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Biomedical subjects

F E May

Publications and source records attributed to F E May.

At least 91 records · Page 5Linked to original sources
PubMed1987

Oestrogen regulates cathepsin D mRNA levels in oestrogen responsive human breast cancer cells.

A cDNA library was constructed from the mRNA of the ZR-75 oestrogen responsive human breast cancer cell line and screened for oestrogen regulated mRNA sequences. Of the recombinants isolated, 30 contained cDNA that corresponded to a single mRNA species of 2.1 kb that was induced between 10 and 15 fold by oestradiol treatment. The sequence of the entire open reading frame and 3' non-coding region of the mRNA was determined and shown to encode the aspartyl protease cathepsin D. The induction of cathepsin D mRNA is specific for oestrogen and is maximal at 3 X 10(-10) M. Cathepsin D mRNA levels were increased by oestrogen in 3 oestrogen responsive breast cancer cell lines. Cathepsin D mRNA was expressed but not regulated in an oestrogen receptor negative breast tumour cell line, BT 20, and in 2 other malignant cell lines, Hela and A431.

Base Sequence↗
PubMed1987

Drug use in an ambulatory elderly population: a five-year update.

Drug usage was studied in an ambulatory elderly population in Dunedin, Florida. Prescription and nonprescription drug use in these 2834 participants was compared with use during a period five years earlier. The average number of medications increased from 3.2 in 1978-80 to 3.7 in 1983-85. The most commonly prescribed medications in this population were hydrochlorothiazide-triamterene (13.5 percent), digoxin (9.6 percent), and hydrochlorothiazide (8.4 percent). There was a large increase in the use of nutritional supplements in the past five years, with 18.0 percent of these subjects reporting the use of vitamin E and 15.7 percent taking vitamin C. The general philosophy in geriatrics is to use the fewest drugs possible; however, it appears that the elderly are, in fact, receiving an increasing number of medications.

Age Factors↗
PubMed1987

Clinical research in the elderly: ethical and methodological considerations.

Clinically oriented research in the elderly is of growing interest because of increasing numbers of older persons, the relative lack of research data with this population, and recent Food and Drug Administration mandates to study drugs in the elderly. Studies of young, healthy persons cannot necessarily be extrapolated to the elderly due to changes associated with aging and the increased number of concomitant disease states and medications. Subject recruitment may be more time consuming in finding subjects with the appropriate inclusion criteria and lack of exclusion criteria who are willing to participate. Additional concern must be placed on protecting the subject's rights while allowing autonomous decision making. Likewise, protocols may need to be flexible enough to include persons with concomitant disease and medications.

Aged↗
PubMed1986

Symptom prevalence in the elderly. An evaluation of age, sex, disease, and medication use.

Prevalence of reported symptoms was studied in 1927 women and 1140 men over 65 years of age in an ambulatory health screening program. Reports of 28 common symptoms were obtained from a standardized questionnaire completed by participants at the time of their fourth annual visit to the program. A comparison was made of the prevalence of specific symptoms by sex, age, disease states, and drug use patterns. The most common symptoms reported by women were nocturia (80.4%), swollen feet or ankles (30.5%), cold feet and/or legs (28.6%), and irregular heartbeat (23.2%), whereas men complained most often of nocturia (79.8%), irregular heartbeat (24.8%), cold feet and/or legs (23.6%), and tinnitus (23.1%). Women reported a mean of 3.99 symptoms compared with 3.22 reported by men (P less than .0001). In women their was a statistically significant association for most symptoms in subjects reporting the use of medication compared with a group who did not use medication. In men the use of medication was less highly correlated with reports of symptoms. Nearly 100% of participants reported having at least one disease state. The number of symptoms reported was strongly related to the number of disease states, and after adjusting for diseases, women reported more symptoms than men. The best predictor of symptom prevalence was the number of disease states followed by the number of drugs used and then age.

Age Factors↗
PubMed1986

Structure of a human retroviral sequence related to mouse mammary tumor virus.

Human sequences that are related to the mouse mammary tumor virus (MuMTV) genome were cloned from breast tumor cell DNA. Of 100 recombinants, only 1 hybridized with two different probes from separate regions of the MuMTV genome (gag-pol and long terminal repeat [LTR]). This sequence, NMWV 4, was shown to have a proviruslike structure. Hybridization to digests of normal and tumor cell DNA indicated that NMWV 4 and a few closely related sequences are endogenous to the human genome. The regions that contain homology to the MuMTV LTR were sequenced. Long repeated sequences with the hallmarks of retroviral LTRs were identified. The NMWV 4 LTR contains transcription initiation and termination signals and is flanked by a polypurine tract (5' LTR) and a primer-binding site (3' LTR). The primer-binding site is complementary to tRNA lysine, the primer used by MuMTV and HTLV-III. The polypurine tract is also similar to those of these two retroviruses.

Breast Neoplasms↗
PubMed1986

Cloning of estrogen-regulated messenger RNA sequences from human breast cancer cells.

A complementary DNA library was constructed from RNA of estrogen-stimulated MCF-7 cells and screened for estrogen-regulated sequences. Four different messenger RNA sequences of varying abundance were isolated. Two of the sequences (pNR-3 and pNR-4) were induced approximately 2-fold, while the other two (pNR-1 and pNR-2) were induced at least 8-fold. The induction of both pNR-1 and pNR-2 requires similar physiological concentrations of estradiol and is near maximal at 10(-10) M. An increase in the levels of the RNAs is seen after 30 min of estrogen treatment, but pNR-1 reaches its maximal concentration faster than pNR-2. pNR-1 and pNR-2 were not expressed in all human breast cancer cell lines tested. pNR-1 was expressed and regulated by estrogen in the estrogen receptor-positive cell lines, MCF-7, T-47D, and ZR 75, whereas pNR-2 was not expressed in the T-47D cell line. pNR-1 and pNR-2 were not detected in two estrogen receptor-negative cell lines (BT20 and HBL 100). As the proliferation of the MCF-7, T47D, and ZR 75 cell lines is stimulated by estradiol, pNR-1 may provide a useful marker of hormone-responsive breast cancer.

Base Sequence↗
PubMed1986

Vitamin E effect on symptoms and laboratory values in the elderly.

The effect of vitamin E use on selected medical disorders and laboratory parameters was studied in a large ambulatory elderly population. Information obtained from a standardized questionnaire concerning reports of numerous clinical disorders, such as hypertension, fatigue, and vaginal bleeding, was used to determine whether the use of vitamin E predisposed to those conditions. During a 2-year period, information was available on 369 vitamin E users and 1,861 non-users. No differences were noted in the prevalence of reported clinical disorders between the two groups, except that men using vitamin E complained more often of shortness of breath (p less than .04) and angina (p less than .03). There were no significant differences between vitamin E users and controls in any hematologic parameters studied. After the groups had been adjusted for age and sex differences, only one biochemical parameter, serum glutamic-oxaloacetic transaminase (SGOT) in men, was found to be significantly different in vitamin E users as compared with controls. Use of vitamin E by the participants in this study appeared to have little influence on clinical disorders or hematologic or biochemical parameters.

Aged↗
PubMed1984

Effects of antiestrogens on the estrogen-regulated pS2 RNA and the 52- and 160-kilodalton proteins in MCF7 cells and two tamoxifen-resistant sublines.

The effects of estradiol and antiestrogens on two estrogen-regulated proteins (52 and 160 kDa) and an estrogen-inducible mRNA (pS2) have been measured in the MCF7 human breast cancer cell line and two tamoxifen-resistant sublines. In MCF7 cells, tamoxifen (or nafoxidine) alone does not significantly affect pS2 mRNA levels nor transcription of the pS2 gene but completely antagonizes the ability of estradiol to increase pS2 RNA levels. The estrogen-mediated increase in pS2 mRNA levels resembles that of two estrogen-regulated proteins (52 and 160 kDa) that are released from MCF7 cells into the culture medium. This is distinct from the estrogen-mediated increase in progesterone receptor which is also obtained by tamoxifen treatment. In the two tamoxifen-resistant sublines (R27 and RTx6), tamoxifen does not increase pS2 mRNA levels or 160-kDa protein production but increases the production of the 52-kDa protein. These results show that in these tamoxifen-resistant cells, tamoxifen has become fully estrogenic for one, but not all estrogen-regulated responses.

Breast Neoplasms↗
PubMed1983

Structure and evolution of the Xenopus laevis albumin genes.

The 68K and 74K albumin genes of Xenopus laevis arose by duplication approximately 30 million years ago. Electron microscopic analysis showed that both genes contain 15 coding sequences. The lengths of corresponding coding sequences are almost identical and are extremely similar to those of mammalian albumin genes. A block of four coding sequences, which in mammals codes for one protein domain, is repeated three times. The corresponding introns are usually different in length and have therefore diverged as a result of insertion/deletion events. The extensive homology between these gene sequences is neither confined to nor most extensive in the coding sequences and similar amounts of homologous sequences are found in the flanking DNAs as in the gene regions. Various structures were formed in the 5'-flanking DNA by mutually exclusive pairing of different homology regions. Analysis of the two 74K albumin gene sequences isolated suggests that the X. laevis genome may contain one 68K albumin gene and two very closely related 74K albumin genes.

Animals↗
PubMed1983

Mouse mammary tumour virus related sequences are present in human DNA.

MuMTV-related sequences have been identified in the DNA of human breast cancer cells using the Southern transfer technique and hybridisation with cloned MuMTV DNA under conditions in which partially mismatched sequences form stable hybrids. Hybridisation with cloned fragments of the MuMTV genome showed that the gag-pol region shares the most homology (estimated to be greater than 80%) with the human MuMTV-related sequences, however, DNA fragments partially homologous to the MuMTV LTR, gag ad env regions were also detected. Analysis of several human DNA samples suggests that the majority of the human MuMTV-related sequences are genetically transmitted but additional Eco R1 fragments were detected in the DNA of one out of three breast cancer cell lines, MCF7. These sequences are potential probes for the human MuMTV-related retroviral sequences and will allow their possible role in human breast cancer to be evaluated.

Animals↗
PubMed1983

In contrast to other Xenopus genes the estrogen-inducible vitellogenin genes are expressed when totally methylated.

The methylation-sensitive restriction enzymes Hha I and Hpa II were used to analyze the methylation pattern of four Xenopus laevis genes in DNA of embryos, of erythrocytes, and of untreated and estrogen-treated hepatocytes. Within these four genes all sites tested are fully modified in embryonic DNA. However, the adult beta 1-globin gene is unmethylated in DNA of erythrocytes, where it is expressed, and the 68 kd albumin gene, active only in hepatocytes, is specifically hypomethylated in hepatic DNA. The vitellogenin genes A1 and A2, in hepatocytes simultaneously expressed upon estrogen treatment, are heavily methylated in all adult tissues, irrespective of expression. Our results reveal that specific genes can be actively transcribed even when they are fully methylated and that changes in the methylation pattern are not a general prerequisite for gene activation.

Animals↗
PubMed1982

Estrogen dramatically decreases albumin mRNA levels and albumin synthesis in Xenopus laevis liver.

The levels of albumin mRNA in Xenopus laevis liver were measured at various times after injection of estradiol using two different methods involving hybridization of cloned albumin cDNA to total liver RNA. The absolute levels of albumin mRNA fell by more than 95% during the first 4 days following estrogen treatment, then slowly returned to normal levels over the following 12 days. Albumin synthesis paralleled the albumin mRNA levels during the first 8 days after injection; but, 16 and 32 days after injection, albumin synthesis again decreased while albumin mRNA remained at normal levels. The time courses of the effects of estrogen on albumin and vitellogenin mRNA levels were different. Whereas albumin mRNA levels were minimal 4 days after estradiol injection, vitellogenin mRNA levels were maximal 8 days after injection.

Albumins↗
PubMed1982

Isolation and characterisation of the Xenopus laevis albumin genes: loss of 74K albumin gene sequences by library amplification.

The blood of the frog X.laevis contains 2 albumins of 68,000 and 74,000 daltons which are encoded in the liver by two related mRNAs. When an amplified X.laevis DNA library was screened with cloned albumin cDNA only 68,000 dalton albumin gene sequences were isolated. Hybridisation of the albumin cDNA to Southern-blots of Eco R1 digested X.laevis DNA showed that the sequences present in the recombinants did not account for all the fragments which hybridised on the Southern-blots. This indicated that 74K albumin gene sequences exist but that they are not present in the amplified DNA library. A X.laevis genomic library was therefore constructed and screened for albumin genes without amplification. Both 68K and 74K albumin gene sequences were isolated. Recombinants containing 74K albumin gene sequences grew extremely poorly and this probably explains why the 74K albumin sequences were ot isolated from the amplified library. Characterisation of the cloned DNA indicates that there is one sequence coding for the 68K albumin but two different sequences coding for the 75K albumin.

Animals↗
PubMed1982

Glucocorticoid receptor of X. laevis: possible effect of phosphorylation on hormone binding.

The cytoplasmic glucocorticoid receptor of X. laevis liver has a high affinity for [3H]dexamethasone (Kd, 0.3 x 10(-8) M), and its binding specificity for a variety of steroids is similar to that found for mammalian glucocorticoid receptors. The ability of this receptor to bind [3H]-dexamethasone is stable at 0 degrees C but is rapidly lost at 10 and 20 degrees C. Alkaline phosphatase increases, whereas molybdate and tungstate decrease, the rate at which the binding activity is lost. These results are consistent with the loss of binding activity being due to dephosphorylation of the receptor. Binding of [3H]dexamethasone to the receptor does not alter the rate at which the binding activity is lost but does increase the stabilizing effect of molybdate. 100 mM molybdate lowers the apparent affinity of the receptor for [3H]dexamethasone, suggesting that molybdate can interact with the X. laevis glucocorticoid receptor. Addition of UTP, but not ATP, GTP or CTP, reactivates the receptor-binding activity, which indicates that the receptor may be phosphorylated by a UTP-dependent protein kinase.

Animals↗
PubMed1982

Vitellogenin genes A1 and B1 are linked in the Xenopus laevis genome.

Genomic clones containing the Xenopus laevis vitellogenin gene B1 have been isolated from DNA libraries and characterized by heteroduplex mapping in the electron microscope, restriction endonuclease analysis, and in vitro transcription in a HeLa whole-cell extract. Sequences from the 3'-flanking region of the previously isolated A1 vitellogenin gene were found in the 5'-flanking region of this B1 gene. Thus, the two genes are linked, with 15.5 kilobase pairs of DNA between them. Their length is about 22 kilobase pairs (A1 gene) and 16.5 kilobase pairs (B1 gene) and they have the following arrangement: 5'-A1 gene-spacer-B1 gene-3'. The analysis of heteroduplexes formed between the two genes revealed several regions of homology. Both genes are in the same orientation and, therefore, are transcribed from the same DNA strand. The possible events by which the vitellogenin gene family arose in Xenopus laevis are discussed.

Animals↗
PubMed1982

Prescribed and nonprescribed drug use in an ambulatory elderly population.

Drug usage was studied in an ambulatory geriatric population. Prescription and nonprescription drug use is described for 3,192 participants in a geriatric screening program (the Dunedin Program). Average drug use by these participants was found to be 3.2 medications. The use of both prescription and nonprescription drugs was higher for the women than for the men. In this population, drug use by both men and women increased with age, and this increase was mainly due to an increased use of prescription drugs. Participants were found to be taking numerous multiple-ingredient drug products.

Aged↗