Structure and receptor binding of PYY analogs.

Differences in the structure of PYY and two important analogs, PYY [3-36] and [Pro34]PYY, are evaluated. Y-receptor subtype ligand binding data are used in conjunction with structural data to develop a model for receptor subtype selective agonists. For PYY it is proposed that potent binding to Y1, Y4 and Y5 receptors requires the juxtaposition of the two termini while Y2 binding only requires the C-terminal helix.

E2 supplementation selectively relieves GH's autonegative feedback on GH-releasing peptide-2-stimulated GH secretion.

Female gender confers resistance to GH autonegative feedback in the adult rat, thereby suggesting gonadal or estrogenic modulation of autoregulation of the somatotropic axis. Here we test the clinical hypothesis that short-term E2 replacement in ovariprival women reduces GH's repression of spontaneous, GHRH-, and GH-releasing peptide (GHRP)-stimulated GH secretion. To this end, we appraised GH autoinhibition in nine healthy postmenopausal volunteers during a prospective, randomly ordered supplementation with placebo vs.

Automation, task difficulty, and aircrew performance.

The effects of an automated system on team processes and performance were assessed in a laboratory simulation. Two-person crews were required to fly a complex emergency-response scenario under conditions of low and high workload. These flights were completed with or without the aid of an autopilot.

It is not how much you have but how you use it: toward a rational use of simulation to support aviation training.

One of the most remarkable changes in aviation training over the past few decades is the use of simulation. The capabilities now offered by simulation have created unlimited opportunities for aviation training. In fact, aviation training is now more realistic, safe, cost-effective, and flexible than ever before.

Growth hormone-releasing peptide-2 stimulates GH secretion in GH-deficient patients with mutated GH-releasing hormone receptor.

GH-releasing peptides (GHRPs) are synthetic peptides that bind to specific receptors and thereby stimulate the secretion of pituitary GH. In vivo it is uncertain whether these peptides act directly on somatotroph cells or indirectly via release of GHRH from the hypothalamus. In this study we compared the pituitary hormone response to GHRP-2 in 11 individuals with isolated GH deficiency (GHD) due to a homozygous mutation of the GHRH receptor (GHRH-R) gene and in 8 normal unrelated controls.

Domain 1.1 of the sigma(70) subunit of Escherichia coli RNA polymerase modulates the formation of stable polymerase/promoter complexes.

The sigma 70 (sigma(70)) subunit of Escherichia coli RNA polymerase specifies transcription from promoters that are responsible for basal gene expression during vegetative growth. When sigma(70) is present within polymerase holoenzyme, two of its domains, 2.4 and 4.

Jurisprudence issues in forensic odontology.

This article exposes the dental profession in the legal environment and the rules that control the acceptance or rejection of expert witness testimony. Written by a practicing dentist and attorney, the author believes that the new forensic dentistry aspirant should develop mentoring relationships with more experienced medico-legal professionals to supplement traditional dental education.

Digital analysis of bite marks and human identification.

This article introduces the dental investigator to the basic concepts of digital imaging techniques as they apply to crime scene photographic evidence. In all aspects of forensic dentistry, analytical comparison methods demand rigorous attention to scale dimensions and the detection of photographic distortion in images of forensic interest. Dental radiographs, photographic slides, negatives, prints, and digital images are all amenable to digital techniques that are useful in controlling quality and expanding the abilities of the forensic dentist to compare known and questioned evidence.

Growth hormone/insulin-like growth factor-1 response to acute and chronic growth hormone-releasing peptide-2, growth hormone-releasing hormone 1-44NH2 and in combination in older men and women with decreased growth hormone secretion.

To better appreciate the interactions of GHRP-2 and GHRH 1-44NH2 on the release of GH in normal adult men and women with decreased GH secretion and low serum IGF-1 levels, a series of acute and chronic studies have been performed (n = 5 men, 5 women). The acute iv bolus GH responses of these subjects to the two peptides alone and together suggest that the decreased GH secretion may be primarily due to a deficiency of the natural endogenous GHRP, ghrelin, rather than a decreased secretion of endogenous GHRH or excess secretion of SRIF. To determine whether the low GH response to GHRH was due to a limited capacity of pituitary to release GH, higher dosages of GHRP-2 alone were administered.

Interactive regulation of postmenopausal growth hormone insulin-like growth factor axis by estrogen and growth hormone-releasing peptide-2.

Estrogen is the proximate sex steroid sustaining GH secretion throughout the human life span in both sexes. However, very little is known about the specific neuroendocrine mechanisms by which estrogen activates and maintains GH secretion in the young or aging human. The identification of somatostatin in 1973 as a key negative peptidyl regulator of the GH axis and the discovery of GH-releasing hormone (GHRH) in 1982 as a dominant feedforward agonist of GH secretion provided an initial basic science foundation for exploring sex-steroid control of the GH-IGF-1 axis.

Interactions of growth hormone secretagogues and growth hormone-releasing hormone/somatostatin.

The class of novel synthetic compounds termed growth hormone secretagogues (GHSs) act in the hypothalamus through, as yet, unknown pathways. We performed physiologic and histochemical studies to further understand how the GHS system interacts with the well-established somatostatin (SRIF)/growth hormone-releasing hormone (GHRH) neuroendocrine system for regulating pulsatile GH secretion. Comparison of the GH-releasing activities of the hexapeptide growth hormone-releasing peptide-6 (GHRP-6) and GHRH administered intravenously to conscious adult male rats showed that the pattern of GH responsiveness to GHRP-6 was markedly time-dependent, similar to that observed with GHRH.

Moderators of stress in parents of children with autism.

Parents of children with autism experience more stress and are more susceptible to negative outcomes than parents of children with other disabilities. The present work examines the relationship between stressors, social support, locus of control, coping styles, and negative outcomes (depression, social isolation, and spousal relationship problems) among parents of children with autism. Fifty-eight parents completed surveys.

Generation of growth hormone pulsatility in women: evidence against somatostatin withdrawal as pulse initiator.

To test whether endogenous hypothalamic somatostatin (SRIH) fluctuations are playing a role in the generation of growth hormone (GH) pulses, continuous subcutaneous octreotide infusion (16 microg/h) was used to create constant supraphysiological somatostatinergic tone. Six healthy postmenopausal women (age 67 +/- 3 yr, body mass index 24.7 +/- 1.

Continuous 24-hour intravenous infusion of recombinant human growth hormone (GH)-releasing hormone-(1-44)-amide augments pulsatile, entropic, and daily rhythmic GH secretion in postmenopausal women equally in the estrogen-withdrawn and estrogen-supplemented states.

How estrogen amplifies GH secretion in the human is not known. The present study tests the clinical hypothesis that estradiol modulates the stimulatory actions of a primary GH feedforward signal, GHRH. To this end, we investigated the ability of short-term (7- to 12-day) supplementation with oral estradiol vs.

Short-term estradiol supplementation augments growth hormone (GH) secretory responsiveness to dose-varying GH-releasing peptide infusions in healthy postmenopausal women.

Estrogen is a prominent stimulus to GH secretion throughout the human life span, albeit via neuroendocrine mechanisms that are incompletely defined. Here, we test the hypothesis that estradiol replacement in postmenopausal women enhances the responsiveness of the hypothalamo-pituitary unit to the GH-releasing effect of GH-releasing peptide-2 (GHRP-2). GHRP-2 is a potent and selective synthetic hexapeptide capable of activating an endogenous GHRP receptor/effector pathway, for which a (3)Ser-octanoylated 28-amino acid ligand was cloned recently.

The design and delivery of crew resource management training: exploiting available resources.

Despite widespread acceptance throughout commercial and military settings, crew resource management (CRM) training programs have not escaped doubts about their effectiveness. The current state of CRM training is an example of how an entire body of pertinent research and development has not had the impact on practice that it could. In this paper we outline additional resources (i.

High-resolution, >1 GHz NMR in unstable magnetic fields.

Resistive or hybrid magnets can achieve substantially higher fields than those available in superconducting magnets, but their spatial homogeneity and temporal stability are unacceptable for high-resolution NMR. We show that modern stabilization and shimming technology, combined with detection of intermolecular zero-quantum coherences (iZQCs), can remove almost all of the effects of inhomogeneity and drifts, while retaining chemical shift differences and J couplings. In a 25-T electromagnet (1 kHz/s drift, 3 kHz linewidth over 1 cm(3)), iZQC detection removes >99% of the remaining inhomogeneity, to generate the first high-resolution liquid-state NMR spectra acquired at >1 GHz.

Decision making in dual-task environments: analysis of hemispheric competition effects.

Performance degradations in multitasking situations have been reported frequently as a predictable effect of competition that arises from different processing demands whose hemispheric locations are too proximal. This model might be useful in explaining performance deficits in complex workplaces. To test this assertion, a laboratory study was designed to create an analogue of the processing demands required by a tactical decision-making task performed by 24 right-handed men.

Synergy of L-arginine and GHRP-2 stimulation of growth hormone in men and women: modulation by exercise.

We investigated the ability of exercise, a multipathway, potent, physiological stimulus for GH release, to alter the synergistic interaction of L-arginine (A) and GH-related peptide (GHRP)-2 (G) observed at rest and the ability of gender to further modulate this putative interaction. Subjects (9 men and 9 early follicular phase women) completed 30 min of constant load aerobic exercise in combination with intravenous infusions of saline (S), A (30 g over 30 min), G (1 microg/kg bolus), or both (AG) in separate study sessions in randomly assigned order. Measures of GH release were logarithmically transformed for statistical analysis.

Synergy of L-arginine and growth hormone (GH)-releasing peptide-2 on GH release: influence of gender.

We test the hypotheses that 1) growth hormone (GH)-releasing peptide-2 (G) synergizes with L-arginine (A), a compound putatively achieving selective somatostatin withdrawal and 2) gender modulates this synergy on GH secretion. To these ends, 18 young healthy volunteers (9 men and 9 early follicular phase women) each received separate morning intravenous infusions of saline (S) or A (30 g over 30 min) or G (1 microg/kg) or both, in randomly assigned order. Blood was sampled at 10-min intervals for later chemiluminescence assay of serum GH concentrations.

Oral estradiol administration modulates continuous intravenous growth hormone (GH)-releasing peptide-2-driven GH secretion in postmenopausal women.

Exactly how estradiol (E2) regulates the human GH-insulin-like growth factor I axis is not known. Here, we explore the impact of oral E2 supplementation on the stimulatory actions of a potent and specific synthetic GH-releasing peptide (GHRP), GHRP-2. To this end, we studied 10 healthy postmenopausal women following the administration of placebo or 17beta-estradiol (1 mg twice daily orally) for 7-12 days in a prospectively randomized, double-blind, within-subject crossover design.

Growth hormone responses during strenuous exercise: the role of GH-releasing hormone and GH-releasing peptide-2.

Purpose And Methods: This study was designed to investigate the role of two effective releasers of growth hormone (GH): GHRH and GHRP-2 during exercise (EX). Eight healthy male subjects (ages: 22 +/- 1.2 (mean +/- SD) yr, BMI: 22.

A novel syndrome of radiation-associated acute myeloid leukemia involving AML1 gene translocations.

AML1 is a transcriptional activator that is essential for normal hematopoietic development. It is the most frequent target for translocations in acute leukemia. We recently identified 3 patients in whom pancytopenia developed almost 50 years after high-level radiation exposure from nuclear explosions during or after World War II.