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Biomedical subjects

E Speck

Publications and source records attributed to E Speck.

8 recordsLinked to original sources
PubMed2000

Melatonin in postmenopausal females.

There is little information about the interaction between melatonin, sexual steroids and neuroendocrine system in postmenopausal females, even if former research showed that melatonin is clearly involved in human physiology and pathophysiology. We evaluated the overnight urinary excretion of 6-sulfatoxymelatonin (6-SMT) using a radioimmunoassay in 60 postmenopausal women. The group has been divided into patients with insomnia (10), hyperprolactinemia (7), depression (9), obesity (7) and controls (27). Compared to controls 6-SMT values were significantly higher in depressive females. Patients with hyperprolactinemia showed a trend toward a significantly elevated average nocturnal melatonin concentration. Melatonin levels were significantly lower in patients with insomnia and obese postmenopausal females than in controls. Since previous studies described lower melatonin levels in postmenopausal than in premenopausal women, the indication of melatonin therapy, especially for sleep disorders in this collective, can be handled more generously. Melatonin should be prescribed restrictively in patients with depression and in those with hyperprolactinemia. The role of melatonin in obese females remains unclear.

Depression↗
PubMed1996

Major histocompatibility complex class II molecules function as a template for the processing of a partially processed insulin peptide into a T-cell epitope.

Our understanding of how an autoantigen is processed and presented during the development of a major histocompatibility complex (MHC) class II-dependent and T-cell-mediated autoimmune disease, such as IDDM, is incompletely understood. We have used insulin as a model autoantigen in IDDM to address the question of whether MHC class II molecules play a role in the generation and/or preservation of an autoantigen peptide that stimulates T-cell activation. Analyses of the requirement of I-Ad class II molecules in the processing of the partially processed porcine insulin peptide A1-A14/B1-B16 demonstrate that the binding of this peptide to I-Ad is essential for it to be further processed and tailored into a T-cell epitope. Based on our observations, we propose a two-step model for insulin processing in which insulin is first processed by an enzyme(s) into an intermediate peptide that binds to class II and then class II functions as a template to guide the processing of this partially processed peptide by cathepsin D into a T-cell epitope. Our data further underscore the important realization that MHC class II-directed processing of an autoantigen (e.g., insulin) may regulate 1) the relative immunodominance of T-cell determinants in an autoantigen, 2) the self-reactivity to cryptic T-cell epitopes in autoantigens, and 3) the susceptibility to autoimmune disease.

Animals↗
PubMed1994

Naturally processed heterodimeric disulfide-linked insulin peptides bind to major histocompatibility class II molecules on thymic epithelial cells.

We determined whether disulfide-linked insulin peptides that are immunogenic in vitro for CD4+ T cells bind to major histocompatibility complex class II in vivo. Radiolabeled recombinant human insulin (rHI) was injected into BALB/c mice, and processed rHI peptides bound to I-Ad molecules on different thymic antigen-presenting cells were characterized. The A6-A11/B7-B19 and A19-A21/B14-B21 disulfide-linked I-Ad-bound rHI peptides were isolated from thymic epithelial cells but not dendritic cells. While both thymic epithelial cells and dendritic cells present rHI to HI/I-Ad-specific T cells, these antigen-presenting cells do not present the reduced or nonreduced forms of the disulfide-linked rHI peptides. Thus, a naturally processed disulfide-linked peptide can bind to major histocompatibility complex class II in vivo. The potential role of these peptides in immunological tolerance is discussed.

Amino Acid Sequence↗
PubMed1993

Thymic T cell anergy in autoimmune nonobese diabetic mice is mediated by deficient T cell receptor regulation of the pathway of p21ras activation.

Thymic T cell anergy, as manifested by thymocyte proliferative unresponsiveness to antigens expressed in the thymic environment, is commonly believed to mediate the acquisition of immunological self-tolerance. However, we previously found that thymic T cell anergy may lead to the breakdown of tolerance and predispose to autoimmunity in nonobese diabetic (NOD) mice. Here, we show that NOD thymic T cell anergy, as revealed by proliferative unresponsiveness in vitro after stimulation through the T cell receptor (TCR), is associated with defective TCR-mediated signal transduction along the PKC/p21ras/p42mapk pathway of T cell activation. PKC activity is reduced in NOD thymocytes. Activation of p21ras is deficient in quiescent and stimulated NOD T cells, and this is correlated with a significant reduction in the tyrosine phosphorylation of p42mapk, a serine/threonine kinase active downstream of p21ras. Treatment of NOD T cells with a phorbol ester not only enhances their p21ras activity and p42mapk tyrosine phosphorylation but also restores their proliferative responsiveness. Since p42mapk activity is required for progression through to S phase of the cell cycle, our data suggest that reduced tyrosine phosphorylation of p42mapk in stimulated NOD T cells may abrogate its activity and elicit the proliferative unresponsiveness of these cells.

Animals↗
PubMed1992

The effects of epidural versus parenteral opioid analgesia on postoperative pain and pulmonary function in adults who have undergone thoracic and abdominal surgery: a critique of research.

Studies comparing epidural and parenteral opioid analgesia for patients experiencing thoracic or abdominal surgery are analyzed with respect to differences in postoperative pain and pulmonary function. Although most studies suggest that epidural analgesia is superior for postoperative pain relief, few clearly demonstrate an improvement in pulmonary function attributable to epidural analgesia. Recommendations for future research are proposed to improve the design, measurement, analysis, and reporting of studies. Research relevant to the nursing care of patients receiving epidural analgesia is suggested.

Abdomen↗
PubMedDate not supplied

A pilot study of pain, analgesia use, and pulmonary function after colectomy with or without a preoperative bolus of epidural morphine.

OBJECTIVE: To determine whether patients who received a preoperative bolus of epidural morphine plus postoperative parenteral analgesia had less pain and better pulmonary function over the first 2 days after a colectomy than patients who received postoperative parenteral analgesia alone. DESIGN: Repeated measures, quasi-experimental, random assignment. SETTING: Northeastern general hospital. SUBJECTS: Thirteen patients were randomized to receive parenteral with (n = 6) or without (n = 7) epidural analgesia. OUTCOME MEASURES: Indicators of pain (intensity of pain and pain-related distress, intensity of words used to describe pain, intramuscular-equivalent amount of morphine administered, duration from start of surgery to first request for analgesia) and pulmonary function (forced expiratory volume in one second FEV1], forced vital capacity [FVC], inspiratory capacity [IC], peripheral oxygen saturation [SaO2] values). MEASUREMENT: Indicators of pain and pulmonary function were obtained the day before surgery, approximately 6 hours after surgery, and the first two mornings after surgery. RESULTS: Six hours after surgery, patients in the epidural group had less pain (p = 0.0177) and related distress (p = 0.0303) and greater FVC (p = 0.0303) and FEV1 (p = 0.0025) than patients in the no-epidural group. On the first postoperative morning, patients in the epidural group had less distress related to pain (p = 0.0350) but similar respiratory rates and spirometry values. Inspiratory capacity was not statistically different but was always larger in the epidural group. Of patients who breathed room air, SaO2 was higher in the epidural group over the first two postoperative days (p = 0.0286 each occasion). Patients in the epidural group received their first on-demand analgesic an average of 30 hours after the start of surgery compared with 6 hours for patients in the no-epidural group (p = 0.0022). There were no significant differences in the total number of words used to describe the type of pain, and both groups described the pain with fewer words than expected on the first and second mornings after surgery. CONCLUSIONS: Results should be confirmed through study of a larger sample with the hypothesis that pain relief, selected aspects of pulmonary function, and peripheral oxygenation may be superior for patients who receive a preoperative bolus of epidural analgesia for abdominal surgery.

Adult↗