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L Olson

Publications and source records attributed to L Olson.

At least 91 records · Page 5Linked to original sources
PubMed1998

High-resolution MRI of intact and transected rat spinal cord.

Spinal cord transection at midthoracic level leads to an immediate loss of hindlimb motor function as well as to a progressive degeneration of descending and ascending spinal cord pathways. Thoracic spinal cord in unlesioned control rats and in rats 2 to 6 months after complete midthoracic transection were imaged in vivo using an ultrahigh-field (4.7 T) magnetic resonance spectrometer. High-resolution spin-echo and inversion-recovery pulse sequences were employed. In addition, the apparent diffusion coefficients (ADCs) in longitudinal and transverse directions of the spinal cord were determined. Anatomical MRI findings were confirmed in histological spinal cord tissue preparations. In healthy spinal cord, gray and white matter were easily discerned in proton density-weighted images. An infield resolution of max. 76 micrometers per pixel was achieved. In animals with chronic spinal cord transection changes in gray-white matter structure and contrast were observed toward the cut end. The spinal cord stumps showed a tapering off. This coincided with changes in the longitudinal/transverse ADC ratio. Fluid-filled cysts were found in most cases at the distal end of the rostral stump. The gap between the stumps contained richly vascularized scar tissue. Additional pathologic changes included intramedullary microcysts, vertebral dislocations, and in one animal compression of the spinal cord. In conclusion, MRI was found to be a useful method for in vivo investigation of anatomical and physiological changes following spinal cord transection and to estimate the degree of neural degeneration. In addition, MRI allows the description of the accurate extension of fluid spaces (e.g., cysts) and of water diffusion characteristics which cannot be achieved by other means in vivo.

Animals↗
PubMed1998

Dopamine D1 and D2 receptor-mediated acute and long-lasting behavioral effects of glial cell line-derived neurotrophic factor administered into the striatum.

To determine the differences in behavioral effects between intrastriatal and intracerebroventricular glial cell-derived neurotrophic factor (GDNF) administration, spontaneous locomotor activity was measured after intrastriatal or intracerebroventricular injection of GDNF (10 microg) in normal adult rats with implanted guide cannulae. In addition, the distribution of GDNF after intracerebral injection was studied immunohistochemically. Intrastriatal administration of GDNF significantly increased rearing behavior 3-4 h after injection. Increases in all three aspects of locomotor activity (motility, locomotion, and rearing) were most pronounced 3 days after intrastriatal injection, and they lasted for several days. This hyperactivity was blocked by the selective dopamine D1 receptor antagonist SCH22390 and by the selective D2 receptor antagonist raclopride at doses of the dopamine receptor antagonists, which by themselves did not affect spontaneous locomotor activity. These results suggest that GDNF has both acute and long-lasting pharmacological effects on dopamine neurons in adult animals and stimulates locomotor activity by activating both dopamine D1 and D2 receptors. On the other hand, intracerebroventricular administration of the same dose of GDNF failed to increase locomotor activity at any time during the test period (12 days). The immunohistochemical study demonstrated widespread distribution of GDNF in the entire body of the striatum within 24 h after intrastriatal injection. It also revealed deep penetration of GDNF from the ventricular space into the brain parenchyma after intracerebroventricular injection. GDNF-immunoreactive neuronal cell bodies were seen in the ipsilateral substantia nigra pars compacta most frequently 6 h after intrastriatal injection. The number of such cell bodies after intracerebroventricular administration, on the other hand, was much lower than that seen after intrastriatal administration. Taken together, these data suggest that intrastriatal administration of GDNF is an effective approach for affecting DA transmission. Long-lasting behavior effects are mediated via dopamine D1 and D2 receptors. Higher doses of GDNF would probably be needed using the intracerebroventricular route as compared to intraparenchymal delivery to exert effects on the nigrostriatal system in Parkinson's disease patients.

Animals↗
PubMed1998

Changes in neurotrophin-3 messenger RNA expression patterns in the prenatal rat tongue suggest guidance of developing somatosensory nerves to their final targets.

While brain-derived neurotrophic factor (BDNF) messenger RNA (mRNA) has been localized in the developing gustatory epithelium, little information is available about neurotrophin-3 (NT-3) mRNA expression pattern in the prenatal developing gustatory and lingual epithelium. In the present study, using in situ hybridization histochemistry, we report on NT-3 mRNA expression in the tongue of rats. At embryonic day (E) 13-17, NT-3 mRNA was expressed subepithelially in the periphery of the developing tongue, as well as among developing muscle. At E19, there was a shift in the expression of NT-3 mRNA. It was then expressed in the surface epithelium of the developing tongue in the developing filiform papillae and, in higher concentrations, in top-surface and fringe epithelium of the developing circumvallate papillae, and top- and lateral-surface epithelium of the developing fungiform papillae. NT-3 mRNA expression in areas rich in somatosensory innervation of the tongue, as well as its specific expression in defined regions compared with BDNF, and the decreased labeling noted from prenatal and early postnatal animals to adults indicate a specific role for NT-3 in the development of lingual somatosensory innervation, as well as for maintenance of this innervation.

Afferent Pathways↗
PubMed1998

On CNS repair and protection strategies: novel approaches with implications for spinal cord injury and Parkinson's disease.

In the adult mammalian central nervous system lost nerve cells are not replaced and there is no regeneration of injured axons in white matter. Together, these two facts mean that there are no spontaneous reparative mechanisms in operation. Instead, the adult central nervous system copes with the risks of injuries and diseases by protective encapsulation in bone, by a multitude of neuroprotective mechanisms, and finally by the fact that many important functions are represented by a much larger number of neurons than minimally needed. The long life expectancy of a human being nevertheless means that the risk that the central nervous system is affected by disease, injury or other forms of insults for which it cannot fully compensate is relatively high. Experimentally, two strategies are being pursued in order to develop ways of minimizing various forms of CNS damage, namely neuroprotective and reparative strategies. Here we present a possible reparative intervention applicable to spinal cord injury based on multiple white-to-gray matter peripheral nerve bridge grafts and work based on the specific role of Nurr1 for dopamine neuron development, suggesting that development of ligands to transcription factor might be a new inroad to neuroprotective treatments in Parkinson's disease.

Adult↗
PubMed1998

Repeated ambulance use by patients with acute alcohol intoxication, seizure disorder, and respiratory illness.

Three chronic conditions were examined--acute alcohol intoxication, seizure disorder, and respiratory illness--to quantify the extent of repetitive emergency medical services (EMS) use in a defined population. Urban EMS system ambulance data from 1992 to 1994 were analyzed for the three designated conditions with respect to transports by condition and individual patient. Analysis by chi2 was used for comparing proportions. Analysis of variance after square root transformation was used to evaluate differences among means. The total number of transports analyzed was 15,541: 7,488 for acute alcohol intoxication, 4,670 for respiratory illness, and 3,383 for seizure disorder. These transports involved 8,692 patients who were transported at least once for one of the three designated conditions. The mean number of transports for alcohol was 1.96 (95% confidence intervals [CI]: 1.92, 2.01), seizure 1.32 (95% CI: 1.27, 1.36), and respiratory 1.18 (95% CI: 1.15, 1.21). Of 369 patients transported five or more times during the study period, 260 (70.5%) were for alcohol, 56 (15.2%) for seizure, and 53 (14.4%) for respiratory complaints. This group comprised only 4.3% of patients, but 28.4% of all transports. Acute alcohol intoxication resulted in more repetitive ambulance transports than either seizure disorder or respiratory illness. A small number of patients were responsible for a large number of transports. Focused intervention for patients with high ambulance transport deserves further study.

Adult↗
PubMed1998

Pre-surgical CT/FEA for craniofacial distraction: I. Methodology, development, and validation of the cranial finite element model.

Recently, surgeons have begun to treat serious congenital craniofacial deformities including craniosynostoses with mechanical devices that gradually distract the skull. As a prospective means of treatment planning for such complex deformities, FE models derived from routine preoperative CT scans (CT/FEA) would provide ideal patient specific engineering analyses. The purpose of this study was to assess the dimensional and predictive accuracy of the CT/FEA process through the development of a 3D model of a dry human calvarium subjected to two-point distraction ex vivo. Comparative skull measurements revealed that CT/FEA construction error did not exceed 1% for transcranial dimensions, and the thickness error did not exceed 8.66% or 0.31 mm. CT/FEA strain predictions for the central region of the skull, between the distraction posts, were not statistically different from homologous gage values at P < 0.05. Peripherally, however, the strain fields were less well behaved and the FE predictions showed only general qualitative agreement with gage recordings.

Biomechanical Phenomena↗
PubMed1998

GFRalpha-3, a protein related to GFRalpha-1, is expressed in developing peripheral neurons and ensheathing cells.

We report here the identification of a gene, termed GFRalpha-3 (glial cell line-derived neurotrophic factor family receptor alpha-3), related to GFRalpha-1 and GFRalpha-2 (also known as GDNFR-alpha and GDNFR-beta), and describe distribution of GDNFalpha-3 in the nervous system and other parts of the mouse body during development and in the adult. GFRalpha-3 in situ hybridization signals were found mainly in the peripheral nervous system, with prominent signals in developing dorsal root and trigeminal ganglia. Sympathetic ganglia were also positive. Developing nerves manifested strong GFRalpha-3 mRNA signals, presumably generated by the Schwann cells. Olfactory ensheathing cells were also positive. Other non-neuronal cells appearing positive during development included chromaffin cells in the adrenal gland and small clusters of cells in the intestinal epithelium. In the central nervous system no robust signals could be detected at any stage investigated with the present probes. Compared with the previously described GFRalpha-1 and GFRalpha-2 mRNAs, which are widely distributed in the central nervous system and peripheral organs, the expression of GFRalpha-3 mRNA is much more restricted. The prominent expression in Schwann cells during development suggests a key role for GFRalpha-3 in the development of the peripheral nervous system. As Schwann cells are known to lack expression of the transducing RET receptor, we propose that a possible function of GFRalpha-3 during development could be to bind Schwann cell-derived GDNF-like ligands, thus presenting such molecules to growing axons.

Amino Acid Sequence↗
PubMed1998

Presurgical finite element analysis from routine computed tomography studies for craniofacial distraction: II. An engineering prediction model for gradual correction of asymmetric skull deformities.

Finite element analysis from routine computed tomography studies (CT/FEA) allows clinicians to predict the mechanical and anatomic consequences of specific distraction systems before human application. A realistic three-dimensional CT/FEA engineering model of an actual plagiocephalic infant with unicoronal synostosis was developed using 4215 parabolic triangular shell elements and intracranial pressure conditions ranging from 10 to 20 mmHg. The completed finite element analysis model was used to predict the anatomic outcome of multiaxial distraction delivered by hypothetical patterns of rod and node distraction units. The predictions for the various patterns of distraction units were also compared quantitatively with respect to force, stress, strain, and intracranial volume. Best anatomic corrections were achieved with bilateral patterns of distraction units that simultaneously elongated the ipsilateral cranium and shortened the contralateral cranium. Greatest strain levels were experienced within the osteotomy callus, greatest stress levels at the appliance anchorage sites, and the greatest rod force at the ipsilateral lower coronal position.

Biomechanical Phenomena↗
PubMed1998

Program for reducing pedestrian-motor vehicle crashes.

Injury prevention has been identified as a component of emergency medicine. However, involvement of emergency physicians in injury prevention has been hindered by clinical responsibilities, lack of financial support, and limited expertise in skills necessary for effective injury prevention programs. This article describes the development and content of a statewide pedestrian safety plan prepared by the Department of Emergency Medicine at the University of New Mexico. The plan included a written document, community input through focus groups, and a public information campaign. The written document included a synthesis of published literature, state-specific data, information on community interventions, and recommendations for state agencies and other groups interested in reducing pedestrian injuries. This project can be modeled at other academic EDs with an interest in injury prevention and pedestrian safety.

Accidents, Traffic↗
PubMed1998

Relationships between ambulance transports for alcohol intoxication and assault.

OBJECTIVE: To evaluate the association between ambulance transports for assault and those for alcohol intoxication. METHODS: A retrospective analysis of emergency medical services (EMS) calls was performed. The authors used logistic regression models to compare patients transported for alcohol intoxication with a control group of patients transported for respiratory distress (asthma or shortness of breath) with respect to whether they had been transported on a separate occasion for a chief complaint of assault. RESULTS: Patients transported for alcohol intoxication had 9 times the risk of transport for assault as compared with the control group (OR = 9.3; 95% CI = 6.4, 13.6). The odds of transport for assault among the alcohol patients increased 17.1% with each alcohol transport (OR = 1.17; 95% CI = 1.14, 1.20) but decreased for the control group (OR = 0.34; 95% CI = 0.26, 0.44). Repeat transports for assault were more common among the alcohol patients than among the control group (OR = 3.3; 95% CI = 1.1, 11.3). The mean number of assault transports was higher among the alcohol patients than among the patients never transported for alcohol intoxication (p < 0.0001). CONCLUSIONS: Patients transported on multiple occasions for acute alcohol intoxication are at relatively high risk for assault. This risk group should be targeted for focused assault prevention interventions that include components designed to reduce incidents of repeat alcohol intoxication.

Adult↗
PubMed1998

NGF, BDNF, NT3, NT4 and GDNF in tooth development.

Neurotrophic factors have robust effects on development, differentiation, maintenance and regeneration of neurons. In the present study, we have used in situ hybridization to determine the specific sites of gene activity of five neurotrophic factors during tooth development. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNAs were mainly detected in the dental papilla/pulp in postnatal rats, and the pattern of expression correlated with onset of dental innervation. In contrast, neurotrophin 3 (NT3) and 4 (NT4) mRNA expression patterns were predominantly epithelial and were strongest during early developmental stages when teeth are not yet innervated. Glial cell line-derived neurotrophic factor (GDNF) mRNA was present in dental epithelium at early stages, but later in development, GDNF mRNA expression was mainly mesenchymal and observed in the odontoblast layer and extending into the subodontoblast zone. Our results suggest that both neurotrophins and GDNF may have multiple functions during tooth development. In addition to an influence on the establishment of the dental innervation, neurotrophic substances might have morphogenetic effects such as modulating the proliferation or differentiation of developing epithelial and mesenchymal cells.

Animals↗
PubMed1997

Neurturin and glial cell line-derived neurotrophic factor receptor-beta (GDNFR-beta), novel proteins related to GDNF and GDNFR-alpha with specific cellular patterns of expression suggesting roles in the developing and adult nervous system and in peripheral organs.

Cloning strategies were used to identify a gene termed glial cell line-derived neurotrophic factor receptor-beta (GDNFR-beta) related to GDNFR-alpha. In situ hybridization was then used to map cellular expression of the GDNF-related trophic factor neurturin (NTN) and GDNFR-beta mRNA in developing and adult mice, and comparisons with GDNFR-alpha and RET were made. Neurturin is expressed in postnatal cerebral cortex, striatum, several brainstem areas, and the pineal gland. GDNFR-beta mRNA was more widely expressed in the developing and adult CNS, including cerebral cortex, cerebellum, thalamus, zona incerta, hypothalamus, brainstem, and spinal cord, and in subpopulations of sensory neurons and developing peripheral nerves. NTN colocalized with RET and GDNFR-alpha in ureteric buds of the developing kidney. The circular muscle layer of the developing intestines, smooth muscle of the urether, and developing bronchiolae also expressed NTN. GDNFR-beta was found in myenteric but not submucosal intestinal plexuses. In developing salivary glands NTN had an epithelial expression, whereas GDNFR-beta was expressed in surrounding tissue. Neurturin and GDNFR-beta were present in developing sensory organs. In the gonads, NTN appeared to be expressed in Sertoli cells and in the epithelium of the oviduct, whereas GDNFR-beta was expressed by the germ cell line. Our findings suggest multiple roles for NTN and GDNFR-beta in the developing and adult organism. Although NTN and GDNFR-beta expression patterns are sometimes complementary, this is not always the case, suggesting multiple modi operandi of GDNF and NTN in relation to RET and the two binding proteins, GDNFR-alpha and GDNFR-beta.

Animals↗
PubMed1997

Plant-derived amino acids increase hippocampal BDNF, NGF, c-fos and hsp70 mRNAs.

Early alterations in mRNAs encoding neurotrophins and stress proteins were investigated following intracerebroventricular injections of beta-N-oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA) in adult rats using in situ hybridization. Major increases in heat-shock protein 70, c-fos and brain-derived neurotrophic factor (BDNF) mRNAs were seen in hippocampus 1 h after BOAA or BMAA injections. Nerve growth factor mRNA was profoundly increased in the dentate gyrus (DG) after both treatments. Four hours after BMAA injections increased hybridization to BDNF mRNA was still seen in hippocampus, in parallel with reduced neurotrophin-3 expression in the DG. These alterations are in accordance with previous findings of BOAA and BMAA as potent glutamate receptor agonists.

Amino Acids, Diamino↗
PubMed1997

Dopamine receptor antagonists block nerve growth factor-induced hyperactivity.

The role of dopamine receptors in mediating nerve growth factor (NGF)-induced locomotor stimulation was investigated by examining the effects of selective dopamine D1 and D2 receptor antagonists on the motor hyperactivity induced by NGF. A single intracerebroventricular administration of NGF (5.1 microg) increased locomotor activity immediately after injection in normal adult rats. This hyperactivity was partly blocked by the dopamine D1 receptor antagonist SCH23390 (R-(+)-7-chloro-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1H-3-benzazepine-8- ol) and by the dopamine D2 antagonist raclopride ((S)-3,5-dichloro-N-((1-ethyl-2-pyrrolidinyl)methyl)-2-hydroxy-6-methoxy benzamide). Effective doses of raclopride did not alter spontaneous levels of activity in control rats. These results suggest that stimulation of both subtypes of dopamine receptors is necessary for eliciting NGF-induced hyperactivity in the rat. The role of the dopamine D2 receptor in mediating the behavioral actions of NGF appears to be more important than that of the dopamine D1 receptor.

Animals↗
PubMed1997

Dopamine neuron agenesis in Nurr1-deficient mice.

Dopamine neurons of the substantia nigra and ventral tegmental area regulate movement and affective behavior and degenerate in Parkinson's disease. The orphan nuclear receptor Nurr1 was shown to be expressed in developing dopamine neurons before the appearance of known phenotypic markers for these cells. Mice lacking Nurr1 failed to generate midbrain dopaminergic neurons, were hypoactive, and died soon after birth. Nurr1 expression continued into adulthood, and brains of heterozygous animals, otherwise apparently healthy, contained reduced dopamine levels. These results suggest that putative Nurr1 ligands may be useful for treatment of Parkinson's disease and other disorders of midbrain dopamine circuitry.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Human islet allografts in patients with type 2 diabetes undergoing liver transplantation.

BACKGROUND: Most patients with cirrhosis have insulin resistance and impaired glucose tolerance, and 20% eventually develop diabetes. Although diabetes in this setting may be reversible after orthotopic liver transplantation (OLTx), immunosuppressive agents administered after transplantation could exacerbate this disease. We report the results of the first pilot trial of islet cell transplantation (ICTx) in patients with diabetes undergoing OLTx. METHODS: Five patients with diabetes and liver cirrhosis underwent OLTx and ICTx. Donor bone marrow cells were also infused to enhance the acceptance of the graft. We identified seven patients who received only OLTx and donor bone marrow cells as historical controls. RESULTS: Preliminary results suggest that ICTx in conjunction with OLTx may improve glucose metabolism (insulin requirement, hemoglobin A1c) in patients with liver cirrhosis. However, there was virtually no change in pre- and posttransplant basal C-peptide levels in the recipients of OLTx + ICTx. CONCLUSIONS: We are planning to further evaluate the effect of OLTx with or without ICTx in a randomized prospective trial, using euglycemic insulin clamp studies.

Adolescent↗
PubMed1997

High-dose donor bone marrow infusions to enhance allograft survival: the effect of timing.

BACKGROUND: The development of strategies to enhance survival of transplanted organs and to potentially lower or even discontinue immunosuppressive therapy would represent a significant advance in posttransplant patient care. The aim of this clinical trial was to determine the effect of timing and dose of peripheral donor bone marrow cell (DBMC) infusion on graft and patient survival after liver transplantation. METHODS: DBMC, obtained from vertebral bodies, were administered in 101 recipients of liver allografts (OLTX). There were 107 patients for whom DBMC could not be obtained; they received OLTX alone (controls). A total of 5 x 10(8)/kg DBMC were infused at day 0 (group 1; n=9); at days 0 and 11 (group 2; n=26); or at days 5 and 11 (group 3; n=26). In group 4 (n=40), patients received up to five infusions of 2 x 10(8)/kg DBMC at days 5, 14, 21, 28, and 90 after OLTX. RESULTS: When the results from patients receiving two or more DBMC infusions (groups 2, 3, and 4) are considered, both patient and graft survival were significantly improved compared with the control group (P=0.02 and P=0.01, respectively). In groups 3 and 4, 88.5% and 95% of patients were alive with mean follow-up of 536 and 265 days, respectively, compared with 77.6% of patients in the control group (average follow-up of 452 days) (P=0.02). Graft survival was also significantly improved in groups 3 (88.5%) and 4 (92.5%), compared with the controls (72%) (P=0.007). CONCLUSIONS: The results suggest that dose and timing of DBMC infusions may be important variables affecting allograft survival. A randomized prospective trial is now in progress to compare group 3 DBMC infusion protocol with controls receiving OLTX alone.

Adult↗