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Biomedical subjects

D R Smith

Publications and source records attributed to D R Smith.

At least 397 records · Page 22Linked to original sources

Effect of age and cognitive status on basal level AP-1 activity in rat hippocampus.

Activator protein-1 (AP-1) was examined at multiple levels (mRNA, DNA binding, composition) in hippocampus of young and aged rats that were behaviorally characterized for spatial memory. GFAP mRNA was measured as a gene product known to increase with aging and to be regulated by AP-1. The activity of Jun-amino terminal-kinase (JNK) was also assessed. Levels of c-jun and c-fos mRNAs were unchanged with aging or spatial learning ability. Abundance of GFAP mRNA was significantly increased in aged hippocampus but did not correlate with spatial learning. Total AP-1 binding activity was unaltered with age or cognitive ability. In hippocampus of young, aged unimpaired and aged impaired rats, AP-1 consists mainly of c-Jun, phosphorylated c-Jun (p-c-Jun), JunD, and smaller amounts of c-Fos. JNK is constitutively active in young and aged hippocampus. We conclude that the basal expression of c-fos and c-jun mRNA, overall AP-1 binding activity and AP-1 composition are not influenced by aging or cognitive ability.

Aging↗

The neurobehavioral effects of subchronic manganese exposure in the presence and absence of pre-parkinsonism.

Recent studies have implicated chronic elevated exposures to environmental agents, such as metals (e.g., manganese, Mn) and pesticides, as contributors to neurological disease. In particular, there is a concern that sensitive subpopulations such as the aged may be at increased risk for the onset of neurologic disorders because elevated exposures to Mn is associated with increased incidence of parkinsonism. Here, we utilized a rat model of pre-parkinsonism to investigate the effects of Mn exposure on neurotoxicity and the exacerbation of parkinsonism. A pre-parkinsonism state was induced using a unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA), followed 4 weeks later by Mn exposure (4.8 mg Mn/kgx3 intraperitoneal injections/week) for 5 weeks. Female Sprague-Dawley rats (n=44) were divided among the following treatments: (A) control, saline/vehicle; (B) Mn only; (C) 6-OHDA only; and (D) 6-OHDA+Mn. Brain Mn levels were measured by ICP-MS. Neurobehavioral function was assessed following Mn exposure using a functional observational battery (FOB) consisting of 10 neurobehavioral tests. Unilateral 6-OHDA lesions produced significant ipsilateral vs. contralateral striatal dopamine depletions (60-70%), but no measurable impairment of neurobehavioral function, thereby substantiating this pre-parkinsonism (i.e., subthreshold) model. In contrast, Mn exposure resulted in significant impairment of neurobehavioral function for eight of the 10 FOB tests. No effects of Mn exposure on striatal dopamine depletion were detected, despite the 3.4-fold increase in brain Mn levels over controls. Notably, Mn exposure in the presence of a pre-parkinsonism state significantly exacerbated the neurobehavioral impairment in the reactivity to handling (P<.049) and hopping contralateral rear limb (P<.033) FOB tests. While the persistence and Mn dose-response relationship of these neurobehavioral effects were not evaluated here, these results nonetheless suggest that chronic Mn exposure may increase the risk of neurobehavioral impairment in subpopulations that are in a pre-parkinsonism state.

Analysis of Variance↗

Biologically active metabolites from Xenorhabdus spp., Part 1. Dithiolopyrrolone derivatives with antibiotic activity.

Five related antibiotic compounds, named xenorhabdins, were isolated from cultures of Xenorhabdus spp., bacteria symbiotically associated with insect-pathogenic nematodes. Their chemical structures were elucidated by X-ray crystallography, nmr, and mass spectral analyses to be N-acyl derivatives of either 6-amino-4,5-dihydro-5-oxo-1,2-dithiolo [4,3-b] pyrrole (compounds 1-3) or 6-amino-4,5-dihydro-4-methyl-5-oxo-1,2-dithiolo[4,3-b] pyrrole (compounds 4 and 5). They are previously unreported members of the pyrrothine family of antibiotics. Antimicrobial and insectidical activities were found. These metabolites are specific to phase one Xenorhabdus.

Anti-Bacterial Agents↗

Interference by nonsteroidal anti-inflammatory drugs in EMIT and TDx assays for drugs of abuse.

Fourteen nonsteroidal anti-inflammatory drugs were evaluated for interference in EMIT and TDx assays for drugs of abuse. Only tolmetin demonstrated significant interferences in the EMIT assay. Urine samples that contained high concentrations of tolmetin (1800 mg/L) had characteristic high molar absorptivity at the wavelength used in EMIT assays (340 nm). Consequently, EMIT analysis of samples resulted in instrument error alarms on a Hitachi 704 instrument and depressed milliabsorbance values (delta A) relative to calibrators. Similar results were obtained with urine samples collected from an arthritic patient after the administration of 200 and 400 mg of tolmetin. When tolmetin samples were mixed with drugs of abuse, depressed delta A values were noted in all assays. Samples containing opiates and cannabinoids tested negative, and instrument error alarms were produced with samples that contained amphetamines. A gas chromatographic-mass spectrometric (GC-MS) assay for benzoylecgonine in the presence of tolmetin was successful, and no interferences were noted. Similar interferences by tolmetin were not observed in TDx assays, probably because of the different wavelength (525 nm) used in this assay. However, a potential for false-positive results in the TDx benzodiazepine assay was noted for urine samples containing high concentrations of fenoprofen, flurbiprofen, indomethacin, ketoprofen, and tolmetin. Generally, it was concluded that the presence of tolmetin in urine samples could lead to the production of unacceptable results by the EMIT assay for drugs of abuse. However, TDx and GC-MS assays were useful alternatives for the analysis of urine samples suspected of containing tolmetin.

Anti-Inflammatory Agents, Non-Steroidal↗

Turkish honeybees: genetic variation and evidence for a fourth lineage of Apis mellifera mtDNA.

The mtDNA of bees from 84 colonies of Turkish honeybees (Apis mellifera) was surveyed for variation at four diagnostic restriction sites and the sequence of a noncoding intergenic region. These colonies came from 16 locations, ranging from European Turkey and the western Mediterranean coast to the Caucasus Mountains along the Georgian border, the eastern Lake Van region, and the extreme south. Combined restriction site and sequence data revealed four haplotypes. Three haplotypes belonged to the eastern Mediterranean mtDNA lineage. The fourth haplotype, which had a novel restriction site pattern and noncoding sequence, was found in samples from the extreme south, near the Syrian border. We found two different noncoding sequences among the eastern Mediterranean haplotypes. The "Caucasian" sequence matches that described from A. m. caucasica, and the "Anatolian" sequence matches that of A. m. carnica. The frequency of the "Caucasian" sequence was highest (98-100%) in sites near the Georgian border and decreased steeply to the south and west. Elsewhere the Anatolian sequence was found. In European Turkey (Thrace) a restriction site polymorphism previously reported from A. m. carnica in Austria and the Balkans was present at high frequency. A novel mtDNA haplotype with a unique restriction site pattern and noncoding sequence was found among bees from Hatay, in the extreme south near the Syrian border. This haplotype differed from the three previously known lineages of honeybee mtDNA--African, western European, and eastern Mediterranean-and may represent a fourth mitochondrial lineage.

Animals↗

Geographical overlap of two mitochondrial genomes in Spanish honeybees (Apis mellifera iberica).

Restriction enzyme cleavage maps of mitochondrial DNA from the Spanish honeybee, Apis mellifera iberica (Hymenoptera: Apidae), were compared with those from the European subspecies A. m. mellifera, A. m. ligustica, and A. m. carnica, and the African subspecies A. m. intermissa and A. m. scutellata. The mitochondrial DNA (mtDNA) of the two African subspecies can be distinguished by restriction fragment polymorphisms revealed by Hinf I digests. Two distinct mtDNA types were found among Spanish honeybees: a west European mellifera-like type, which predominates in the north of Spain, and an African intermissa-like type, which predominates in the south. Spain appears to be a region of contact and hybridization between the two subspecies A. m. intermissa and A. m. mellifera, which respectively represent African and west European honeybee lineages. This natural boundary between European and African honeybee populations in the Old World may provide a model for predicting the eventual outcome of the colonization of North America by introduced African honeybees.

Africa↗

Allozyme polymorphisms in Spanish honeybees (Apis mellifera iberica).

Earlier studies have shown two types of mitochondrial DNA in Spanish honeybees (Apis mellifera iberica): a western European or A. m. mellifera type, which predominates in northern Spain, and a north African or A. m. intermissa type, which predominates in southern Spain. Adult workers from 28 colonies sampled in northern and southern Spain were surveyed for polymorphisms at eight allozyme loci. Polymorphisms were found in Mdh1 (two alleles) and Pgm (five alleles). Three of the Pgm alleles have not been described previously. The frequencies of Mdh1 alleles in northern and southern samples are significantly different: Mdh1(80) = 0.94 in the north and 0.75 in the south. The frequencies of Pgm alleles in northern and southern samples do not differ significantly. The Hk allele (Hk100) found in all Spanish samples is the same as that found in other European populations. The results are consistent with the presence of a hybrid zone between African and west European honeybee subspecies in the Iberian peninsula or north Africa. The high number and frequency of novel Pgm alleles in the Spanish bees resembles the "rare allele" phenomenon observed in other hybrid populations.

Animals↗

Medullary carcinoma of the thyroid masquerading as idiopathic vocal cord paralysis.

The following conclusions may be drawn as a result of our study: 1. Serum calcitonin by radioimmunoassay proved to be the only valid preoperative indicator in a case of medullary carcinoma of the thyroid occurring with vocal cord paralysis. This test should be considered in all cases of idiopathic recurrent laryngeal nerve paralysis, especially when obscure thyroid pathology is suspected. 2. Provocative calcitonin testing, such as a calcium infusion test, may help verify presence or absence of disease in equivocal cases of calcitonin assay. 3. Vocal cord paralysis may be the first sign of intrathroid malignancy. 4. In the furture, serum calcitonin assay (drawn posttreatment) may be a valuable prognostic indicator and may guide the need for additional treatment.

Adult↗

Measurement of spinal cord blood flow by the microsphere technique.

Differential spinal cord blood flow was measured in dogs by the radioactive microsphere injection method. The mean spinal cord blood flow was 10.8 +/- 0.53 (SE) ml/100 g/minute. The flow values for the white and gray matter were 7.1 +/- 0.65 (SE) and 26.3 +/- 2.2 (SE) ml/100 g/minute, respectively.

Animals↗

Effects of alum and aluminum chloride on phosphorus runoff from swine manure.

Phosphorus (P) runoff from fields fertilized with swine (Sus scrofa domesticus) manure may contribute to eutrophication. The objective of this study was to evaluate the effect of aluminum sulfate (alum) and aluminum chloride applications to swine manure on P runoff from small plots cropped to tall fescue (Festuca arundinacea Shreb.). There were six treatments in this study: (i) unfertilized control plots, (ii) untreated manure, (iii) manure with alum at 215 mg Al L(-1), (iv) manure with aluminum chloride at 215 mg Al L(-1), (v) manure with alum at 430 mg Al L(-1), and (vi) manure with aluminum chloride at 430 mg Al L(-1). Manure application rates were equivalent to approximately 125 kg N ha(-1). Alum and aluminum chloride additions lowered soluble reactive phosphorus (SRP) levels from about 130 mg P L(-1) to approximately 30 mg P L(-1) at low rates. At high rates, SRP levels in swine manure were around 1 mg P L(-1). Soluble reactive P concentrations in runoff were 5.50, 3.66, 3.00, 0.87, 0.87, and 0.55 mg P L(-1), for normal manure, low alum, low aluminum chloride, high alum, high aluminum chloride, and unfertilized control plots, respectively. Hence, high alum and aluminum chloride reduced SRP concentrations in runoff by 84% and were not statistically different from SRP concentrations in runoff from unfertilized control plots. These data indicate that treating swine manure with alum or aluminum chloride could result in significant reductions in nonpoint-source P runoff.

Alum Compounds↗

Reducing phosphorus runoff from swine manure with dietary phytase and aluminum chloride.

Phosphorus (P) runoff from fields fertilized with swine (Sus scrofa) manure has been implicated in eutrophication. Dietary modification and manure amendments have been identified as best management practices to reduce P runoff from manure. This study was conducted to compare the effects of dietary modification and aluminum chloride (AlCl3) manure amendments on reducing P in swine manure and runoff. Twenty-four pens of nursery swine were fed either a normal diet or a phytase-amended diet. Each pen was connected to a separate manure pit, which was treated with AlCl3 to give final concentrations in the liquid manure of 0 (control), 0.25, 0.50, or 0.75% (v/v). Manure was collected and applied to plots cropped with tall fescue (Festuca arundinacea Schreb.), and simulated rainfall was applied at 50 mm h(-1), sufficient to generate a minimum of 30 min of continuous runoff. Samples of manure and runoff were analyzed for P and Al concentrations. Phytase reduced manure soluble reactive phosphorus (SRP) by 17%, while AlCl3 reduced manure SRP by as much as 73% compared with normal manure. Phosphorus runoff was reduced from 5.7 to 2.6 mg P L(-1) (a 53% reduction) using AlCl3. The mean SRP concentration in runoff from phytase diets without AlCl3 was 7.1 mg P L(-1) during the first rainfall simulation. When phytase and AlCl3 were used together, both manure SRP and P runoff were reduced more than if either treatment were used without the benefit of the other. Use of AlCl3 did not increase soluble Al in manure or Al lost in runoff. Results from this study indicate that producers should use dietary manipulation with phytase and AlCl3 manure amendments to reduce potential P losses from fields fertilized with swine manure.

6-Phytase↗

Egocentric localization changes following unilateral strabismus surgery.

We measured spatial localization (using an open-loop pointing task) monocularly in each eye of eight patients undergoing unilateral strabismus surgery. Most of these patients had some degree of binocular vision. We found that, in most cases, changes in spatial localization produced by surgery on the operated eye paralleled those found in the other eye, both in magnitude and duration. Unilateral surgery can have central effects on egocentric localization.

Adolescent↗

Community ambulation by children with myelomeningocele and high-level paralysis.

It has frequently been noted that high-level paralysis precludes community ambulation for children with myelomeningocele. Of the 87 children in our population with high-level paralysis, however, 45 (52%) did achieve community ambulation by 5 years of age, while 42 (48%) did not. There was no significant difference between these two groups by sex, shunt status, scoliosis, or hip surgery prior to 5 years of age. Among the community ambulating group, there were significantly (p less than 0.001) more children who were not retarded, had received physical therapy for walking, and had compliant parents. We concluded, therefore, that community ambulation is a realistic goal for many children with myelomeningocele and high-level paralysis.

Adolescent↗

Nuclear criticality accidents.

Criticality occurs when a sufficient quantity of fissionable material is accumulated, and it results in the liberation of nuclear energy. All process accidents have involved plutonium or highly enriched uranium, as have most of the critical experiment accidents. Slightly enriched uranium systems require much larger quantities of material to achieve criticality. An appreciation of criticality accidents should be based on an understanding of factors that influence criticality, which are discussed in this article.

Accidents, Occupational↗