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Biomedical subjects

G T Smith

Publications and source records attributed to G T Smith.

At least 19 recordsLinked to original sources

Experimental charge-density study on the nickel(II) coordination complex [Ni(H3L)][NO3][PF6] [H3L = N,N',N''-tris(2-hydroxy-3-methylbutyl)-1,4,7-triazacyclononane]: a reappraisal.

The experimental charge density in the title complex has been re-examined. The original work, reported some 8 years ago [Smith et al. (1997). J. Am. Chem. Soc. 119, 5028-5034], was undertaken using a very early version of the XD software, which contained serious programming errors. A re-refinement, using the original data and a recent version of the XD software, shows that many of the unusual aspects of this earlier study are artefacts due to these programming errors. The topological properties of the newly obtained experimental density compare well with those calculated from a theoretical DFT (density-functional theory) UHF-SCF (unrestricted Hartree Fock-self-consistent field) density. This report corrects several erroneous conclusions regarding the charge density in the title complex--in particular, the highly unusual diffuse Laplacian distribution about the Ni atom, and the trifurcated bond path from the Ni atom to the alcohol oxygen donor atoms are no longer observed. An examination of a range of topological properties of the metal-ligand bonds leads to the conclusion that the Ni-N and Ni-O bonds have an intermediate character, with a significant shared interaction, but with a substantial ionic component. This new study also reveals a previously unrecognized intramolecular H...H interaction in the macrocyclic ligand.

Journal Article↗

Simulation of emission tomography using grid middleware for distributed computing.

SimSET is Monte Carlo simulation software for emission tomography. This paper describes a simple but effective scheme for parallel execution of SimSET using NetSolve, a client-server system for distributed computation. NetSolve (version 1.4.1) is "grid middleware" which enables a user (the client) to run specific computations remotely and simultaneously on a grid of networked computers (the servers). Since the servers do not have to be identical machines, computation may take place in a heterogeneous environment. To take advantage of diversity in machines and their workloads, a client-side scheduler was implemented for the Monte Carlo simulation. The scheduler partitions the total decay events by taking into account the inherent compute-speeds and recent average workloads, i.e., the scheduler assigns more decay events to processors expected to give faster service and fewer decay events to those expected to give slower service. When compute-speeds and sustained workloads are taken into account, the speed-up is essentially linear in the number of equivalent "maximum-service" processors. One modification in the SimSET code (version 2.6.2.3) was made to ensure that the total number of decay events specified by the user is maintained in the distributed simulation. No other modifications in the standard SimSET code were made. Each processor runs complete SimSET code for its assignment of decay events, independently of others running simultaneously. Empirical results are reported for simulation of a clinical-quality lung perfusion study.

Computer Communication Networks↗

Hippocampal volume does not change seasonally in a non food-storing songbird.

Seasonal differences in hippocampal morphology have been reported in food-storing birds. Non food-storing species have not been investigated however. It is therefore unclear whether seasonal changes in the hippocampus are specifically related to food-storing or reflect a more general seasonal mechanism that occurs in both food-storing and non food-storing birds alike. We determined the volumes of the hippocampal formation and remaining telencephalon in the non-storing male song sparrow (Melospiza melodies morphna) in two experiments comparing birds collected in the spring and fall of 1992-94 (Experiment 1) and 1997 (Experiment 2). Although pronounced seasonal changes in song control nuclei such as the HVC and RA were previously reported for the same brains used in Experiment 1, we found that hippocampal volume did not change with season in either Experiment 1 or 2 for these song sparrow brains. These results suggest that seasonal changes in the hippocampus do not occur in this non food-storing species and may be specific to food-storing birds.

Animals↗

Hamster and rat fetal cells have low spontaneous mutation frequencies and rates.

Somatic cells of whole Syrian hamster fetuses (gestation day 13) were isolated and tested by an in vivo/in vitro mutation assay for spontaneous mutation frequencies using independent 6-thioguanine (6-TG), diphtheria toxin (DT), and ouabain mutation selection systems. Optimum conditions were ascertained. For 6-TG mutants, a total of 21 mutants were found in cells from 24 litters on 1993 plates, for an overall mutant frequency of 1.8 x 10(-7) per viable cell with 12 positive litters. In all, 26 litters were tested using DT; 77 mutants were found in 840 plates, yielding an overall mutant frequency of 2.6 x 10(-7), with 20 positive litters. No correlations or familial effects were found among 23 litters tested for both DT and 6-TG. Of 14 litters which were tested for ouabain mutants, 4 were positive, with a total of 5 mutants found on 988 plates, for an overall mutant frequency of 7.6 x 10(-8). For 14 F344 rat fetuses, the overall 6-TG spontaneous mutation frequency was determined to be 1.6 x 10(-7). From the data, estimates of mutation rates were calculated. For mutation to 6-TG resistance the rate was 8.3 x 10(-8), for mutation to DT resistance the rate was 8.1 x 10(-8) and for ouabain, the spontaneous mutation rate was 5.7 x 10(-8). For F344 rat, the spontaneous mutation rate was 1.1 x 10(-7). Induced mutant frequencies after in utero exposure to 1 mmol/kg N-ethyl-N-nitrosourea (ENU) were 311, 135 and 200 times the spontaneous value for 6-TG, DT and ouabain, respectively, for Syrian hamster fetal cells and 125 times the spontaneous 6-TG value for fetal F344 rat cells. Both spontaneous mutation frequencies and underlying spontaneous mutation rates are low, consistent with the view that fetal cells exercise extremely tight control over DNA fidelity.

2-Aminopurine↗

The role of family of origin food-related experiences in bulimic symptomatology.

OBJECTIVE: With the goal of developing a model relating family of origin experiences to maladaptive cognitions to bulimic symptom formation, the authors developed a measure of family of origin food-related experiences called the Family History Inventory. METHOD: A number (N = 662) of sixth to eighth-grade adolescents completed the inventory, eating and dieting expectancy measures, and the Bulimia Test-Revised (BULIT-R). RESULTS: Fourteen scales were identified in the inventory. They emphasized family teasing about weight, negative maternal modeling regarding food, and family rules concerning eating. Eleven of the 14 scales correlated with the BULIT-R. Two superordinate factors called Family Teasing and Negative Maternal Modeling summarized 8 of the 14 subscales. Statistical tests were consistent with the hypothesis that eating and dieting expectancies mediate the influence of Family Teasing and Negative Maternal Modeling on bulimic symptomatology. DISCUSSION: There was good evidence for the validity of the Family History Inventory. The theoretical implications of the mediation tests are discussed.

Adolescent↗

Integrating disinhibition and learning risk for alcohol use.

In this study the authors tested the acquired preparedness model of problem drinking, which holds that trait disinhibition, defined as neurotic extraversion by C. M. Patterson and J. P. Newman (1993), leads to the biased formation of positive over negative alcohol expectancies. Positive expectancies thus mediate disinhibition's influence on drinking. The authors also hypothesized that disinhibition moderates the expectancy-drinking relationship such that disinhibited individuals are more likely to act on their positive expectancies. In Study 1, positive expectancies both mediated and moderated the disinhibition-drinking relationship. In Study 2, learning task results indicated that disinhibited individuals sought reward, even when passive avoidance of punishment was indicated. Study 2 also replicated Study I hypotheses for men but generally not for women.

Adult↗

NADPH-diaphorase activity and nitric oxide synthase-like immunoreactivity colocalize in the electromotor system of four species of gymnotiform fish.

The electric organ discharge (EOD) of gymnotiform electric fish is controlled by a well-characterized neural circuit in the brainstem and spinal cord. NADPH-diaphorase (NADPH-d) activity was previously found in phase-locking and/or rapidly firing neurons in the electromotor and electrosensory systems of Apteronotus leptorhynchus [Turner and Moroz, 1995]. These findings suggested that nitric oxide synthase (NOS) is expressed in these neurons and may regulate their precise, high frequency firing. We extended these results by examining the distribution of both NADPH-d activity and NOS-like immunoreactivity (NOS-lir) in the electromotor systems of four gymnotiform species that differ in the frequency and modulation of their EODs. NOS-lir colocalized with NADPH-d staining throughout the electromotor system, indicating that NADPH-d is a faithful indicator of NOS in this system. The distribution of NOS-lir and NADPH-d was similar in the electromotor systems of all four species in this study, with one exception: NOS and NADPH-d staining was consistently less intense in pacemaker and relay cells in Sternopygus macrurus, which produces low frequency EODs, than in the three other species that produce higher frequency EODs. This species difference in NOS expression in the pacemaker nucleus may be related to species differences either in EOD frequency or in modulations of the EOD (e.g., the jamming avoidance response). In Apteronotus species, NOS-lir and NADPH-d were concentrated in bands along the axons of their nerve-derived electric organs. These bands corresponded to regions surrounded by little or no staining with a Schwann cell-specific antibody, suggesting that the NOS-positive regions lie near nodes of Ranvier. In Sternopygus and Eigenmannia, the innervated, posterior membranes of muscle-derived electrocytes were more intensely labeled for NADPH-d and NOS than inexcitable portions of the membrane. Thus, in both muscle- and nerve-derived electric organs, NOS is concentrated near excitable membranes. These results indicate that NOS is well-positioned within the electromotor system to regulate the frequency, precision, amplitude, and waveform of EODs.

Animals↗

Disinhibition and expectancy in risk for alcohol use: comparing black and white college samples.

OBJECTIVE: This study tested several predictions of the "acquired preparedness" model in both black and white samples of college students. The acquired preparedness model holds that trait disinhibition affects alcohol-related learning and, ultimately, alcohol use. This model maintains that the reward focus typical of disinhibited individuals increases the likelihood of forming overly positive expectancies about the effects of alcohol. Alcohol expectancy, then, acts as a mediator of the relationship of disinhibition and drinking behavior. METHOD: Participants (N = 479, 341 women) were 279 white and 200 black college students. Self-reported alcohol expectancy, disinhibition and drinking behavior were assessed. Covariance structure analysis was used to test hypotheses separately for each sample, controlling for socioeconomic status. RESULTS: Black participants scored significantly lower on disinhibition, expectancy and drinking. However, invariance testing indicated that the relationships between these variables were not different across groups. Results were consistent with the stated hypotheses in both samples--alcohol expectancy functioned as a mediator of the disinhibition-drinking relationship. Results did not differ across expectancy content. CONCLUSIONS: These results provide support for the validity of the acquired preparedness model. Despite mean differences in risk and drinking levels between black and white samples, psychosocial learning appears to mediate the influence of disinhibition on drinking for both groups.

Adolescent↗

Parvocells: a novel interneuron type in the pacemaker nucleus of a weakly electric fish.

Gymnotiform weakly electric fish produce electric organ discharges (EODs) that function in electrolocation and communication. The command signal for the EOD is produced by the medullary pacemaker nucleus, which contains two well-characterized neuron types: pacemaker cells and relay cells. In this study, we characterized a third neuron type in the pacemaker nucleus. These neurons, which we have named parvocells, were smaller (7-15 microm in diameter) than relay and pacemaker cells. The parvocells were labeled with an antibody against the neuronal calcium-binding protein, parvalbumin, and were not labeled with several glial-specific antibodies. Parvocells had one to three fine processes that often terminated at the periphery of relay and pacemaker cell bodies. The parvalbumin-positive terminals of the parvocells colocalized with immunoreactivity for SV-2, suggesting that the parvocells form chemical synapses on the relay and pacemaker cells. Parvalbumin-positive neurons are frequently gamma-aminobutyric acid (GABA)ergic or glycinergic, and the cytoplasm of the parvocell somata was immunoreactive with a glycine antibody. Antibodies against glycine receptors and gephyrin, however, did not label any cells in the pacemaker nucleus, suggesting that the pacemaker nucleus does not contain glycine or GABA((A)) receptors. Electron microscopy revealed gap junctions between the membranes of parvocells and adjacent terminal-like structures. Furthermore, neurobiotin injected into individual pacemaker or relay cells labeled parvocells as well as other pacemaker and relay cells, demonstrating that the parvocells are dye-coupled to the other neuron types in the pacemaker nucleus. These findings indicate that the parvocells are histochemically distinct from relay and pacemaker cells and that they receive electrotonic inputs from and make chemical synapses back onto pacemaker and relay cells. Further study is needed to investigate the function of these neurons in regulating the EOD.

Animals↗

Pharmacological characterization of ionic currents that regulate the pacemaker rhythm in a weakly electric fish.

Electric organ discharge (EOD) frequency in the brown ghost knifefish (Apteronotus leptorhynchus) is sexually dimorphic, steroid-regulated, and determined by the discharge rates of neurons in the medullary pacemaker nucleus (Pn). We pharmacologically characterized ionic currents that regulate the firing frequency of Pn neurons to determine which currents contribute to spontaneous oscillations of these neurons and to identify putative targets of steroid action in regulating sexually dimorphic EOD frequency. Tetrodotoxin (TTX) initially reduced spike frequency, and then reduced spike amplitude and stopped pacemaker activity. The sodium channel blocker muO-conotoxin MrVIA also reduced spike frequency, but did not affect spike amplitude or production. Two potassium channel blockers, 4-aminopyridine (4AP) and kappaA-conotoxin SIVA, increased pacemaker firing rates by approximately 20% and then stopped pacemaker firing. Other potassium channel blockers (tetraethylammonium, cesium, alpha-dendrotoxin, and agitoxin-2) did not affect the pacemaker rhythm. The nonspecific calcium channel blockers nickel and cadmium reduced pacemaker firing rates by approximately 15-20%. Specific blockers of L-, N-, P-, and Q-type calcium currents, however, were ineffective. These results indicate that at least three ionic currents-a TTX- and muO-conotoxin MrVIA-sensitive sodium current; a 4AP- and kappaA-conotoxin SIVA-sensitive potassium current; and a T- or R-type calcium current-contribute to the pacemaker rhythm. The pharmacological profiles of these currents are similar to those of currents that are known to regulate firing rates in other spontaneously oscillating neural circuits.

4-Aminopyridine↗

Flexible iris hooks for phacoemulsification in patients with iridoschisis.

Flexible iris hooks, or retractors, can be used to facilitate cataract removal by phacoemulsification in patients with primary iridoschisis. This rare condition is associated with fibrillary degeneration of the iris, narrow drainage angles, and cataract. In addition to their conventional use as iris retractors, iris hooks can control the degenerate fibrillary iris stroma to improve the view and access to the lens, preventing further damage during phacoemulsification and cortical cleanup. Iris hooks are widely available, easily handled, and can transform a difficult case into one that is almost routine.

Aged↗

On the sins of short-form development.

The empirical short-form literature has been characterized by overly optimistic views of the transfer of validity from parent form to short form and by the weak application of psychometric principles in validating short forms. Reviewers have thus opposed constructing short forms altogether, implying researchers are succumbing to an inappropriate temptation by trying to abbreviate measures. The authors disagree. The authors do not oppose the development of short forms, but they do assert that the validity standards for short forms should be quite high. The authors identify 2 general and 9 specific methodological sins characterizing short-form construction and offer methodological suggestions for the sound development of short forms. They recommend a set of 6 a priori steps researchers should consider and 9 methodological procedures researchers can use to develop valid abbreviated forms of clinical-assessment procedures.

Bias↗