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Biomedical subjects

E J Thomas

Publications and source records attributed to E J Thomas.

At least 19 recordsLinked to original sources
PubMed1995

Retinoic acid receptors and retinoid binding proteins in endometrial adenocarcinoma: differential expression of cellular retinoid binding proteins in endometrioid tumours.

Retinoic acid is apparently required for the normal differentiation of reproductive epithelium. Cellular abnormalities in retinoid homeostasis could be a factor in the development of endometrial malignancy. We have thus investigated the expression of nuclear retinoic acid receptors (RARs and RXRs) and cellular binding proteins for retinol (CRBP) and retinoic acid (CRABP) in endometrial adenocarcinoma of the endometrioid histological subtype. Ten grade I, II grade 2 and 10 grade 3 tumour samples, as well as 4 samples of severe atypical precancerous endometrial hyperplasia, were studied. No significant difference in expression of RAR-beta was detected in tumour samples compared with normal epithelial cells. RAR-gamma was significantly elevated in grade 1 and 2 carcinomas, but this may be due to greater stromal cell involvement in these lower grade tumours. There was significant elevation of CRBP I mRNA in tumour samples. Furthermore, although undetectable in normal endometrial epithelium, CRABP I was expressed in 3/II grade 2 and 9/10 grade 3 carcinomas, with expression being significantly higher where the primary tumour had invaded more than 50% of the total myometrial thickness. Analysis of 2 epithelial-like endometrial adenocarcinoma cell lines supported the idea that CRABP I expression is characteristic of poorly differentiated endometrial adenocarcinoma. Our data suggest that alterations in mechanisms of retinoid homeostasis are a feature of endometrial adenocarcinoma and may contribute to the severity of disease.

Adenocarcinoma↗
PubMed1995

Endometriosis, 1995--confusion or sense?

OBJECTIVE: To review current understanding of endometriosis. METHOD: A review of etiology, pathogenesis, relationship with infertility, medical and surgical treatment. RESULTS: It is likely that endometriosis occurs in most women at some stage in their reproductive years. Exposure to menstruation and estrogen are important etiologically. Current evidence suggests that implantation of menstrual endometrium is the commonest mechanism of pathogenesis. Clinical symptoms and signs are important in the diagnosis while laparoscopy remains the prime diagnostic technique. Treatment is not indicated for infertility but is for symptoms. Danazol and progestogens represent the best first-line therapy although gonadotropin-releasing hormone agonists are appropriate if economically justifiable. Both open and laparoscopic surgery are important especially in reconstructive work. The value of laser ablation in the treatment of infertility is unknown but it is effective in pain. The disease should be regarded as a recurrent problem and treatment strategies designed appropriately. CONCLUSION: Endometriosis still represents an intellectual and therapeutic challenge but successful treatment is possible especially if it is individualized for each patient.

Adult↗
PubMed1995

Effects of the pure anti-oestrogen ICI 182780 on oestrogen receptors, progesterone receptors and Ki67 antigen in human endometrium in vivo.

The new steroidal pure anti-oestrogen ICI 182780 was studied for the first time in pre-menopausal women. A total of 30 patients requiring hysterectomy for benign gynaecological disease were randomized to ICI 182780, 12 mg/day i.m. (n = 19) or no treatment (n = 11) for 7 days prior to surgery. Immunohistochemical measurements were made in the snap-frozen, resected endometrium for oestrogen receptors (ER), progesterone receptors (PgR) and Ki67, a nuclear antigen whose expression is closely related to proliferation. Five control patients ovulated prior to surgery and, as expected, the secretory endometria had lower Ki67 antigen concentrations than endometria had lower proliferative phase. The endometria from patients treated with ICI 182780 had reduced Ki67 compared with controls. This demonstration of reduced proliferative activity indicates that the pharmacological effectiveness of the treatment was maintained despite increased plasma oestradiol concentrations. In contrast to results from rodents, ICI 182780 did not markedly reduce ER expression, although there was significantly lower ER in the myometrial cells of the treated group. The lack of effect on PgR shows a dissociation between the drug's effect on this oestrogen-dependent protein and its effects on proliferation.

Adult↗
PubMed1995

Variations in concentrations of the major endometrial secretory proteins (placental protein 14 and insulin-like growth factor binding protein-1) in assisted conception regimes.

We have previously shown that placental protein 14 (PP14) concentrations were depressed in two pregnancies that followed down-regulation of the anterior pituitary and exogenous hormone support prior to a frozen-thawed embryo transfer. We now report on a more comprehensive series of pregnancies following this form of treatment, in-vitro fertilization (IVF) and natural cycle frozen-thawed embryo transfer. Serum specimens were analysed for PP14 and insulin-like growth factor binding protein-1 12 days after embryo transfer and at 7 weeks gestation. At 12 days after embryo transfer, the mean serum PP14 concentrations in the IVF and natural cycle were significantly higher in those who conceived than those who did not (82 versus 23 and 107 versus 39 micrograms/l respectively, P < 0.001). Although the mean PP14 concentration in the hormone-supported pregnant patients was higher than in the non-pregnant patients, this had not reached statistical significance 12 days after embryo transfer (49 versus 31 micrograms/l). By 7 weeks gestation the PP14 concentrations in the hormone-supported pregnant patients were significantly higher than in the non-pregnant patients (152 versus 31 micrograms/l, P < 0.001). However, the PP14 concentrations for hormone-supported pregnant patients were significantly lower (P < 0.001) than those for pregnant IVF or natural cycle patients at 7 weeks gestation (152, 777 and 660 micrograms/l respectively). The PP14 concentrations in the pregnant patients, although lower than those in IVF and natural cycle pregnancies, were higher than those previously reported in ovarian failure and Turner's syndrome ovum donation cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Carrier Proteins↗
PubMed1995

Variation in the expression of cellular retinoid binding proteins in human endometrium throughout the menstrual cycle.

Human endometrium is a glandular epithelial tissue with a substantial underlying stroma. Under the influence of ovarian steroids, endometrium undergoes a cyclical pattern of proliferation followed by secretory differentiation. Since retinoids promote the differentiation of many epithelia to secretory phenotypes they may be involved in controlling the secretory differentiation of human endometrial epithelium. Cytosolic binding proteins for retinol (cellular retinol binding protein) and retinoic acid (cellular retinoic acid binding protein) may play an important part in regulating the availability of retinoic acid to its nuclear receptors and we have therefore asked whether expression of mRNA for these proteins varies in relation to endometrial differentiation. In a series of 54 endometrial biopsies, both endometrial epithelial and stromal cells expressed mRNA for cellular retinol binding protein type I at a constant level throughout the menstrual cycle. Cellular retinoic acid binding protein type II was also expressed but the level of expression varied dramatically, being elevated in the proliferative phase and depressed during the secretory phase of the menstrual cycle in both epithelial and stromal cells. These data suggest that cytosolic binding proteins modulate the supply of retinoic acid to the nuclei of endometrial cells during the menstrual cycle and that retinoic acid is involved in the cyclical control of endometrial differentiation.

Amino Acid Sequence↗
PubMed1995

Interactions between oestradiol and epidermal growth factor in endometrial stromal proliferation and differentiation.

The relationship between oestradiol and epidermal growth factor (EGF) in the control of endometrial proliferation and differentiation in cultures of human endometrial stromal cells was investigated. Oestradiol at a concentration of 10 nmol l-1 increased the incorporation of both [3H]thymidine and [3H]leucine but the differences were significantly different from control only for [3H]leucine incorporation. Concentrations of 0.16, 1.6 and 16 nmol EGF l-1 significantly increased both [3H]thymidine (P < 0.01) and [3H]leucine incorporation (P < 0.01). The pure steroidal antioestrogen, ICI 182,780, inhibited any increase in [3H]thymidine and [3H]leucine incorporation stimulated by oestradiol in endometrial stroma. The monoclonal antibody, ICR 16, directed against the EGF receptor did not inhibit the oestradiol action in stromal cells, indicating that, in this model system, oestradiol does not act by inducing synthesis or release of EGF. However, ICI 182,780 potently inhibited the incorporation of [3H]thymidine stimulated by EGF in endometrial stromal cells, suggesting interdependence between oestradiol and EGF in the control of endometrial stromal proliferation. Oestrogen-free conditioned medium from endometrial stromal cultures did not stimulate either [3H]thymidine or [3H]leucine incorporation, suggesting that oestradiol did not stimulate the secretion of a trophic factor from endometrial stromal cells.

Blotting, Western↗
PubMed1994

The influence of ovarian follicular activity on late proliferative phase serum IGFBP-1 in down-regulated assisted conception cycles.

Serum insulin-like growth factor binding protein-1 (IGFBP-1) concentrations were measured at the end of the proliferative phase in infertility patients undergoing normal menstrual cycle frozen embryo transfer, exogenous hormone-supported frozen embryo transfer and in-vitro fertilization (IVF) treatment cycles. These patients were divided into five groups according to their ovarian follicular activity. The exogenous hormone-supported frozen embryo transfer group, who had no ovarian follicles, and the IVF groups (number of follicles ranging from 4-38) showed statistically higher serum IGFBP-1 concentrations when compared to the normal menstrual cycle group (P < or = 0.01). There was no significant difference in the serum IGFBP-1 concentrations between the exogenous hormone support frozen embryo transfer group and the poor or normal response IVF groups (number of follicles ranging from 4 to 16). An IVF group that displayed an excessive response to our standard human menopausal gonadotrophin stimulation (> 20 mature follicles or oestradiol > 10,000 pmol/l) showed a significantly higher serum IGFBP-1 concentration when compared with the other groups (P = 0.001). This subgroup was subsequently given a modified (follicle-stimulating hormone) stimulation regime which resulted in a significant reduction in serum IGFBP-1 concentrations (P < 0.05). There was no correlation between serum oestradiol and IGFBP-1 overall or within the patient groups. We conclude that serum IGFBP-1 concentrations in our down-regulated assisted conception cycles did not increase in line with ovarian follicular activity, unless an excessive response was displayed.

Adult↗
PubMed1993

Immunohistochemical localization of acidic and basic fibroblast growth factors in normal human endometrium and endometriosis and the detection of their mRNA by polymerase chain reaction.

Growth factors play a role in the cyclical growth and vascularization of normal endometrium. Abnormal endometrial proliferation and neovascularization may result in endometriosis. This study determines the presence and localization of acidic and basic fibroblast growth factors (aFGF and bFGF respectively) in endometrium of normal women, and in normal and ectopic endometrium of women with endometriosis. Endometrium was obtained at curettage or hysterectomy for benign disease, or laparoscopy for endometriosis. aFGF- and bFGF-immunoreactivity was detected at different phases of the menstrual cycle by immunohistochemistry using primary polyclonal rabbit antibodies. Expression of mRNA for aFGF and bFGF was determined in normal endometrium by nested reverse transcriptase polymerase chain reaction (RT-PCR). aFGF- and bFGF-immunoreactivity were both detected in endometrium from normal women, and in normal and ectopic endometrium of women with endometriosis. The pattern of staining with the two different FGFs was the same: immunoreactivity was predominantly confined to glandular epithelial cells and did not change throughout the menstrual cycle. Little or only light staining was seen in stromal cells and myometrium, and the pattern of staining did not differ between endometriotic and normal tissue. The presence of mRNA for aFGF and bFGF was demonstrated in normal endometrium. The detection of aFGF and bFGF mRNA in normal endometrium and aFGF- and bFGF-immunoreactivity in normal and endometriotic tissues suggests that these peptides may play a role in the proliferation and angiogenesis of normal and ectopic human endometrium.

Base Sequence↗
PubMed1992

Reverse transcription with nested polymerase chain reaction shows expression of basic fibroblast growth factor transcripts in human granulosa and cumulus cells from in vitro fertilisation patients.

Basic fibroblast growth factor (bFGF) is a potent angiogenic factor that has also been implicated in granulosa cell and oocyte maturation. We now report the expression of messenger ribonucleic acid (mRNA) encoding bFGF in human granulosa and cumulus cells obtained at oocyte recovery in in vitro fertilisation patients. It was necessary to use the sensitive technique of a nested polymerase chain reaction (PCR) after reverse transcription (RT) to detect transcripts. This finding in conjunction with a recent report showing the presence of transcripts for transforming growth factor beta (TGF beta) in the same type of cells by PCR indicates that mechanisms are in place for controlling extracellular proteolysis and cell differentiation.

Base Sequence↗
PubMed1992

Nagging and other drinking control efforts of spouses of uncooperative alcohol abusers: assessment and modification.

This article presents a conception of spouse drinking control and an approach to assessment and modification to reduce the customary drinking control efforts of spouses of alcohol abusers unmotivated to enter treatment. Modification of the nonalcoholic spouse's customary drinking control is offered as an important early step in helping to prepare him or her to become a positive rehabilitative influence. Based on its use in unilateral family therapy with 68 spouses of uncooperative alcohol abusers, procedural guidelines, criteria for use, and two case examples from a crossover experimental dyad are described. Also presented are clinical results illustrating the success of the program, benefits and conditions relating to its use, and areas of possible application.

Alcohol Drinking↗
PubMed1992

Characterization of human purified epithelial and stromal cells from endometrium and endometriosis in tissue culture.

OBJECTIVE: To initiate in vitro cultures of separate stromal and epithelial elements from endometriotic tissue and to compare the characteristics of these cells with those of cultured endometrial cells. DESIGN: The study involved testing the viability of a culture system for endometriotic tissue and examination of the phenotype of the cells. SETTING: Fresh tissue samples were collected from the operating theater and transferred to the tissue culture laboratory. PATIENTS, PARTICIPANTS: Twenty patients undergoing laparotomy for endometriosis and patients undergoing surgery for benign conditions were recruited. INTERVENTIONS: Endometrium and endometriotic tissue were separated, cultured in vitro, and labeled by indirect immunofluorescence with monoclonal antibodies against cytoskeletal components and epithelial mucins. MAIN OUTCOME MEASURES: Endometriotic cells have been maintained in vitro and found to resemble endometrial cells closely. RESULTS: With respect to the staining patterns for cytokeratins 18 and 19, vimentin, and three different epithelial mucins, cultured cells from both endometrium and endometriotic tissue had similar properties. Cytokeratins were located in epithelial cells, and vimentin was expressed in both stromal and epithelial cells. The antimucin antibodies all gave distinct patterns of intracellular staining of epithelial cells. CONCLUSIONS: Our results indicate a close similarity between cultured stromal and epithelial cells from endometrium and endometriotic deposits. Culture of these cell populations will permit study of their properties and interactions and may provide some insight into the cause of endometriosis.

Antigens, Neoplasm↗
PubMed1992

The expression of retinoic acid receptors in cultured human endometrial stromal cells and effects of retinoic acid.

Patterns of expression of retinoic acid receptors (RAR) in cultures of human endometrial stromal cells are described. Transcripts for all three classes of RAR were expressed in these cells but RAR-beta was expressed at a low level by comparison with RAR-alpha and RAR-gamma. The abundance of RAR-beta transcripts was elevated by treating the cells with retinoic acid, but there was no effect on the level of expression of RAR-alpha and RAR-gamma. The induction of RAR-beta by retinoic acid was detectable within 4 h and at low concentrations of retinoic acid (10(-10) M). Adenosine 3':5'-cyclic monophosphate (cAMP) analogues and forskolin, an adenylate cyclase activator, had no effect on the retinoic acid-mediated induction of RAR-beta, contrary to recent observations on embryonal carcinoma cells. However, the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (IBMX), forskolin and 8-bromo-cAMP depressed basal levels of RAR-beta expression. These data suggest that endometrial stromal cells may be a target tissue of retinoic acid in vivo, and imply a role for retinoic acid in the cyclical differentiation of human endometrium.

Blotting, Northern↗
PubMed1992

Ovarian steroid receptor expression in endometriosis and in two potential parent epithelia: endometrium and peritoneal mesothelium.

Endometriosis is an oestrogen dependent condition and it is expected that the tissue of origin of endometriosis will express receptors for the ovarian steroids. Two epithelia, endometrium and peritoneal mesothelium, are the potential parent epithelium. Oestrogen and progesterone receptor expression has been studied immunohistochemically in (i) timed endometrial biopsies from 25 normal subjects and 27 patients with endometriosis, (ii) 25 endometriotic biopsies and (iii) 42 peritoneal biopsies. Endometrium but not peritoneal mesothelium expresses both oestrogen and progesterone receptors. No difference in the intensity of staining between endometria of normal subjects compared with the endometria of patients with endometriosis was noted. In paired endometrial and endometriotic biopsies, the intensity of staining for the oestrogen receptor in stromal cells and for the progesterone receptor in both glandular and stromal cells was less in the endometriotic biopsies. These data provide circumstantial evidence for an endometrial origin for endometriosis although quantitative differences exist in receptor expression between endometrium and endometriosis.

Endometriosis↗
PubMed1992

A randomized double blind placebo controlled trial of the effects on bone metabolism of the combination of nafarelin acetate and norethisterone.

OBJECTIVE: We observed the effects on bone metabolism of the addition of different doses of oral norethisterone during treatment with the GnRH agonist nafarelin (Synarel, Syntex). PATIENTS: Ninety-four women with a subjective complaint of heavy menstrual blood loss or objective evidence of endometriosis received intra-nasal nafarelin 400 micrograms daily for 6 months and also received, in a randomized, double blind manner, either 0.7 mg (n = 24), 1.4 mg (n = 23) or 2.45 mg (n = 23) of oral norethisterone or placebo (n = 24) daily. Follow-up was continued for a further 6 months after treatment. RESULTS: Thirty-one patients (33%) left the study prematurely and three patients were non-compliant with the study drug. By 6 months significant increases in urinary calcium/creatinine ratio were seen, compared to baseline, in the nafareline and placebo (P = 0.001, n = 14), 0.7 mg (P = 0.04, n = 13) and 1.4 mg norethisterone groups (P = 0.009, n = 17) but not in the nafarelin or 2.45 mg norethisterone groups (P = 0.72, n = 16). Densitometry of the spine, however, showed decreases at 6 months in all groups: 6.14% (P = 0.0004, n = 11), 5.46% n = 0.0006, n = 13), 3.93% (P = 0.008, n = 14) and 4.04% (P = 0.004, n = 16) for the groups receiving nafarelin and placebo, nafarelin and norethisterone 0.7, 1.4 and 2.45 mg respectively. Six months after stopping nafarelin, with or without norethisterone, bone mass was not different from baseline. CONCLUSION: The concomitant daily use of up to 2.45 mg of norethisterone does not eliminate the bone demineralization seen during GnRH agonist therapy with nafarelin in premenopausal women.

Administration, Oral↗
PubMed1992

Epidermal growth factor receptor expression in normal endometrium and endometriosis: an immunohistochemical study.

OBJECTIVE: To study epidermal growth factor (EGF) receptor expression in endometrium throughout the menstrual cycle and to compare EGF-receptor expression in endometrium from patients with endometriosis with receptor expression in synchronously sampled endometriosis and in endometrium from healthy women. DESIGN: An immunohistochemical study of receptor expression using murine monoclonal antibodies and timed endometrial and endometriotic biopsies. SUBJECTS: 25 healthy women and 27 patients with a diagnosis of endometriosis. RESULTS: Positive staining for EGF receptors was observed in 24 of 25 samples from normal women and in 26 of 27 endometrial samples from patients with endometriosis. In neither group was there any variation in the intensity of staining throughout the menstrual cycle and both glands and stroma were stained. EGF-receptor expression was observed in the glands of 15 out of 17 endometriotic lesions and in 12 of these biopsies positive staining was also present within endometriotic stroma. CONCLUSION: This study shows no difference in the intensity of staining of EGF receptors in endometrium throughout the menstrual cycle or between the glands of normal endometrium and those of endometriosis.

Endometriosis↗