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Biomedical subjects

J D Smith

Publications and source records attributed to J D Smith.

At least 217 records · Page 12Linked to original sources

Subglottic cysts in the premature infant.

Supraglottic cysts in the newborn are a well-recognized entity, but subglottic cysts have been rarely reported. Over the past 6 years we have observed subglottic cysts in nine patients with relatively long intubations from the neonatal intensive care unit of two university hospitals. Most frequently the patients were extubated and did well for weeks or months, but then they had progressive biphasic stridor. On endoscopy the patients had a subglottic stenosis that was irregular but with a smooth mucosal lining. Usually the cysts were apparent, but in two patients the mucosa was thickened and the patients were treated as a subglottic stenosis with tracheostomy. These subglottic cysts were recognized at the time of laryngotracheoplasty. In six patients the cysts were managed either by marsupialization with cup forceps, endoscopic diathermy, or carbon dioxide laser without recurrence. It is our belief that this condition is most likely due to scarring and obstruction of mucus glands of the subglottic area from prolonged intubation. This entity should be recognized and looked for in the neonate who has an acquired subglottic stenosis and should first be treated conservatively with endoscopic marsupialization.

Child, Preschool↗

Aesthetic preference and syntactic prototypicality in music: 'tis the gift to be simple.

In the dominant aesthetic theory, composers are said to use unpredictable events to tease the listener, and make music optimally challenging and therefore aesthetically pleasing. We tested this claim that events optimally discrepant from a schema will be most pleasing. Experts and novices evaluated harmonic progressions at seven levels of syntactic prototypicality. Four results emerged: (1) even novices were extremely sensitive to syntactic atypicality; (2) all subjects found atypical progressions more interesting and complex; (3) novices and undergraduate music students preferred harmonic prototypes, contrary to most aesthetic theories; (4) only music graduate students preferred atypical progressions. We discuss the striking sensitivity of novices to harmonic syntax. We describe differences between an aesthetic theory based on information and uncertainty, and one based on schemas and schema divergence. We also consider the tonal conservatism of most subjects. This conservatism constrains aesthetic theories, and may have implications for music's stylistic evolution.

Adult↗

The relationship between situational stress and phantom limb pain: cross-lagged correlational data from six month pain logs.

This study reports the results of the first investigation into the relationship between situational stress and phantom limb pain. Twenty-seven male amputees recorded their pain and overall stress levels daily for 180 days using a 1-10 rating scale. Three possible relationships into the etiology and/or maintenance of phantom limb pain were examined using cross-lagged correlational techniques: an isomorphic relationship (same time increases in pain lead to same time increases in stress and vice versa), a consequence relationship (increases in pain precede increases in stress), and a precursor relationship (increases in stress precede increases in pain). Thirty-seven per cent of subjects demonstrated some significant precursor relationship. Although support was found for all three hypotheses, the most frequently observed relationship was the isomorphic one. Seventy-four per cent of subjects demonstrated some significant stress-pain relationship. The results lend support to the psychological theory underlying the use of psychophysiological interventions such as biofeedback and relaxation therapy in amputees with phantom limb pain.

Adult↗

(-)PPAP: a new and selective ligand for sigma binding sites.

Most agents employed for the investigation of sigma (sigma) binding sites display relatively low affinity for these sites, bind both at sigma sites and at either phencyclidine (PCP) sites or dopamine receptors with similar affinity, and/or produce some dopaminergic activity in vivo. We describe a new agent, (-)PPAP or R(-)-N-(3-phenyl-n-propyl)-1-phenyl-2-aminopropane hydrochloride, that binds with high affinity and selectivity at sigma (IC50 = 24 nM) versus either PCP sites (IC50 greater than 75,000 nM) or D1 and D2 dopamine receptors (IC50 greater than 5,000 nM). The sigma affinity of this agent is comparable to that of the standard ligands (+)-3-PPP and DTG. Furthermore, although (-)PPAP is structurally related to amphetamine, it neither produces nor antagonizes amphetamine-like stimulus effect in rats trained to discriminate 1 mg/kg of S(+)amphetamine from saline.

Animals↗

Role of hydrogen bonding in ligand interaction with the N-methyl-D-aspartate receptor ion channel.

Displacement of [3H]MK-801 (dizocilpine, 1) binding to rat brain membranes has been used to evaluate the affinities of novel dibenzocycloalkenimines related to 1 for the ion channel binding site (also known as the phencyclidine or PCP receptor) on the N-methyl-D-aspartate (NMDA) subtype of excitory amino acid receptor. In common with many other agents having actions in the central nervous system, these compounds contain a hydrophobic aromatic moiety and a basic nitrogen atom. The conformational rigidity of these ligands provides a unique opportunity to evaluate the importance of specific geometrical properties that influence active-site recognition, in particular the role of the nitrogen atom in hydrogen-bonding interactions. The relative affinities (IC50s) of hydrocarbon-substituted analogues of 1 and ring homologated cyclooctenimines illustrate the importance of size-limited hydrophobic binding of both aryl rings and of the quaternary C-5 methyl group. Analysis of the binding of a series of the 10 available structurally rigid dibenzoazabicyclo[x.y.z]alkanes, by using molecular modeling techniques, uncovered a highly significant correlation between affinity and a proposed ligand-active site hydrogen bonding vector (r = 0.950, p less than 0.001). These results are used to generate a pharmacophore of the MK-801 recognition site/PCP receptor, which accounts for the binding of all of the known ligands.

Animals↗

Calcium-independent cell volume regulation in human lymphocytes. Inhibition by charybdotoxin.

The properties of the K+ pathway underlying regulatory volume decrease (RVD) in human blood lymphocytes were investigated. Evidence is presented for the existence of three types of K+ conductance in these cells. Ionomycin, a Ca2+ ionophore, induced a K(+)-dependent hyperpolarization, indicating the presence of Ca2(+)-activated K+ channels, which were blocked by charybdotoxin (CTX). CTX also induced a depolarization of the resting membrane potential, even at subphysiological cytosolic [Ca2+]([Ca2+]i), which suggests the existence of a second CTX-sensitive, but Ca2(+)-independent conductance. A CTX-resistant K+ conductance was also detected. RVD in blood lymphocytes was partially (approximately 75%) blocked by CTX. However, volume regulation was not accompanied by detectable changes in [Ca2+]i, nor was it prevented by removal of extracellular Ca2+ and depletion or buffering of intracellular Ca2+. These observations suggest that K+ loss during RVD is mediated by Ca2(+)-independent, CTX-sensitive channels or that Ca2(+)-dependent channels can be activated by cell swelling at normal or subnormal [Ca2+]i. The former interpretation is supported by findings in rat thymic lymphocytes. These cells also displayed a CTX-sensitive Ca2(+)-dependent hyperpolarization. However, CTX did not significantly alter the resting potential, suggesting the absence of functional Ca2(+)-independent, toxin-sensitive channels. Volume regulation in thymic lymphocytes was less efficient than in human blood cells. In contrast to blood lymphocytes, RVD in thymocytes was not affected by CTX. These observations indicate that, though present in lymphocytes, Ca2(+)-activated K+ channels do not play an important role in volume regulation. Instead, RVD seems to be mediated by Ca2(+)-independent K+ channels. We propose that two types of channels, one CTX sensitive and the other CTX insensitive, mediate RVD in human blood lymphocytes, whereas only the latter type is involved in rat thymocytes.

Calcium↗

Epidemiologic evidence that prior antimicrobial exposure decreases resistance to infection by antimicrobial-sensitive Salmonella.

Exposure to antimicrobials is known to increase the risk of infection with antimicrobial-resistant strains of Salmonella, but this effect has not been previously demonstrated with antimicrobial-sensitive strains. The effect of prior antimicrobial exposure was studied during a multistate outbreak of salmonellosis caused by an antimicrobial-sensitive strain of Salmonella havana: 19 (26%) of 72 persons infected had taken an antimicrobial within 30 days before onset of symptoms. Antimicrobial therapy was begun a mean of 15.9 days before and stopped a mean of 7.9 days before onset. In a case-control study, 11 (31%) of 35 case-patients had taken antimicrobials within 30 days of onset compared with 9 (13%) of 70 age- and neighborhood-matched controls (matched odds ratio, 4.3; 95% confidence interval, 1.3, 13.5). The association remained when controlled for the presence of underlying illness or immunosuppression. Prior antimicrobial exposure appears to increase the risk of infection with antimicrobial-sensitive and resistant strains of Salmonella. The delay between antimicrobial use and onset of symptoms suggests that the effect may be due to prolonged alteration of the colonic bacterial flora, resulting in decreased resistance to colonization.

Adolescent↗

Recovery of hepatitis A virus from a water supply responsible for a common source outbreak of hepatitis A.

An outbreak of hepatitis A occurred in a north Georgia trailer park served by a private well. Of 18 residents who were serosusceptible to hepatitis A virus (HAV), 16 (89%) developed hepatitis A. Well water samples were collected 3 months after illness onset in the index case and 28 days after illness onset in the last trailer park resident. Hepatitis A virus antigen (HAVAg) was detected in the samples by enzyme immunoassay from three of the five cell lines following two 30-day passages and from a fourth cell line following a third passage of 21 days.

Adult↗

Aneurysmal bone cyst of the mandible.

Aneurysmal bone cyst is an uncommon benign lesion that rarely presents in the craniofacial region. No prior reports of this entity involving the mandible could be found in the otolaryngologic literature, and it has been reported only infrequently in the maxilla. Two previously unreported cases originating in the mandible are presented with a review of the literature, pathology, and diagnosis of this lesion. Treatment of this lesion consists of complete surgical removal and immediate bone grafting for reconstruction.

Adolescent↗

Insulin resistance in uremia: an in vivo and in vitro study.

Insulin-mediated glucose metabolism was examined in vivo and in vitro in a chronically uremic (4-week) rat model established by a 90% nephrectomy. Using the euglycemic insulin clamp technique, uremic rats demonstrated a 28% reduction (P less than .01) in total body glucose disposal compared with pair-fed controls. Suppression of hepatic glucose production by insulin was not impaired. The ability of insulin to promote glycogen synthesis by the soleus muscle in vitro was normal in uremic rats. In contrast, the ability of insulin to enhance both glycolysis and glucose oxidation by the soleus muscle was significantly reduced (P less than .01) in uremic rats. These results provide evidence that at least two intracellular metabolic defects, ie, in the glycolytic and glucose oxidative pathways, contribute to the insulin resistance of chronic uremia.

Animals↗

N-(phthalimidoalkyl) derivatives of serotonergic agents: a common interaction at 5-HT1A serotonin binding sites?

Several classes of agents are known to bind at central 5-HT1A serotonin sites In order to challenge the hypothesis that these agents bind in a relatively similar manner (i.e., share common aryl and terminal amine sites), we prepared N-(phthalimidobutyl) derivatives of examples of several such agents. With regard to arylpiperazines, we had previously shown that introduction of this functionality at the terminal amine is tolerated by the receptor and normally results in a significant (greater than 10-fold) enhancement in affinity. The results of the present study show that this bulky functionality is also tolerated by the receptor when incorporated into examples of all other major classes of 5-HT1A agents (e.g., 2-aminotetralin, phenylalklamine, indolylalkylamine, and (aryloxy)alkylamine derivatives). The length of the alkyl chain that separates the terminal amine from the phthalimido group is of major importance, and a four-carbon chain appears optimal. Alteration of the length of this chain can have a significant influence on affinity; decreasing the chain length from four to three carbon atoms can reduce affinity by an order of magnitude, and further shortening can have an even more pronounced effect.

Animals↗

"Enacted" auditory images are ambiguous; "pure" auditory images are not.

Previous research indicates that visual images are inherently unambiguous. The present study extends this argument to auditory imagery. In Experiment 1, subjects were able to reinterpret an imaged ambiguous auditory figure, but covert subvocalization apparently aided this reinterpretation. When subvocalization was blocked, reinterpretations were eliminated. Experiments 2 and 3 generalize this finding to different procedures and stimuli. Experiment 4 explores further the role of subvocalization, by showing that the likelihood of reinterpreting an imaged stimulus is directly proportional to the degree of enactment allowed. We argue that subvocalization or enactment provides an internal stimulus that is subject to reinterpretation. Without enactment, the "pure" auditory image is as unambiguous as a visual image. Thus, in both visual and auditory modalities, images come into being as representations and so are inherently meaningful.

Adult↗

Regulation of Embryo Dormancy by Manipulation of Abscisic Acid in Kernels and Associated Cob Tissue of Zea mays L. Cultured in Vitro.

Sectors of Zea mays cobs, with and without kernels were cultured in vitro in the presence and absence of fluridone. Cultured kernels, cob tissue, and embryos developed similarly to those grown in the field. Abscisic acid (ABA) levels in the embryos were evaluated by enzyme-linked immunosorbant assay. ABA levels in intact embryos cultured in the presence of fluridone were extremely low and indicate an inhibition of ABA synthesis. ABA levels in isolated cob tissue indicate that ABA can be produced by cob tissue. Sections containing kernels cultured in the presence of fluridone were transferred to medium containing fluridone and ABA. Dormancy was induced in more than 50% of the kernels transferred from 13 to 15 days after pollination, but all of the kernels transferred at 16 days after pollination or later were viviparous. ABA recovered from kernels that were placed in medium containing fluridone and ABA suggest that ABA can be transported through the cob tissue into developing embryos and that ABA is required for induction of dormancy in intact embryos.

Journal Article↗

Selective inhibition of [3H]nitrendipine binding to brain and cardiac membranes by bacitracin.

The effects of bacitracin were investigated on [3H]nitrendipine binding to rat brain and cardiac membranes in a low ionic strength (5 mM Tris-HCl) buffer. Bacitracin inhibited [3H]nitrendipine binding to rat brain and cardiac membranes with IC50 values of 400 +/- 100 and 4600 +/- 400 micrograms/mL, respectively. Scatchard analysis in brain membranes revealed that bacitracin inhibited [3H]nitrendipine binding primarily by reducing the Bmax but also by producing a small increase in the Kd. In brain membranes, Na+ (100 mM) and Ca2+ (2 mM) reduced the potency of bacitracin to inhibit [3H]nitrendipine binding by approximately sixfold with IC50 values of 2600 +/- 300 and 2100 +/- 400 micrograms/mL observed for bacitracin in the presence of 100 mM Na+ and 2 mM Ca2+, respectively. The EC50 values for the effects of Na+ and Ca2+ were 800 +/- 200 microM and 25 +/- 5 mM. K+, Mg2+, choline, and increasing the assay buffer of Tris-HCl to 50 mM also decreased the inhibition of [3H]nitrendipine binding by bacitracin. These results suggest that bacitracin specifically modulates [3H]nitrendipine binding in a cation-dependent manner and that brain and cardiac dihydropyridine binding sites are either biochemically different or exist in a different membrane environment.

Animals↗

Internal pH-sensitive site couples Cl-(-)HCO3- exchange to Na+-H+ antiport in lymphocytes.

Parallel exchange of Na+-H+ and Cl-(-)HCO3- is thought to be central to the translocation of electrolytes and water during cell volume regulation and in transepithelial transport. Coupling between these transporters is thought to be indirect, through changes in the concentration of HCO3-, which result from alterations in cytosolic pH (pHi). The possibility of a more direct, HCO3-(-)independent interaction between Cl-(-)HCO3- exchange and the Na+-H+ antiport was studied in rat thymic lymphocytes. Measurements of radioactive Cl- flux and of HCO3-(-)dependent pHi changes demonstrated the presence of a Na+-independent, 4,4'diisothiocyanostilbene-2,2'-disulfonic acid-sensitive Cl-(-)HCO3- exchanger. At constant external pH, the rate of Cl-(-)HCO3- exchange was markedly accelerated by increasing pHi between 7.0 and 7.4. This activation was not related to variations in the concentration of HCO3- and is likely caused by a direct effect of intracellular H+ (OH-) on the exchanger. Osmotic shrinking of the cells induced a cytoplasmic alkalinization, due to activation of the Na+-H+ antiport. Concomitantly, the rate of anion exchange also increased. The stimulation of Cl-(-)HCO3- exchange was eliminated when the alkalinization caused by Na+-H+ exchange was precluded. These observations suggest that the exquisite pHi sensitivity of the Cl-(-)HCO3- exchange system provides a mechanism whereby the rates of cation and anion transport are closely coupled.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗