first isolated in 1997 in dairy butter. This dairy began delivery to a tertiary care hospital (TCH) in June 1998. From June 1998 to April 1999, 25 case patients were identified (20 with sepsis, 4 with meningitis, and 1 with abscess; 6 patients died). Patients with the outbreak strain were more likely to have been admitted to the TCH than were patients with other strains of L. monocytogenes (60% vs. 8%; odds ratio, 17.3; 95% confidence interval, 2.8-136.8). Case patients admitted to the TCH had been hospitalized longer before cultures tested positive than had matched controls (median, 31 vs. 10 days; P=.008). An investigation found the outbreak strain in packaged butter served at the TCH and at the source dairy. Recall of the product ended the outbreak.
17beta-hydroxysteroid dehydrogenase (17HSD) type I converts the weakly active estrogen, estrone, into highly active estradiol. In addition to being essential for gonadal estradiol biosynthesis, the enzyme is also expressed in a significant proportion of breast tumors. In order to study the role of the enzyme in estrogen-dependent growth of breast cancer, MCF-7 breast-cancer cells stably expressing human 17HSD type I were generated. In control MCF-7 cells a very low 17HSD activity was observed and, in line with its low estrogenic activity, estrone was devoid of the growth-enhancing effect of estradiol. The presence of the enzyme in the stably transfected MCF-7 cells resulted in a rapid conversion of estrone into estradiol but did not alter the estrogen-receptor concentration in the cells. However, in transfected cells, estrone had a growth-promoting effect practically identical to that of estradiol. The presence or absence of 17HSD type I in breast-cancer cells may therefore be decisive with regard to estrogen exposure and the estrogen-responsive growth of breast-cancer tissues.
A controlled intervention trial, with the purpose of testing the hypothesis that the incidence of coronary heart disease (CHD) could be decreased by the use of serum-cholesterol-lowering (SCL) diet, was carried out in 2 mental hospitals near Helsinki in 1959--71. The subjects were hospitalized middle-aged men. One of the hospitals received the SCL diet, i.e. a diet low in saturated fats and cholesterol and relatively high in polyunsaturated fats, while the other served as the control with a normal hospital diet. Six years later the diets were reversed, and the trial was continued another 6 years. The use of the SCL diet was associated with markedly lowered serum-cholesterol values. The incidence of CHD, as measured by the appearance of certain electrocardiographic patterns and by the occurrence of coronary deaths, was in both hospitals during the SCL-diet periods about half that during the normal-diet periods. An examination of a number of potential confounding variables indicated that the changes in them were small and failed to account for the considerable reduction in the incidence of CHD. It is concluded that the use of the serum-cholesterol-lowering diet exerted a substantial preventive effect on CHD.
Dioxins are known to decrease bone strength, architecture and density. However, their detailed effects on bone material properties are unknown. Here we used nanoindentation methods to characterize the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on nanomechanical behaviour of bone matrix. Pregnant rats were treated with a single intragastric dose of TCDD (1 microg/kg) or vehicle on gestational day 11. Tibias of female offspring were sampled on postnatal day (PND) 35 or 70, scanned at mid-diaphysis with pQCT, and evaluated by three-point bending and nanoindentation. TCDD treatment decreased bone mineralization (p
Estrogen action in the target cells is dependent on estrogen receptor activity and intracellular estrogen concentration, which, in turn, is affected by the serum concentration and local metabolism in these cells. During the reproductive years the main source of estrogens is the ovarian follicles, but in postmenopausal women most of the estrogens are formed in peripheral tissues. 17Beta-hydroxysteroid dehydrogenases (17HSDs) catalyze the reaction between 17beta-hydroxysteroids and 17-ketosteroids, and several distinct 17HSD isoenzymes have been characterized. 17HSD type 1 catalyzes the reaction from low-activity estrone to high-activity estradiol. The type 2 enzyme has an opposite activity, thereby reducing the exposure of tissues to estrogen action. 17HSD type 1 is expressed both in steroidogenic tissues and in the target tissues of steroid action, such as normal and malignant breast tissue, where it may be responsible for maintaining the high intracellular estradiol concentration seen in breast cancer specimens. Therefore, 17HSD type 1 inhibitors may be useful in the treatment and/or prevention of estrogen-dependent malignancies, such as breast cancer. This article deals mainly with 17HSD types 1 and 2 and their role in estrogen action in breast tissue.
17 beta-Hydroxysteroid dehydrogenase (17HSD) isoenzymes catalyse the interconversion between highly active 17 beta-hydroxy- and low-activity 17-keto-steroids and thereby regulate the biological activity of sex steroids. The present study was carried out to characterize 17HSD activity and the expression of 17HSD type 1 and 2 isoenzymes in several human cell types and tissues. The data indicate that in cultured cells the direction of 17HSD activity is exclusively determined by the expression of these distinct isoenzymes. The intracellular environment could not modulate the direction of the enzyme activities in any of the cell types analysed. 17HSD type 1 acts as a reductase converting oestrone into oestradiol, whereas 17HSD type 2 possesses oxidative activity inactivating oestradiol by converting it into oestrone. The data, furthermore, suggest that of the two 17HSD type 1 mRNAs (1.3 and 2.3 kb), expression of the 1.3 kb mRNA is related to enzyme concentration in all the cell types studied. This mRNA is principally expressed in cells of placental and ovarian origin, but is also present in malignant breast epithelial cells. In contrast, 17HSD type 2 is more widely expressed. It is present in several oestradiol-metabolizing tissues as well as in some target cells of sex steroid action. The opposite reaction directions observed in the cultured cells, together with differences in the distribution of the isoenzymes, suggest that type 1 is involved in oestradiol production in females while type 2 plays a role in the inactivation of this sex steroid in peripheral tissues, both in females and in males. However, some examples exist of simultaneous expression of both enzymes in the same cell type or tissue.