The coincidence counting technique for orders of magnitude background reduction in data obtained with the magnetic recoil spectrometer at OMEGA and the NIF.

A magnetic recoil spectrometer (MRS) has been built and successfully used at OMEGA for measurements of down-scattered neutrons (DS-n), from which an areal density in both warm-capsule and cryogenic-DT implosions have been inferred. Another MRS is currently being commissioned on the National Ignition Facility (NIF) for diagnosing low-yield tritium-hydrogen-deuterium implosions and high-yield DT implosions. As CR-39 detectors are used in the MRS, the principal sources of background are neutron-induced tracks and intrinsic tracks (defects in the CR-39). The coincidence counting technique was developed to reduce these types of background tracks to the required level for the DS-n measurements at OMEGA and the NIF. Using this technique, it has been demonstrated that the number of background tracks is reduced by a couple of orders of magnitude, which exceeds the requirement for the DS-n measurements at both facilities.

Pharmacology of GABA rho 1 and GABA alpha/beta receptors expressed in Xenopus oocytes and COS cells.

1. The rho 1 protein, which we previously cloned from retina, assembles as a homooligomer that transduces the binding of gamma-aminobutyric acid (GABA) into robust chloride currents. However, its insensitivity to bicuculline, pentobarbitone and benzodiazepines, all potent agents at typical GABAA receptors, suggested that it may react atypically to other GABA agonists and antagonists. 2. cDNAs for the rho 1 and the alpha 5 beta 1 receptors for GABA were expressed as homo- and heterooligomers, respectively, in Xenopus oocytes. The selectivities of the respective receptors for various agonists were investigated using concentration-response experiments in voltage clamped cells. 3. The most potent agonists at the rho 1 receptor were trans-4-aminocrotonic acid (TACA) > GABA > muscimol; at the alpha 5 beta 1 receptor the rank order was muscimol > GABA > 4,5,6,7-tetrahydroisoxazole[4,5-c]pyridine-3-ol (THIP). The most specific agonists were cis-(2-(aminomethyl)-cyclopropyl-carboxylic acid (CAMP) and THIP for the rho 1 and the alpha 5 beta 1 receptors, respectively. 4. Comparing GABA, TACA and cis-aminocrotonic acid (CACA) at rho 1 receptors expressed in COS cells gave results almost indistinguishable from those found at oocytes; the pharmacology of rho 1 seems independent of the expression system. 5. Agonists THIP, piperidine-4-sulphonic acid (P4S), and isoguvacine, whose C-C-C-N chains are constrained by rings into a folded conformation and were potent at the alpha 5 beta 1 receptor, were among the weakest at the rho 1 receptor. However CACA and CAMP, which align better with the extended than the folded conformation, were weakest at the alpha 5 beta 1 receptor but moderately potent at the pl receptor. These findings suggest that the rho l receptor recognizes agonists in the extended conformation, in contrast to GABAA receptors, which are believed to recognize agonists in the partially folded conformation.6. In contrast to the alpha 5 beta 1 receptor, gradations in maximum responses were apparent in the rho l receptor,suggesting various degrees of partial agonism. In particular, imidazole-4-acetic acid (I4AA), whose maximum response was only 3% of GABA's maximum, had an apparent Kd for activating the rho l receptor of 16 microM; but it had an apparent Kd for competitively blocking the receptor of 0.64 microM. This difference suggests that steric constraints in the activated (open channel) receptor are tighter than in the resting receptor.7. Hill coefficients approached 2 at the rho l receptor, but were closer to unity at the alpha 5 beta 1 receptor. Thus,the rho l receptor displayed higher cooperativity.8. Unlike typical GABAA receptors, the rho l receptor was insensitive to the competitive antagonists bicuculline, SR95531, securinine, and (+)-tubocurarine.

New concepts in managing diabetic foot infections.

Recent enhanced attention to diabetic foot infection--in both clinical care and research--has yielded a modified picture of this disorder. It suggests that certain diabetic patients may have important risk factors for the development of infection, and further, infections in these patients may not have the same clinical characteristics as the soft tissue or bony infections found in nondiabetic subjects. Treatment of diabetic patients should therefore be modified to conform to the particular characteristics of their infections.

Ligand autoradiographic receptor screening. II. Expression of receptor cDNA in transfected COS cells grown on polyester disks and its recovery.

A receptor autoradiographic method that can detect expressed receptor cDNA in 0.002% of plasmid clones and can allow cDNA recoveries and enrichments up to 300-fold in one cycle of screening is described.

Inhibition of synaptosomal accumulation of l-norepinephrine II: N-aryloxyalkylphentermines, quaternary d-amphetamines, and 3-aryloxypropylamines.

The inhibitory potencies of a series of N-substituted phentermines on the synaptosomal uptake of l-norepinephrine were found to be similar to those of the corresponding amphetamines. Quaternization of N, N-dimenthyl-d-amphetamine diminished, but did not abolish, its inhibitory potency, indicating that a permanently charged cation is also effective. Since the addition of an aromatic moiety at the end of a four-atom chain originating at the nitrogen of amphetamine or phentermine significantly increased inhibitor strength, several 3-aryloxypropylamines and 4-phenylbutylamine were tested, but they were much weaker inhibitors than dl-amphetamine. Thus, the observed increase in inhibitor potency apparently was not simply the result of a specific interaction of the "nonmimic" portion of the N-substituted amphetamines or phentermines.

Inhibition of synaptosomal accumulation of l-norepinephrine. I: N-arylalkyl and N-aryloxyalkyl dl-amphetamines and related compounds.

The ability of a group of systematically modified amphetamines to inhibit the accumulation of l-norepinephrine by nonstriatal synaptosomes was investigated. N-Substitution by the proper bulky hydrophobic groups can be well tolerated. Structure-activity relationships generate a qualitative picture of the inhibitor-carrier interaction site.

Production and characterization of antibodies to meperidine.

A mepridine-bovine serum albumin (Mep-BSA) conjugate with 15-20 moles of meperidine per mole of BSA was synthesized and characterized. Rabbits immunized with Mep-BSA produced antibodies that were assayed utilizing saturated ammonium sulfate to separate 3H-meperidine (3H-M) bound to antibody from free 3H-M. Antibody specificity was assessed by competitive inhibition studies. The nanomoles of inhibitor required to decrease the binding of 3H-M by 50% were: meperidine .046; meperidine acid, 3.2; alphaprodine, 7.8; dextromethorphan, 20; codeine, 50; and morphine 55. The sensitivity of the assay is approximately 30 ng/ml; sufficient for pharmacokinetic studies of the disposition of meperidine in man.