Phenylpiperidine opioid antagonists that promote weight loss in rats have high affinity for the kappa 2B (enkephalin-sensitive) binding site.

Certain opioid antagonists of the phenylpiperidine series (PPAs), such as LY255582, seem uniquely efficacious at producing weight loss in lean and meal-fed obese Zucker rats. Comparison of the pharmacological and receptor binding profile of PPAs that promote marked weight loss with those that do not has failed to find any obvious differences between these two groups of narcotic antagonists, which might explain the differences in their biological activities. The potent stimulatory effect of dynorphin, and other kappa agonists, on feeding behavior suggests that the antagonists that promote weight loss might have high affinity for kappa receptors.

Transepicardial defibrillation dose response: current versus energy.

In pentobarbital-anesthetized dogs, we compared the relative efficacy of current versus energy in applying the dose response method in transcardiac defibrillation. Damped sinusoidal shocks via epicardial patches were administered by a custom defibrillator permitting precise current delivery. Following the establishment of an initial estimated defibrillation threshold for energy and current, the dose response method was performed with regard to either energy defibrillation threshold (group E, n = 8) or current defibrillation threshold (group C, n = 8).

A constraint reasoning system for automating sequence-specific resonance assignments from multidimensional protein NMR spectra.

AUTOASSIGN is a prototype expert system designed to aid in the determination of protein structure from nuclear magnetic resonance (NMR) measurements. In this paper we focus on one of the key steps of this process, the assignment of the observed NMR signals to specific atomic nuclei in the protein; i.e.

Quality of pediatric care at a freestanding emergency facility.

The last decade has seen the introduction of freestanding emergency facilities, which provide an alternative to hospital emergency departments. The contribution made by these facilities to the clinical welfare of patients depends on their availability to deliver quality medical care without the need for frequent referral. This study describes the clinical experience of one such facility with pediatric patients and attempts to assess the quality of their care.

6-substituted decahydroisoquinoline-3-carboxylic acids as potent and selective conformationally constrained NMDA receptor antagonists.

We have prepared a series of 6-substituted decahydroisoquinoline-3-carboxylic acids, and structurally similar analogs, as potential N-methyl-D-aspartate receptor antagonists. There is a large body of evidence to support the use of such compounds as cerebroprotective agents in a variety of acute and chronic neurodegenerative disorders, where some component of glutamate-mediated excitotoxicity may exist. The compounds prepared were evaluated in vitro in both receptor binding assays ([3H]CGS19755, [3H]AMPA, and [3H]kainic acid) and in a cortical wedge preparation (versus NMDA, AMPA, and kainic acid) to determine affinity, potency, and selectivity.

Molecular structure and pharmacological characterization of humEAA2, a novel human kainate receptor subunit.

A cDNA encoding a novel human glutamate receptor subunit protein was isolated from a human hippocampal library. This cDNA, termed humEAA2, is most closely related to rat cDNAs for kainate receptor proteins and, when expressed in COS cells, is associated with high affinity kainate receptor binding. The relative potency of compounds in displacing [3H]kainate binding was kainate greater than quisqualate greater than domoate greater than L-glutamate much greater than 6,7-dinitroquinoxaline-2,3-dione greater than dihydrokainate greater than 6-cyano-7-nitroquinoxaline-2,3-dione greater than (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid.

Tibia vara in a patient with Bardet-Biedl syndrome.

The Bardet-Biedl syndrome is characterized by polydactyly, hypogonadism, obesity, mental retardation, and retinitis pigmentosa. Several other skeletal findings include hip dysplasia, short stature, and skull deformities. The patient described in this report has the classic findings of Bardet-Biedl syndrome in conjunction with tibia vara and irregular physes of the lower extremities.

Evidence for peptide transport across microsomal membranes.

Antigenic peptides bound to class I molecules of the major histocompatibility complex (MHC) are recognized by T-cell receptors during development of an antiviral immune response. T cells respond to peptides derived from cytoplasmic viral proteins as well as viral membrane proteins, indicating that a pathway exists for the transport of proteins or peptides from the cytosol into the compartment(s) where the MHC class I molecules assemble. To investigate this pathway, we have developed an in vitro assay for the transport of peptides into microsomal vesicles.

Cyclic interdigestive pancreatic exocrine secretion: is it mediated by neural or hormonal mechanisms?

Cyclic interdigestive exocrine pancreatic secretion and duodenal motility are closely linked. However, the mechanisms controlling this association are not well understood. The aim of this study was to determine whether a neural or hormonal mechanism controls the temporal association of interdigestive secretion and duodenal motility.

Somatomedin C/insulin-like growth factor I levels after treatment of acromegaly.

An in-house method was used, including dissociation of Somatomedin C/insulin-like Growth Factor I (Sm-C/IGF-I) binding proteins with acid and extraction of Sm-C/IGF-I by C-2 cartridge before radioimmunoassay, to measure plasma Sm-C/IGF-I levels in three groups of patients--total of 19--with acromegaly who underwent transsphenoidal removal of pituitary tumors. In group A (n = 7), the Sm-C/IGF-I levels did not decrease to normal on postoperative day 1 even though the growth hormone concentration had decreased to normal. In group B (n = 4), the Sm-C/IGF-I level decreased to normal in three of the four patients on postoperative day 4, but it remained elevated in one.

Radiation therapy for diabetes insipidus caused by Langerhans cell histiocytosis.

Hypothalamic-pituitary radiation therapy has been the standard treatment for the diabetes insipidus of Langerhans cell histiocytosis. The goal of this study was to assess the role of radiation therapy in Langerhans cell histiocytosis-associated diabetes insipidus and to compare the results with nonirradiated controls. Forty-seven patients with pathologically confirmed Langerhans cell histiocytosis were diagnosed with diabetes insipidus between 1950 and 1989 and were treated at the Mayo Clinic.

Central administration of the opioid antagonist, LY255582, decreases short- and long-term food intake in rats.

A variety of opioid antagonists have been reported to decrease short-term food intake, but few appear to reduce long-term intake. In the present study we evaluated the effect of a relatively new class of opioid antagonists, 3,4-dimethyl-4-phenylpiperidines, on short-term and long-term food intake after central administration. We also evaluated their affinities for the mu and kappa opioid receptor sites in synaptosomal membranes derived from rat whole brain tissue (minus cerebellum) and guinea-pig cortex, respectively.

Reconsiderations of the routine and preferential use of lidocaine in the emergent treatment of ventricular arrhythmias.

Objective: Despite a history of widespread use, the utility of lidocaine as an antiarrhythmic and antifibrillatory agent is questionable. The objective of this article is to examine the theoretical basis for the use of lidocaine in light of recent experimental and clinical data. This article reviews the effects of lidocaine on: a) ventricular arrhythmias under ischemic and nonischemic conditions; b) the energy and current requirements for defibrillation; and c) the propensity for asystole during cardiac arrest.

Limitations of the countershock dose response: a study of transthoracic current.

Dose response assessment of countershock efficacy has been widely determined with respect to energy but not current. The purpose of this study was to examine the utility of the dose response method in a current-based model of transthoracic defibrillation (pentobarbital anesthetized dogs, n = 8). Ventricular fibrillation induction lasting 15 seconds was separated by 5-minute intervals.

Acute toxicity, genotoxicity, and dermal carcinogenicity assessment of isooctyl acrylate.

Isooctyl acrylate (IOA) monomer is a complex mixture comprised predominantly of isomeric, eight-carbon alkyl esters of acrylic acid. Limited evidence from animal studies suggests that certain acrylate esters may be carcinogenic by the dermal route of exposure. The following studies were performed with IOA monomer: acute oral toxicity limit test in rats, primary dermal and ocular irritancy in rabbits, Ames Salmonella microsome assay, Saccharomyces cerevisiae D3 recombinogenicity assay, L5178Y TK +/- mouse lymphoma cell assay, and C3H/10T1/2 mouse embryo cell transformation assay.

Mental illness and psychotropic medication use in the nursing home.

The authors examined mental illness and psychotropic medications use among nursing home residents. Data were drawn from the Texas Long-Term Care Reimbursement Project, a 1986 study of nearly 2,000 residents in 49 nursing homes. The study measured the use of antipsychotics and other psychotropic medications, physical health conditions, mental illness diagnoses, behavior, and nursing and other direct-care time for sampled residents.

An ATP-binding membrane protein is required for protein translocation across the endoplasmic reticulum membrane.

The role of nucleotides in providing energy for polypeptide transfer across the endoplasmic reticulum (ER) membrane is still unknown. To address this question, we treated ER-derived mammalian microsomal vesicles with a photoactivatable analogue of ATP, 8-N3ATP. This treatment resulted in a progressive inhibition of translocation activity.

Further evidence for Coren and Hakstian's "Methodological implications of interaural correlation: count heads not ears" and an alternative correction formula.

Coren and Hakstian (1990) identified a serious methodological problem that arises in auditory research because of interaural correlation. When measures from both ears of the subjects are pooled together in an experimental design that assumes independence of measures, there can be spuriously high apparent statistical significance. The present paper provides further evidence in support of Coren and Hakstian's argument and also derives a formula that effectively corrects inflated test statistics resulting from interaural correlation.

Characterization of the rough endoplasmic reticulum ribosome-binding activity.

The rough endoplasmic reticulum membranes of mammalian cells contain specific ribosome-binding sites. A purification to apparent homogeneity of a negatively charged protein (ERp180) of relative molecular mass 180,000 (180 K) was reported which was proposed to function as a rough endoplasmic reticulum ribosome receptor. We report here that ribosome-binding site activity quantitatively solubilized from rough endoplasmic reticulum membranes does not cofractionate with ERp180.

Direct responses to selection for increased litter size, decreased age at puberty, or random selection following selection for ovulation rate in swine.

Nine generations of selection for high ovulation rate were followed by two generations of random selection and then eight generations of selection for increased litter size at birth, decreased age at puberty, or continued random selection in the high ovulation rate line. A control line was maintained with random selection. Line means were regressed on generation number and on cumulative selection differentials to estimate responses to selection and realized heritabilities.

The effect of the opioid antagonist LY255582 on body weight of the obese Zucker rat.

The effects of the phenylpiperidine opioid antagonist, LY255582, on food consumption, water consumption and body weight gain of the meal-fed obese Zucker rat have been determined. A single subcutaneous dose of LY255582 (0.31 mg/kg) decreased food and water consumption of the meal-fed obese rat.