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Biomedical subjects

M J Peterson

Publications and source records attributed to M J Peterson.

At least 19 recordsLinked to original sources

A direct demonstration of cortical LTP in humans: a combined TMS/EEG study.

Repetitive transcranial magnetic stimulation (rTMS) is increasingly being used to promote cortical reorganization, under the assumption that it can induce long-term potentiation (LTP) of neural responses. This assumption is supported by several lines of indirect evidence. For example, rTMS of motor cortex can induce a potentiation of muscle motor evoked potentials that outlasts the stimulation by several minutes. In animal models, a direct demonstration of LTP is typically obtained by high-frequency electrical stimulation coupled with local field recordings of population responses. In this study, we exploited a new approach based on combined rTMS/high-density electroencephalography (hd-EEG) to obtain direct, noninvasive evidence for LTP in humans. Cortical responses to single TMS pulses were measured with hd-EEG before and after applying rTMS to motor cortex (5Hz, 1500 pulses). The results demonstrate that, after rTMS, EEG responses at latencies of 15-55ms were significantly potentiated. A topographic analysis revealed that this potentiation was significant at EEG electrodes located bilaterally over premotor cortex. Thus, these findings provide a direct demonstration in humans of LTP induced by rTMS.

Electroencephalography↗

Trace element contamination in benthic macroinvertebrates from a small stream near a uranium mill tailings site.

Direct measurement of the accumulation of non-radioactive trace elements in aquatic biota near uranium mining or processing sites has been relatively rare, with greater focus on the radiological activity in the adjacent soils and groundwater. To evaluate the potential ecological concern associated with trace elements at a former uranium mill site in southeastern Utah, benthic macroinvertebrates were collected and analyzed for 17 trace elements from multiple locations within a small on-site stream, Montezuma Creek, and a nearby reference stream. Key questions of this study relate to the spatial and temporal extent of contamination in aquatic biota, the potential ecological risks associated with that contamination, and the usefulness of benthic macroinvertebrates as a monitoring tool at this site. Composite samples of similar macroinvertebrate taxa and functional feeding groups were collected from each site over a two year period that was representative of normal and dry-year conditions. In both years, mean concentrations of arsenic, molybdenum, selenium, and vanadium were significantly higher (a factor of 2-4 times: P < 0.05) in macroinvertebrates collected from one or both of the two Montezuma Creek sites immediately downstream of the mill tailing site in comparison to concentrations from reference locations. Mean uranium concentrations in invertebrates immediately downstream of the mill site were more than 10 times higher than at reference sites. The site-to-site pattern of contamination in Montezuma Creek invertebrates was similar in 1995 and 1996, with mill-related trace elements showing a downstream decreasing trend. However, nine of seventeen contaminant concentrations were higher in the second year of the study, possibly due to a higher influx of deep groundwater during the drier second year of the study. A preliminary assessment of ecological risks, based on the benthic macroinvertebrate bioaccumulation data, suggests that aquatic and terrestrial population risks are low. Benthic macroinvertebrates appeared to be sensitive integrators of trace element inputs to the aquatic environment from a former uranium mill tailing site, and provided useful spatial and temporal patterns of contamination not easily obtained using conventional surface water or groundwater measures.

Animals↗

Spatial associations among density of cattle, abundance of wild canids, and seroprevalence to Neospora caninum in a population of beef calves.

OBJECTIVE: To determine the epidemiologic plausibility of a sylvatic transmission cycle for Neospora caninum between wild canids and beef cattle. DESIGN: Spatial analysis study. ANIMALS: 1,009 weaned beef steers from 94 beef herds in Texas. PROCEDURE: Calves were grouped on the basis of seroprevalence for N caninum and ecologic region in Texas. The Morans I test was used to evaluate spatial interdependence for adjusted seroprevalence by ecologic region. Cattle density (Number of cattle/259 km2 [Number of cattle/100 mile2] of each ecologic region) and abundance indices for gray foxes and coyotes (Number of animals/161 spotlight-transect [census] km [Number of animals/100 census miles] of each ecologic region) were used as covariates in spatial regression models, with adjusted seroprevalence as the outcome variable. A geographic information system (GIS) that used similar covariate information for each county was used to validate spatial regression models. Results-Spatial interdependence was not detected for ecologic regions. Three spatial regression models were tested. Each model contained a variable for cattle density for the ecologic regions. Results for the 3 models revealed that seroprevalence was associated with cattle density and abundances of gray foxes, coyotes, or both. Abundances of gray foxes and coyotes were collinear. Results of a GIS-generated model validated these spatial models. CONCLUSIONS AND CLINICAL RELEVANCE: In Texas, beef cattle are at increased risk of exposure to N caninum as a result of the abundance of wild canids and the density of beef cattle. It is plausible that a sylvatic transmission cycle for neosporosis exists.

Animals↗

Human myeloid zinc finger gene MZF produces multiple transcripts and encodes a SCAN box protein.

The myeloid zinc finger gene 1 (MZF1) encodes a C(2)H(2) zinc finger transcription factor that regulates granulopoiesis and may have a regulatory role in cellular proliferation and oncogenesis. The MZF1 gene has been previously reported to be 3kb and without introns. However, at least three transcripts of approximately 3, 7.5, and 9kb are detected by MZF1-specific probes in northern blot analysis and the identity of the transcripts has not been addressed. We screened a K562 cDNA library and identified novel transcripts, MZF1B and MZF1C. The 2.9kb MZF1B cDNA encodes a putative 734 aa protein and MZF1C maintains an identical open reading frame with 320 nucleotides deleted in the 5'-untranslated region. The MZF1B/1C protein contains all but the first eight amino acids of MZF1. Thus, MZF protein isoforms share 100 aa, as well as the bipartite 13 zinc finger DNA binding domain. In addition, MZF1B/1C encodes a unique 257 aa MZF1B/C amino terminus containing a SCAN box, or leucine-rich domain, which has recently been demonstrated to facilitate protein interactions. Sequence analysis reveals that the MZF gene contains six exons and spans 11kb and may be the most telomeric gene on chromosome 19q13. Exons 1-6 produce MZF1B/C cDNA, whereas MZF1 cDNA initiates within intron 5 and continues through exon 6. The 7.5 and 9kb transcripts are incompletely processed and contain intron sequences. These studies are the first description of the complete human MZF gene and of the composition of the multiple transcripts that are detected by northern blot analysis.

Alternative Splicing↗

Identification of a novel SCAN box-related protein that interacts with MZF1B. The leucine-rich SCAN box mediates hetero- and homoprotein associations.

The SCAN box or leucine-rich (LeR) domain is a conserved motif found within a subfamily of C(2)H(2) zinc finger proteins. The function of a SCAN box is unknown, but it is predicted to form alpha-helices that may be involved in protein-protein interactions. Myeloid zinc finger gene-1B (MZF1B) is an alternatively spliced human cDNA isoform of the zinc finger transcription factor, MZF1. MZF1 and MZF1B contain 13 C(2)H(2) zinc finger motifs, but only MZF1B contains an amino-terminal SCAN box. A bone marrow cDNA library was screened for proteins interacting with the MZF1B SCAN box domain and RAZ1 (SCAN-related protein associated with MZF1B) was identified. RAZ1 is a novel cDNA that encodes a SCAN-related domain and arginine-rich region but no zinc finger motifs. Co-immunoprecipitation assays demonstrate that the SCAN box domain of MZF1B is necessary for association with RAZ1. By yeast two-hybrid analysis, the carboxyl terminus of RAZ1 is sufficient for interaction with the MZF1B SCAN box. Furthermore, MZF1B and RAZ1 each self-associate in vitro via a SCAN box-dependent mechanism. These data provide evidence that the SCAN box is a protein interaction domain that mediates both hetero- and homoprotein associations.

Alternative Splicing↗

Long-term increased bioaccumulation of mercury in largemouth bass follows reduction of waterborne selenium.

Average mercury concentrations in largemouth bass from Rogers Quarry in east Tennessee were found to increase steadily following the elimination of selenium-rich discharges of fly ash to the quarry in 1989. From 1990 to 1998, mean mercury concentrations (adjusted to compensate for the covariance between individual fish weight and mercury concentration) in bass rose from 0.02 to 0.61 mg/kg. There was no indication that the rate increase was slowing or that mercury concentrations in fish were approaching a plateau or steady state. Mean selenium concentrations in bass declined from 3 to 1 mg/kg over the first five years of the study, but remained at 1-1.5 mg/kg (about twice typical concentrations in bass from local reference sites) for the last three years of the study. Gross physical abnormalities were common in fish from the site in the first three years after elimination of fly ash discharges but disappeared after two more years. Although it remains possible that other chemical or physical changes related to fly ash disposal in the system were associated with increased mercury bioaccumulation, the most likely explanation is that selenium played a critical role. It appears as though aqueous selenium enrichment was capable of having a profound effect on mercury bioaccumulation in this system but at the cost of causing a high incidence of gross abnormalities in fish. However, it is possible that selenium concentrations between the national ambient water quality criterion for the protection of aquatic life, 5 microg/l, and that now found in Rogers Quarry (<2 microg/l) could reduce mercury bioaccumulation without causing adverse effects on aquatic biota and fish-eating wildlife.

Animals↗

Combining the arts: an applied critical thinking approach in the skills laboratory.

The quality of care that nurses provide to patients is strongly influenced by the nurses' ability to think critically and to solve problems. In response to the dynamic changes in healthcare and rapid technological advancements, nursing educators must prepare nursing students to meet the challenges. Baccalaureate nursing students must be taught to utilize critical thinking skills for problem solving during the application of the nursing process. Nursing students who use critical thinking skills will provide high quality and efficient patient care in the acute care and community settings. During the simulated laboratory experience, incorporating creative teaching strategies to promote critical thinking and enhance problem-solving skills can enable nursing graduates to enter the workforce feeling confident and competent.

Education, Nursing↗

Determinants of retinopathy progression in type 1 diabetes mellitus.

PURPOSE: To determine the risk factors for retinopathy progression in type 1 (insulin-dependent) diabetes mellitus in a prospective cohort study. SUBJECTS AND METHODS: Subjects were 485 participants in the Sorbinil Retinopathy Trial, a randomized trial of aldose reductase inhibition among patients aged 18 to 56 years with type 1 diabetes mellitus (duration of 1 to 15 years) and no or only mild retinopathy. Retinopathy progression, assessed by seven-field stereoscopic fundus photography, was defined as worsening by two or more levels on a standardized grading scale at the end of follow-up (median, 41 months). RESULTS: The relative risks for retinopathy progression according to successively greater quintiles of total glycosylated hemoglobin level at baseline, after adjusting for age, diabetes duration, sorbinil assignment, and other variables, were 1.0, 2.0, 1.6, 3.7, and 4.4 (P trend <0.0001). Risk increased with greater baseline diastolic blood pressure: 1.0 for <70 mm Hg, 1.2 for 70 to 79 mm Hg, and 1.8 for > or =80 mm Hg (P for trend = 0.04). Diastolic blood pressure was a significant risk factor for progression in participants with mild baseline retinopathy (P for trend <0.02) but not in those without retinopathy at entry. Systolic blood pressure, by comparison, was not associated with progression. Baseline total cholesterol level was a marginally significant predictor of retinopathy progression when examined as a categorical variable (relative risks for increasing quartiles; 1.0, 1.6, 1.8, 1.9; P for trend = 0.03) but not when it was examined as a continuous variable or when hypercholesterolemic patients were compared with those with normal levels. Furthermore, when cholesterol levels were updated in subsequent visits, it was not a significant predictor of progression, and low density lipoprotein (LDL) cholesterol levels did not predict progression no matter how analyzed. Smoking was not associated with progression of retinopathy. CONCLUSIONS: Levels of hyperglycemia and diastolic blood pressure predicted progression of retinopathy in type 1 diabetes mellitus. We found only a suggestion of an association between total cholesterol level (but not of LDL cholesterol level) and progression of retinopathy; resolution of this issue will require additional studies with larger sample sizes and longer follow-up.

Adult↗

Serologic and parasitologic survey of the endangered Attwater's prairie chicken.

Because conservation biologists have postulated that infectious diseases may have potentiated the endangerment of the Attwater's prairie chicken (Tympanuchus cupido attwateri), free-living prairie chickens were surveyed from all remaining populations for helminthic endoparasites and antibody against the etiological agents of nine infectious diseases. Samples from 4 of 27 adult males were positive for anti-Pasteurella multocida antibody. All other serologic tests were negative (n = 19). We identified Dispharynx nasuta, a parasite previously associated with disease in other grouse from North America, in one of three adult Attwater's prairie chickens examined. Evidence of Trichostrongylus cramae was found for eight of nine suitable samples, which represents the first report of this parasite in prairie grouse. The mean intensity of T. cramae in Attwater's prairie chicken was 1,019.3 (Range = 3-1,906; n = 3). Further work is needed to determine whether P. multocida, T. cramae, or D. nasuta are detrimental to Attwater's prairie chicken populations. If so, conservation biologists could reduce the prevalence and incidence of these parasites and potentially gain more time to address the habitat conditions thought to be the ultimate cause of population declines.

Animals↗

Northern bobwhites as disease indicators for the endangered Attwater's prairie chicken.

Because of limited access to the endangered Attwater's prairie chicken (Tympanuchus cupido attwateri), we used a related species, the northern bobwhite (Colinus virginianus), as a surrogate for disease evaluation. Free-living northern bobwhites (n = 62) on the Attwater Prairie Chicken National Wildlife Refuge (near Eagle Lake, Texas, USA) were examined during spring and fall 1993 for helminthic endoparasites and specific antibodies against the infectious agents responsible for nine infectious diseases. Trichostrongylus cramae, Raillietina sp., and Strongyloides avium were collected from 97, 44, and 32% of northern bobwhites examined, respectively. Dispharynx nasuta and Syngamus trachea also were found. No gross lesions due to parasites were observed. Specific antibody to Pasteurella multocida was found in 3 of 53 plasma samples. It is possible that potentially pathogenic species such as P. multocida, T. cramae, and D. nasuta could threaten sympatric Attwater's prairie chickens.

Age Distribution↗

Application of multiple bioindicators to differentiate spatial and temporal variability from the effects of contaminant exposure on fish.

Bioindicators of fish health were measured from 1989 through 1994 in populations of redbreast sunfish (Lepomis auritus) at three sites within a stream receiving inputs of mixed contaminants from an industrial facility, and at two reference sites. Bioindicator responses differed for fish from contaminated and reference sites throughout the study period, but temporal trends at contaminated sites reflected improved water quality associated with pollution-control efforts. Temporal variability unrelated to contaminant exposure strongly influenced the response of bioindicators at both reference and contaminated sites, but spatial variability rarely influenced these responses. Temporal variability was less influential on slower responding indicators at higher levels of biological organization. The diverse response characteristics of indicators increased the ability to differentiate natural from anthropogenic sources of variability. Integrated bioindicator responses were compared among site-year groups by multivariate canonical analysis. The primary canonical variable, associated with differences in growth, exhibited trends consistent with the timing of pollution-control efforts. Two indicators of contaminant exposure (7-ethoxyresorufin O-deethylase activity and polychlorinated biphenyls in fish muscle) also exhibited trends consistent with the timing of pollution-control efforts, but the likelihood of possible mechanistic linkages cannot be assessed with available data.

Animals↗

Form of mercury in stream fish exposed to high concentrations of dissolved inorganic mercury.

The form of mercury predominating in mercury-contaminated fish from both pristine and industrialized waters in North America and Europe has almost universally been methylmercury. Sunfish (Lepomis auritus) living in a stream contaminated with 0.5-1 micrograms/L dissolved inorganic mercury accumulated greater concentrations of total mercury at headwater sites, where the dissolved mercury concentrations were greatest, than they did at downstream sites. However, despite evidence from laboratory studies that dissolved inorganic mercury is rapidly accumulated by fish without transformation to methylmercury, methylmercury constituted 85% or more of the total mercury concentration in fish at all sites.

Animals↗

Pharmacokinetics of the aldose reductase inhibitor, zopolrestat, in humans.

The pharmacokinetics of zopolrestat, an aldose reductase inhibitor that may be useful for the treatment of complications of diabetes, have been investigated using oral doses ranging from 50 to 1200 mg administered to healthy male volunteers. In a single-dose study, Cmax, AUC(0-48), and urinary elimination of zopolrestat increased linearly with increasing dose. The amount of zopolrestat excreted unchanged in the urine within 48 hours ranged from 34 to 45% of the administered dose. Renal clearance ranged from 2.6 to 5.6 mL/min, and appeared to decrease as the dose was increased. In a 2-week multiple dose study, the mean steady-state minimum and maximum plasma concentrations, Cmin and Cmax, were 91.5 and 196 micrograms/mL for subjects administered 800 mg/day, and 131 and 281 micrograms/mL for subjects administered 1200 mg/day. Steady-state AUC(0-24) was also dose proportional. The mean steady state half life of about 30.3 hours was consistent with the observed 2.2-fold accumulation in plasma. Apparent oral clearance (Clpo) was 5.2 mL/min, and apparent volume of distribution (Vdss/F) was 12 L. Mean renal clearance was 2.2 mL/min, and approximately 45% of the administered dose was excreted into the urine at steady state. There was no effect of food consumption during dosing on the extent of absorption of zopolrestat. In in vitro studies, extensive, concentration-dependent binding of zopolrestat to plasma proteins was observed. These data indicate that once-daily dosing of zopolrestat will provide suitable exposure in the treatment of diabetic complications.

Administration, Oral↗

Speract receptors are localized on sea urchin sperm flagella using a fluorescent peptide analog.

In two species of sea urchins, Strongylocentrotus purpuratus and Lytechinus pictus, the egg jelly-associated decapeptide, speract, binds to specific sperm surface receptors resulting in increased sperm motility and respiration rate. Previously, a peptide analog, GGG[Y2]-speract, was used to identify a 77-kDa receptor on intact sperm cells using chemical cross-linking. In this paper we describe the synthesis and characterization of a fluorescent derivative of GGG[Y2]-speract for use as a probe for the sperm receptor. Fluorescein isothiocyanate (FITC) was conjugated to the amino terminus of GGG[Y2]-speract and the resulting analog (FITC-GGG[Y2]-speract) was purified by size exclusion chromatography and reverse-phase HPLC. Competition binding studies with the fluorescent peptide and intact spermatozoa yielded IC50 values which were indistinguishable from native speract and GGG[Y2]-speract (approximately 20 nM). FITC-GGG[Y2]-speract half-maximally stimulated sperm respiration at a concentration nearly identical to that of the native peptide (EC50 approximately 50 pM). Using digitally enhanced video imaging fluorescence microscopy, FITC-GGG[Y2]-speract was used to localize the speract receptor on the flagella of intact sperm. Excess concentrations of both unlabeled speract and GGG[Y2]-speract abolished the binding of the fluorescent analog, yet unrelated peptides did not. Further, results of cross-linking experiments using 125I-GGG[Y2]-speract and purified sperm flagella and heads were consistent with the fluorescent labeling results on whole cells. The finding that the speract receptor is localized exclusively to the sperm flagella may reveal its role in the regulation of flagellar motility.

Amino Acid Sequence↗

Changes in concentrations of selenium and mercury in largemouth bass following elimination of fly ash discharge to a quarry.

Elimination of slurried fly ash discharges to a water-filled quarry was followed by a steady increase in concentrations of mercury in the axial muscle of resident largemouth bass (Micropterus salmoides). Average mercury concentrations in bass (adjusted for covariance with fish weight) increased from 0.02 micrograms/g to 0.17 micrograms/g in three years. Aqueous selenium concentrations in the quarry decreased from 25 micrograms/L to < 2 micrograms/L after elimination of fly ash discharges, but selenium concentrations in bass remained about three times background levels. Previous studies have shown selenium addition to be a viable means of ameliorating mercury contamination in fish in low alkalinity, low pH waters of northern Europe and Canada. These results suggest that selenium may also be effective at blocking the accumulation of methylmercury in harder, more alkaline waters.

Animals↗

Effects of phorbol ester on mitogen-activated protein kinase kinase activity in wild-type and phorbol ester-resistant EL4 thymoma cells.

Phorbol ester-sensitive and -resistant EL4 thymoma cell lines differ in their ability to activate mitogen-activated protein kinase (MAPK) in response to phorbol ester. Treatment of wild-type EL4 cells with phorbol ester results in the rapid activations of MAPK and pp90rsk kinase, a substrate for MAPK, while neither kinase is activated in response to phorbol ester in variant EL4 cells. This study examines the activation of MAPK kinase (MAPKK), an activator of MAPK, in wild-type and variant EL4 cells. Phosphorylation of a 40-kDa substrate, identified as MAPK, was observed following in vitro phosphorylation reactions using cytosolic extracts or Mono Q column fractions prepared from phorbol ester-treated wild-type EL4 cells. MAPKK activity coeluted with a portion of the inactive MAPK upon Mono Q anion-exchange chromatography, permitting detection of the MAPKK activity in fractions containing both kinases. This MAPKK activity was present in phorbol ester-treated wild-type cells, but not in phorbol ester-treated variant cells or in untreated wild-type or variant cells. The MAPKK from wild-type cells was able to activate MAPK prepared from either wild-type or variant cells. MAPKK activity could be stimulated in both wildtype and variant EL4 cells in response to treatment of cells with okadaic acid. These results indicate that the failure of variant EL4 cells to activate MAP kinase in response to phorbol ester is due to a failure to activate MAPKK. Therefore, the step that confers phorbol ester resistance to variant EL4 cells lies between the activation of protein kinase C and the activation of MAPKK.

Amino Acid Sequence↗

An enzyme-linked immunosorbent assay for detecting anthrax antibody in white-tailed deer (Odocoileus virginianus): evaluation of anthrax vaccination and sera from free-ranging deer.

An enzyme-linked immunosorbent assay for anthrax antibody in white-tailed deer (Odocoileus virginianus) was developed and used to evaluate a vaccination study and compare sera from hunter-killed deer in anthrax endemic and non-endemic areas. Deer subcutaneously vaccinated with anthrax avirulent spore vaccine developed specific antibody to protective antigen (PA) which was significantly higher than the non-vaccinated controls at 30, 60, 90, and 240 days post-vaccination. There was no difference between the levels of antibody to PA between deer in anthrax endemic and non-endemic areas.

Animals↗