PubMed Health⌕ Search

Biomedical subjects

S J Spencer

Publications and source records attributed to S J Spencer.

16 recordsLinked to original sources
PubMed1996

Apoptosis in the human female reproductive tract.

Throughout fetal and adult life, the balance of cell proliferation and cell death determines the size of cell populations in tissues throughout the body. Apoptosis, or programmed cell death, is the physiologic process of cell deletion. Cell death is critical in morphogenesis in the embryo and fetus as well as in maintaining tissue homeostasis in the adult. Throughout the menstrual cycle, cell death and renewal occur in the female reproductive tract in a highly regulated sequence. The process of follicular atresia and the cyclic shedding of the endometrium involve the process of apoptosis. In pathologic states, resistance to cell death by apoptosis may play a fundamental role in tumorigenesis. Because apoptosis is such a fundamental biologic process in a variety of physiologic and pathologic states, many unique to the female reproductive tract, it is imperative that clinicians be conversant with the rapidly expanding information in this area. Although apoptotic cell death has been recognized histologically for over 20 years (1), the molecular mechanisms that regulate apoptosis have only recently begun to be elucidated. The identification of some of these regulators, such as the p53 gene, has improved our understanding of the mechanisms of tumor response to chemotherapy. This review will summarize our current knowledge of the mechanisms of apoptosis in the ovary and endometrium, and in the normal development and malignant transformation of the breast.

Adult↗
PubMed1993

Endogenous catecholamines augment the inhibitory effect of opioids on luteinizing hormone secretion during the midluteal phase.

OBJECTIVE: Our purpose was to test the hypothesis that endogenous catecholamines may interact with endogenous opioid peptides to influence gonadotropin secretion during the midluteal phase in normal women. STUDY DESIGN: Normal cycling women studied during the midluteal phase were randomized to one of four treatment groups: (1) alpha-methyl-para-tyrosine, (2) naloxone, (3) alpha-methyl-para-tyrosine and naloxone, and (4) control. Mean treatment luteinizing hormone levels were compared by analysis of variance. Pulse frequency, amplitude, and integrated area under the curve were assessed by CLUSTER analysis and compared by means of nonparametric analyses. RESULTS: Mean luteinizing hormone levels were significantly higher in the naloxone and alpha-methyl-para-tyrosine plus naloxone groups compared with alpha-methyl-para-tyrosine or placebo. Coadministration of alpha-methyl-para-tyrosine and naloxone caused a significant increase in large-burst luteinizing hormone pulses compared with the group receiving naloxone only. CONCLUSION: Endogenous catecholamines augment the inhibitory effect of opioids on luteinizing hormone secretion during the midluteal phase in normal cycling women.

Adolescent↗
PubMed1993

Self-image resilience and dissonance: the role of affirmational resources.

It was predicted that high self-esteem Ss (HSEs) would rationalize an esteem-threatening decision less than low self-esteem Ss (LSEs), because HSEs presumably had more favorable self-concepts with which to affirm, and thus repair, their overall sense of self-integrity. This prediction was supported in 2 experiments within the "free-choice" dissonance paradigm--one that manipulated self-esteem through personality feedback and the other that varied it through selection of HSEs and LSEs, but only when Ss were made to focus on their self-concepts. A 3rd experiment countered an alternative explanation of the results in terms of mood effects that may have accompanied the experimental manipulations. The results were discussed in terms of the following: (a) their support for a resources theory of individual differences in resilience to self-image threats--an extension of self-affirmation theory, (b) their implications for self-esteem functioning, and (c) their implications for the continuing debate over self-enhancement versus self-consistency motivation.

Adaptation, Psychological↗
PubMed1992

HLA class II specificities in vasculitis with antibodies to neutrophil cytoplasmic antigens.

HLA class II genes were examined in patients with small vessel vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA) using restriction fragment length polymorphism and allele specific oligonucleotide typing. Fifty-nine patients were studied, 34 with Wegener's granulomatosis and 25 with microscopic polyarteritis, and their results were compared with those from 1103 British Caucasoid controls. The frequency of HLA-DQw7 was significantly increased in patients with vasculitis (patients 53%; controls 27.8%, chi 2 17.8, Pc less than 0.0025, relative risk 2.9), and all the DQw7 bearing haplotypes commonly found in Caucasoid populations contributed to the increase. By contrast, the frequency of HLA-DR3 bearing haplotypes was decreased in the patients (patients 6.8%; controls 21.6%, chi 2 6.7, P less than 0.01). HLA specificities were similar in the groups of patients presenting with Wegener's granulomatosis and microscopic polyarteritis and with different types of ANCA assessed by indirect immunofluorescence. However, patients with the DQw7, DR4 haplotype were significantly more likely to have transiently positive tests for ANCA than patients with other DQw7 bearing haplotypes, whereas patients with DR2 bearing haplotypes were more likely to have persistently positive ANCA. These results show that HLA class II genes are associated with small vessel vasculitis and may influence the duration of the associated autoimmune response.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1992

Activin-A as an intraovarian modulator: actions, localization, and regulation of the intact dimer in human ovarian cells.

The actions, localization, and regulation of activin in the human ovary are unknown. Therefore, the aims of this study were (a) to define the effects of recombinant activin-A and its structural homologue, inhibin-A, on mitogenesis and steroidogenesis (progesterone secretion and aromatase activity) in human preovulatory follicular cells; (b) to localize the activin-A dimer in the human ovary by immunohistochemistry; and (c) to examine regulation of intracellular activin-A production in cultured human follicular cells. In addition to stimulating mitogenic activity, activin-A causes a dose- and time-dependent inhibition of basal and gonadotropin-stimulated progesterone secretion and aromatase activity in human luteinizing follicular cells on day 2 and day 4 of culture. Inhibin-A exerts no effects on mitogenesis, basal or gonadotropin-stimulated progesterone secretion and aromatase activity, and does not alter effects observed with activin-A alone. Immunostaining for dimeric activin-A occurs in granulosa and cumulus cells of human ovarian follicles and in granulosa-lutein cells of the human corpus luteum. cAMP, and to a lesser degree human chorionic gonadotropin and follicle-stimulating hormone, but not inhibin-A, activin-A, or phorbol 12-myristate 13-acetate, increased the immunostaining for activin-A in cultured granulosa cells. These results indicate that activin-A may function as an autocrine or paracrine regulator of follicular function in the human ovary.

Activins↗
PubMed1992

Activin and inhibin in the human adrenal gland. Regulation and differential effects in fetal and adult cells.

Recent experimental data have revealed that activins and inhibins exert pivotal effects on development. As part of our studies on growth and differentiation of the human fetal adrenal gland, we examined the subunit localization, as well as the mitogenic and steroidogenic actions of activin and inhibin in human fetal and adult adrenals. All three activin and inhibin subunit proteins (alpha, beta A, and beta B) were detected in the fetal and adult adrenal cortex. Immunoreactive activin-A dimer was demonstrated in midgestation fetal and neonatal adrenals. ACTH1-24-stimulated fetal adrenal cell expression of alpha and beta A subunit messenger RNA. In addition, ACTH elicited a rise in levels of immunoreactive alpha subunit secreted by fetal and adult adrenal cells. Human recombinant activin-A inhibited mitogenesis and enhanced ACTH-stimulated cortisol secretion by cultured fetal zone cells, but not definitive zone or adult adrenal cells. Recombinant inhibin-A had no apparent mitogenic or steroidogenic effects. Thus, activin selectively suppressed fetal zone proliferation and enhanced the ACTH-induced shift in the cortisol/dehydroepiandrosterone sulfate ratio of fetal zone steroid production. These data indicate that activin-A may be an autocrine or paracrine factor regulated by ACTH, involved in modulating growth and differentiated function of the human fetal adrenal gland.

Activins↗
PubMed1991

Isolation and characterization of three forms of joining peptide from adult human pituitaries: lack of adrenal androgen-stimulating activity.

Three structural variants of the joining peptide (JP) fragment of POMC have been purified from human pituitaries. Ion exchange and reverse phase tissue extraction procedures were combined with reverse phase HPLC to achieve complete purification of each form of JP. Fragments resulting from tryptic hydrolysis of each form were characterized by amino acid analysis and fast atom bombardment mass spectrometry. The predominant form of human JP, accounting for about 50% of the total purified, was found to be conjugated to glutathione through the lone cysteine residue at position 9. The other two variants were identified as human JP with a free cysteine residue and human JP dimer and accounted for 35% and 15%, respectively, of the total purified. Recently, human JP-(1-18) has been suggested as having adrenal androgen-stimulating activity. None of the three JP variants or their respective 1-20 amino-terminal fragments resulting from tryptic hydrolysis showed any ability to promote the secretion of dehydroepiandrosterone sulfate by cultured human fetal adrenal cells. Similarly, no potentiation of the stimulatory effects of ACTH-(1-39) was observed. The three variants of human JP as well as JP purified from rat, porcine, and bovine pituitaries were tested for their ability to stimulate androgenic steroids from dispersed fetal rabbit adrenal cells. None showed any significant biological activity either in stimulating steroid secretion or in potentiating the action of ACTH-(1-39).

Adrenal Glands↗
PubMed1990

Recombinant human activin-A promotes proliferation of human luteinized preovulatory granulosa cells in vitro.

Ovarian granulosa cells synthesize and secrete activin, a member of the transforming growth factor-beta (TGF-beta) peptide family, during the follicular phase of the menstrual cycle. We examined the growth-promoting activity of human recombinant activin-A on human luteinized preovulatory granulosa cells obtained from women undergoing in vitro fertilization. Activin-A induced proliferation of granulosa cells on day 5 of culture in a dose-dependent manner. Maximal effects were seen at concentrations greater than or equal to 100 ng/mL with an ED50 of 15 ng/mL. We suggest that activin-A is able to modulate growth of ovarian granulosa cells.

Activins↗
PubMed1990

Human recombinant activin-A inhibits proliferation of human fetal adrenal cells in vitro.

Activins and inhibins are dimeric peptides which are structurally and functionally related to transforming growth factor-beta (TGF-beta). The mRNA for the activin and inhibin subunits is expressed in the adrenal gland. Because members of the TGF-beta superfamily have effects on mitogenesis, we examined the effect of recombinant human activin-A (rh-activin-A) on proliferation of midgestation human fetal adrenal cells in vitro. Dose-dependent growth inhibition by rh-activin-A was obtained, with an ED50 of 1 ng/ml. Rh-activin-A inhibited basal and epidermal growth factor (EGF)-stimulated fetal zone cell proliferation, but did not alter basic fibroblast growth factor (bFGF)-stimulated growth. TGF-beta combined with rh-activin-A demonstrated additive inhibition of fetal adrenal growth. These findings suggest a potential autocrine or paracrine role for activin-A in modulating the growth and/or subsequent involution of the human fetal adrenal gland.

Activins↗
PubMed1975

Problems of a temporary adolescent psychiatrist.

I have tried to describe just less than one year of learning experience on my part in one type of adolescent unit. Only 16 inpatients were treated at a time while I was there: there were only 25 discharges and 19 admissions in my time. We knew we were making little inroad into our whole regional problem of adolescent disturbance; but we believe that as a team, able to work closely with each other and with our patients and their relatives, in a therapeutic community of undogmatic ideology, we were able to give a little to almost all and, to those who did best, a great deal. Very few ex-inpatients lost all touch with us. Nearly all came back from scattered homes for our Christmas discotheque. Even our very modest aim, to reset and then foster the natural development of the personalities of our patients, rather than break them down in deep analysis and radically reconstruct them, required an intensity of psychotherapeutic effort which engaged all we had to offer, and often drained us at the end of the day. Yet those who joined us transiently, particularly student nurses and medical students, seemed to find the experience significant--occasionally deeply so--and came back to visit us. Our social worker has now departed to have a baby. Our three senior nurses have left, two to university as mature students, one to prepare for a no. 7 post. Possibly the intensity of the demand upon them would have made them leave, anyway. For myself, it was a year of development of my psychotherapeutic sensitivity and of close working with a valued team of colleagues in a setting new to me, which I shall never forget.

Adolescent↗