Mixed lipolytic activities of an enzyme preparation from the pancreas.
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Biomedical subjects
Publications and source records attributed to W R Miller.
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Parabens are used as preservatives in many thousands of cosmetic, food and pharmaceutical products to which the human population is exposed. Although recent reports of the oestrogenic properties of parabens have challenged current concepts of their toxicity in these consumer products, the question remains as to whether any of the parabens can accumulate intact in the body from the long-term, low-dose levels to which humans are exposed. Initial studies reported here show that parabens can be extracted from human breast tissue and detected by thin-layer chromatography. More detailed studies enabled identification and measurement of mean concentrations of individual parabens in samples of 20 human breast tumours by high-pressure liquid chromatography followed by tandem mass spectrometry. The mean concentration of parabens in these 20 human breast tumours was found to be 20.6 +/- 4.2 ng x g(-1) tissue. Comparison of individual parabens showed that methylparaben was present at the highest level (with a mean value of 12.8 +/- 2.2 ng x g(-1) tissue) and represents 62% of the total paraben recovered in the extractions. These studies demonstrate that parabens can be found intact in the human breast and this should open the way technically for more detailed information to be obtained on body burdens of parabens and in particular whether body burdens are different in cancer from those in normal tissues.
The protein product of the H-ras oncogene, p21, has been measured semiquantitatively in solubilized particulate fractions of 160 primary tumours from patients presenting without evidence of distant metastatic breast cancer. Levels of p21 have then been related to factors of established prognostic significance, and to clinical outcome after primary treatment in terms of disease-free interval and survival times. p21 was detected by Western blotting in all tumour fractions, but amounts varied markedly between different tumours. There was no significant relationship between levels of p21 and the menopausal status of the patient, tumour oestrogen receptors, grade, and clinical stage. However, there was a significant trend for tumours to be associated with lymph node involvement as p21 was increasingly expressed. Elevated levels of p21 were also significantly related to early disease recurrence and death from cancer. Multivariate stepwise analysis showed that both p21 and lymph node status were independent statistically significant factors for disease recurrence and survival, and that no other parameter was significant for clinical outcome after adjustment for p21 and lymph node status. These results indicate that tumour levels of p21 are an important prognostic variable in patients with early breast cancer.
Because intratissue levels of estrogens may be more important for the understanding of the endocrine status of an organ than are peripheral plasma levels, the concentrations of estrone and estradiol have been measured in normal and pathological breast and uterine specimens. Some breast tumors were collected in countries with differences in incidence and natural history of the disease. In other samples the subcellular distribution of the steroids was studied. Estrone levels did show much less variation than estradiol levels. Not related to estrogen receptors, estradiol levels were higher in uterine than in breast tissues. Also, the subcellular distribution observed could not be explained by changes in receptors. Malignant breast tumors of premenopausal and postmenopausal women contained similar amounts of estradiol. Unexplained large differences were found in the intratissue estradiol levels obtained in different countries.