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Biomedical subjects

S L Peterson

Publications and source records attributed to S L Peterson.

At least 19 recordsLinked to original sources

Biocompatible semiconductor optoelectronics.

We investigate optoelectronic properties of integrated structures comprising semiconductor light-emitting materials for optical probes of microscopic biological systems. Compound semiconductors are nearly ideal light emitters for probing cells and other microorganisms because of their spectral match to the transparency wavelengths of biomolecules. Unfortunately, the chemical composition of these materials is incompatible with the biochemistry of cells and related biofluids. To overcome these limitations, we investigate functionalized semiconductor surfaces and structures to simultaneously enhance light emission and the flow of biological fluids in semiconductor microcavities. We have identified several important materials problems associated with the semiconductor/biosystem interface. One is the biofluid degradation of electroluminescence by ionic diffusion into compound semiconductors. Ions that diffuse into the active region of a semiconductor light emitter can create point defects that degrade the quantum efficiency of the radiative recombination process. In this paper we discuss ways of mitigating these problems using materials design and surface chemistry, and suggest future applications for these materials.

Animals↗

Focal microinjection of carbachol into the periaqueductal gray induces seizures in the forebrain of the rat.

Previous studies have reported that the repetition of running-bouncing and tonic-clonic seizures mediated by brainstem structures eventually elicits seizure activity in the forebrain. The purpose of the present study was to determine if the periaqueductal gray (PAG) region is a component of the neural network through which brainstem seizures elicit forebrain seizures. Bilateral microinjection of 40 nmol carbachol into the PAG region of rats induced arrested, staring behavior accompanied by epileptiform electrocorticogram (ECoG) afterdischarge recorded from the parietal cortex. In two animals limbic seizure activity similar to kindled amygdala seizures was also induced. The carbachol effect was dose-related as the 40 nmol dose induced a significantly greater duration of ECoG afterdischarge than a 20 nmol dose. The carbachol effect was mediated by muscarinic receptors as bilateral 50 nmol atropine microinjection 1 min prior to 40 nmol carbachol microinjection inhibited all seizure activity. Immunohistochemical detection of the proto-oncogene c-fos was used to verify that seizure activity was induced in forebrain regions. Rats with seizures induced by PAG carbachol microinjections exhibited dense c-fos-like immunoreactivity in the dentate gyrus but not the CA(1) or CA(3) regions, amygdala, piriform cortex, perirhinal cortex or hypothalamus. In addition, PAG microinjection of 10 nmol N-methyl-D-aspartic acid (NMDA) induced wild-running convulsions while 400 pmol bicuculline induced clonic spasms, myoclonic activity or limbic seizures. These results indicate that stimulation of the PAG, a brainstem structure, is sufficient to induce forebrain seizures. Since the forebrain seizures were induced by a single carbachol administration, it is proposed that the PAG serves as a pathway for caudal-rostral seizure generalization.

Animals↗

Asymmetric synthesis of the balanol heterocycle via a palladium-mediated epimerization and olefin metathesis.

[formula: see text] The enantioselective formal synthesis of balanol, a potent protein kinase C inhibitor, was accomplished from D-serine utilizing a Pd-catalyzed equilibration of diastereomeric 5-vinyloxazolines to set the stereochemistry of the vicinal amino and hydroxyl groups. A ruthenium-catalyzed ring-closing metathesis was employed to form the seven-membered nitrogen heterocyle.

Alkenes↗

Muscarinic receptors mediate carbachol-induced inhibition of maximal electroshock seizures in the nucleus reticularis pontis oralis.

PURPOSE: Previous reports from this laboratory indicated a role for N-methyl-D-aspartic acid (NMDA) and gamma-aminobutyric acid (GABA) receptors among the neuronal mechanisms of the nucleus reticularis pontis oralis (RPO) that regulate the tonic hindlimb extension (THE) component of maximal electroshock seizures (MESs) in rats. This study was intended to determine the role of cholinergic mechanisms in the RPO regulation of THE. METHODS: Rats were surgically prepared with microinjection guide cannulas for the focal administration of drug solutions directly into the RPO. MES was induced with corneal electrodes. RESULTS: RPO microinjection of carbachol significantly inhibited the incidence of THE. RPO microinjection of atropine by itself had no effect on the seizure response but significantly antagonized the anticonvulsant effect induced by RPO microinjection of carbachol. The selective nicotinic agonist dimethylpiperizinium (DMPP) by itself had no effect on THE. RPO microinjection of 10 ng pertussis toxin by itself had no effect on THE but significantly antagonized the anticonvulsant effect induced by RPO microinjection of carbachol. CONCLUSIONS: RPO microinjection of carbachol inhibited the THE component of MESs in rats. The carbachol effect appeared to be mediated by muscarinic receptors as the anticonvulsant activity was antagonized by atropine, and the selective nicotinic agonist DMPP induced no anticonvulsant activity. Because pertussis toxin acts to inhibit muscarinic receptor-linked G proteins, the pertussis toxin antagonism of carbachol also supports a muscarinic mechanism of action.

Animals↗

Seizures induced by theophylline and isoniazid in mice.

Isoniazid-induced seizures respond poorly to anticonvulsants but well to pyridoxine (Vitamin B6); theophylline produces difficult-to-treat seizures with substantial morbidity and mortality. Theophylline therapy depresses plasma pyridoxal-5'-phosphate (PLP), the active metabolite of pyridoxine, suggesting that theophylline-induced seizures might be amenable to treatment with pyridoxine. Our study established the dose-response relationship for convulsions due to isoniazid and theophylline in mice and determined if pyridoxine antagonized such seizures. Female CD-1 outbred mice weighing 25 to 30 g were used. Clonic seizures had clonic activity lasting 5 sec; tonic seizures had loss of the righting reflex with tonic hindlimb extension. Groups of 10 mice received single doses of 50, 100, 150, 200, 250 or 300 mg aminophylline/kg i.p. or 100, 150, 200, 250, 300 or 350 mg isoniazid/kg i.p. and were observed for seizures or death. Pyridoxine or saline with aminophylline or isoniazid were administered simultaneously. The LD50 for aminophylline was 266 mg/kg; for isoniazid it was 160 mg/kg. Doses of 150 mg aminophylline/kg or 100 mg isoniazid/kg did not induce seizures. Pyridoxine with aminophylline or isoniazid did not alter the frequency or time of onset of seizures or death. This was unexpected because pyridoxine antagonizes theophylline-induced seizures in mice and reverses isoniazid-induced seizures in humans. We found no evidence that PLP depletion in mice is a mechanism for seizures induced by isoniazid or aminophylline in a fashion similar to isoniazid in humans.

Animals↗

Neuronal degeneration in rat forebrain resulting from D-amphetamine-induced convulsions is dependent on seizure severity and age.

Neuronal damage and degeneration in the rat forebrain was characterized by B4 isolectin and Fluoro-Jade labeling techniques after 4 doses of 15 mg/kg amphetamine i.p. in 70- and 180-day-old Sprague-Dawley rats. In amphetamine-dosed rats some seizure activity occurred in all rats exhibiting pronounced hyperthermia but the degree of seizure activity varied greatly between individual rats. Over 90% of the rats in both age groups that showed behavioral signs of limbic seizures had somatic degeneration in the taenia tecta within 3 days of amphetamine exposure. Degenerating small star-shaped cells were seen in the septum and hippocampus in 70-day-old rats having extensive seizure activity. Although somatic degeneration only sporadically occurred in the piriform cortex of the younger rats, extensive B4 isolectin binding to activated microglia was observed in this area. In older rats prominent somatic degeneration was seen in the piriform cortex and orbital and insular areas of the frontal cortex of rats having seizures. Damage to the basal ganglia and related areas, including the thalamus, parietal cortex and dorsal medial striatum, occurred in rats with pronounced hyperthermia but only correlated with seizures in older rats. In the more severe cases of thalamic damage the highest density of neurodegeneration was localized perivascularly. Thus, amphetamine can produce notable damage to the limbic system when seizures occur and to the basal ganglia and related areas when hyperthermia occurs but the neurotoxicity profiles in these areas are age-dependent and not produced solely by hyperthermia. Further studies to determine whether neuronal damage is the result of or the cause of amphetamine-induced seizures are necessary.

Age Factors↗

Evaluating a more cost-efficient alternative to providing in-home feedback to parents: the use of spousal feedback.

We evaluated the contribution of spousal feedback to a parent education curriculum designed for parents of children with autism. A modified multiple baseline design across 3 husband-and-wife dyads was used to examine the effects of teaching parents to give each other feedback on their teaching performance. For 5 of 6 participants, improvement in teaching performance occurred following didactic presentations. However, additional improvement was observed for 5 participants when the spousal feedback component was implemented.

Autistic Disorder↗

Leukocytes modulate 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity in human granulosa-lutein cell cultures.

It is well established that there are interactions between the immune and reproductive systems. The ovary contains indigenous macrophages, as well as other classes of leukocytes in smaller numbers. Cytokines secreted by these cells have been shown to have the ability to regulate ovarian steroidogenesis. In the present study, the effect of leukocytes on 11beta-hydroxysteroid dehydrogenase (11beta-HSD) in human granulosa-lutein cells was examined. In addition, individual cytokines were also tested for their ability to regulate this enzyme. The follicular aspirates of patients undergoing IVF treatment were used as a source of granulosa cells. Cells isolated from these aspirates were found to contain between 15 and 60% leukocytes as assessed by flow cytometry (FACS). Leukocytes were removed from the sample preparations by the use of immunomagnetic beads coated with CD45 antibody, which recognises a surface antigen on all classes of leukocyte. Removal of leukocytes significantly decreased the 11beta-HSD activity in the granulosa cells, assayed after 3 days of culture, from 7.3 (2-20) to 3.5 (1-10) pmol cortisone formed/50000 cells/4 h (medians and ranges, n = 15). Addition of IL-5 and IL-6 significantly increased the 11beta-HSD activity in granulosa cell cultures both in the presence and absence of leukocytes. Addition of IL-4 and IFN-gamma increased 11beta-HSD activity only in the leukocyte-depleted granulosa cell cultures, whereas IL-2 had no effect on either of the cultures. The data suggests that leukocytes interact with the ovarian cells through cytokine secretion and/or cell-cell contact to increase the 11beta-HSD activity in human granulosa cells.

11-beta-Hydroxysteroid Dehydrogenases↗

The effect on maximal electroshock seizures induced by GABA agents and antiepileptic drugs microinfused into the nucleus reticularis pontis oralis.

The nucleus reticularis pontis oralis (RPO) is necessary for the expression of tonic hindlimb extension (THE) in maximal electroshock seizures (MES) of rats. Previous work in this laboratory has demonstrated that focal RPO microinfusion of NMDA antagonists inhibited THE while focal RPO microinfusion of NMDA induced convulsive activity similar to the audiogenic seizure response of rats. The purpose of the present study was to identify other receptors in the RPO that influence THE or induce convulsive activity. Bilateral microinfusion of bicuculline had no effect on the THE component of MES except when the bicuculline induced wild-running convulsions in which case the subsequent THE response to the MES stimulus was inhibited. The GABAergic agents muscimol, baclofen or 2-hydroxysaclofen neither altered the THE response nor induced convulsions. In addition, bilateral RPO microinfusion of the clinically effective antiepileptic drugs phenytoin, phenobarbital, valproate, ethosuximide or felbamate had no effect on the THE component of MES. These results indicate that the role of GABAergic receptors in the anticonvulsant activity mediated by the RPO is not prominent and that the RPO is unlikely to be the site of antiepileptic drug action in MES.

Animals↗

Infusion of NMDA antagonists into the nucleus reticularis pontis oralis inhibits the maximal electroshock seizure response.

The nucleus reticularis pontis oralis (RPO) is necessary for the expression of tonic hindlimb extension (THE) in maximal electroshock (MES) seizures of rats. Previous work in this laboratory has demonstrated that both systemic administration and focal RPO microinfusion of D-cycloserine inhibits THE. The purpose of the present study was to characterize specific components of the NMDA receptor/ionophore complex that regulate the anticonvulsant activity mediated by the RPO. Bilateral RPO microinfusion of the competitive NMDA antagonists (-)AP7 and D-CPP as well as the uncompetitive antagonist dizocilpine ((+)MK-801) inhibited THE in a dose-related fashion. Bilateral RPO microinfusion of NMDA did not affect the THE response to MES but did induce convulsions resembling audiogenic seizures in genetically epilepsy prone rats. Bilateral RPO microinfusion of the strychnine-insensitive glycine site partial agonist D-cycloserine and the antagonist 5,7-dichlorokynurenic acid inhibited THE. The strychnine-insensitive glycine partial agonists (+)HA-966 and ACPC, as well as the agonists glycine and D-serine, did not significantly affect the THE response. Strychnine microinfusions in the RPO had no effect on THE. The results support a hypothesis that the RPO is a site of anticonvulsant drug action in MES and indicate that either competitive or uncompetitive NMDA antagonist action regulates the anticonvulsant activity mediated by the RPO. The role of the strychnine-insensitive glycine site in the regulation of the anticonvulsant activity medicated by the RPO is uncertain.

Animals↗

Diazepam potentiation by glycine in pentylenetetrazol seizures is antagonized by 7-chlorokynurenic acid.

This study evaluated a possible mechanism by which glycine potentiates the activity of diazepam (DZP) and valproic acid (VAL) against the clonic seizures induced by pentylenetetrazol (PTZ) in rats. Neither 7-chlorokynurenic acid (7-CLKYNA) nor strychnine in doses of 10, 50, or 100 nmol ICV significantly altered the clonic seizure response to PTZ. However, 7-CLKYNA (100 nmol, ICV), but not strychnine (100 nmol, ICV), antagonized the anticonvulsant activity induced by coadministration of DZP (1.0 mg/kg, IP) and glycine (40 mmol/kg, PO). Neither 7-CLKYNA (100 nmol, ICV) nor strychnine (100 nmol, ICV) significantly altered the anticonvulsant activity induced by coadministration of VAL and glycine. 7-CLKYNA (100 nmol, ICV) had no effect on the anticonvulsant activity of DZP or VAL in the absence of glycine. These results provide evidence that the glycine potentiation of the anticonvulsant activity of DZP in clonic seizures induced by PTZ may be mediated by the strychnine-insensitive glycine receptor.

Animals↗

Administrative support team. A structural innovation.

In response to societal, organization, and leadership changes, an innovative nursing structure was implemented and evaluated. An administrative support team was developed to provide specialized internal consultation and support to a flattened and decentralized nursing division. The four administrative support team roles provided an organization perspective that ensured constancy of purpose throughout the division. This structural innovation proved to be congruent with nursing shared governance and total quality management initiatives occurring in the organization. Evaluation studies indicated that the model has effectively supported 5 years of continuing organizational change.

Hospital Bed Capacity, 300 to 499↗

Effect of in utero radiation dose fractionation on rat postnatal development, behavior and brain structure: 3-hour interval.

Effect of In Utero Radiation Dose Fractionation on Rat Postnatal Development, Behavior and Brain Structure: 3-Hour Interval. Neurotoxicology 15(1): 183-190, 1994. We have previously shown that exposure of the rat fetus to ionizing radiation produces dose-dependent (0.25-1.25 Gy) changes in postnatal growth and behavior, and decreases in cerebral cortex thickness. Pregnant rats were exposed to single doses of 0.5 or 1.0 Gy, or to two doses of 0.5 Gy (separated by a 3 h interval) on gestational day 15. Pups were weighed and subjected to behavioral tests (righting reflex; reflex suspension; negative geotaxis; continuous corridor; and length, width, and sine of gait) over postnatal days 7-28. The rats were then sacrificed and brains removed for histology. The fractionated doses produced responses that were generally intermediate between those produced by the single doses and which, by interpolation, could be expressed as equivalent to a single dose between 0.5 and 1.0 Gy. Overall, exposure of the fetal rat to two doses of 0.5 Gy separated by 3 h produced effects equivalent to a single dose of 0.85 Gy. We conclude that fractionation of radiation dose results in less damage to the developing rat cerebral cortex, as measured by postnatal growth, behavioral tests, and morphological assessment.

Animals↗

The anticonvulsant activity of D-cycloserine is specific for tonic convulsions.

D-Cycloserine has been shown to exert anticonvulsant activity in maximal electroshock seizures. The purpose of the present study was to evaluate the spectrum of D-cycloserine anticonvulsant activity using other experimental models of epilepsy. D-Cycloserine induced a dose-related decrease in the incidence of tonic convulsions induced by 120 mg/kg of pentylenetetrazol. The ED50 of D-cycloserine for the inhibition of the tonic convulsions was 109 mg/kg. The anticonvulsant activity was specific for the D-isomer at L-cycloserine (400 mg/kg) had no effect on the tonic convulsions. D-Cycloserine had no effect on the pentylenetetrazol-induced clonic convulsions induced by either 70 or 120 mg/kg pentylenetetrazol, electrically induced nonkindled hippocampal seizures or kindled amygdala seizures. D-Cycloserine had no effect on strychnine-induced tonic convulsions. These results indicate that D-cycloserine is inactive against clonic convulsions and may be active only against tonic convulsions mediated by brainstem sites.

Animals↗

Patient care and nursing practice when staff requirements exceed staff availability.

This study examined the Workload Management System for Nurses at a tertiary-care Army hospital to determine the incongruence between recommended nursing care hours and actual nursing care hours provided. The purpose of the study was to describe patient care and nursing practice when calculated staff requirements exceed actual staff availabilty. The findings of the study indicated that basic nursing care tasks were accomplished; however, professional development activities were sacrificed. The data reveal that nurses do not have the time to grow professionally through research or education, and they are reduced to assembly-line mentality as they go from task to task without being able to care for a patient as a person.

Adult↗

Changes in catalase activity and concentration during ovarian development and differentiation.

The ovaries of immature rats were used to prepare a peroxisome-enriched fraction by differential centrifugation. Following gonadotropin stimulation, which caused large numbers of follicles to develop into corpora lutea, the specific activity of catalase in the peroxisome-enriched fraction increased 5-fold, while catalase recovered in the post-30,000 x g supernatant did not increase in activity. The increase in catalase specific activity in the peroxisome enriched fraction was shown to be due to an increased concentration of the enzyme as determined by Western blotting. Catalase in pig granulosa cells also increased in specific activity as the follicles aged and luteinized. This increase appeared to parallel increases in the concentration of cytochrome P-450scc. We conclude there is a differential regulation of the peroxisomal and cytosolic pools of rat ovarian catalase.

Animals↗