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Biomedical subjects

S L Hansen

Publications and source records attributed to S L Hansen.

At least 19 recordsLinked to original sources

Growth, reproductive performance, and manganese status of heifers fed varying concentrations of manganese.

An experiment was conducted to examine the effects of dietary Mn on growth, reproductive performance, and Mn status of beef heifers. Eighty Angus (n = 40) and Simmental (n = 40) heifers, averaging 249 kg, were stratified by BW within a breed and randomly assigned to 1 of 4 treatments providing 0 (control), 10, 30, or 50 mg of supplemental Mn/kg of DM from MnSO(4). Heifers were individually fed a diet containing cottonseed hulls, corn gluten feed, citrus pulp, and ground corn, and the control diet contained 15.8 mg of Mn/kg of DM by analysis. Average daily gain, DMI, and G:F for the 196-d period were not affected by Mn supplementation. Control heifers had reduced (P = 0.04) liver Mn when contrasted with the 3 levels of supplemental Mn. Serum cholesterol was greater (P = 0.001) in Angus compared with Simmental heifers over the course of the 196-d experiment but was not affected by treatment. Dietary Mn did not significantly affect measures of reproductive performance. Results of this study indicate that 15.8 mg of Mn/kg of diet DM should be adequate for growth, onset of estrus, and conception of beef heifers.

Animal Feed↗

Feeding a low manganese diet to heifers during gestation impairs fetal growth and development.

A study was conducted to examine the effects of low dietary Mn on growth performance of pregnant heifers and fetal development of their offspring. Twenty pregnant Angus (n = 9) and Simmental (n = 11) heifers averaging 17 mo of age and 447.6 kg of initial body weight were used in the 267-d study. Heifers were selected from a previous study examining the effects of supplemental Mn on growth and reproductive performance of heifers. Ten pregnant heifers per treatment from the control (analyzed at 15.8 mg of Mn/kg of DM) and supplemental Mn (50 mg/kg of DM) treatments were randomly selected at the conclusion of the previous study to continue on their respective dietary treatments through gestation and early lactation. Serum cholesterol for the 267-d period was not affected by treatment. Whole-blood Mn concentration of heifers on d 267 was not affected by treatment. Whole-blood Mn concentration at birth was lower in calves born to control heifers than in those born to supplemented heifers. Calves born to control heifers weighed less at birth than those born to heifers receiving supplemental Mn. Calves born to control heifers suffered from varying signs of Mn deficiency, including superior brachygnathism, unsteadiness, disproportionate dwarfism, and swollen joints. Results suggest that feeding gestating heifers a diet containing 16.6 mg of Mn/kg of DM is not adequate for proper fetal development. Supplementation of 50 mg of Mn/kg of DM to the control diet was sufficient to overcome any signs of Mn deficiency in calves.

Animal Feed↗

Levetiracetam prevents changes in levels of brain-derived neurotrophic factor and neuropeptide Y mRNA and of Y1- and Y5-like receptors in the hippocampus of rats undergoing amygdala kindling: implications for antiepileptogenic and mood-stabilizing properties.

The amygdala-kindling model has been proposed as a model of sensitization processes with relevance to epilepsy as well as affective disorders. Levetiracetam is a novel anticonvulsant drug that delays the process of kindling, i.e., possesses antiepileptogenic properties. Preliminary reports also suggest a mood-stabilizing potential for levetiracetam. Brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY) are central modulators of seizure activity, which undergo plastic changes during kindling epileptogenesis. Consequently, we investigated the regulation of BDNF and NPY mRNA and Y1-, Y2-, and Y5-like receptor binding in the hippocampus of vehicle-pretreated, partially and fully amygdala-kindled rats and corresponding levetiracetam-pretreated rats (40 mg/kg i.p.). The present data indicate that the process of kindling is associated with an upregulation of hippocampal BDNF and NPY mRNA levels and downregulation of Y1- and particularly Y5-like receptors. Pretreatment with levetiracetam markedly delays the progression of kindling and, in addition, exhibits a clear anticonvulsant effect. These effects are associated with abolition of the kindling-induced rise in BDNF and NPY mRNA and increasing levels of Y1- and particularly Y5-like receptors in all hippocampal subfields. Lastly, the present study reveals that an identical dose of levetiracetam reduced immobility in the rat forced swim test, the first experimental evidence indicative of an antidepressant and/or mood stabilizer-like profile of this drug. Considering that animal depression models display impairments in hippocampal NPY systems that become normalized following mood-stabilizing treatment, and that exogenous NPY exerts anticonvulsant as well as antidepressive-like activity in rodents, it is a heuristic possibility that increased hippocampal excitability and affective symptomatology may converge on an impaired hippocampal NPY function. Speculatively, the ability of levetiracetam to increase hippocampal Y1- and Y5-like receptor levels may have implications for the antiepileptic properties of levetiracetam, as well as its purported mood-stabilizing properties.

Affect↗

Effects of GABA(A) receptor partial agonists in primary cultures of cerebellar granule neurons and cerebral cortical neurons reflect different receptor subunit compositions.

Based on an unexpected high maximum response to piperidine-4-sulphonic acid (P4S) at human alpha1alpha6beta2gamma2 GABA(A) receptors expressed in Xenopus oocytes attempts to correlate this finding with the pharmacological profile of P4S and other GABA(A) receptor ligands in neuronal cultures from rat cerebellar granule cells and rat cerebral cortex were carried out. GABA and isoguvacine acted as full and piperidine-4-sulphonic acid (P4S) as partial agonists, respectively, at alpha1beta2gamma2, alpha6beta2gamma2 and alpha1alpha6beta2gamma2 GABA receptors expressed in Xenopus oocytes with differences in potency. Whole-cell patch-clamp recordings were used to investigate the pharmacological profile of the partial GABA(A) receptor agonists 4,5,6,7-tetrahydroisoxazolo-(5,4-c)pyridin-3-ol (THIP), P4S, 5-(4-piperidyl)isoxazol-3-ol (4-PIOL), and 3-(4-piperidyl)isoxazol-5-ol (iso-4-PIOL), and the competitive GABA(A) receptor antagonists Bicuculline Methbromide (BMB) and 2-(3-carboxypropyl)-3-amino-6-methoxyphenyl-pyridazinium bromide (SR95531) on cerebral cortical and cerebellar granule neurons. In agreement with findings in oocytes, GABA, isoguvacine and P4S showed similar pharmacological profiles in cultured cortical and cerebellar neurones, which are known to express mainly alpha1, alpha2, alpha3, and alpha5 containing receptors and alpha1, alpha6 and alpha1alpha6 containing receptors, respectively. 4-PIOL and iso-4-PIOL, which at GABA(A) receptors expressed in oocytes were weak antagonists, showed cell type dependent potency as inhibitors of GABA mediated responses. Thus, 4-PIOL was slightly more potent at cortical neurones than at granule neurones and iso-4-PIOL was more potent in inhibiting isoguvacine-evoked currents at cortical than at granule neurons. Furthermore the maximum response to 4-PIOL corresponded to that of a partial agonist, whereas that of iso-4-PIOL gave a maximum response close to zero. It is concluded that the pharmacological profile of partial agonists is highly dependent on the receptor composition, and that small structural changes of a ligand can alter the selectivity towards different subunit compositions. Moreover, this study shows that pharmacological actions determined in oocytes are generally in agreement with data obtained from cultured neurons.

Animals↗

GABAA receptor subunit interactions important for benzodiazepine and zinc modulation: a patch-clamp and single cell RT-PCR study.

The expression of mRNAs for the GABAA receptor subunits alpha1, alpha6, beta2, beta3, gamma2 and delta in single mouse cerebellar granule cells and cortical interneurons were analysed by RT-PCR and correlated to their midazolam and zinc modulation of agonist-induced receptor currents. The registration of molecular and electrophysiological data from each cell allowed us to estimate the significance of individual subunits and their two-factor interaction for modulation. The presence of alpha6 decreased midazolam modulation, but statistical analysis also suggested interactions of alpha6 with beta3 and gamma2 with respect to midazolam modulation. Zinc modulation was decreased by the presence of gamma2, and analysis points to an beta3 effect as well as an interaction between gamma2 and delta in zinc modulation. Thus, our model confirmed, in single native cells, the known effects of alpha6 in midazolam and gamma2 in zinc modulation, and additionally pointed to significant subunit interactions that need to be further tested in recombinant receptors. The present study offers a method to identify subunit interactions in heteromeric receptor complexes.

Animals↗

Managing burn emergencies.

Learn how to provide emergency care for a burn patient, from safety at the scene to patient stabilization, and, if necessary, transport to a burn center.

Burns↗

Role of serology in the diagnosis of Lyme disease.

Numerous concerns regarding the potential for misdiagnosis of Lyme disease using commercial assays have been voiced by the US Food and Drug Administration (FDA). We attempted to clarify the clinical value of serologic testing for Lyme disease using the results of commonly marketed assays for detecting antibody to Borrelia burgdorferi, the organism that causes Lyme disease. We reviewed published studies on B burgdorferi test performance published through 1998, package insert labeling from FDA-cleared test kits for B burgdorferi, and Lyme Disease Survey Set LY-A from the College of American Pathologists. We assessed the sensitivity and specificity of commercial serologic tests (enzyme-linked immunosorbent assay [ELISA], immunofluorescence antibody [IFA], and immunodot) for diagnosis of Lyme disease. To reduce this risk of misdiagnosis, it is important that clinicians understand the performance characteristics and limitations of these tests. These tests, in common use in clinical or commercial laboratories, should be used only to support a clinical diagnosis of Lyme disease, not as the primary basis for making diagnostic or treatment decisions. Serologic testing is not useful early in the course of Lyme disease because of the low sensitivity of tests in early disease. Serologic testing may be more useful in later disease, at which time sensitivity and specificity of the test are improved. Positive or equivocal results on an ELISA, IFA, or immunodot assay requires supplemental testing with a Western blot assay. A negative result on the Western blot or ELISA indicates that there is no serologic evidence of infection by B burgdorferi at the time the sample was drawn.

Antibodies, Bacterial↗

Identification and quantitation of volatile compounds in two heated model compounds, trilinolein and linoleic acid esterified propoxylated glycerol.

Static headspace (HS) and capillary gas chromatography/infrared spectroscopy-mass spectrometry (GC/IR-MS) were used to collect, separate, identify, and quantitate the oxidative and thermal decomposition products in two heated model compounds, linoleic acid esterified propoxylated glycerol (EPG-08 linoleate) and trilinoleylglycerol, both without added antioxidants. Approximately 4 L of EPG-08 linoleate or trilinoleylglycerol was heated in a deep-fat fryer at 192 +/- 8 degrees C for 12 h each day until the oil sample contained > or =20% polymeric material, which occurred after 24 h of heating. The major volatile compounds both in heated EPG-08 linoleate and in heated trilinoleylglycerol were pentane, hexanal, 2-heptenal, 1-octen-3-ol, 2-pentylfuran, 2-octenal, and 2, 4-decadienal. The identified volatile compounds from heated EPG-08 linoleate are those generally expected from the oxidative and thermal decomposition of fats and oils containing linoleic acid, except acetoxyacetone (1-acetoxy-2-propanone). Acetoxyacetone was found at 2.1, 3, and 2.4 ppm in the unheated, 12 h heated, and 24 h heated samples, respectively.

Aldehydes↗

Differential blockade of gamma-aminobutyric acid type A receptors by the neuroactive steroid dehydroepiandrosterone sulfate in posterior and intermediate pituitary.

Dehydroepiandrosterone sulfate (DHEAS) is a neuroactive steroid with antagonist action at gamma-aminobutyric acid type A (GABAA) receptors. Patch-clamp techniques were used to investigate DHEAS actions at GABAA receptors of the rat pituitary gland at two distinct loci: posterior pituitary nerve terminals and intermediate pituitary endocrine cells. The GABA responses in these two regions were quite different, with posterior pituitary responses having smaller amplitudes and desensitizing more rapidly and more completely. DHEAS blockade of GABAA receptors in the two regions also was different. In posterior pituitary, a site with an apparent dissociation constant of 15 microM accounted for most of the blockade, but a small fraction of blockade may be related to a site with a dissociation constant in the nanomolar range. In the intermediate lobe, DHEAS sensitivities in the nanomolar and micromolar ranges were clearly evident, in proportions that varied widely from cell to cell. Regardless of whether the GABA response of a cell was highly sensitive or weakly sensitive to DHEAS, GABA alone evoked currents that were indistinguishable in terms of amplitude, desensitization kinetics, and GABA sensitivity. Thus, the structural elements responsible for DHEAS blockade have a highly selective impact on receptor function. GABAA receptors with nanomolar sensitivity to DHEAS have not been described previously. This suggests that DHEAS may have an important role in the modulation of neuropeptide secretion, and the diverse properties of GABAA receptors in the rat pituitary provide mechanisms for selective regulation of the different peptidergic systems of this gland.

Animals↗

Transferrin receptor mutation analysis in hereditary hemochromatosis patients.

The Cys282-->Tyr mutation in the HFE gene is carried by the majority of hereditary hemochromatosis patient chromosomes, yet some patients do not seem to harbor any mutation in this gene. This suggests a possibility that these patients may have a mutation in other genes in the same pathway as HFE. We analyzed the cDNA sequences of transferrin receptor (TFR), which was recently shown to interact with HFE, in twenty-one hereditary hemochromatosis patients including sixteen individuals who did not carry a Cys282-->Tyr mutation. A nucleotide substitution (424A-->G), which resulted in the Ser142-->Gly amino acid substitution, was the only amino acid polymorphism detected in the open reading frame of the TFR gene in these patients. This amino acid substitution was a rather common polymorphism in the general population (49%) and its frequency did not significantly differ in the hereditary hemochromatosis (HH) patients regardless of the HFE genotype. Thus, amino acid changes in the TFR gene do not appear to play a role in HH even when the patients do not have a HFE mutation. However, this study does not rule out the possibility of the involvement of mutations in non-coding regions.

Amino Acid Substitution↗

HLA class II haplotype and sequence analysis support a role for DQ in narcolepsy.

A systematic haplotype and sequencing analysis of the HLA-DR and -DQ region in patients with narcolepsy was performed. Five new (CA)n microsatellite markers were generated and positioned on the physical map across the HLA-DQB1-DQA1-DRB1 interval. Haplotypes for these new markers and the three HLA loci were established using somatic cell hybrids generated from patients. A four-marker haplotype surrounding the DQB1(*)0602 gene was found in all narcolepsy patients, and was identical to haplotypes observed on random chromosomes harboring the DQB1(*)0602 allele. Eighty-six kilobases of contiguous genomic sequence across the region did not reveal new genes, and analysis of this sequence for single nucleotide polymorphisms did not reveal sequence variation among DQB1(*)0602 chromosomes. These results are consistent with other studies, suggesting that the HLA-DQ genes themselves are among the predisposing factors in narcolepsy.

Causality↗

Treatment outcome following radiotherapy in elderly patients with bladder cancer.

BACKGROUND AND PURPOSE: The optimal treatment of elderly patients with bladder cancer is not established. This study aimed to evaluate prognostic variables for survival and morbidity, which may be important for treatment strategy. MATERIAL AND METHODS: The medical records of 94 patients aged > or = 75 years receiving curatively intended radiotherapy for bladder cancer were reviewed retrospectively. RESULTS: Median age was 78 years (range 75-93 years). Fifty patients had T1-2 tumors, and 42 patients had T3-4 tumors. The total planned dose was 57.6-62.6 Gy in 24-30 fractions in 6 weeks. In 76 patients, a 2 week rest period was planned after 16 fractions (split course). Half of the patients were hospitalized during or after the treatment because of gastrointestinal or urogenital side effects. Median survival was 13.9 months (range 0.6-150.0 + months), 29% survived for 2 years and 7% survived for 5 years. Patients aged > 78 years survived for a shorter period than patients aged 75-78 years (13.4 versus 16.1 months). Univariate survival analysis revealed that low stage (T1-2), good performance status (PS < or = 1), split course treatment, no treatment interruption due to side effects, and no hospitalization during treatment were associated with long survival. In multivariate analyses, T-stage, split course treatment, and performance status were independent prognostic factors. CONCLUSION: The results confirm that curative intended radiotherapy is feasible in elderly patients, but patients with stage T3-4 and PS > 1 have a short survival. These patients should be offered palliative treatment.

Age Factors↗

Post-traumatic regeneration, neurogenesis and neuronal migration in the adult mammalian brain.

Unlike the peripheral nervous system (PNS), the mammalian central nervous system (CNS) clearly lacks the robust regenerative characteristics and capacity of the former. Despite this fact, two unique regions of the adult mammalian CNS possess such regenerative potential and are capable of active regeneration following injury or structural compromise. These unique areas are the olfactory system and the neurohypophyseal system of the endocrine hypothalamus. Furthermore, it has been clearly demonstrated that primordial neuroblasts regarded as stem cells emerge from the subependymal parenchyma of the walls and floor of the third cerebral ventricle, migrate to the ventricular surface and undergo compensatory synaptogenesis within one week following hypophysectomy. In situ hybridization studies have unequivocally demonstrated that the up-regulation of nitric oxide synthase (NOS) is essential for neural (axonal) regeneration and neuronal (stem cell) migration to occur. Moreover, neuronal migration is reliably inhibited following the administration of the NO antagonist, nitroarginine. The current investigation serves to confirm a remarkable degree of plasticity and regeneration in the adult mammalian neurohypophyseal system coupled with the emergence of primordial neuroblasts that undergo apparent differentiation, migration and compensatory synaptogenesis in response to the up-regulation of NO that occurs following the trauma of hypophysectomy. Evidence from the current investigation appears to confirm that specialized glia of the neurohypophyseal system, the so-called pituicyte, proliferate following hypophysectomy and may serve as a growth matrix or structural template that may target and direct regenerating Supraoptic (SON) and Paraventricular (PVN) axons toward endothelial primordia in the regenerating neural stem and lobe.

Adult↗

Fibrin structures during tissue-type plasminogen activator-mediated fibrinolysis studied by laser light scattering: relation to fibrin enhancement of plasminogen activation.

The aim was to relate fibrin structure and the stimulatory effect of fibrin on plasminogen activation during t-PA-mediated fibrinolysis using Lys78-plasminogen as activator substrate. Structural studies were undertaken by static and dynamic laser light scattering, cryo transmission electron microscopy and by the measurement of conversion of fibrin to X-, Y- and D-fragments. The kinetics of plasmin formation were monitored by measurement of the rate of pNA-release from Val-Leu-Lys-pNA. The process of fibrin formation and degradation comprised three phases. In the first phase, protofibrils with an average length of about 10 times that of fibrinogen were formed. The duration of this phase decreased with increasing t-PA concentration. The second phase was characterized by a sudden elongation and lateral aggregation of fibrin fibers, most pronounced at low levels of t-PA, and by formation of fragment X-polymer. The third phase was dominated by fragmentation of fibers and by formation of Y- and D-fragments. Plasmin degraded the fibers from within, resulting in the formation of long loose bundles, which subsequently disintegrated into thin filaments with a length of less than 10 and a mass per length close to one relative to fibrinogen. Plasmin generation at high t-PA concentrations sets in just prior to (and at low t-PA concentrations shortly after) the onset of the rapid second phase of elongation and lateral aggregation of fibrin fibers. The maximal rate of plasmin formation per mol t-PA was the same at all concentrations of activator and was achieved close to the time of the peak level of fragment X-polymer. Plasmin formation ceased after formation of substantial amounts of Y- and D-fragments. At this stage the length was between 300 and 3 and the mass per length close to 1, both relative to fibrinogen. In conclusion our results indicate that (1) formation of short fibrin protofibrils is the minimal requirement for the onset of the stimulatory effect of fibrin on plasminogen activation by t-PA, (2) formation of fragment X protofibrils is sufficient to induce optimal stimulation of plasminogen activation, and (3) plasmin degrades laterally aggregated fibrin fibers from within, resulting in the conversion of the fibers into long loose bundles, which later disintegrate into thin filaments.

Amino Acid Sequence↗

Correlation between college students' driving offenses and their risks for alcohol problems.

This study was designed to investigate the correlation between college students' driving offenses and their risk for alcohol problems. The CORE Alcohol and Drug Survey was administered to 22 undergraduate students enrolled in an alcohol and drug education program. Participants had committed an offense of driving under the influence of alcohol (DUI) or a non-DUI alcohol-related offense. The authors examined the relationship between DUI and non-DUI offenses and the following variables: age of first use, binge drinking, average number of drinks, and grade point average. The DUI group engaged in binge drinking more often and had been younger at the time of first use of alcohol than the non-DUI group. The high overall consumption and frequency of binge drinking among DUI and non-DUI offenders appears to validate alcohol and drug education programs that focus on reducing high-risk behaviors.

Adolescent↗