A His-Pro-Aib peptide that exhibits an Asx-Pro-turn-like structure.

[formula: see text] Small peptides 1 and 2, which differ only in that 1 possesses a BOC-Phe residue at the N-terminus, where 2 bears a BOC-(tau-benzyl)His, were found to exhibit very different structures. In both the solid state (X-ray) and in solution (NMR and IR), peptide 1 exists as a beta-turn, whereas peptide 2 exists in a conformation that resembles the Asx-Pro motif.

A comparison of two controlled-release delivery systems for the delivery of amiloride to control angiogenesis.

The diuretic amiloride has been reported to inhibit both Na+-H+ antiport and the urokinase-type plasminogen activator. As a consequence of these inhibitions, neovascularization may also be inhibited. We hypothesized that if amiloride could be effectively delivered in a site-specific manner, a system might be developed that could inhibit localized angiogenesis.

Capillary density of skeletal muscle: a contributing mechanism for exercise intolerance in class II-III chronic heart failure independent of other peripheral alterations.

Objectives: The study was conducted to determine if the capillary density of skeletal muscle is a potential contributor to exercise intolerance in class II-III chronic heart failure (CHF).

Background: Previous studies suggest that abnormalities in skeletal muscle histology, contractile protein content and enzymology contribute to exercise intolerance in CHF.

Methods: The present study examined skeletal muscle biopsies from 22 male patients with CHF compared with 10 age-matched normal male control patients.

Altered expression of myosin heavy chain in the vastus lateralis muscle in patients with COPD.

This study was designed to further characterize peripheral skeletal muscle alterations in patients with chronic obstructive pulmonary disease (COPD) and to evaluate the possible relationship between myosin heavy chain (MyoHC) isoform expression and exercise tolerance in these individuals. MyoHC composition from biopsy of the vastus lateralis muscle was examined in 12 COPD patients (forced expiratory volume in one second (FEV1)=31+/-9% predicted, peak oxygen consumption (V'O2)=15+/-4 mL x kg(-1) x min(-1)) and 10 age-matched normal male subjects (peak V'O2=20+/-5 mL x kg(-1) x min(-1)). The proportion of MyoHC type I was smaller in COPD than in normals (27+/-17% versus 41+/-9%, p<0.

MEK kinase 3 directly activates MKK6 and MKK7, specific activators of the p38 and c-Jun NH2-terminal kinases.

Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) activates the c-Jun NH2-terminal kinase (JNK) pathway, although no substrates for MEKK3 have been identified. We have examined the regulation by MEKK3 of MAPK kinase 7 (MKK7) and MKK6, two novel MAPK kinases specific for JNK and p38, respectively. Coexpression of MKK7 with MEKK3 in COS-7 cells enhanced MKK7 autophosphorylation and its ability to activate recombinant JNK1 in vitro.

Phenotypic differences in the GnRH neuronal system of deer mice Peromyscus maniculatus under a natural short photoperiod.

The neural mechanisms by which short photoperiod induces gonadal regression among seasonally breeding mammals are not well understood. One hypothesis suggests that the proximate cause of seasonal gonadal regression is a photoperiod-induced modification in GnRH secretion. This hypothesis is indirectly supported by our recent findings using immunocytochemistry which identified specific photoperiod-induced adjustments in the number and morphology of GnRH containing neurones between reproductively competent and reproductively regressed laboratory housed male deer mice.

Regulation of extracellular-signal regulated kinase and c-Jun N-terminal kinase by G-protein-linked muscarinic acetylcholine receptors.

Extracellular signal-regulated kinases (ERKs) and c-Jun N-terminal kinases (JNKs, or stress-activated protein kinases) are activated by diverse extracellular signals and mediate a variety of cellular responses, including mitogenesis, differentiation, hypertrophy, inflammatory reactions and apoptosis. We have examined the involvement of Ca2+ and protein kinase C (PKC) in ERK and JNK activation by the human G-protein-coupled m2 and m3 muscarinic acetylcholine receptors (mAChR) expressed in Chinese hamster ovary (CHO) cells. We show that the Ca2+-mobilizing m3 AChR is efficiently coupled to JNK and ERK activation, whereas the m2 AChR activates ERK but not JNK.

Neuromuscular effects of low level exposures to Sarin, pyridostigmine, DEET, and chlorpyrifos.

A study is being initiated to investigate subtle neurobehavioral effects and neuropathology in rats due to exposure to combinations of low levels of Sarin (GB), N,N-diethyl-m-toluamide (DEET), chlorpyrifos (CPF), and pyridostigmine bromide (PB). A similar study is being initiated in rhesus monkeys to investigate neurophysiologic effects and neuromuscular pathology due to exposure to a combination of GB, DEET, CPF, and PB, along with vaccination with botulinum toxoid. A description of these studies is presented.

Rostral-caudal variation in troponin T and parvalbumin correlates with differences in relaxation rates of cod axial muscle.

Relaxation rate is an important determinant of axial muscle power production during the oscillatory contractions of undulatory locomotion. Recently, significant differences have been reported in the relaxation rates of rostral versus caudal white muscle fibers of the Atlantic cod Gadus morhua L. The present study investigates the biochemical correlates of this rostral-caudal physiological variation.

Human adenosine A1 receptor and P2Y2-purinoceptor-mediated activation of the mitogen-activated protein kinase cascade in transfected CHO cells.

1. The mitogen-activated protein (MAP) kinase signalling pathway can be activated by a variety of heterotrimeric Gi/Go protein-coupled and Gq/G11 protein-coupled receptors. The aims of the current study were: (i) to investigate whether the Gi/Go protein-coupled adenosine A1 receptor activates the MAP kinase pathway in transfected Chinese hamster ovary cells (CHO-A1) and (ii) to determine whether adenosine A1 receptor activation would modulate the MAP kinase response elicited by the endogenous P2Y2 purinoceptor.

In situ observations of a high-pressure phase of H2O Ice.

A previously unknown solid phase of H2O has been identified by its peculiar growth patterns, distinct pressure-temperature melting relations, and vibrational Raman spectra. Morphologies of ice crystals and their pressure-temperature melting relations were directly observed in a hydrothermal diamond-anvil cell for H2O bulk densities between 1203 and 1257 kilograms per cubic meter at temperatures between -10 degrees and 50 degreesC. Under these conditions, four different ice forms were observed to melt: two stable phases, ice V and ice VI, and two metastable phases, ice IV and the new ice phase.

p21WAF1 is dynamically associated with JNK in human T-lymphocytes during cell cycle progression.

We have examined the regulation of the c-Jun NH2-terminal kinase (JNK) subfamily of mitogen-activated protein kinases (MAPKs) in response to inhibition of DNA replication during the cell cycle of human T-lymphocytes. In this study, we demonstrate that JNK is rapidly activated following release of T-lymphocytes from G1/S-phase arrest and that this activation precedes resumption of DNA synthesis upon S-phase progression. We also show that activation of JNK correlates with dissociation of the cyclin-dependent protein kinase (CDK) inhibitor, p21WAF1, from JNK1.

Mailing strategies and costs of recruiting heavy smokers in CARET, a large chemoprevention trial.

Recruitment costs represent a major portion of the budget for large clinical trials during the initial years of the study. Further, the rate of recruitment affects allocation of resources in future years. To learn about the costs and yields of recruiting from different populations and under different mailing strategies, we monitored recruitment yields of eligible heavy smokers for the Carotene and Retinol Efficacy Trial (CARET) at the Portland Study Center.

A domain for G protein coupling in carboxyl-terminal tail of rat angiotensin II receptor type 1A.

To delineate domains essential for Gq protein coupling in the C-terminal region (C-tail) of rat angiotensin II (Ang II) receptor type 1A (AT1A), we modified the putative cytosolic regions of the receptor by truncation or alanine substitution and determined resultant changes in the guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) effect on Ang II binding and inositol trisphosphate production by the agonist. Independently, we studied the effect of synthetic C-tail peptides (P-5) and its alanine substitution analogs on [35S]GTPgammaS binding to Gq. Effects of GTPgammaS on Ang II binding (shift to a low affinity form) and inositol trisphosphate production in the deletional mutant receptor 1-317 AT1A was similar to wild type AT1A, whereas in shorter C-terminal deletion mutants 1-309, 1-311, 1-312, 1-313 AT1A, and substitutional mutants Y312A, F313A, and L314A these activities were markedly reduced.

Characterization of the mitogen-activated protein kinase kinase 4 (MKK4)/c-Jun NH2-terminal kinase 1 and MKK3/p38 pathways regulated by MEK kinases 2 and 3. MEK kinase 3 activates MKK3 but does not cause activation of p38 kinase in vivo.

We previously reported the isolation of cDNAs encoding two mammalian mitogen-activated protein kinase (MAPK)/extracellular-regulated kinase (ERK) kinase kinases, designated MEKK2 and MEKK3 (Blank, J.L., Gerwins, P.

Comparison of an in vitro skin model to normal human skin for dermatological research.

EpiDerm, an in vitro human skin equivalent (HSE), was compared to normal human breast skin (NHS) to morphologically and biochemically assess its feasibility for dermatological research. Intralot and interlot variability was studied in day 0, 1, 2, and 3 in vitro cultures and in day 0, 3, 5, and 7 NHS. For NHS, light microscopy (LM) at day 0 showed stratified epidermis which exhibited an increase in vacuoles and dark basal cells as storage increased to 3, 5, and 7 days.

Phenotypic variation in seasonal adjustments of testis size, body weight, and food intake in deer mice: role of pineal function and ambient temperature.

We investigated pineal function as well as reproductive and energetic characteristics in male deer mice (Peromyscus maniculatus) that differentially respond to short photoperiod with full, partial or no gonadal regression. In mice at both high (23 degrees C) and low temperature (1 degree C), these phenotypic differences in reproductive responses to short days were not reflected by differences in urinary excretion of 6-sulphatoxy-melatonin, the main metabolite of pineal melatonin. Neither duration nor amplitude or phase-angle of nocturnal peaks in 6-sulphatoxymelatonin significantly differed between reproductive phenotypes at either temperature.

Cloning of a novel mitogen-activated protein kinase kinase kinase, MEKK4, that selectively regulates the c-Jun amino terminal kinase pathway.

Mitogen-activated protein kinases (MAPKs) are components of sequential kinase cascades that are activated in response to a variety of extracellular signals. Members of the MAPK family include the extracellular response kinases (ERKs or p42/44(MAPK)), the c-Jun amino-terminal kinases (JNKs), and the p38/Hog 1 protein kinases. MAPKs are phosphorylated and activated by MAPK kinases (MKKs or MEKs), which in turn are phosphorylated and activated by MKK/MEK kinases (Raf and MKKK/MEKKs).

Photoperiod and steroid-dependent adjustments in hypothalamic gonadotropic hormone-releasing hormone, dopamine, and norepinephrine content in male deer mice.

The purpose of this study was twofold: 1) to examine photoperiod-dependent and steroid-dependent adjustments in hypothalamic GnRH and catecholamine content in male deer mice, Peromyscus maniculatus, and 2) to evaluate whether the commonly used measure of GnRH accumulation serves as an accurate indicator of altered reproductive function in short-day-housed rodents. Deer mice provide a unique animal model in which to evaluate the effect of short day length on the neural substrates directing reproductive function, since individual deer mice respond to short photoperiod with a range of neuroendocrine, endocrine, metabolic, and thermoregulatory adjustments. These adjustments, in part, result in two distinct reproductive phenotypes; reproductively competent "nonresponsive" mice, and gonad-regressed "responsive" mice.

Cutaneous histopathologic features in weanling pigs after exposure to three different doses of liquid sulfur mustard.

Sulfur mustard (2,2' dichlorodiethyl sulfide, HD) is a chemical warfare agent that is easily produced, and may be used against civilian populations as well as against military troops. However, good therapeutic and prophylactic measures await a better understanding of the pathophysiology of lesions produced by this agent. Because the skin remains is one of the principal routes for HD exposure and damage, the study of HD-induced skin lesions is of major interest.

Evaluation of the Neer system of classification of proximal humeral fractures with computerized tomographic scans and plain radiographs.

The intraobserver reliability and inter-observer reproducibility of the Neer classification system were assessed on the basis of the plain radiographs and computerized tomographic scans of twenty fractures of the proximal part of the humerus. To determine if the observers had difficulty agreeing only about the degree of displacement or angulation (but could determine which segments were fractured), a modified system (in which fracture lines were considered but displacement was not) also was assessed. Finally, the observers were asked to recommend a treatment for the fracture, and the reliability and re-producibility of that decision were measured.

The distal radioulnar joint in rheumatoid arthritis.

This article outlines the relevant pathoanatomy and kinematics, clinical and radiographic findings, and treatment alternatives for the rheumatoid distal radioulnar joint. A summary of the authors preferred techniques is presented.

Molecular cloning of mitogen-activated protein/ERK kinase kinases (MEKK) 2 and 3. Regulation of sequential phosphorylation pathways involving mitogen-activated protein kinase and c-Jun kinase.

Mitogen-activated protein/ERK kinase kinases (MEKKs) phosphorylate and activate protein kinases which in turn phosphorylate and activate the p42/44 mitogen-activated protein kinase (MAPK), c-Jun/stress-activated protein kinases (JNKs), and p38/Hog1 kinase. We have isolated the cDNAs for two novel mammalian MEKKs (MEKK 2 and 3). MEKK 2 and 3 encode proteins of 69.