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Biomedical subjects

F E May

Publications and source records attributed to F E May.

At least 55 records · Page 3Linked to original sources

Modulation of the proliferative response of breast cancer cells to growth factors by oestrogen.

A number of growth factors have been implicated in the control of the proliferation of breast cancer cells and some have been reported to mediate the proliferative effects of oestradiol. MCF-7 cells were treated with growth factors in the presence and absence of oestradiol. Oestradiol increased the response of cells to the proliferative effects of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha) and basic fibroblast growth factor (bFGF). Platelet derived growth factor (PDGF) and cathepsin D had no effect in the presence or absence of oestradiol while TGF-beta slightly reduced the stimulation by oestradiol. In the absence of oestradiol, there was little effect of combinations of growth factors although the effects of bFGF and IGF-I were additive. In the presence of oestradiol, the effects of bFGF and TGF-alpha were additive whereas bFGF acted as an IGF-I antagonist. Overall, bFGF had the greatest effect on cell proliferation although this was less marked than the previously described effect of the IGFs and insulin. The effects of oestradiol on the sensitivity of cells to the proliferative effects of bFGF did not appear to result from regulation of bFGF receptor expression.

Breast Neoplasms↗

Nocturia: a risk factor for falls in the elderly.

OBJECTIVE: To determine if nocturia is a risk factor for reported falls and bone fractures in older persons. DESIGN: Cross-sectional study comparing falls in men and women with and without nocturia. SETTING: Longitudinal health screening program of ambulatory elderly participants. PARTICIPANTS: Participants included 988 (65.5%) women and 520 (34.5%) men who had completed their tenth annual visit to the program. MAIN OUTCOME MEASURES: Reported falls in the past year and reported bone fractures in the past 5 years. RESULTS: Participants who reported nocturia at least twice during the night were at significantly greater risk to report falls (Odds Ratio = 1.84; 95% CI = 1.05-3.22), and the risk increased in subjects reporting more than three nocturia events (Odds Ratio = 2.15; 95% CI = 1.04-4.44). The significant increase in falls reported by nocturia participants did not result in an increase in reported bone fractures in the past 5 years (P < 0.4360). CONCLUSIONS: Nocturia is an important risk factor for falls in ambulatory elderly persons. Preventive measures should be taken to decrease nocturia events and to decrease the risk of falling during these nocturia events.

Accidental Falls↗

Lack of association of nonsteroidal anti-inflammatory drug use and cognitive decline in the elderly.

Folstein Mini-Mental State Examination (MMSE) scores obtained in an ambulatory elderly population were used to examine the effect of nonsteroidal anti-inflammatory drug (NSAID) use on cognitive performance. There were 1,310 participants who met the inclusion criteria for the study, of whom 873 (66.6%) were women and 437 (33.3%) were men. There were no differences in mean MMSE scores or in the five dimensions of cognitive function measured by the MMSE for subjects reporting NSAIDs or aspirin use.

Aged↗

Expression of the antimetastatic gene nm23 in human breast cancer: an association with good prognosis.

The nm23 gene was identified in murine melanoma cells, in which its expression is associated with the cells' metastatic potential. Expression of nm23 has been detected in human breast tumors by means of hybridization and immunocytochemistry. We measured nm23 mRNA in 71 patients with primary breast cancer and found variable levels of nm23 expression. The nm23 gene was expressed at higher levels in well-differentiated tumors (P less than .02). There was a significant inverse relationship between nm23 expression and nodal status (P less than .02). Expression of nm23 was positively associated with longer disease-free survival and overall survival, and the relationships were significant (P less than .002 and P less than .003, respectively). This study showed that nm23 expression in human breast cancer was associated with good prognosis and a lack of lymph node metastasis and suggests that the nm23 gene product may play an important role in suppressing the metastatic phenotype.

Adult↗

Antipeptide antibodies against the pNR-2 oestrogen-regulated protein of human breast cancer cells and detection of pNR-2 expression in normal tissues by immunohistochemistry.

Five peptides, corresponding to regions of the predicted protein sequence of the oestrogen-regulated pNR-2 protein which is expressed in oestrogen-responsive human breast cancer cells, were synthesized. Two peptides were immunogenic in rabbits and antisera against one peptide reacted with the pNR-2 protein in sections of formalin-fixed, paraffin-embedded breast tumour. There was a significant correlation between the extent of pNR-2 protein expression detected by immunohistochemistry and pNR-2 mRNA levels determined by hybridization with a cDNA probe in a series of primary breast tumours. pNR-2 expression was assessed immunohistochemically in a panel of normal tissues. Expression was detected in normal breast, small intestine, and stomach (body and antrum).

Amino Acid Sequence↗

Enteroviruses and idiopathic dilated cardiomyopathy.

Previous studies have suggested that some cases of idiopathic dilated cardiomyopathy (IDC) are due to persistent viral infection following an episode of viral myocarditis. Viral RNA sequences have recently been detected in material from patients with IDC using molecular biological techniques. We tested 40 samples from recipients' hearts explanted at cardiac transplantation for the presence of enteroviral RNA sequences, using a Northern blotting technique. Material from 19 cases of IDC and 21 cases of non-cardiomyopathic cardiac failure was examined together with Coxsackie-virus-infected neonatal mouse heart as a positive control and non-infected adult mouse heart as a negative control. A sharp band of viral RNA was detected in the positive control sample. No hybridization signal attributable to viral RNA was obtained for the negative control or for any of the test samples. We conclude that the role of enteroviruses in the pathogenesis of cardiomyopathy is not fully established and that further study is warranted.

Adult↗

Effect of psyllium hydrophilic mucilloid on serum cholesterol in the elderly.

The effect of psyllium hydrophilic mucilloid (PHM) when used as a laxative and/or stool softener on serum cholesterol concentrations was examined in 176 ambulatory elderly participants attending a health screening program. The change in one-year serum cholesterol concentration in subjects using PHM was compared with the change in cholesterol in 741 participants who did not report the use of PHM. Serum cholesterol concentration decreased by 0.073 mmol/liter (2.82 mg/dl) in the treatment group compared with a decrease of 0.036 mmol/liter (1.39 mg/dl) in the control group. After adjusting for confounding factors, excluding psyllium dose, by using a multiple regression model there was no significant difference in the change in serum cholesterol concentration (P = 0.935). PHM dosage information was available for 158 participants. After adjusting for baseline serum cholesterol and confounding factors using multiple regression analysis, it was found that the dose of PHM administered was significantly correlated with the change in serum cholesterol (P = 0.0120). For every 1-g increase in daily PHM dose there was a 0.022 mmol/liter (0.84 mg/dl) decrease in serum cholesterol concentration.

Aged↗

A longitudinal evaluation of drug use in an ambulatory elderly population.

Participants in a geriatric health screening program were studied longitudinally to determine the patterns of drug use over a 10 year period. There were 314 (34.0%) men and 610 (66.0%) women who completed 10 yearly health screening evaluations. The mean number of prescribed and non-prescribed drugs used per participant increased from 2.90 in 1978-79 to 4.08 in 1987-88 (p less than 0.0001). There was no significant difference between men and women in the rate of increased drug use. There was no significant increase in the mean number of drug ingredients per participant used over the 10 year period. The most frequently reported therapeutic categories for 1978-79 were antihypertensives, analgesic-antipyretics, antirheumatics, multiple vitamins, cathartics and vitamin E, which represented 10.2, 7.2, 6.5, 4.9, 4.8 and 3.8% of all categories used. There was a decline in all of these categories between interval 1 and 10. Increased use of drugs, particularly prescribed medications, by the elderly population may present problems of adverse drug reactions, drug interactions and medication compliance in the future. Changing patterns of drug use may have resulted, in part, from introduction of new therapeutic classes and from new treatment concepts over the 10 year study period.

Aged↗

pNR-2/pS2 immunohistochemical staining in breast cancer: correlation with prognostic factors and endocrine response.

Expression of the oestrogen-regulated pNR-2/pS2 protein has been studied in paraffin sections of a series of 172 primary breast cancers using an immunohistochemical technique. Positive staining of tumour cells was found in 117 tumours (68%): most of these tumours contained only a small proportion of positive cells. pNR-2 immunohistochemical staining correlated positively and significantly with the presence of oestrogen receptor. Mean percentages of pNR-2 positive cells were lower in tumours from postmenopausal women. Smaller, better differentiated tumours were significantly more likely to stain positively for pNR-2. The percentages of pNR-2 positive tumour cells in primary tumours and synchronously excised lymph node metastases were very similar. pNR-2 expression showed an unexpected positive association with lymph node metastasis. We were unable to find any significant association between pNR-2 immunohistochemical staining and either time to relapse or overall survival. There was a significant association between pNR-2 expression in primary tumours and response to endocrine therapy on relapse: positive pNR-2 immunohistochemical staining in primary tumours is predictive of response to hormonal therapy on relapse.

Aminoglutethimide↗

Expression of the pNR-2/pS2 protein in diverse human epithelial tumours.

The pNR-2/pS2 protein is regulated by oestrogens in breast cancer cell lines. This report describes a systematic survey of pNR-2/pS2 expression in a number of common epithelial tumours. Expression was evaluated immunohistochemically in an archival series using antisera raised against the C-terminus of the pNR-2/pS2 protein. Expression of pNR-2/pS2 by malignant epithelial tumours was widespread. Intense immunohistochemical staining was found in tumour cells in a proportion of pancreatic (6/8), large intestinal (7/12), gastric (9/16) and endometrial (4/12) carcinomas. Positive staining for the pNR-2/pS2 protein was also found in both benign and malignant ovarian epithelial tumours and was very significantly associated with mucinous differentiation (P less than 0.00001). Small numbers of carcinomas of bladder (2/10) and prostate (2/7) showed less intense staining and single examples of cervical carcinoma (1/7) and lung carcinoma (1/19) stained positively. None of the renal carcinomas (0/16) examined stained positively. Positive staining showed no correlation with gender. Although there are reports of oestrogen receptor expression in most of the tumour types considered, the possibility of other regulatory influences must also be considered. The pNR-2/pS2 protein may well have a more general role in human epithelial neoplasia than hitherto realised.

Estrogens↗

Changing patterns of therapeutic agents in the elderly: a ten-year overview.

Drug use patterns in a large ambulatory elderly population were studied cross-sectionally over a 10-year period. There were 24192 drug histories obtained on 4509 individuals during the period from 1 August 1978 to 31 July 1988. The average number of drugs used per person increased from 3.22 in 1978-9 to 3.94 in 1987-8. Prescribed drug use increased by 0.52 per person compared with an increase of 0.21 for nonprescribed medication. Analysis of two mutually exclusive groups of participants from 1978-9 and 1987-8 revealed a significant (p less than 0.0001) increase in the use of nonprescribed medication but no significant increase in the use of prescribed medication after adjusting for age and sex effects. The four most frequently used therapeutic classes of drugs in 1978-9 as a percentage of all drugs used were antihypertensives (10.8%), analgesic-antipyretics (6.4%), antirheumatic (6.4%), and cathartics (5.4%) compared with the antihypertensives (9.5%), analgesic-antipyretics (5.9%), anticoagulants (5.5%), and antirheumatic (4.6%) for the 1987-8 period.

Age Factors↗

Correlates of cognitive dysfunction in an ambulatory elderly population.

Mini-Mental State Examination (MMSE) scores were studied in an ambulatory elderly population to identify correlates with self-reported signs, symptoms, diseases, drugs and laboratory values. A total of 1,264 subjects were studied including 844 women and 420 men. In this study, 5.0% of men and 5.3% of women scored less than 24 on the MMSE. A linear-regression model revealed eleven factors of significance in predicting scores on the MMSE. The most important predictors were age (p less than 0.0001), self-reported memory loss (p less than 0.0001), complaints of swollen feet or ankles (p less than 0.0010), the total number of diseases reported (0.0006) and the serum lactate dehydrogenase concentration (p less than 0.0098). Results suggest that cognitive function in the elderly is not related to the general level of health or consistently affected by specific disease states.

Aged↗

Public values and beliefs toward nursing as a career.

The purpose of this study was to compare the perceptions of "ideal career" and "nursing as a career." The goal was to provide information for development of innovative recruitment strategies. The sample of 1,116 included college freshmen, students in grades 6 through 12, parents, school nurses, teachers, and counselors. Data were analyzed by t test and analysis of variance to determine differences in attitudes between "ideal career" and "nursing as a career." Similar perceptions for both were opportunities for employment, application of intellectual abilities, caring for people, and an opportunity for academic and scholastic achievement. An "ideal career" was seen as more financially rewarding, more respected, and more powerful than nursing, and as providing more opportunities for leadership, for making decisions, for obtaining and applying knowledge, and for working in a safe environment. Recommendations include strategies to improve recruitment and retention of nurses.

Adolescent↗

Correlates of Beck Depression Inventory scores in an ambulatory elderly population: symptoms, diseases, laboratory values, and medications.

BACKGROUND: Depression is one of the most important psychiatric disorders of older people. Between 1% and 5% of elderly persons who live in the community have major depression. Depressed elderly people are thought to be more likely to complain of symptoms such as headache, constipation, and pain than of disordered mood. The purpose of this study was to determine whether certain symptoms, diseases, or drugs used by older people correlate with scores on the Beck Depression Inventory. METHODS: Beck Depression Inventory scores were obtained in an ambulatory elderly population to identify correlates with self-reported signs, symptoms, diseases, drugs, and laboratory values. A total of 1048 participants were studied, including 712 women and 336 men. RESULTS: In this study, 13.7% of the men and 20.7% of the women had scores suggesting possible depression. A linear regression model revealed eight factors of significance in predicting scores on the Beck Depression Inventory. The most important predictors were the total number of symptoms reported by the patient (P less than .0001), and subjective complaints of memory loss (P less than .0003) and of pain in the abdomen (P less than .0004). CONCLUSIONS: Clinically, the results of this study suggest that depression is underdiagnosed in older patients and that multiple somatic symptoms are the best indicator of depression in this population.

Abdominal Pain↗

Role of insulin-like growth factors and the type I insulin-like growth factor receptor in the estrogen-stimulated proliferation of human breast cancer cells.

Estrogen sensitizes the MCF-7 estrogen-responsive breast cancer cell line to the mitogenic effect of insulin and the insulin-like growth factors (IGFs). This sensitization is specific for estrogen and occurs at physiological concentrations of estradiol. Dose-response experiments with insulin, IGF-I, and IGF-II suggested that the sensitization is mediated through the type I IGF receptor. Binding experiments with 125I-IGF-I and hybridization of a type I IGF receptor probe to RNA showed that the levels of the type I IGF receptor and its mRNA are increased 7- and 6.5-fold, respectively, by estradiol. IGF-I and estradiol had similar synergistic effects on other estrogen-responsive breast cancer cell lines, but IGF-I alone increased the proliferation of the MDA MB-231 cell line which is not responsive to estrogens. These experiments suggest that an important mechanism by which estrogens stimulate the proliferation of hormone-dependent breast cancer cells involves sensitization to the proliferative effects of IGFs and that this may involve regulation of the type I IGF receptor.

Breast Neoplasms↗

Prognostic significance of the estrogen-regulated protein, cathepsin D, in breast cancer. An immunohistochemical study.

Expression of the estrogen-regulated lysosomal protease, cathepsin D, was studied in a series of 94 breast cancers using an immunohistochemical technique. Granular staining of tumor cell cytoplasm was detected in 62 cases. Positive staining was associated with a significant increase in overall time to relapse and when survival was analyzed in terms of intensity of cathepsin D staining there was a significant trend for both increased time to relapse and increased length of survival. The presence of estrogen receptor was associated with positive cathepsin D immunostaining, and in the subgroup of estrogen receptor-positive tumors cathepsin D staining was associated with significantly prolonged survival; this was not the case for estrogen receptor-negative tumors. Positive cathepsin D immunostaining was associated with significant prognostic advantage in patients with confirmed lymph node metastasis but not in node-negative patients. It is suggested that cathepsin D expression reflects the functional integrity of the estrogen response pathway. Cathepsin D may prove a clinically useful adjunct to assessment of estrogen receptor status.

Adult↗