Biomedical subjects

F E May

Publications and source records attributed to F E May.

At least 73 records · Page 4Linked to original sources

PubMed1990

NCL-CB11, a new monoclonal antibody recognizing the internal domain of the c-erbB-2 oncogene protein effective for use on formalin-fixed, paraffin-embedded tissue.

The c-erbB-2 proto-oncogene encodes a 190 k Mr protein representing a putative growth factor receptor with considerable homology to the EGF receptor. Gene amplification and overexpression of the oncogene protein have been demonstrated in a variety of tumours including breast cancer, where it is associated with a poor prognosis. In this study we have produced and characterized a mouse monoclonal antibody, designated NCL-CB11, to the c-erbB-2 protein. NCL-CB11 was generated to a synthetic peptide sequence corresponding to a site of predicted antigenicity near the C-terminus of the internal domain of the protein. NCL-CB11 produces intense membrane-associated immunohistochemical staining in a proportion of human cancer cells. The specificity of the antibody is supported by Western blotting and immunoprecipitation studies. Reactivity with an internal site of the protein is confirmed by the necessity of cell permeabilization for reactivity in fluorescence-activated cell sorter (FACS) analysis. A high degree of correlation between immunohistochemical staining using NCL-CB11, and c-erbB-2 gene amplification has been observed. NCL-CB11 should prove to be a valuable reagent for investigations into the pathological significance of c-erbB-2 protein expression.

Animals↗

PubMed1990

Expression of the oestrogen regulated pNR-2 mRNA in human breast cancer: relation to oestrogen receptor mRNA levels and response to tamoxifen therapy.

The pNR-2 mRNA is regulated by oestrogens in cell lines established from metastatic human breast cancer cells. The levels of the pNR-2 and oestrogen receptor RNAs have been measured in 96 tumour samples from patients undergoing surgery for breast cancer. Oestrogen receptor mRNA was detected in 90% of the 60 primary breast tumour samples from patients not receiving endocrine therapy at the time of surgery, whereas the pNR-2 RNA was detected in 57%. In primary tumours the expression of pNR-2 was entirely dependent upon oestrogen receptor RNA expression. When the 60 primary tumours were considered, pNR-2 and oestrogen receptor mRNA levels were significantly correlated. There was no significant correlation for pNR-2 positive tumours. pNR-2 mRNA levels were similar in tumours of pre- and post-menopausal patients and were independent of tumour differentiation and nodal status. Oestrogen receptor and pNR-2 mRNA levels were also measured in 21 tumour samples from patients receiving primary tamoxifen therapy. Eleven of these had shown an objective response and a significantly larger number of tumours from these patients contained pNR-2 mRNA than from patients who did not respond (chi 2 = 6.08, P less than 0.025).

Breast Neoplasms↗

PubMed1989

Characterization of sequences related to the mouse mammary tumor virus that are specific to MCF-7 breast cancer cells.

Mouse mammary tumour virus (MuMTV) DNA hybridized more strongly to two human EcoRI fragments (6.6 and 9.5 kilobases) in DNA from the MCF-7 human breast cancer cell line than in DNA from normal human placenta. Seven recombinants (NMWV 1E1-7) containing these MuMTV-related sequences were identified. Hybridization of NMWV 1E probes to Southern transfers of human DNA suggested that these probes hybridize to multiple sequences in the human genome. The pattern obtained was very similar to that obtained using MuMTV gag-pol DNA. Analysis of the cloned DNA showed that the NMWV 1E MuMTV-related sequences are arranged as tandem repeats and are contained in EcoRI fragments of 6.6 or 9.5 kilobases. Only two NMWV 1E EcoRI fragments (9.5 and 15 kilobases) were detected in 17 DNA samples prepared from human placenta and blood. In contrast the 6.6-kilobase EcoRI fragment was detected in two (MCF-7 and EFM-19) of seven breast cancer cell lines and the MDA MB-231 cell line contained NMWV 1E sequences in an EcoRI fragment of 9.8 kilobases.

Animals↗

PubMed1989

Effects of oestrogen and the antioestrogens, tamoxifen and LY117018, on four oestrogen-regulated RNAs in the EFM-19 breast cancer cell line.

The EFM-19 cell line is a new breast cancer cell line whose proliferation has been reported to be stimulated by oestrogens and inhibited by the antioestrogen tamoxifen. Oestrogen receptor mRNA levels are higher in EFM-19 cells than in other oestrogen-responsive cell lines. The levels of four oestrogen-inducible RNAs [pNR-1, pNR-2, pNR-25 and pNR-100] were measured in EFM-19 cells. Oestradiol treatment increased the levels of the four regulated RNAs between 3-fold (pNR-100) and greater than 100-fold (pNR-2). The induction was half maximal between 1.5 x 10(-11) and 1.5 x 10(-10) M oestradiol. The effects of two antioestrogens, tamoxifen and LY117018, were measured on the expression of the oestrogen-regulated RNAs. Tamoxifen was a partial oestrogen agonist for the induction of the pNR-1 and pNR-25 RNAs but had very little effect on the pNR-2 and pNR-100 RNA levels. The pNR-2 RNA levels were less induced by tamoxifen in EFM-19 cells than in MCF-7 cells. LY117018 did not increase the levels of any RNA. The oestrogen-induced levels of the four RNAs were reduced by both antioestrogens to the RNA levels present in cells treated with the antioestrogens alone. LY117018 was at least 100-fold more potent than tamoxifen as an oestrogen antagonist.

Breast Neoplasms↗

PubMed1989

Effects of the antioestrogen, ICI 164,384, on oestrogen induced RNAs in MCF-7 cells.

The effects of ICI 164,384 on the expression of six oestrogen-regulated RNAs (pNR-1, pNR-2, pNR-13, pNR-17, pNR-25 and pNR-100) and the 46 kDa secreted protein were measured in MCF-7 cells. In marked contrast to tamoxifen, an antioestrogen commonly used in the treatment of breast cancer, ICI 164,384 administered alone had little or no effect on the RNAs or protein. ICI 164,384 completely inhibited the induction of the RNAs and 46 kDa protein by oestradiol. Although ICI 164,384 has an affinity for the human oestrogen receptor only slightly less than that of oestradiol, half maximal inhibition of oestradiol action was attained with between a 50 and 150-fold molar excess of ICI 164,384. The pNR-1 RNA is induced by tamoxifen but this induction was abolished by ICI 164,384. Thus, ICI 164,384 acts as a potent antioestrogen for the regulation of the expression of specific oestrogen-responsive genes in human breast cancer cells.

Breast Neoplasms↗

PubMed1989

Regulation of progesterone receptor mRNA by oestradiol and antioestrogens in breast cancer cell lines.

The induction of progesterone receptor mRNA by oestradiol and antioestrogens has been characterised in the MCF-7 breast cancer cell line. Progesterone receptor mRNA was induced more than 100-fold by oestradiol. The induction was half-maximal in the presence of 10(-10) M oestradiol and maximum levels were reached after 24 h treatment. Progesterone receptor mRNA was induced to 10% of the oestrogen-induced level by tamoxifen and its metabolite 4'-hydroxytamoxifen. The increase was half-maximal in the presence of 5 X 10(-8) M tamoxifen or 5 X 10(-10) M 4'-hydroxytamoxifen. In contrast, neither the benzothiophene antioestrogen LY117018 nor the 7 alpha-alkyl steroidal antioestrogen ICI 164,384 had any effect on progesterone receptor mRNA. The progesterone receptor mRNA was also induced by oestrogen in a T47D subline and in two other oestrogen-responsive breast cancer cell lines (ZR-75, EFM-19). Tamoxifen was a partial oestrogen for progesterone receptor mRNA induction in each of these cell lines. The large induction of the progesterone receptor mRNA by oestrogen in all 4 breast cancer cell lines supports the contention that the progesterone receptor may be a good predictive marker of hormonal response in human breast cancer.

Animals↗

PubMed1989

Oestrogenic activity of tamoxifen and its metabolites on gene regulation and cell proliferation in MCF-7 breast cancer cells.

The effects of tamoxifen, three of its in vivo metabolites and 3-hydroxytamoxifen on cellular proliferation and the induction of four oestrogen-regulated RNAs (pNR-1, pNR-2, pNR-25 and cathepsin D) have been measured in MCF-7 breast cancer cells in phenol red-free culture medium. Tamoxifen and 3-hydroxytamoxifen acted as partial oestrogens to stimulate cell growth and the levels of the pNR-2 and pNR-25 RNAs. They were full oestrogens for the induction of cathepsin D RNA and induced the pNR-1 RNA above the level found in oestrogen-treated cells. N-Desmethyltamoxifen and 4-hydroxytamoxifen behaved like tamoxifen except that N-desmethyltamoxifen did not induce the pNR-2 RNA and was only a partial oestrogen for the induction of cathepsin D RNA, and 4-hydroxytamoxifen did not induce the pNR-2 or pNR-25 RNAs. In the presence of oestradiol, the four anti-oestrogens prevented the stimulation of growth and reduced (pNR-2 and pNR-25) or increased (pNR-1) the RNA levels to those present in MCF-7 cells treated with the anti-oestrogen alone. In contrast, for cathepsin D RNA levels there was a synergistic effect of the anti-oestrogens and oestradiol. The concentration at which each anti-oestrogen was effective was related to its affinity for the oestrogen receptor. Metabolite E was a full oestrogen for the induction of cell proliferation and the oestrogen-regulated RNAs. pNR-25 and pNR-2 RNA levels correlated most closely with effects on cell proliferation. These RNAs are therefore potentially the most useful for predicting the response of breast cancer patients to tamoxifen therapy.

Breast Neoplasms↗

PubMed1989

Incidence of hypertension in an ambulatory elderly population.

Investigations of the natural history of blood pressure have generally evaluated mean systolic and diastolic pressure changes. While information, this information is not directly applicable to clinical practice settings, in which patients are usually classified as normotensive or hypertensive. We measured the actual incidence of hypertension, using two different definitions, in an ambulatory elderly population of 2,584 individuals over an 8-year period. Using the less stringent blood pressure definition (systolic blood pressure greater than 140 mmHg and diastolic blood pressure greater than or equal to 90 mmHg), 884 (34.2%) participants were normotensive and 1,700 (65.8%) were hypertensive at an initial screening. The average annual incidence of hypertension over the subsequent eight years was 13.2%, and life tables demonstrated a gradual risk of developing hypertension. The development of hypertension was not associated with gender or age; while older age groups had a greater chance of developing hypertension than younger, the difference did not reach statistical significance.

Age Factors↗

PubMed1989

Resting heart rates in an ambulatory elderly population: an evaluation of age, sex, symptoms, and medication.

In a cross-sectional analysis of 2,301 ambulatory elderly subjects, the mean resting heart rate for women (66.2/min) was significantly higher than for men (63.6/min), p less than 0.0001, and heart rate was positively correlated with age for both men and women. Resting heart rate was positively correlated with the number of drugs used (p less than 0.05), number of symptoms reported (p less than 0.05), systolic (p less than 0.01), and diastolic (p less than 0.0001) blood pressure. Of 975 participants who were followed longitudinally over an 8-year period there was a significant decrease in resting heart rate of approximately 2.75/min, p less than 0.0001.

Aged↗

PubMed1988

Oestrogen regulates oestrogen receptor mRNA levels in an oestrogen-responsive human breast cancer cell line.

The EFM-19 human breast cancer cell line contains high levels of oestrogen receptor mRNA and is oestrogen responsive for growth. The oestrogen receptor gene appears to be specifically regulated by oestrogens in EFM-19 cells. The induction by oestradiol is half-maximal in the presence of 3 x 10(-11) M oestradiol. LY117018 is a potent antioestrogen with a similar affinity to oestradiol for the oestrogen receptor. LY117018 completely blocks the induction of the oestrogen receptor mRNA by oestradiol when it is present in a 50-fold molar excess. The ability of oestrogens to control the levels of their own receptor in human breast cancer cells has implications for the understanding of oestrogen responsiveness and the amelioration of endocrine therapy.

Breast Neoplasms↗

PubMed1988

Identification and characterization of estrogen-regulated RNAs in human breast cancer cells.

Two cDNA libraries have been constructed with RNA prepared from the estrogen-responsive breast cancer cell lines, MCF7 and ZR 75. They were screened by differential hybridization for estrogen-regulated sequences. A total of 11 different RNAs were isolated from the MCF7 cell cDNA library and four from the ZR 75 cell cDNA library. Only two sequences were isolated from both libraries. The levels of the 13 different RNAs are induced between 2.5- and 100-fold by estrogen in MCF7 cells. The expression and regulation by estrogen of the RNAs was examined in eight different human tumor cell lines. The relative abundance of each RNA varied in the different cell lines. The expression of three RNAs (pNR-1, pNR-2, and pNR-25) was detected only in estrogen-responsive breast cancer cells. The sequences that were expressed in all eight cell lines were regulated by estrogen only in the three estrogen-responsive breast cancer cell lines. The response of the RNAs to other classes of steroids and to different concentrations of estrogen was characterized in more detail. The extent to which different concentrations of estradiol induced each RNA varied, but half-maximal induction of most of the RNAs occurred between 2 and 5 X 10(-11) M. The time at which increased RNA levels were first detected following exposure to estradiol also varied. Estrogen increased the levels of some RNAs within 15 min, while for others there was a lag of 4 h.

Breast Neoplasms↗

PubMed1988

Cataracts in Dunedin Program participants: an evaluation of risk factors.

A geriatric health screening program in Dunedin, Florida, was used to evaluate risk factors leading to development of cataracts. A total of 2,787 participants completed the fourth yearly visit to the program. At the time of the fourth visit, 49.3% of women (mean age 75.1 years) and 38.2% of men (mean age 75.4 years) reported the presence of cataracts. Age was found to be the most significant risk factor in cataract development (P less than .0001). Both men and women with cataracts had significantly lower serum cholesterol concentrations than subjects without cataracts. After adjusting for age and sex, diazepam (P less than .03), furosemide (P less than .04), isosorbide (P less than .003), and ibuprofen (P less than .03) were found to be positively associated with cataracts; triamterene (P less than .05) had a negative association, indicating a protective relationship. Aspirin was not shown to have a protective effect on reported cataracts.

Age Factors↗

PubMed1988

Measurement of oestrogen receptor mRNA levels in human breast tumours.

A sensitive single-stranded hybridisation probe for the oestrogen receptor mRNA was synthesised using T3 polymerase from oestrogen receptor cDNA cloned in the Bluescript vector. This probe was used to measure oestrogen receptor mRNA in total RNA extracted from breast tumours. Oestrogen receptor mRNA was detected in 41 of 47 (87%) tumours whereas cytosolic oestrogen receptor protein was detected in only 18 out of 39 (46%). There was a significant correlation between the levels of the oestrogen receptor, as measured by 3H-oestradiol binding, and the oestrogen receptor mRNA. Oestrogen receptor mRNA was detected in 15 of the 21 tumours that did not contain detectable oestrogen receptor protein. This suggests that detection of the mRNA is a more sensitive means for establishing oestrogen receptor status than the radioligand oestrogen receptor assay. Oestrogen receptor mRNA was found in all histological tumour types examined. Its level was related to tumour differentiation. All the tumours that did not contain oestrogen receptor mRNA and most of the tumours that contained only low levels of oestrogen receptor mRNA were classified as grade III according to Bloom and Richardson: the median of the oestrogen receptor mRNA levels was significantly lower in this group.

Adult↗

PubMed1988

Epidemiology of intermittent claudication: evaluation of risk factors.

Information from a geriatric health screening programme (Dunedin Program) was used to study the prevalence and risk factors predisposing to intermittent claudication (IC) in 1704 ambulatory elderly subjects. Risk factors studied included reported symptoms and diseases, mediation use, haematological and biochemical findings. The prevalence of IC reported by Dunedin participants was 14.1% for women and 14.4% for men. There was a positive relationship between IC and the number of other diseases and symptoms reported (P less than 0.0001). Serum glucose, cholesterol, and triglycerides were significantly higher in subjects reporting IC. Systolic blood pressure was higher in men and women reporting IC, but no significant relationship was observed with diastolic blood pressure.

Aged↗

PubMed1988

Meprobamate use in the elderly. A report from the Dunedin program.

Meprobamate use was studied in an ambulatory elderly population in Dunedin, Florida. All participants taking this medication were mailed a questionnaire concerning their pattern of use. From 2,278 subjects, 30 (1.3%) reported the use of this drug. The average age of participants using this drug was 81.3 years. Five participants began using the drug over 27 years ago and over one-half of the respondents reported using the drug on a regular basis for over 10 years. With this type of history of meprobamate use, one might expect to encounter a large number of patients in the future who, in a similar manner, have been using benzodiazepines for many decades.

Aged↗

PubMed1988

Expression of human sequences related to those of mouse mammary tumor virus.

Sequences related to those of the mouse mammary tumor virus (MuMTV) genome have been cloned from human DNA by screening a library prepared from the DNA of a human breast cancer cell line with MuMTV gag-pol DNA. Nine distinct groups of (MuMTV-related) sequences were identified among 100 lambda recombinants by cross-hybridization experiments with subcloned fragments containing gag-pol-related DNA. The largest group, of 64 recombinants, contains the MuMTV-related sequences cloned by others. The other eight groups contain MuMTV-related sequences that have not been described previously. The gag-pol regions of one recombinant from each of the nine groups were hybridized to RNA prepared from five human breast cancer cell lines, from placenta, and from two cell lines derived from other malignancies. RNAs were detected by probes for seven of the groups. The RNAs ranged in size from 1.2 to 12 kilobases. Probes for six of the groups detected large RNAs that could represent transcripts of full-length proviral DNA. Two of the probes detected RNA in one breast cancer cell line only. Most of the RNAs were detected in more than one cell line.

Animals↗

PubMed1988

Effect of zinc supplementation on the development of cardiovascular disease in the elderly.

Supplemental zinc intake by an ambulatory elderly population was examined. Health questionnaire, electrocardiogram, laboratory, and medication use data from a geriatric health screening program were compared for 69 participants who were taking zinc supplements and 1,832 participants who were not taking zinc supplements during 1985. A major purpose of this study was to evaluate whether ingestion of zinc supplements by elderly persons is a risk factor for development of cardiovascular disease. No association between zinc supplementation and increased risk of developing cardiovascular disease was found for the indices examined. More information is needed to resolve the question of whether or not zinc supplementation is a risk factor for the development of cardiovascular disease. It is important that elderly persons be provided information to evaluate the possible risk versus benefit of taking zinc supplements.

Aged↗

PubMed1987

Effects of tamoxifen and 4-hydroxytamoxifen on the pNR-1 and pNR-2 estrogen-regulated RNAs in human breast cancer cells.

The estrogenic and antiestrogenic activities of tamoxifen and 4-hydroxytamoxifen have been measured on the expression of two estrogen-regulated RNAs (pNR-1 and pNR-2) in the MCF7 human breast cancer cell line cultured in phenol red-free medium. The two antiestrogens increased the level of the pNR-1 RNA to about 80% of the estradiol-induced level, and the induction by estradiol was not significantly antagonized by either antiestrogen. In contrast, the pNR-2 mRNA was only increased to about 10% of the estradiol-induced level, and its induction by estradiol was antagonized by both tamoxifen and 4-hydroxytamoxifen. Thus, the two RNAs respond in dramatically different ways to these antiestrogens. 4-Hydroxytamoxifen and estradiol have similar affinities for the estrogen receptor; however, the induction of both RNAs by 4-hydroxytamoxifen required a 10-fold higher concentration than estradiol for maximum agonist activity, and a 500-fold molar excess was required to antagonize the induction by estradiol. Tamoxifen has a 20-100-fold lower affinity than estradiol for the estrogen receptor. A 200-fold higher concentration was required for maximum agonist activity and a 10,000-fold molar excess to antagonize the induction by estradiol. These results emphasize the complexity of antiestrogen action in human breast cancer cells.

Breast Neoplasms↗