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Biomedical subjects

J A Anderson

Publications and source records attributed to J A Anderson.

At least 55 records · Page 3Linked to original sources

A gastroesophageal electrode for electrophysiological studies.

A novel gastroesophageal electrode has been developed capable of atrial and ventricular pacing. We performed electrophysiological studies using the gastroesophageal electrode (Esothoracic) and compared the results with the standard endocardial approach. The flexible polythene gastroesophageal electrode was passed into the stomach under light sedation. Five ring electrodes, now positioned in the lower esophagus were used for bipolar atrial pacing and recording. Ventricular pacing was performed using a cathodic point source on the gastroesophageal electrode tip; the indifferent electrode (anode) was a high impedance chest pad. Parameters of sinus and AV nodal function were obtained by atrial pacing. Programmed ventricular stimulation was performed using a standard protocol. These electrophysiological parameters were subsequently determined using the endocardial approach. There was close correlation between measurements of sinus and AV node function using the two approaches in 48 subjects: sinus node recovery time (SNRT) r2 = 0.70, corrected sinus node recovery time (CSNRT) r2 = 0.87, AV Wenckebach cycle length (AVWCL) r2 = 0.97. The degree of agreement between the two approaches was estimated by the mean difference delta and standard deviation of the difference sigma (SNRT delta = 40 ms, sigma = 257 ms; CSNRT sigma = 14 ms, delta = 164 ms; AVWCL sigma = 7 ms, delta = 16 ms). Programmed ventricular stimulation was performed in 15 of 48 subjects with known or suspected ventricular tachyarrhythmias. Seven had ventricular tachycardia induced using both esothoracic and endocardial programmed ventricular stimulation. One subject was noninducible using esothoracic programmed ventricular stimulation, but inducible at endocardial electrophysiological studies. Another subject was inducible at esothoracic electrophysiological studies, but noninducible using endocardial programmed ventricular stimulation. Six subjects were noninducible using both endocardial and esothoracic programmed ventricular stimulation. The gastroesophageal electrode permits reliable atrial and ventricular pacing without transvenous catheterization or fluoroscopy. Electrophysiological parameters determined using this electrode are similar to those obtained using endocardial stimulation.

Adult↗

The nucleocapsid domain is responsible for the ability of spleen necrosis virus (SNV) Gag polyprotein to package both SNV and murine leukemia virus RNA.

Murine leukemia virus (MLV)-based vector RNA can be packaged and propagated by the proteins of spleen necrosis virus (SNV). We recently demonstrated that MLV proteins cannot support the replication of an SNV-based vector; RNA analysis revealed that MLV proteins cannot efficiently package SNV-based vector RNA. The domain in Gag responsible for the specificity of RNA packaging was identified using chimeric gag-pol expression constructs. A competitive packaging system was established by generating a cell line that expresses one viral vector RNA containing the MLV packaging signal (Psi) and another viral vector RNA containing the SNV packaging signal (E). The chimeric gag-pol expression constructs were introduced into the cells, and vector titers as well as the efficiency of RNA packaging were examined. Our data confirm that Gag is solely responsible for the selection of viral RNAs. Furthermore, the nucleocapsid (NC) domain in the SNV Gag is responsible for its ability to interact with both SNV E and MLV Psi. Replacement of the SNV NC with the MLV NC generated a chimeric Gag that could not package SNV RNA but retained its ability to package MLV RNA. A construct expressing SNV gag-MLV pol supported the replication of both MLV and SNV vectors, indicating that the gag and pol gene products from two different viruses can functionally cooperate to perform one cycle of retroviral replication. Viral titer data indicated that SNV cis-acting elements are not ideal substrates for MLV pol gene products since infectious viruses were generated at a lower efficiency. These results indicate that the nonreciprocal recognition between SNV and MLV extends beyond the Gag-RNA interaction and also includes interactions between Pol and other cis-acting elements.

Amino Acid Sequence↗

Adolescent self-esteem: a foundational disposition.

Based on results of a concept synthesis and concept derivation, an argument is made that self-esteem is a human foundational disposition within the self-care deficit theory of nursing and, as such, is a component of an individual's self-care agency. Guided by research literature, the basic conditioning factors of age, gender, developmental state, family systems, sociocultural orientation, health state, and environmental factors are discussed in regard to their influence on the adolescent's developing self-esteem and emerging self-care agency.

Adolescent↗

Pre- and postnatal toxicity of the HMG-CoA reductase inhibitor atorvastatin in rats.

Atorvastatin is a potent inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate and constitutes the rate-limiting step in the biosynthesis of cholesterol. Steroid hormones derived from cholesterol, as well as mevalonate and its isoprenoid derivatives, provide important contributions to the maternal animal during pregnancy and lactation, as well as to the growth and development of the offspring; these contributions may potentially be influenced by inhibition of HMG-CoA reductase. To investigate the effects of atorvastatin on various aspects of reproduction and development, female Sprague-Dawley rats received 0, 20, 100, or 225 mg/kg daily by gavage from gestation day 7 through lactation day 20. Maternal toxicity, characterized by morbidity/mortality (13%), reduced body weight gain and food consumption, and pathologic lesions in the nonglandular mucosa of the stomach, occurred at 225 mg/kg. Offspring survival at birth and during the neonatal period at 225 mg/kg was reduced relative to control by up to 45%, and 28% of litters had no viable offspring by 10 days postpartum. Additional effects on offspring included reduced body weight during the neonatal and maturation periods (100, 225 mg/kg), delayed appearance of pinnae detachment and incisor eruption (225 mg/kg), impaired rotorod performance (females only; 100, 225 mg/kg), reduced acoustic startle responding (males only; 20, 100, 225 mg/kg), and transient effects on shuttle avoidance (females only; 225 mg/kg). No treatment-related effects were observed on offspring reproduction. In a separate experiment, a single dose of 10 mg/kg atorvastatin administered to female Wistar rats on gestation day 19 or lactation day 13 provided evidence of placental transfer and excretion into the milk. Results of this study indicate that pre- and postnatal administration of atorvastatin to female rats produces developmental toxicity in their offspring via in utero and/or lactational exposure, and in the presence or absence of maternal toxicity.

Animals↗

Concurrent fluoroscopy and manometry reveal differences in laparoscopic Nissen and anterior fundoplication.

A prospective double-blind randomized trial was initiated to examine two types of laparoscopic fundoplication (Nissen and anterior). Thirty-two patients with proven gastroesophageal reflux disease presenting for primary laparoscopic antireflux surgery were randomized to undergo either Nissen fundoplication (N = 13) or anterior hemifundoplication (N = 19). Postoperative fluoroscopic and manometric examination was carried out concomitantly. Nissen fundoplication resulted in significantly greater elevation of resting (33.5 vs 23 mm Hg) and residual lower esophageal sphincter pressures (17 vs 6.5 mm Hg) and lower esophageal ramp pressure (26 vs 20.5 mm Hg) than the anterior partial fundoplication. A smaller radiologically measured sphincter opening diameter was seen following Nissen fundoplication (9 mm) compared with anterior fundoplication (12 mm). Lower esophageal ramp pressure correlated weakly (r = 0.37, P = 0.04) with postoperative dysphagia. It is concluded that the type of fundoplication performed significantly influences postoperative manometric and video barium radiology outcomes. The clinical relevance of this requires further investigation.

Barium Sulfate↗

Pollutant transport during a regional O3-episode in the mid-Atlantic states.

Ozone (O3) concentrations in the Baltimore-Washington (B-W) metropolitan area frequently exceed the National Ambient Air Quality Standard (NAAQS) in the summer months. The most extreme O3 events occur in multi-day high O3 episodes. These events can be regional in scale, with O3 concentrations exceeding the NAAQS at numerous locations along the eastern U.S. seaboard, and are typically associated with slow-moving or stagnant high pressure systems. In the B-W region, the most extreme events typically occur with surface high pressure overhead or just west of the region and an upper air high-pressure area (ridge) to the west or northwest. Besides providing conditions conductive to local O3 production (subsidence and strong low-level inversions, weak horizontal winds, little cloud cover), this weather pattern may also result in transport of O3 and its precursors from heavily industrialized areas west and north of the B-W region. In this paper, observations and back trajectories made during the severe regional O3 event of July 12-15, 1995, are used to confirm the hypothesis that significant regional-scale transport of O3 and its precursors occur during extreme O3 events of the standard type in the B-W area.

Air Pollution↗

Correlated template-switching events during minus-strand DNA synthesis: a mechanism for high negative interference during retroviral recombination.

Two models for the mechanism of retroviral recombination have been proposed: forced copy choice (minus-strand recombination) and strand displacement-assimilation (plus-strand recombination). Each minus-strand recombination event results in one template switch, whereas each plus-strand recombination event results in two template switches. Recombinant proviruses with one and more than one template switches were previously observed. Recombinants with one template switch were generated by minus-strand recombination, while recombinants containing more than one template switch may have been generated by plus-strand recombination or by correlated minus-strand recombination. We recently observed that retroviral recombination exhibits high negative interference whereby the frequency of recombinants containing multiple template-switching events is higher than expected. To delineate the mechanism that generates recombinants with more than one template switch, we devised a system that permits only minus-strand recombination. Two highly homologous vectors, WH204 and WH221, containing eight different restriction site markers were used. The primer binding site (PBS) of WH221 was deleted; although reverse transcription cannot initiate from WH221 RNA, it can serve as a template for DNA synthesis in heterozygotic virions. After one round of retroviral replication, the structures of the recombinant proviruses were examined. Recombinants containing two, three, four, and five template switches were observed at 1.4-, 10-, 65-, and 50-fold-higher frequencies, respectively, than expected. This indicates that minus-strand recombination events are correlated and can generate proviruses with multiple template switches efficiently. The frequencies of recombinants containing multiple template switches were similar to those observed in the previous system, which allowed both minus- and plus-strand recombination. Thus, the previously reported high negative interference during retroviral recombination can be caused by correlated template switches during minus-strand DNA synthesis. In addition, all examined recombinants contained an intact PBS, indicating that most of the plus-strand DNA transfer occurs after completion of the strong-stop DNA.

DNA Replication↗

Retroviral recombination rates do not increase linearly with marker distance and are limited by the size of the recombining subpopulation.

Recombination occurs at high frequencies in all examined retroviruses. The previously determined homologous recombination rate in one retroviral replication cycle is 4% for markers 1.0 kb apart in spleen necrosis virus (SNV). This has often been used to suggest that approximately 30 to 40% of the replication-competent viruses with 7- to 10-kb genomes undergo recombination. These estimates were based on the untested assumption that a linear relationship exists between recombination rates and marker distances. To delineate this relationship, we constructed three sets of murine leukemia virus (MLV)-based vectors containing the neomycin phosphotransferase gene (neo) and the hygromycin phosphotransferase B gene (hygro). Each set contained one vector with a functional neo and an inactivated hygro and one vector with a functional hygro and an inactivated neo. The two inactivating mutations in the three sets of vectors were separated by 1.0, 1.9, and 7.1 kb. Recombination rates after one round of replication were 4.7, 7.4, and 8.2% with markers 1.0, 1.9, and 7.1 kb apart, respectively. Thus, the rate of homologous recombination with 1.0 kb of marker distance is similar in MLV and SNV. The recombination rate increases when the marker distance increases from 1.0 to 1.9 kb; however, the recombination rates with marker distances of 1.9 and 7.1 kb are not significantly different. These data refute the previous assumption that recombination is proportional to marker distance and define the maximum recombining population in retroviruses.

Genome, Viral↗

Milk, eggs and peanuts: food allergies in children.

True food allergies are much less prevalent than is generally believed. They are more common in infants and children under age three than in older children and adults. Infant colic generally is not caused by a food allergy. In infants, urticaria, eczema or gastrointestinal bleeding may be due to foods such as milk and eggs, but clinical tolerance usually develops within a few years. Peanuts, tree nuts, seafood and seeds, as well as milk and eggs, can cause anaphylaxis in highly allergic children, and reexposure to such foods presents the risk of life-threatening reactions. Immediate-reacting allergy skin tests and in vitro IgE antibody tests can be used to screen for food allergy. Only food challenge, however, can confirm a reaction to a particular food. Management of food allergy, once the initial symptoms are confirmed, consists of avoidance of specific foods, sometimes for a lifetime. All children at risk for food anaphylaxis should be identified, and their parents or caretakers should be prepared to administer epinephrine before taking the child to the emergency room.

Animals↗

Zygotic transcription is required to block a maternal program of apoptosis in Xenopus embryos.

At the midblastula transition during Xenopus development, the cell cycle is remodeled, and zygotic transcription is initiated. Additionally, cyclin E1 is degraded at the midblastula transition independently of protein synthesis, the number of cell cycles, and the nuclear-to-cytoplasmic ratio. In the studies reported here, cell cycles were delayed by transient inhibition of protein synthesis with cycloheximide (100 microg/ml) prior to the midblastula transition. Even after reaccumulation of mitotic cyclins and resumption of cell divisions, cycloheximide-treated embryos did not resume DNA synthesis, failed to initiate transcription, and synchronously became apoptotic before the gastrula stage. These results were independent of the stage at which embryos were treated or the duration of treatment. Inhibition of zygotic transcription with alpha-amanitin also induced apoptosis. These data suggest that a developmental checkpoint at the midblastula transition is maternally regulated and can trigger apoptosis. Apoptosis induced by cycloheximide or alpha-amanitin was blocked by injection of RNA encoding Xenopus Bcl-2, suggesting that this maternal program is normally blocked by expression of an apoptotic inhibitor. Embryos pulsed with lower doses of cycloheximide (10 microg/ml) delayed development prior to the midblastula transition but resumed DNA synthesis, initiated transcription, and gastrulated normally. This indicates that the apoptotic response is initiated only when delayed embryos are unable to support initiation of zygotic transcription.

Amanitins↗

Representing geometrical knowledge.

This paper introduces perspex algebra which is being developed as a common representation of geometrical knowledge. A perspex can currently be interpreted in one of four ways. First, the algebraic perspex is a generalization of matrices, it provides the most general representation for all of the interpretations of a perspex. The algebraic perspex can be used to describe arbitrary sets of coordinates. The remaining three interpretations of the perspex are all related to square matrices and operate in a Euclidean model of projective space-time, called perspex space. Perspex space differs from the usual Euclidean model of projective space in that it contains the point at nullity. It is argued that the point at nullity is necessary for a consistent account of perspective in top-down vision. Second, the geometric perspex is a simplex in perspex space. It can be used as a primitive building block for shapes, or as a way of recording landmarks on shapes. Third, the transformational perspex describes linear transformations in perspex space that provide the affine and perspective transformations in space-time. It can be used to match a prototype shape to an image, even in so called 'accidental' views where the depth of an object disappears from view, or an object stays in the same place across time. Fourth, the parametric perspex describes the geometric and transformational perspexes in terms of parameters that are related to everyday English descriptions. The parametric perspex can be used to obtain both continuous and categorical perception of objects. The paper ends with a discussion of issues related to using a perspex to describe logic.

Cognition↗

Determination of key structural requirements of a K+ channel pore.

Among the highly conserved sites in K+ channel pores, the tyrosine-glycine sequence is believed to play an important role in selectivity. Here we describe a novel approach in which comprehensive mutagenesis of the YG sites of the voltage-gated K+ channel, Kat1, is combined with phenotypic screening in Saccharomyces cerevisiae and electrophysiological analysis in Xenopus oocytes to determine the roles of these sites in K+ selectivity. We show that structural constraints necessitate a tyrosine or phenylalanine at the first position to confer full K+ selectivity. Substitution to arginine creates a channel titratable by external pH, suggesting that the side group at this position may line the channel pore. Permeation is abolished by any increase in bulk at the adjacent glycine position unless accompanied by a compensatory mutation at the tyrosine site. These results suggest a model in which the selectivity filter of the K+ channel requires an aromatic residue paired with glycine within the pore loop in order to maintain maximal K+ selectivity.

Amino Acid Sequence↗

Ventricular pacing with a novel gastroesophageal electrode: a comparison with external pacing.

Temporary endocardial pacing is a technically demanding invasive procedure requiring sterile precautions and access to fluoroscopy. External (transcutaneous) pacing requires high current for capture and is poorly tolerated in the conscious patient. An esothoracic pacing system has been developed capable of reliable ventricular capture. The flexible gastroesophageal electrode is passed into the stomach. The distal 6 cm is angled to 90 degrees with an internal pulley system, positioning the tip of the gastroesophageal electrode in the fundus of the stomach. Ventricular pacing is performed with a spherical electrode (cathode) mounted on the gastroesophageal electrode tip in conjunction with a chest pad (anode) positioned medial to the cardiac apex. Of 91 subjects in which esothoracic pacing was attempted, 86 (94.5%) demonstrated successful ventricular capture at the maximum pulse duration used (40 msec). Threshold current for ventricular capture ranged from 22.5 +/- 8.1 mA at a pulse duration of 40 msec to 29.9 +/- 8.6 mA at a pulse duration of 10 msec. Esothoracic pacing was compared with external pacing in a subgroup (n = 30) of patients. Ventricular capture with the gastroesophageal electrode was more common when compared with the external approach (27 [90%] of 30 vs 13 [43.3%] of 30, p < 0.001). In those subjects in whom ventricular capture was obtained with both methods, threshold current for capture was significantly lower with the esothoracic approach. This gastroesophageal electrode may be useful in the emergency management of acute bradyarrhythmias.

Adult↗

Assimilation of volatiles from ripe apples by Sporidiobolus salmonicolor and Tilletiopsis washingtonensis.

Sporidiobolus salmonicolor ATCC 623 and Tilletiopsis washingtonensis NRRL Y-2555 grew on carbon resources provided as volatiles by ripe 'Golden Delicious' apples. This ability was not correlated with the reported natural habitats of the 21 species (26 strains) tested. Ethylene, the major volatile produced, was not utilized but butyl acetate, hexyl acetate and hexyl-2-methyl-butanoate (identified by GC-MS) were. These yeasts also assimilated ethanol, butanol, hexanol (Tilletiopsis excepted), acetate, propionate, butyrate and ethyl acetate at appropriately low concentrations. Ethanol and acetate aside, this is the first report of such assimilations by any yeast.

Fruit↗

Ionizing radiation induces apoptosis and elevates cyclin A1-Cdk2 activity before but not after the midblastula transition in Xenopus.

After the twelfth cell division in Xenopus embryos, zygotic gene transcription is activated, cells become motile, and cell division becomes asynchronous. This developmental change is termed the midblastula transition. High doses of gamma-irradiation (gamma-IR) before the midblastula transition induced apoptotic cell death and increased the levels of cyclin A1 and cyclin A1-Cdk2 activity. The addition of recombinant cyclin A1-Cdk2 induced the formation of apoptotic nuclei in Xenopus egg extracts, suggesting a role for cyclin A1-Cdk2 in apoptosis. Hallmarks of apoptosis, such as internucleosomal DNA fragmentation, pyknotic and uniformly condensed nuclei, and loss of intercellular attachments, were evident in embryos exposed to gamma-IR before the midblastula transition. Apoptotic cells accumulated in the blastocoel, suggesting that before the midblastula transition Xenopus embryos use apoptosis to eliminate cells containing damaged DNA. However, embryos treated with the same dose of gamma-IR after the midblastula transition developed normally and exhibited no signs of apoptosis, no change in cyclin A1 level, and no increase in cyclin A1-Cdk2 activity. These results indicate that there is a change in the response to DNA damage at the midblastula transition in Xenopus embryos.

Animals↗

A gastroesophageal electrode for atrial and ventricular pacing.

Temporary transvenous cardiac pacing requires technical expertise and access to fluoroscopy. We have developed a gastroesophageal electrode capable of atrial and ventricular pacing. The flexible polythene gastroesophageal electrode is passed into the stomach under light sedation. Five ring electrodes, now positioned in the lower esophagus, are used for atrial pacing. A point source (cathode) on the distal tip of the electrode, now positioned in the gastric fundus, is used for ventricular pacing. Two configurations of atrial and ventricular pacing were compared: unipolar and bipolar. During unipolar ventricular pacing the indifferent electrode (anode) was a high impedance chest pad. For bipolar ventricular pacing the indifferent electrode was a ring electrodes placed 2 cm proximal to the tip. Unipolar atrial pacing was performed with 1 of 5 proximal ring electrodes acting as cathode ("cathodic") or as anode ("anodic") in conjunction with a chest pad. Bipolar atrial pacing was performed using combinations of 2 of 5 ring electrodes. Atrial capture was obtained in all 55 subjects attempted. When all electrode combinations were compared, atrial capture was significantly more frequent using the bipolar approach (153/210 bipolar, 65/210 unipolar; t = 7.37, P < 0.001). For unipolar atrial pacing, cathodic stimulation (from esophagus) was more successful than anodic stimulation (cathodic 62/105, anodic 20/105; t = 5.81, P < 0.001). In 43 subjects attempted unipolar ventricular pacing resulted in a higher frequency of capture than the bipolar approach (unipolar 41/43 (95.3%), bipolar 19/43 (44.2%); P < 0.001). In conclusion, atrial pacing was optimal using pairs of ring electrodes ("bipolar") while ventricular pacing was optimal using the distal electrode tip (cathode) in conjunction with a chest pad electrode ("unipolar"). This gastroesophageal electrode may be useful in the emergency management of acute bradyarrhythmias and for elective electrophysiological studies.

Adult↗

The role of cytokines, adhesion molecules, and chemokines in interleukin-2-induced lymphocytic infiltration in C57BL/6 mice.

IL-2 mediates the regression of certain malignancies, but clinical use is limited because of associated toxicities, including parenchymal lymphocytic infiltration with multiple organ failure. Secondarily induced cytokines are important mediators of IL-2 toxicity and IL-2-induced lymphocyte-endothelial adherence and trafficking. The recently discovered C-C chemokines, RANTES (regulated on activation, normal T expressed and secreted) and macrophage inflammatory protein-1alpha, have also been implicated in lymphocytic migration. We hypothesized that IL-2 alters cytokine, C-C chemokine, and adhesion molecule expression in association with parenchymal lymphocytic infiltration. C57BL/6 mice were injected with 3x10(5) IU of IL-2 or 0.1 ml of 5% dextrose intraperitoneally every 8 h for 6 d, then killed. IL-2 induced massive lymphocytic infiltration in the liver and lung and moderate infiltration in the kidney in association with organ edema and dysfunction. Immunostaining showed increased intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression in association with this organ-specific lymphocytic infiltration. Flow cytometry showed increased expression of the corresponding ligands (lymphocyte function-associated antigen-1 and very late antigen-4) on splenocytes. IL-2 increased TNF-alpha mRNA and protein expression in the liver. Organs infiltrated by lymphocytes had increased TNF-alpha mRNA, whereas RANTES mRNA was increased in all organs, regardless of lymphocytic infiltration. IL-2 toxicity involves organ-specific TNF-alpha and RANTES production with increased ICAM-1 and VCAM-1 expression as potential mechanisms facilitating lymphocytic infiltration and organ dysfunction.

Animals↗