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Biomedical subjects

E Webster

Publications and source records attributed to E Webster.

15 recordsLinked to original sources
PubMed1997

The hypothalamic-pituitary-adrenal axis and the female reproductive system.

The hypothalamic-pituitary-adrenal (HPA) axis and the female reproductive system are intertwined and exhibit a complex relationship. Thus, the HPA axis exerts profound, mostly inhibitory effects, on the reproductive axis, with corticotropin-releasing hormone (CRH) and CRH-induced propiomelanocortin peptides inhibiting hypothalamic GnRH secretion, and with glucocorticoids inhibiting pituitary LH and ovarian estrogen and progesterone secretion and rendering estrogen-target tissues, such as the endometrium, resistant to the gonadal steroid. These effects of the HPA axis are responsible for the "hypothalamic" amenorrhea of stress, depression and eating disorders, and the hypogonadism of Cushing's syndrome. Conversely, estrogen directly stimulates the CRH gene, which may explain the slight hypercortisolism of females and the preponderance of depressive, anxiety, and eating disorders, as well as Cushing's disease in women. Interestingly, several components of the HPA axis and their receptors are present in reproductive tissues, as autocoid regulators of their various functions. These include ovarian and endometrial CRH, which may participate in the inflammatory processes of the ovary, that is, ovulation and luteolysis, and of the endometrium, that is, implantation and menstruation. Finally, the hypercortisolism of the latter half of pregnancy can be explained by high levels of placenta CRH in plasma. This hypercortisolism causes a transient adrenal suppression in the postpartum period, which may explain the postpartum blues/depression and autoimmune phenomena of this period.

Corticotropin-Releasing Hormone↗
PubMed1996

The non-ligand binding beta-isoform of the human glucocorticoid receptor (hGR beta): tissue levels, mechanism of action, and potential physiologic role.

BACKGROUND: Alternative splicing of the transcripts of the human glucocorticoid receptor gene results in two mutually exclusive products, the classic, ligand-binding glucocorticoid receptor (hGR alpha), and a dominant negative non-ligand-binding isoform, hGR beta. MATERIALS AND METHODS: We examined the existence of and quantified both hGR alpha and hGR beta isoforms in a panel of human tissues, as well as in intact and fractionated HeLa cells, using specific quantitative Western blots and/or immunocytochemistry. We studied the potential interactions of hGR beta with heat shock protein (hsp) 90 and/or hGR alpha using cross-immunoadsorption/precipitation procedures followed by Western blots. RESULTS: For the first time, we demonstrated the natural existence of the hGR beta protein, which was widely expressed in human tissues. The ratio of immunoreactive hGR alpha to hGR beta varied from 0.2 to 1.0 among different tissues, and was approximately 0.2 in HeLa cells. In the latter, both isoforms were distributed in the cytoplasm and nucleus in the absence of the hormonal ligand, and translocated into the nucleus after addition of dexamethasone. The cytosolic and nuclear hGR alpha-to-hGR beta ratio remained the same before and after dexamethasone exposure, suggesting that upon activation the two isoforms translocated into the nucleus in equal proportions. hGR alpha- and hGR beta-specific antibodies cross-adsorbed and precipitated cytosolic and nuclear glucocorticoid hGR alpha and hGR beta, respectively, as well as hsp90, suggesting that hGR alpha and hGR beta are in complex with hsp90 and/or each other. CONCLUSIONS: The hGR beta protein is widely expressed throughout the human body and present mostly in the cytoplasm of human cells, in complex with hsp90 and other proteins. In the presence of glucocorticoid, hGR beta probably heterodimerizes with ligand-bound hGR alpha and translocates into the nucleus to act as a dominant negative inhibitor of the classic receptor.

Alternative Splicing↗
PubMed1995

Receptors for melanocortin peptides in the hypothalamic-pituitary-adrenal axis and skin.

The syndromes of hereditary IGD and triple A syndrome are potentially life threatening and severely disabling diseases. Clinical awareness of these syndromes is of considerable prognostic and therapeutic importance. The defects in the ACTH receptor causing IGD help illuminate the mechanisms of ligand binding and signal transduction by this receptor. Identification of the molecular defect(s) responsible for IGD cases with a normal ACTH receptor structural gene and for the triple A syndrome remains a challenge, which will hopefully eventually provide further insight into the mechanisms of adrenocortical function. The cloning of the melanocortin receptors has been a giant step towards a better insight into the physiological role of the POMC-derived peptides. It is now becoming apparent that the differential processing of POMC in the brain, the pituitary, and peripheral tissues, yielding a number of different biologically active melanocortin peptides, combined with the distinct tissue distribution and pharmacological profile of the melanocortin receptors will help elucidate the molecular basis of these functions.

Adrenal Cortex Neoplasms↗
PubMed1995

Stress-induced intracranial mast cell degranulation: a corticotropin-releasing hormone-mediated effect.

Stress is known to precipitate or worsen a number of disorders, such as migraines, in which mast cells are suspected of being involved by releasing vasoactive, nociceptive, and proinflammatory mediators. However, no functional association has been demonstrated yet between a migraine trigger and brain mast cell activation. Nontraumatic immobilization (restrain) stress has been shown to stimulate the hypothalamic-pituitary-adrenal axis and to cause redistribution of immune cells. Here, restrain stress caused degranulation in 70% of rat dura mast cells within 30 min, as shown both by light and electron microscopy. These morphologic findings were accompanied by cerebrospinal fluid elevation of rat mast cell protease I, but not II, indicating secretion from connective tissue type mast cells. Mast cell activation due to stress was abolished in animals that had been treated neonatally with capsaicin, indicating that neuropeptides in sensory nerve endings are involved in this response. Complete inhibition was also achieved by pretreating the animals ip with polyclonal antiserum to CRH. Mast cells in the dura were localized close to nerve processes containing substance P, but no CRH-positive fibers were identified even though these were found close to mast cells in the median eminence. This is the first time that stress is shown to activate intracranial mast cells; apparently through the sequential action of CRH and sensory neuropeptides. These findings may have implications for the pathophysiology and possible therapy of neuroinflammatory disorders such as migraines, which are induced or exacerbated by stress.

Animals↗
PubMed1992

Eye tests in the elderly: factors associated with attendance and diagnostic yield in non-attenders.

Patients aged 60-75 years registered with one inner city general practice were sent a questionnaire asking when they last received an eye check by an optometrist. Of the 193 (77%) who responded, 110 (59%) had attended in the last 2 years, and 138 (74%) in the last 3 years. Males and those with mobility problems were less likely to have had their eyes checked. Seventy-seven previous non-attenders were offered an appointment with an optometrist and this was accepted by 34 (44%). These individuals showed a high level of ophthalmic morbidity. Discussion of optometric checks should be included in general practice health checks and the elderly surveillance programme.

Aged↗
PubMed1992

Voiding cystourethrography in children: value of digital fluoroscopy in reducing radiation dose.

Voiding cystourethrography is a commonly used fluoroscopic procedure in children that can directly irradiate the gonads. As a consequence, much attention has been given to reducing the dose of radiation received during the procedure. A digital fluoroscope, especially adapted for use in children, was evaluated for potential reduction of the dose of radiation during the procedure. Entrance and midplane doses were calculated on child-sized phantoms by using the digital fluoroscope, digital spot films, and 105-mm spot films. Subsequently, data were collected on 47 children, grouped by ages (neonate to 1 year, 1-5 years, and 5-7 years), in whom voiding cystourethrography was performed by using the same exposure factors as those for the phantoms. On the basis of the exposure doses for the phantoms and recorded clinical peak kilovoltages, milliamperes, milliseconds, and fluoroscopic time, average skin and ovarian doses were calculated for each group of children. These doses were compared with previously reported doses for fluoroscopic and radionuclide voiding cystourethrography. Results of line-pair resolution studies for the digital spot films and 105-mm spot films were similar. Images from the digital device and 105-mm images obtained on a conventional fluoroscope were considered equally adequate for clinical decision making. The average midplane and skin doses with digital spot films for children less than 5 years old were equal to or less than 0.66 and 2.37 mGy, respectively, as opposed to 1.37 and 5.32 mGy with the 105-mm spot films. Previously reported ovarian doses range from 2.52 to 10.0 mGy for fluoroscopic voiding cystourethrography and from 0.04 to 0.05 mGy for radionuclide voiding cystourethrography. The use of digital spot films reduced dose approximately 50% compared with 105-mm spot films; the ovarian dose was 0.62 mGy greater than that for radionuclide voiding cystourethrography.

Child↗
PubMed1988

'Rhupus' syndrome.

Occasionally patients with overlapping features of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), termed "rhupus," have been encountered. We wanted to ascertain the frequency of such patients and determine whether they represent a unique overlap syndrome. Of approximately 7000 new patients evaluated over 11 years, we identified six patients who had, on the average, 6.7 American Rheumatism Association criteria for RA and 4.2 criteria for SLE. Criteria for RA included chronic symmetric arthritis with morning stiffness (six patients); subcutaneous nodules (two patients); positive rheumatoid factors test (four patients); and radiologic erosions (four patients). The criteria for SLE included malar rash (three patients); discoid lupus erythematosus (two patients); biopsy-proved nephritis (one patient); photosensitivity (one patient); leukopenia/thrombocytopenia (four patients); positive antinuclear antibodies or lupus erythematosus cell test (six patients); hypocomplementemia (two patients); and abnormal results from skin biopsy (two patients). During observations of up to ten years, the conditions of three patients were stable or improved, one died, and two were unavailable for follow-up. Patients usually did not have conditions that evolved to classic rheumatic disease patterns. Rhupus was not common and did not occur more frequently (0.09% prevalence among our patients) than expected from chance concurrence of SLE and RA (calculated at 1.2%). These observations confirm that rhupus indeed exists as a syndrome manifested by patients sharing features of probable coincidental concurrence of RA and SLE, but not as a unique clinical pathologic or immunologic syndrome. Appreciation of these patients with rhupus is important since their therapy and outcome differ from those having RA or SLE alone.

Arthritis, Rheumatoid↗
PubMed1986

Is running associated with degenerative joint disease?

Little information is available regarding the long-term effects, if any, of running on the musculoskeletal system. We therefore compared the prevalence of degenerative joint disease among 17 male runners (mean age, 56 years; height, 180 cm [5 ft 11 in]; and weight, 73.02 kg [161 lb] with 18 male nonrunners (mean age, 60 years; height, 178 cm [5 ft 10 in]; and weight, 78 kg [171 lb]). Running subjects (53% marathoners) ran a mean of 44.8 km (28 miles)/wk for 12 years. Pain and swelling of hips, knees, ankles, and feet and other musculoskeletal complaints among runners were comparable with those among nonrunners. Radiologic examinations (for osteophytes, cartilage thickness, and grade of degeneration) also were without notable differences among groups. We did not find an increased prevalence of osteoarthritis among the runners. Our observations suggest, within the limits of our study, that long-duration, high-mileage running need not be associated with premature degenerative joint disease in the lower extremities.

Aged↗
PubMed1978

Relative effects of drugs and diet on hyperactive behaviors: an experimental study.

In a test of Feingold's hypothesis that food additives trigger the hyperactive response, 26 hyperactive children were randomly assigned to treatment conditions whereby they were given active or placebo medications in combination with challenge cookies with artificial food colors or control cookies without the additives. The children were crossed over into each of the four treatment conditions and experimental procedures were employed, including double-blind assessments through the completion of behavior checklists, by teachers and parents. Stimulant medications were clearly more effective than diet in reducing hyperactive behavior. The parent ratings indicate strong drug effects and inconclusive diet effects. Drug effects are marked in teacher ratings as well. However, when the children were receiving placebos, their hyperactive behaviors in the classroom were greater when eating cookies with artificial colors than when eating cookies without artificial colors. According to the ratings, approximately seven children were no longer hyperactive. There is evidence to suggest that the behavior of three to eight children was diet-responsive, depending on the criteria used. There is evidence, particularly in teacher ratings, in support of Feingold's hypothesis if it is modified. Further research is required to specify which subtypes of hyperactive children respond to a diet free of artificial food colors.

Adolescent↗