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Biomedical subjects

E Anderson

Publications and source records attributed to E Anderson.

At least 163 records · Page 9Linked to original sources

Variations in steroid receptor status with disease stage in breast cancer.

Oestrogen and progesterone receptor (ER and PgR) distribution in three clinical subgroups of 421 breast carcinomas was analysed. The groups comprised (1) early breast cancer (T1-2a, N0M0; n = 64); (2) untreated advanced fungating cancer (n = 27) and (3) advanced cancer relapsing after endocrine therapy (n = 29). Receptor distribution in each of the subgroups was compared to that of the total population. The advanced fungating group contained no ER--ve/PgR--ve tumours and the distribution was also significantly different from the total population (P less than 0.001 by Chi-squared test). The proportion of tumours in the total population that contained greater than 40 fmol/mg ER was 187/421 (44.4%). There was no significant difference between the early breast cancer group and the total population (P greater than 0.9). However, the proportion of tumours containing ER greater than 40 fmol/mg in the advanced fungating cancer group (16/27, 59.3%) was significantly higher than in the total population (P less than 0.01). This difference may be partially explained by the older age at presentation in this group. In the relapsed after endocrine therapy group only four of 29 (13.8%) contained ER greater than 40 fmol/mg which was significantly different from the total (P less than 0.001). There was a higher proportion of early breast cancers containing PgR greater than 40 fmol/mg than in the total population (P less than 0.001). There was no significant difference between PgR distribution in the advanced fungating and relapsed groups compared to the total population. The data suggest that patients presenting with advanced fungating cancer are more likely to respond to endocrine therapy than the population as a whole, and that in breast cancer that has relapsed following endocrine therapy receptor levels decrease with progression of the disease.

Aged↗

Androgen receptors in colorectal adenomas.

To evaluate the potential effect of androgens on the development and growth of human colorectal adenomas, the prevalence and concentration of cytosolic androgen receptors (AR) were analysed in 26 adenomas and 19 samples of normal colonic mucosa by a hybrid ligand receptor-binding assay. AR were detected in 7 of the adenomas (26.9%), and in 6 of the normal mucosa samples (31.6%). In the adenomas, AR levels demonstrated were low, ranging from 6 to 31 fmol/mg cytosol protein, and dissociation constants (Kds) ranged from 0.17-2.7 X 10(-9) M. Of 13 adenomas excised from men, 6 (46%) had positive receptor activity, whereas only 1 of 13 (7.7%) from women was positive (P = 0.03, Fisher's exact test). There was no correlation between AR titre and patient age, or between adenoma size and histological type or degree of dysplasia. In normal mucosa, AR levels ranged from 7 to 33 fmol/mg and Kds ranges from 0.24-3.1 X 10(-9) M. There was no significant difference between either AR prevalence or levels in the adenomas and normal mucosa. The sex difference was exclusive to the adenoma. Endogenous androgen may play a role in adenoma development early in the promotional process.

Adenoma↗

The development of mouse oocyte cortical reaction competence is accompanied by major changes in cortical vesicles and not cortical granule depth.

The basis for the incompetence of the cortical reaction in germinal vesicle stage (GV) mouse oocytes was studied by evaluating cortical granules (CGs) and vesicles in GV and mature oocyte cortices. Dark and light CGs had a similar mean distance of 0.4-0.6 micron from the plasma membrane for GV and mature cortices. The cortex of mature oocytes had a large population of membrane-bounded, 0.1-1.0 micron (diameter) vesicles. More than three times as many vesicles were observed in the CG domains of mature oocytes as were observed in GV oocytes. This lack of cortical vesicles (with their potential to store calcium) and not CG depth may account for cortical reaction incompetence in GV oocytes.

Calcium↗

Quantitative studies of changes in cortical granule number and distribution in the mouse oocyte during meiotic maturation.

Cortical granules (CGs) undergo a substantial change in distribution in the mouse oocyte cortex during meiotic maturation. In order to determine the mechanism of their change in distribution near the time of ovulation, CG density, total number per oocyte, and domain areas were quantitated. CGs were visualized microscopically by Lens culinaris agglutinin-biotin and Texas red-strepavidin fluorescence as well as by electron microscopy. Immature germinal vesicle stage (GV) oocytes from adult mice had a continuous cortical localization with some interior granules. Mature oocytes had an asymmetric cortical distribution with a CG-free domain, overlying the meiosis II metaphase spindle, occupying 40% of the cortex. The mean CG densities of the granule-occupied cortex of mature oocytes and the entire cortex of GV oocytes were 43 and 34 CGs/100 micron 2, respectively. The mean total numbers of CGs/oocyte were 4127 (mature) and 7440 (GV), and staining was absent in fertilized oocytes with two pronuclei. Calcium ionophore (A23187)-activated mature oocytes had a mean total number of 1235 CGs, some of which may have been in the process of exocytosis. The first polar body had few CGs, and thus was unlikely to account for the difference in CG number between GV and mature oocytes. The smaller total number and higher density of CGs in mature mouse oocytes suggests that both exocytosis and redistribution are plausible mechanisms for the development of the CG-free domain. Prefertilization exocytosis could account for the locus of sperm penetration which others have reported to occur in the hemisphere opposite the meiotic spindle in the mouse.

Animals↗

A hybrid ligand method for androgen receptor measurement.

Existing techniques for androgen receptor (AR) assay are complicated by cross-reactivity of ligand binding affinities that can lead to incorrect estimation of receptor concentration. Two most frequently used ligands are [3H]dihydrotestosterone [( 3H]DHT) and [3H]methyltrienolone [( 3H]R1881), which in addition to binding to AR also bind to sex hormone binding globulin (SHBG; Kd = 1.5 nM) and progesterone receptors (PgR; Human Kd = 1 nM, rat Kd = 6 nM) respectively. Triamcinolone acetonide (TMA) is commonly used to block binding of [3H]R1881 to PgR, however at high concentrations TMA itself will bind AR (Kd = 7 microM). We have developed a hybrid ligand method for the measurement of AR in the presence of SHBG and PgR. This method used [3H]R1881 as the high specific activity labelled tracer and DHT as the unlabelled competitor of specific AR binding. Using this assay, 20% of human colorectal carcinomas were found to contain AR.

Animals↗

An in vitro study of the effects of androgens on the cytoskeleton of ovarian granulosa cells with special reference to actin.

Ovarian granulosa cells from small antral follicles from immature rats were cultured in a serum-free medium for 1-6 days with or without the presence of 10(-5) M dehydroepiandrosterone (DHEA) or 10(-5) M-androstenedione (delta 4-A). Control cultures reveal that the cells are flattened and contain many filamentous bundles organized as stress fibers, numerous scattered cytoplasmic actin filaments, microtubules and vimentin. Alpha actinin and myosin were shown by immunocytochemistry to have a punctate pattern along the stress fibers. For the most part, cells exposed to androgens did not flatten; however, they assumed a varied shape and contained fewer stress fibers and actin filaments. Many of these cells did not develop stress fibers and those that did develop were fewer in number and displayed--actinin and myosin in a punctate pattern. Microtubules and vimentin filaments remained unaltered when compared to controls. It is believed that the deficiency of actin filaments, coupled with certain other degenerative changes which express themselves in other cellular compartments, leads to an early atresia of the granulosa cell cultured in high concentrations of androgens.

Actinin↗

Relationships between polyamine, deoxyribonucleic acid and oestrogen receptor binding site concentrations in human breast tumours.

Concentrations of polyamines, DNA and oestrogen receptor (ER) binding sites have been estimated in 23 malignant and 2 benign breast tumours. Polyamine and DNA concentrations, expressed per unit wet weight of tissue, were significantly higher in ER-poor (less than 10 fmol/mg cytosol protein) than in ER-rich tumours. Spermidine/spermine ratios were similar in ER-poor and ER-rich tumours. There was a relationship between polyamine and DNA levels and when polyamine concentrations were expressed per unit weight of DNA those in ER-poor tumours did not differ from those in ER-rich tumours. Possible reasons for these findings are discussed.

Breast Neoplasms↗

Corneal re-graft: indications and outcome.

The results of 62 repeat penetrating keratoplasties (41 eyes) over a 10-year period are presented. The common indications for the primary graft include herpes simplex keratitis, pseudophakic bullous keratopathy, aphakic bullous keratopathy, Fuch's endothelial dystrophy, and chronic ulceration. All cases of pseudophakic bullous keratopathy had the iris-clip type of intraocular lens. Graft failure was attributed to rejection, endothelial failure, recurrent ulceration, herpes simplex keratitis, melting, trauma, and recurrent dystrophy. At the end of the study period 28 grafts (68%) were clear and 13 (32%) were opaque. Visual improvement occurred in 28 eyes (68%), deterioration in four (10%), and six (15%) remained unchanged (visual result was not available in three eyes). These data are encouraging in terms of visual outcome and graft clarity in cases of repeat penetrating keratoplasty. Comparison is made between the primary indications and outcome of these re-grafts and eyes requiring only one graft. Initial indications for grafting in both groups were similar, other than keratoconus, which was a significantly more common indication in eyes that required only one graft. Final visual results were better in those eyes undergoing only one graft, compared with those that required multiple surgery.

Aged↗

Effects of danazol on incidence of progesterone and oestrogen receptors in benign breast disease.

Results from a continuing clinical trial in benign breast disease indicate that danazol may induce progesterone receptors and that this effect persists after treatment. In women given danazol the number of biopsy specimens that were positive for progesterone receptors rose from 14 out of 31 before treatment to 23 out of 30 at the end of six months' treatment and remained raised at 21 out of 31 six months later. The number of biopsy specimens that were positive for oestrogen receptors rose transiently from eight out of 31 to 12 out of 30 and then fell to six out of 31. A satisfactory clinical response was achieved in 26 of the 31 patients but was maintained in only 11 six months or more after the end of treatment. It was only in this group that a significant and long-standing increase in progesterone receptors was observed. These findings suggest that in some women with benign breast disease who have been treated with danazol changes occur that may have long term benefit.

Adult↗

Characteristics of menopausal women seeking assistance.

Using a questionnaire approach, we have determined the demographic, social, and clinical characteristics of the first 100 participants attending our menopause clinic. Of the respondents, 79% reported onset of significant physical symptoms and 63% significant emotional symptoms during the menopause. Among the participants, 65% had varying degrees of depression as determined by the Zung self-rating depression scale. This seemed to be more prevalent in patients with previous pelvic operations. Only half the women were on a regimen of estrogen replacement therapy, and most were receiving estrogen in an unopposed fashion. In our menopause clinic, more than half the women were over their ideal body weight, which is in contrast to the popular misconception that only thin women develop menopausal symptoms. Data from our patients suggest the need for multidisciplinary menopause clinics to adequately address the physical and emotional problems of menopausal women.

Adult↗

Androgen-induced changes in rat ovarian granulosa cells in vitro.

Ovarian granulosa cells collected from small antral follicles from immature rats were cultured in McCoy's 5A medium, for 1-6 days in the presence of delta 4-androstenedione, testosterone, dihydrotestosterone, and dehydroepiandrosterone (10(-5) M and 10(-7) M). Granulosa cells examined by electron microscopy demonstrated many lipid droplets, mitochondria with tubular cristae and profiles of smooth endoplasmic reticulum, all suggestive of active metabolism in the cell. Cells cultured in androstenedione, testosterone, dihydrotestosterone and dehydroepiandrosterone produced estrogen and progesterone as measured by radioimmunoassay. By day 4, cells cultured in androgen had almost completely degenerated. The control cells acquired none of the aforementioned characteristics and survived up to beyond 6 days, at which time the experiments were terminated. This study supports the hypothesis that high concentrations of androgens in cultured granulosa cells contribute to their degeneration through altered structure, which is associated with functional change.

Androgens↗

Termination of paroxysmal supraventricular tachycardia by digital rectal massage.

A 71-year-old woman with an episode of paroxysmal supraventricular tachycardia (PSVT) complicated by angina pectoris and hypotension had her arrhythmia abruptly terminated by digital rectal massage (DRM) after other vagotonic maneuvers had failed. DRM termination of PSVT has not been heretofore reported. In treating PSVT by physical vagotonic maneuvers, DRM may be preferable to other techniques because of the decreased likelihood of complications noted with other such maneuvers.

Aged↗

Oestrogen and progesterone receptor distribution in the cancerous breast.

To test the hypothesis that steroid hormone receptor expression is particularly pronounced in breast tumours when compared with non-neoplastic tissue, mastectomy samples were divided into 16 sectors. Multifocal tumours, of varying receptor phenotype were found in 4 patients and in addition different regions of large tumours also showed varying receptor contents. Remaining samples were found to consist of normal tissue, with fat, connective tissue and some benign breast disease. In the 9 patients with oestrogen receptor positive tumours (ER), ER content was invariably much greater in the tumours than in the remainder of the breast. Progesterone receptor (PR) content was not closely related to ER, and was lowest in the poorly differentiated tumours. This relation to differentiation was not seen in ER. The data support the view that ER concentration in ER positive tumours may reflect the transformed nature of neoplastic tissue.

Adult↗

Amniotic fluid index measurements during pregnancy.

Amniotic fluid volume assessment has become an important part of antepartum fetal surveillance. The amniotic fluid index (AFI), or four-quadrant technique, has been suggested for this purpose. While previous reports have outlined this technique and correlated the results with pregnancy outcome, none have reviewed the changes in AFI throughout pregnancy. We studied AFI changes from 11 through 43 weeks' gestation. As part of the entry criteria, only patients with good dates were evaluated. The AFI was determined by the summation of the vertical diameter of the largest pocket in each of the four quadrants. All amniotic fluid studies were conducted using real-time linear array B-scan. During the study period, 197 patients with good dates confirmed clinically and sonographically underwent 262 AFI assessments. From 11 to 26 weeks the AFI rose progressively. Thereafter until term, the AFI remained approximately 16.2 +/- 5.3 cm. After 38 weeks the AFI appeared to gradually decline. Data obtained from this study population corroborate previously defined normal amniotic fluid volumes. These results also suggest that serial measurements of the AFI may be an effective means of assessing fetal status throughout pregnancy.

Amniotic Fluid↗

Effects of age on nocturnal activity rhythms in rats.

Running wheel data were analyzed to examine changes in nocturnal activity rhythms with age in Long Evans rats. Five male animals 30 days of age, the same five rats at 70 days of age, and five older animals at 13 months were given free access to activity wheels in a colony room maintained on an LD12:12 cycle. All subjects demonstrated enhancement of activity during the dark phase of the 24-h cycle. A statistically significant decrease in activity of old rats in comparison with weanling rats was observed only in the dark phase (P less than .0001). The age difference was marginal in the light phase compared to that in the dark phase. However, a marked increase in percentage of time spent active in the light phase was observed in the old animals. This may be a combined result of visual hyposensitivity and insomnia that became apparent with increasing age. Mechanisms that control initiation and maintenance of locomotor behavior may become less responsive with age to periodic alternative of light and dark phases.

Aging↗