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Biomedical subjects

G R Parker

Publications and source records attributed to G R Parker.

14 recordsLinked to original sources

Dynamics of induction and expression of long-term synaptic facilitation in Aplysia.

Serotonin (5HT)-induced short-term facilitation and long-term facilitation (STF and LTF) of the monosynaptic connection between tail sensory neurons (SNs) and motor neurons (MNs) in Aplysia have been useful in delineating possible cellular mechanisms contribution to short-term and long-term memory. Previous work from our laboratory showed that LTF can be produced in the absence of STF, suggesting that these processes may be functionally independent. In the present study, we explored this hypothesis by examining the temporal relationship between STF and LTF. We recorded intracellularly from pairs of monosynaptically connected SNs and MNs in isolated pleural-pedal ganglia. In the first experimental series, we followed the time course of LTF across a 24 hr period after its induction by five applications of 10 microM 5HT. STF completely decayed to baseline several hours before the expression of LTF. This biphasic expression profile of STF and LTF further supports the hypothesis that LTF is not a simple elaboration of STF. In the second experimental series, we monitored the immediate expression of facilitation during and after different numbers of 5HT applications. We identified a rapidly decaying STF (lasting 15-30 min) after one to four pulses of 50 microM 5HT and a unique, prolonged intermediate-term facilitation (ITF; lasting up to 90 min) after five pulses of 50 microM 5HT. These results raise the possibility that STF, ITF, and LTF may reflect components of different memory phases in the intact animal.

Animals

Efficacy of a recombinant-derived phytase in improving the bioavailability of phosphorus in corn-soybean meal diets for pigs.

Three experiments involving 162 pigs were conducted to assess the efficacy of phytase (Natuphos; BASF, Mount Olive, NJ) in low-P, corn-soybean meal-based diets. The phytase was produced by a recombinant Aspergillus niger. The phytase supplement contained 5,000 phytase units (PTU)/g. In Exp. 1 (66 pigs) and 2 (60 pigs), growing-finishing pigs were fed fortified corn-soybean meal diets formulated to be adequate (.50%), marginal (.425%), or inadequate (.35%) in P during the growing phase (23 to 60 kg BW) followed by adequate (.40%), marginal (.35%), or inadequate (.30%) P, respectively, during the finishing phase (to 104 kg BW). Dicalcium phosphate was the source of supplemental P. In addition, the low-P sequence (.35/.30% P) was supplemented with phytase at 250, 500, or 1,000 PTU/kg. Rate and efficiency of gain decreased linearly (P < .01) and bone breaking strength decreased quadratically (P < .01) as the concentration of P was decreased in the diets. Responses in growth and bone traits to increasing levels of phytase activity in the low-P diet were linear (P < .01). The highest level of phytase in the low-P diet restored growth rate and bone breaking strength to levels that approached or met those of pigs fed the adequate P diet.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Phytase

Interviews with children who experienced major life stress: family and child attributes that predict resilient outcomes.

Demographically comparable groups of children exposed to major life-stress, with stress resilient (SR) and stress affected (SA) outcomes at ages 10 to 12, were interviewed to assess perceptions of their caregiving environments, peer relationships, and themselves. SR children compared with SA children reported more: (1) positive relationships with primary caregivers, (2) stable family environments, (3) inductive and consistent family discipline practices, and (4) positive expectations for their futures. SR girls viewed their mothers as more nurturing than did SA girls. Perceptions of fathers, quality of peer relationships, and global self-concept did not differentiate the groups. A discriminant function analysis identified four variables that correctly classified 74% of the subjects as SR or SA. Findings support the view that caregiver-child relationships play a key role in moderating children's developmental outcomes under conditions of high stress.

Adaptation, Psychological

Developmental and family milieu correlates of resilience in urban children who have experienced major life stress.

Reports findings from interviews with parents of demographically-comparable groups of highly-stressed urban children with stress-resilient (SR) and stress-affected (SA) outcomes at ages 10-12. SR and SA children were compared on family milieu and child development variables assessed within a developmental framework. Compared to SAs, parents of SRs scored higher on variables reflecting parent perceptions of a nurturant caregiver-child relationship and self-views as effective caregivers, in the context of positive discipline practices, a child's positive early temperament, and support for primary caregivers. A discriminant function analysis identified seven variables that optimally differentiated the groups and correctly classified 86% of the Ss as SR or SA.

Adaptation, Psychological

Isolation from lugworm (Arenicola cristata) of four proteases that activate cyclic AMP phosphodiesterase.

1. Four cyclic AMP phosphodiesterase-activating activities, designated as A, B, C and D, were isolated from lugworm, Arenicola cristata, by preparative flat-bed isoelectric focusing. Activators C and D were further purified by TSK 3000SW HPLC to homogeneity. 2. Activators A, B, C, and D corresponded to pIs of 4.4, 5.0, 5.2 and 5.4; their mol wts were estimated to be 36,200, 30,500, 30,200 and 28,300 respectively. 3. The protease nature of these activities were confirmed by the inhibition by several trypsin inhibitors of their activation of phosphodiesterase and by their hydrolysis of TAME, a synthetic trypsin substrate. Only protease A also hydrolyzed BTEE, a chymotrypsin substrate.

3',5'-Cyclic-AMP Phosphodiesterases

Correlation of log P with molecular connectivity in hydroxyureas: influence of conformational system on log P.

The correlation of log P (in octanol--water) with the nonempirical, topologically dependent, calculated molecular connectivity index (1chiv) delineates substituted hydroxyureas into two families of linearly related groups of compounds. The first group, composed of the 3-substituted ethyl, n-propyl, and n-butyl analogs, is more hydrophilic than the 1-substituted methyl and ethyl and the 3-substituted isopropyl and tert-butyl analogs. The unsubstituted model compound hydroxyurea appears between the two groups in equal volumes of octanol. In octanol--water ratios of 5:1, log P approaches the range of the more hydrophilic group in high concentrations and becomes more lipophilic (similar to the other group) in lower concentrations. The differences in the relative hydrophilicities--lipophilicities of the two groups are rationalized in terms of the equilibri of internally hydrogen-bonded, conformers to those that allow optimal interactions with solvent, water, or other hydroxyurea molecules. The concentration dependency observed with hydroxyurea appears to be due to the ease of interconversion of intermolecularly bonded conformers to those interacting with water, whereas the involvement of internally bonded conformers, which are apparently present to a greater degree in lower concentrations, increases the relative lipophilicity.

Hydroxyurea

Solvent-dependent conformational system of hydroxyureas in octanol-water and in inhibition of ribonucleotide reductase.

The carbonyl nitrogen IR absorption region of selected hydroxyureas was examined in octanol. The spectra indicated appreciably different absorptions prior to and after equilibration with water. Stability studies on the hydroxyureas indicated that the absorption differences were not due to chemical decomposition in the equilibration process but were due to solvent conformation and/or tautomeric dependency of the system. Preliminary in vitro inhibition of the enzyme ribonucleoside diphosphate reductase by selected hydroxyureas also indicated an apparent solvent dependency, which may involve the conformational and/or tautomeric properties of these agents. The implications of the solvent-dependent conformation-tautomeric system observed are discussed in relation to this property in the biological action of these agents.

Chemical Phenomena

Effect of the solvent-dependent conformational system of hydroxyureas on predicted vs. observed log P.

Calculated and observed log P values are reported and compared with in vivo and in vitro biological action (L1210 leukemia ILS % and ribonucleotide reductase ID50) for hydroxyurea, the 1-N methyl and ethyl, and the 3-N ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, phenyl, and p-chlorophenyl analogues. The log P values were calculated via the method of Hansch and Leo from literature f values and the observed log P values were obtained by direct determination after equilibration between octanol and water. Calculations of log P for hydroxyurea were found to be appreciably more hydrophilic than the values obtained experimentally. Differences in calculated and observed log P (delta log P) for the substituted analogues were lowest with the 1-N and the bulky 3-N substituents and greatest with the 3-N-substituted straight-chain analogues (delta log P = 0.70). Different structural species were observed by infrared spectroscopy in dry octanol vs. octanol after water equilibration and drying, and this is proposed as due to changes in conformational equilibrium in the hydroxyurea systems. Differences between calculated and observed log P are explained via the stabilization of internally hydrogen-bonded conformers in the case of 1-N or bulky 3-N analogues or destabilization of various conformers allowing maximal interactions with solvent or water which is the case with straight chain 3-N analogues.

Chemical Phenomena

Solvent-dependent conformational system in hydroxyureas detected by NMR spectroscopy.

The proton magnetic resonance spectra of the antileukemia agent hydroxyurea and substituted hydroxyureas in several solvents were recorded and correlated with structural features. Solvent-dependent differences in conformational preferences due to effects on internal hydrogen bonding, a temperature-dependent conformational feature, anthe exchangeability of protons with deuterium oxide and acetone-d6 were observed. The conformational features consistent with the spectral data are discussed.

Chemical Phenomena