Acanthocephaloides cyrusi n. sp. (Acanthocephala: Arhythmacanthidae) from southeast African teleost fishes

A new species,Acanthocephaloides cyrusi, is described from the fishesSolea bleekeri andPomadasys commersoni from Lake St. Lucia, Natal, South Africa. It is distinguished from the other species in the genus by the more marked sexual dimorphism in length, the arrangement of hooks, the proboscis with the longest hooks at the anterior-most extremity and the greater size of the proboscis hooks and body spines. An acanthella, which may represent this species, was found in the tanaidApseudes digitalis.     

Stereoselectivity and regioselectivity of uridine-5'-diphosphoglucuronosyltransferase toward vicinal dihydrodiols of polycyclic aromatic hydrocarbons

The ability of a purified rat liver microsomal uridine-5'-diphosphoglucuronosyltransferase to catalyze the glucuronidation of stereoisomeric trans- and cis-9, 10-dihydroxy-9, 10-dihydrophenanthrenes and 4, 5-dihydroxy-4,5-dihydrobenzo[alpha]pyrenes is examined. The enzyme shows the ability to discriminate kinetically between the antipodes of trans-9, 10-dihydroxy-9, 10-dihydrophenanthrene with turnover numbers of 0.070 and 1.4 s-1 and kc/Kmapp values of 4.4 X 10(3) and 1.1 X 10(3) M-1 s-1 for the 9R, 10R and 9S, 10S stereoisomers. Glucuronidation of the nondissymmetric cis-9, 10-dihydroxy-9, 10-dihydrophenanthrene proceeds with a turnover number of 0.037 s-1 and kc/Kmapp of 18 X 10(3) M-1 s-1 to give a 60/40 mixture of the two possible diastereomeric products. Three of the four stereoisomers of 4,5-dihydroxy-4,5-dihydrobenzo[alpha] pyrene are regioselectively glucuronidated by the enzyme with a high degree of kinetic discrimination. Turnover numbers for the 4S,5S, 4R,5R, and 4S,5R stereoisomers are 4.1, 0.37, and 0.23 s-1 with kc/Kmapp values of 23.8 X 10(3), 0.23 X 10(3), and 3.15 X 10(3) M-1 s-1, respectively. The 4R,5S cis isomer is not a substrate. Enzyme-catalyzed reactions of the 4S,5S and 4S,5R isomers give exclusively (greater than or equal to 95%) the 4-glucuronide with the 4R,5R isomer giving the 5-glucuronide. The kinetic and regiochemical results indicate that the enzyme recognizes hydroxyl groups on the beta-face or bottom face of the 4,5-dihydroxy-4,5-dihydrobenzo[alpha]pyrenes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phase resetting and fixed-delay stimulation of a simple model of respiratory rhythm generation.

In a previous study (Lewis et al., 1990), the response of the respiratory rhythm to a perturbing stimulus was investigated using two different stimulus protocols: phase resetting and fixed-delay stimulation. The first protocol consists of measuring the effects of perturbing an oscillator at different phases of the cycle on the duration of the perturbed cycle. The resulting phase response curves (PRCs) can be used to characterize the properties of the oscillator (Winfree, 1980). A second protocol, fixed-delay stimulation, involves perturbing an oscillator at a fixed latency from the onset of the cycle, repeated every n-th cycle. If a single stimulus produces an effect that lasts longer than a single cycle, complicated responses can be expected from fixed-delay stimulation (Lewis et al., 1987). A simple three-phase model for respiratory rhythm generation based on a hypothesis by Richter and coworkers (1982, 1983, 1986) was investigated in the context of these experimental studies. Phase resetting and fixed-delay stimulation protocols were simulated in the model. PRCs of the model resemble those obtained experimentally: a phase-dependent prolongation or shortening of the inspiratory phase depending on the stimulus magnitude, and a slight prolongation of the expiratory phase. Stimuli delivered to the model repetitively during successive inspiratory periods at a fixed-delay produced various combinations of shortened and prolonged cycles, similar to those observed in the experiments. However, the marked increases in cycle duration observed in the experiments during, as well as after, stimulation were not evident in the model. These comparisons suggest that (1) PRCs may not be an adequate way to evaluate certain models of rhythmogenesis, and (2) to improve the present simplified formulation of the three-phase model of the respiratory oscillator, time-varying stimulus dependent effects should be incorporated.     

Optimization of 2-piperidin-4-yl-acetamides as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists: Designing out hERG inhibition

Herein, we disclose the discovery and optimization of 2-piperidin-4-yl-acetamide derivatives as MCH-R1 antagonists. Structural investigation of piperidin-4-yl-amide and piperidin-4-yl-ureas identified 2-piperidin-4-yl-acetamide-based MCH-R1 antagonists with outstanding in vivo efficacy but flawed with high affinity towards the hERG potassium channel. While existing hERG SAR information was employed to discover highly potent MCH-R1 antagonists with minimized hERG inhibition, additional hurdles prevented their subsequent clinical exploration.     

Membrane dynamics of lymphocyte interaction with antigen and tolerogen.

The principle of hapten-specific carrier-dependent immunologic tolerance was used to study the in vivo and in vitro interaction of lymphocyte membrane receptors with antigen (DNP-KLH) and tolerogen (DNP-MGG). Direct fluorescent techniques were employed to illustrate the binding of tolerogeu and antigen to the same population of lymphoid cells and the subsequent in vivo and in vitro events related to capping and regeneration of membrane receptors.