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Biomedical subjects

E Carpenter

Publications and source records attributed to E Carpenter.

31 records · Page 2Linked to original sources
PubMed1996

Ca2+ channel currents in type I carotid body cells of normoxic and chronically hypoxic neonatal rats.

Whole-cell patch-clamp recordings were used to study voltage-gated Ca2+ channel currents in type I carotid body cells of young rats born and reared in normoxia or in a chronically hypoxic (CH) environment (10% O2). Currents activated at potentials of -40 mV and more positive, and typically peaked at 0 mV in both groups of cells. Steady-state inactivation curves were similar in the two populations. Ca2+ currents were significantly larger in CH type I cells, but this was accounted for by the increased size of CH cells: current density was similar in both cell types. Nifedipine (5 microM) always partially inhibited currents and Bay K 8644 (2-5 microM) always enhanced currents, indicating the presence of L-type channels. In a small number of cells from each group, the N-type channel blocker omega-conotoxin GVIA caused partial, irreversible inhibition, but in most cells was without discernible effect. These results indicate that type I cells possess L-type Ca2+ channels, that N-type are expressed in some cells and that non-L, non-N-type channels are also present. Furthermore, chronic hypoxia does not appear to cause specific adaptive changes in the properties of Ca2+ channels in type I cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1996

Opioid receptor independent inhibition of Ca2+ and K+ currents in NG108-15 cells by the kappa opioid receptor agonist U50488H.

The whole-cell patch clamp technique was used to investigate the actions of the opioid agonist U50488H on Ca2+ and K+ currents in differentiated NG108-15 cells. U50488H (5-50 microM) caused a concentration-dependent, reversible inhibition of high voltage-activated Ca2+ currents which persisted in the presence of nifedipine (2 microM), indicating a blockade of N-type Ca2+ channels. The actions of U50488H were also observed in the presence of 30 microM naloxone, which fully abolished current inhibition caused by a selective delta opioid receptor agonist. U50488H also inhibited Ca(2+)-insensitive, voltage-gated K+ currents in NG108-15 cells in the presence of naloxone. Our results indicate that U50488H can inhibit neuronal ionic channels via a mechanism which does not involve activation of kappa opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1996

Inhibition of Ca(2+)-sensitive K+ currents in NG 108-15 cells by substance P and related tachykinins.

1. The whole-cell patch-clamp technique was used to investigate the actions of substance P and other agonists at neurokinin (NK) receptors on voltage-gated K+ and Ca+ channel currents in undifferentiated mouse neuroblastoma x rat glioma NG 108-15 cells. 2. Both substance P (0.3-30 microM) and the NK1 receptor selective agonist GR73632 (10 nM-10 microM) caused concentration-dependent inhibition of K+ currents. GR64349 and senktide (agonists at NK2 and NK3 receptors respectively) also inhibited K+ currents, but only at concentrations which were several orders of magnitude greater than GR73632, suggesting that current inhibition was mediated via NK1 receptors. 3. Substance P and GR73632 were without effect on residual K+ currents recorded in the presence of extracellular Co2+ (4 mM) to abolish the Ca(2+)-sensitive component (IKca) of the K+ current. Ca2+ channel currents, recorded with either Ba2+ or Ca2+ as charge carrier, were unaffected by NK1, NK2 and NK3 receptor ligands. 4. Iontophoretic application of GR73632 produced a current-dependent reduction of K+ currents. In the presence of the non-peptide NK1 antagonists, CP-99,994 and RP67580, and the peptide antagonist, GR82334, the current-response relationship was reversibly shifted to the right. This indicates that the response is mediated by NK1 receptors. 5. Our results indicate that activation of NK1 receptors leads to the selective inhibition of IKca in undifferentiated NG 108-15 cells.

Animals↗
PubMed1995

Crystal structure of the complex of a catalytic antibody Fab fragment with a transition state analog: structural similarities in esterase-like catalytic antibodies.

The x-ray structure of the complex of a catalytic antibody Fab fragment with a phosphonate transition-state analog has been determined. The antibody (CNJ206) catalyzes the hydrolysis of p-nitrophenyl esters with significant rate enhancement and substrate specificity. Comparison of this structure with that of the uncomplexed Fab fragment suggests hapten-induced conformational changes: the shape of the combining site changes from a shallow groove in the uncomplexed Fab to a deep pocket where the hapten is buried. Three hydrogen-bond donors appear to stabilize the charged phosphonate group of the hapten: two NH groups of the heavy (H) chain complementarity-determining region 3 (H3 CDR) polypeptide chain and the side-chain of histidine-H35 in the H chain (His-H35) in the H1 CDR. The combining site shows striking structural similarities to that of antibody 17E8, which also has esterase activity. Both catalytic antibody ("abzyme") structures suggest that oxyanion stabilization plays a significant role in their rate acceleration. Additional catalytic groups that improve efficiency are not necessarily induced by the eliciting hapten; these groups may occur because of the variability in the combining sites of different monoclonal antibodies that bind to the same hapten.

Antibodies, Catalytic↗
PubMed1995

Oral transmucosal fentanyl citrate for preanaesthetic medication of paediatric cardiac surgery patients.

The safety and efficacy of oral transmucosal fentanyl citrate (OTFC) as a preanaesthetic medication were evaluated in 42 children aged two to twelve years scheduled to undergo general anaesthesia for open cardiac surgery. Patients were randomly assigned to receive either a placebo lozenge or a lozenge of 15-20 micrograms.kg-1) OTFC 45 min preoperatively and were managed in a double-blinded manner. Heart rate, respiratory rate (RR), blood pressure, and digital pulse oximetry (SpO2) were monitored throughout the study. Scoring systems were utilized to evaluate sedation, anxiety, cooperation, and ease and quality of parental separation and anaesthetic induction. Adverse effects were noted. Preoperatively, sedation was observed in both groups, but children receiving OTFC had significantly less distress at time of separation from parents. Clinically significant less distress at and SpO2 were observed more frequently in children in the OTFC group than in the placebo group. The authors conclude that, in paediatric cardiac surgical patients, OTFC induces preoperative sedation and facilitates separation of the patients from their parents, but is associated with decreases in respiratory rate and SpO2 that may be of clinical importance.

Administration, Oral↗
PubMed1994

Microcrystals of the beta 1 isoenzyme of protein kinase C: an electron microscopic study.

Microcrystals of protein kinase C beta 1 have been grown from solutions of poly(ethylene glycol). Image analysis of electron micrographs of the protein crystals, which diffracted to 5.0 nm, revealed p3 symmetry with a unit cell of about 10.3 nm x 10.3 nm. The electron stain-excluding densities showed a three-domain ring structure in projection, giving kidney bean-shaped molecules of about 7.0 nm x 4.5 nm diameter, packed as trimers. The implications of these observations for the function of the enzyme are discussed.

Crystallography↗
PubMed1987

Conservation and variation in orf virus genomes.

The genomes of several orf virus strains were analyzed with the restriction endonucleases EcoRI, HindIII, BamHI, and KpnI, and cleavage site maps were deduced. In general, the right half of the genome showed conservation of restriction sites compared with the left half. Variations in size of up to 0.5 kbp were found within an inverted terminal repetition, and a 1-kbp deletion was detected in some strains in a subterminal fragment at the left end. A region of approximately 20 kbp, some 12 kbp in from the left end, showed the greatest cleavage site variability although there was no evidence of large deletions in this region. A 1.55-kbp cloned DNA fragment from the internal variable region of NZ2 failed to hybridize to the DNA from three other strains. A fragment in the variable region of strain NZ7 was cloned and compared by hybridization and restriction endonuclease analysis with cloned NZ2 fragments from the same region. The region of nonhomology extended for at least 2.75 kbp. It is suggested that this internal variable region may provide sites for the insertion of foreign genes.

Animals↗
PubMed1986

Pictures in sentences: understanding without words.

To understand a sentence, the meanings of the words in the sentence must be retrieved and combined. Are these meanings represented within the language system (the lexical hypothesis) or are they represented in a general conceptual system that is not restricted to language (the conceptual hypothesis)? To evaluate these hypotheses, sentences were presented in which a pictured object replaced a word (rebus sentences). Previous research has shown that isolated pictures and words are processed equally rapidly in conceptual tasks, but that pictures are markedly slower than words in tasks requiring lexical access. The lexical hypothesis would therefore lead one to expect that rebus sentences will be relatively difficult, whereas the conceptual hypothesis would predict that rebus sentences would be rather easy. Sentences were shown using rapid serial visual presentation (RSVP) at a rate of 10 or 12 words per second. With one set of materials (Experiments 1 and 2), readers took longer to judge the plausibility of rebus sentences than all-word sentences, although the accuracy of judgment and of recall were similar for the two formats. With two new sets of materials (Experiments 3 and 5), rebus and all-word sentences were virtually equivalent except in one circumstance: when a picture replaced the noun in a familiar phrase such as seedless grapes. In contrast, when the task required overt naming of the rebus picture in a sentence context, latency to name the picture was markedly longer than to name the corresponding word, and the appropriateness of the sentence context affected picture naming but not word naming (Experiment 4). The results fail to support theories that place word meanings in a specialized lexical entry. Instead, the results suggest that the lexical representation of a noun or familiar noun phrase provides a pointer to a nonlinguistic conceptual system, and it is in that system that the meaning of a sentence is constructed.

Adolescent↗