PubMed Health⌕ Search

Biomedical subjects

L Olson

Publications and source records attributed to L Olson.

At least 163 records · Page 9Linked to original sources
PubMed1995

Transmission of hepatitis C virus by kidney transplantation: impact of perfusion techniques and course of viremia post transplant.

Hepatitis C virus (HCV) infection is the leading cause of post-transplant non-A, non-B hepatitis. Although many end-stage renal disease patients present for transplantation already infected with HCV, some recipients acquire the infection by transmission from the donor organ. We have detected serological evidence for HCV infection in 6.8% of our organ donors using second-generation anti-HCV assays. Approximately one-third of the patients who received an organ from a HCV carrier donor developed chronic transaminasemia and 8 of 14 (56%) patients converted from HCV RNA negative to positive in the posttransplant period. Demonstration of the course of viremia and transaminasemia is presented for 2 patients in whom transmission of HCV occurred. Using pulsatile machine perfusion, we were able to demonstrate that a standard perfusion of 20 h reduced the viral load in the kidney by 75%, additional flushes and a subsequent perfusion reduced the total viral titer by more than 99%. Thus, although transmission of HCV does occur with solid-organ transplantation, differences in the incidence of transmission between centers may be related to techniques of organ preservation.

Hepacivirus↗
PubMed1995

Differential brain area vulnerability to long-term subcortical excitotoxic lesions.

To investigate the long-term effects of excitatory amino acid microinjections into the basal forebrain and its correlation with a possible Ca2+ imbalance associated with the excitotoxic process, ibotenic acid, mainly an N-methyl-D-aspartate receptor agonist, and quisqualic acid, an agonist of non-N-methyl-D-aspartate receptors, were injected into two regions rich in cholinergic neurons, namely the medial septal nucleus and the ventral globus pallidus. Within the globus pallidus but not within the medial septal nucleus, 13 days and one year postlesion, nerve cell death was associated with the appearance of calcium deposits within the large putative GABAergic pallidal neurons, being more pronounced in ibotenic acid than quisqualic acid-lesioned rats. An intermediate two month post-lesion study with alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and ibotenic acid microinjections in globus pallidus demonstrated that the AMPA subtype of glutamate receptor may also be involved in this Ca2+ imbalance, together with the N-methyl-D-aspartate and metabotropic subtype receptors. Quisqualic acid lesions in globus pallidus and medial septum were associated with a substantial disappearance of cholinergic cell bodies and their nerve terminal networks within the cerebral cortex and hippocampal formation respectively, as assessed by choline acetyltransferase and acetylcholine esterase immunocytochemistry. Ibotenic acid lesions resulted in a lower reduction of cholinergic markers. One year after septal lesions induced either by ibotenic or quisqualic acid, a marked atrophy of the entire dorsolateral septal nucleus was observed. Our results support the hypothesis that brief and intense glutamate exposure can induce long-term neurodegenerative processes and give evidence that long-term excitotoxic lesions of the two areas studied result in marked differences in neuronal damage, including intracellular calcium deposits which do not correlate with the cholinergic deficits produced by multiple glutamate receptor subtypes.

Animals↗
PubMed1995

Occupational injury mortality in New Mexico.

STUDY OBJECTIVE: To examine specific risks for occupational injury deaths in New Mexico. DESIGN: Retrospective review of state medical investigator reports from 1980 through 1991 with regard to industry, agent of death, gender, ethnicity, location, and alcohol and other drug involvement. PARTICIPANTS: New Mexico residents who were fatally injured while on the job. RESULTS: We identified 613 deaths: 87.1% unintentional, 10.6% homicides, and 2.3% suicides. Industries with the most fatalities were construction (11.8%), oil/gas (10.6%), and farming (8.6%). The primary agents of death were motor vehicles (41.7%), firearms (10.1%), and falling objects (10.0%). Almost all (95.6%) of the decedents were male. However, females were overrepresented among homicide deaths (P < .0001). Most unintentional injuries occurred in rural areas (69.1%), whereas most homicides (73.4%) and suicides (71.4%) occurred in urban areas. Drug or alcohol use was evident in 19.4% of cases. CONCLUSION: New Mexico has a high rate of occupational injury death, which appears to be associated with rural location and use of motor vehicles and alcohol.

Accidents, Occupational↗
PubMed1995

Fibrin glue used as an adhesive agent in CNS tissues.

One of the limitations of many bridging experiments in neural transplantation is that the CNS tissues cannot be sutured. Fibrin glue is a two-component system derived from whole blood which, when mixed, reproduces the final stage of blood coagulation and solidifies. Many experimental studies of humans and animals show that fibrin glue repair of peripheral nerves is almost equivalent to microsurgical sutures. In this study, we attempted to extend its use to CNS tissues and transplants. Two techniques were tried: (1) Bilateral parietal knife cuts were performed by stereotaxic technique in six rats. Fibrin glue was applied in the right-side cortical lesion. Immunohistochemistry using antisera to tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP), laminin and neurofilament (NF) was essentially similar between the control and treatment groups. The immunoreactivity of each marker revealed no significant differences between the two groups on days 1, 7 and 30. There was no difference in terms of gliosis or microvascular proliferation. (2) Embryonic day 16 fetal locus coeruleus was grafted together with E16 cortex to the anterior chamber of sympathectomized eyes. In the six eyes of the glue treatment group, the parietal cortical piece and the locus coeruleus piece were joined together before grafting by immersing them in the solution of fibrin glue. In the eight eyes of the control group, pieces of parietal cortex and locus coeruleus were introduced individually and approximated by gently pressing the cornea. The sizes of double grafts showed no significant difference between group during six weeks postgrafting. The immunohistochemical pictures using antisera against TH, GFAP and laminin were similar in both groups. Catecholaminergic fibers from the grafted locus coeruleus were found bridging over into the parietal cortical piece in both the control and treatment groups. There was no significant difference in TH-positive nerve fiber density between tissue glue-joined and control double intraocular grafts. In conclusion, fibrin glue can be used as an adhesive agent in CNS tissues without hampering the outgrowth of neurites or causing adverse tissue reactions in fetal or adult nervous tissues.

Adhesives↗
PubMed1995

Expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNAs in human cortical xenografts.

Trophic factors play an important role in the development of neurons and glia. In order to study the involvement of neurotrophins in human cortical development, human fetal parietal cortical tissue, obtained after early elective abortions, was transplanted to cortical cavities in immunosuppressed rats. Using in situ hybridization it was demonstrated that nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNAs are expressed in developing human cortical xenografts. We conclude that neurotrophins may play a role in human cortical development and rat-derived astroglial cells could be involved in establishing reciprocal "permissive sites".

Animals↗
PubMed1995

Time-course of trimethyltin effects on the monoaminergic systems of the rat brain.

The normalization of certain behavioral functions after a trimethyltin (TMT) insult indicates that compensatory processes may occur (Paule and McMillan, 1986; Bushnell and Angell, 1992). The monoamine (MA) neurons are known to be sensitive to TMT, however, a detailed temporal description of the effects is lacking. One week after TMT exposure, 8 mg/kg i.p. to adult male Sprague-Dawley rats, the levels of serotonin (5-HT) and noradrenaline (NA) were decreased in several brain regions, whereas the levels of dopamine were unaltered. In addition, a reduced density of 5-HT immunoreactive fibers was seen in hippocampus and cortex. The lesion in the serotonergic and noradrenergic systems was followed by a recovery. Twelve weeks after TMT treatment, 5-HT and NA levels were increased in hippocampus, and 5-HT levels in striatum. In cerebellum, NA, 5-HT and 5-HIAA levels were decreased at 12 weeks. Compensatory processes led to recovered levels of 5-HT and NA in all regions but cerebellum, although regionally specific increases developed with time possibly due to hyperinnervation. Inhibition of the aromatic amino acid decarboxylase with NSD1015 yields accumulation of catecholamine and 5-HT precursors. Two weeks after TMT, levels of 5-HTP and L-dopa were not different in the TMT-treated rats as compared to controls, indicating that TMT does not affect MA synthesis.

Animals↗
PubMed1994

Spinal cord-skeletal muscle cografts: trophic and functional interactions.

Skeletal muscle from embryonic day 20 (E20) was combined with E15 rat spinal cord in the anterior chamber of the eye of adult albino rats. The two grafts were either transplanted concomitantly or sequentially, in which case muscle tissue was added 4 months after the spinal cord. Control groups received a single graft of either spinal cord or skeletal muscle. Survival and intraocular growth were observed through the cornea. After maturation in oculo, the double grafts were examined immunohistologically utilizing antisera to neurofilament (NF) and acetylcholinesterase (AChE). The grafts were also evaluated using electrical stimulation to determine functional connectivity. The spinal cord and skeletal muscle grafts were found to exert reciprocal trophic effects on each other, evidenced as a larger muscle mass in skeletal muscle grafts allowed to develop in the presence of spinal cord tissue, and a larger volume of spinal cord grafts allowed to develop together with a skeletal muscle graft, respectively. Immunohistochemistry revealed NF-positive nerve fibers leaving the spinal cord graft and entering the muscle tissue. AChE-positive endplates developed in the muscle grafts. Electrical stimulation of the spinal cord part of double-graft combinations generally elicited contractile responses in specific areas of the muscle cograft. These results demonstrate both structural and functional connections between grafts of spinal cord and skeletal muscle tissue in vivo. The fact that such connections were also established between a mature (adult) spinal cord graft and fetal skeletal muscle tissue suggests that some alpha-motoneurons are able to survive for many months in the intraocular grafts without an appropriate target, and that they are able to subsequently innervate skeletal muscle targets.

Animals↗
PubMed1994

Depletion of hepatitis C virus from procured kidneys using pulsatile perfusion preservation.

The safety of the use of kidneys procured from a hepatitis C virus (HCV)-positive cadaver donors in transplantation has recently been the subject of controversy. One factor that is important in determining the transmission of the virus and/or viral liver disease is the total viral inoculum to which the renal allograft recipient is exposed as a result of the transplant. We have studied the effect of a standard pulsatile renal preservation procedure and variations of it on the number of viral copies in organs from HCV-positive donors. An HCV-RNA quantitative reverse transcription-polymerase chain reaction (RT-PCR) method was utilized with a recombinant competitive inhibitor substrate added after cDNA synthesis with the PCR primers within the relatively non-polymorphic 5' untranslated region of the HCV genome. Additionally, strain specificity was found to be detectable using a modification of the technique of restriction fragment-length polymorphism (RFLP-PCR), so that virus from the organ donor could be specifically identified and quantified in the recipient. It was observed that standard preservation procedures using pulsatile perfusion were able to eliminate 75% of the virus from the organ in 20 hr. By modifying this procedure to include additional wash steps and a second pulsatile perfusion, greater than 99% of the virus could be eliminated from the kidney. In a related study, we used quantitative PCR to study requirements for filtration of the virus using HCV-positive serum. It was found that a high-flow-rate ultrafilter with a molecular weight cut-off (MWCO) of 300,000 daltons placed in series to the preservation apparatus was very efficient in eliminating the virus from perfusion solution in less than 2 hr. It can therefore be proposed that with the use of these molecular techniques, pulsatile perfusion coupled with additional viral depletion steps (dilution, and/or filtration) may allow the practical reduction of HCV transmission risk in recipient follow-up studies. The means are thereby presented for similar manipulation of other known or, as yet, unknown transmissible agents.

Base Sequence↗
PubMed1994

Human fetal neocortical tissue grafted to rat brain cavities survives, leads to reciprocal nerve fiber growth, and accumulates host IgG.

The human-to-rat xenograft approach offers possibilities to study aspects of primate cortex development and function without monkeys. Human fetal cortical tissue was grafted to prepared cortical cavities of immunosuppressed host rats. Fetal tissue fragments were collected after routine low-pressure vacuum aspiration abortions performed in the first trimester of gestation. Human derived neurons and human nerve fiber outgrowth were visualized by immunohistochemistry with antibodies against human neurofilament protein 70 kD (hNFP70). Ingrowth from rat host striatum or cortex into the grafts was analyzed by immunohistochemistry with antibodies against tyrosine hydroxylase. Astrocytes were evaluated by immunohistochemistry with antibodies against glial fibrillary acidic protein. The grafts grew into different sizes (1-10 mm in diameter) and contained large numbers of hNFP70-positive nerve fibers. All grafts gave rise to outgrowth of hNFP70-positive fibers into the host with partly a cortical layering; layers III and IV received a majority of the human fibers. In several cases, the graft-derived nerve fibers entered the host brain at restricted areas, while there was no crossing over of nerve fibers at the rest of the graft-host interface. Tyrosine hydroxylase-positive fibers were usually not abundant in the grafts. Interestingly, cases of massive ingrowth occurred from host striatum into the graft in a pattern suggesting "permissive sites" at the graft-host interface in the same way as outgrowth from graft to host was found. Additionally, tyrosine hydroxylase-immunoreactive fibers from host cortex were found to grow into the transplant. Glial fibrillary acidic protein immunoreactivity was increased at the interfaces between graft and host cortex or host striatum. Immunohistochemistry using antibodies against rat IgG indicated the presence of rat IgG within the grafts, and in bordering areas of host brain, possibly indicating a defective graft-host barrier. Taken together, these results show that human cortical tissue pieces grafted to cortical cavities of immunosuppressed rats survive grafting and develop, and that reciprocal nerve fiber growth between grafts and hosts occur. Human cortical neurons can grow into the rat host brain in a pattern which is partly determined by host cortical architecture.

Animals↗
PubMed1994

Human angiotensinogen is highly expressed in astrocytes in human cortical grafts.

Human fetal parietal cortical tissue was transplanted to cortical cavities in immunosuppressed rats. Protoplasmic astrocytes in the human cortical grafts highly expressed human angiotensinogen mRNA as identified with 35S-labeled and digoxigenin-labeled riboprobes combined with immunohistochemistry for glial fibrillary acidic protein. Antibodies to human specific neurofilament protein 70 KD were used to characterize neurons in the graft and fiber outgrowth into the host brain. Immunohistochemistry revealed human angiotensinogen-like immunoreactivity in many small protoplasmic astrocytes and very few large neurons. These results demonstrate that human angiotensinogen mRNA and protein is synthesized in immature human glia. We assume that angiotensinogen is transformed into angiotensin peptides, which may participate in the regulation of growth processes. The results suggest that human angiotensinogen may play a role during human embryogenesis.

Angiotensinogen↗
PubMed1994

Trimethyltin-induced expression of GABA and vimentin immunoreactivities in astrocytes of the rat brain.

Adult Sprague-Dawley rats were given a single dose of trimethyltin chloride (TMT). Three days following treatment, a neuronal alteration was observed in the CA3c pyramidal cell layer of hippocampus which was not accompanied by any apparent astrocyte reaction. At 1 as well as 2 weeks after treatment, a gliosis in hippocampus, piriform, and entorhinal cortices was detected by glial fibrillary acidic protein (GFAP) immunohistochemistry. Concomitant with the enhanced astrocytic GFAP, astrocytes were swollen and expressed immunoreactivity to vimentin and gamma-aminobutyric acid (GABA). The astrocytic GABA immunoreactivity may reflect a trimethyltin-induced alteration in astrocyte phenotype, or alterations in compartmentalization and/or metabolism of GABA.

Animals↗
PubMed1994

Alterations in central monoamine systems after postnatal lead acetate treatment in rats.

The present study was undertaken to investigate the effects of postnatal lead exposure on central monoamine systems. Newborn male Sprague-Dawley rats were given 1 or 8 mg/kg lead acetate intraperitoneally for 20 days postnatally. Two groups of control rats received sodium acetate, or sodium acetate in oversized litters to compensate for lead-induced malnutrition in the high lead dose group, while nontreated animals also served as controls. At Day 21 or 51 regional tissue levels of monoamines were determined using HPLC techniques. No major changes were seen after the lead exposures in the levels of dopamine, noradrenaline, and serotonin, or metabolites of dopamine and serotonin, when compared to respective control groups. On the other hand, in the control group given sodium acetate in over-sized litters some alterations of the monoamine levels were observed in frontal cortex and striatum at Day 21 compared to controls. At Day 51, the striatal homovanillic acid and 5-hydroxyindoleacetic acid levels were higher in the low lead dose group compared to those in the controls. No other changes in the monoamine levels were seen at Day 51. At 50-70 days postnatally, potassium-stimulated dopamine overflow was studied in striatum with in vivo chronoamperometry. In the high lead dose group the amplitudes of signals were lower in both the dorsal and ventral striatum compared to the controls, while no difference was seen in the clearance time of dopamine. The capacity of the dopamine terminals to respond to repeated stimulation was not affected by the lead exposure. Thus, the steady-state levels of monoamines were essentially unaltered after postnatal lead exposure in rats, while functional aspects of striatal dopamine transmission were affected after exposure to the higher dose of lead. These findings support the hypothesis that lead-induced changes in motor skills and exploratory behavior may be related to altered dopamine neurotransmission.

Adolescent↗
PubMed1994

Brain-derived neurotrophic factor and trkB receptor mRNAs in grafts of cortex cerebri.

Trophic factors are expressed by neurons throughout several areas of the CNS. We studied the mRNA expression of a member of the neurotrophin family, brain-derived neurotrophic factor (BDNF), and of the two receptor transcripts, full-length trkB and truncated trkB in single intraocular cortex cerebri grafts and in double cortex cerebri grafts. All single as well as double intraocular cortex grafts grew well, reaching a maximal size 4 weeks postgrafting. BDNF mRNA was moderately expressed in neurons in all intraocular grafts and significantly increased compared to that in adult rat cortex. Truncated trkB mRNA was strongly expressed in neurons and glia, while full-length trkB mRNA was moderately expressed only in neurons in the intraocular cortical grafts. The expression of the two trkB transcripts in the grafted cortex did not differ from that of adult rat cortex. No difference in the expression of mRNAs for full-length or truncated trkB was found between single grafts grown for 4 or 8 weeks or between single and double grafts. Similarly, no difference in expression of BDNF mRNA in single grafts grown for 4 or 8 weeks was detected. However, BDNF mRNA levels were significantly lower in grafts which were placed in close contact with previously grafted cortex in the eye chamber. Moreover, contact with a second graft led to downregulation of BDNF mRNA in the first graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Increase of basic fibroblast growth factor (bFGF, FGF-2) messenger RNA and protein following implantation of a microdialysis probe into rat hippocampus.

In vivo microdialysis is an established tool for sampling extracellular fluid compartments. However, microdialysis faces the problem that the implantation of the probe damages the microenvironment from which measurements are derived. In this study, we examined the expression of basic fibroblast growth factor mRNA and protein at the cellular level after implantation of a microdialysis probe into the dorsal hippocampus and found that 8 h after inserting the probe bFGF mRNA was markedly increased in a relatively large area centered around the probe, involving both the dorsal hippocampus and the overlying cerebral cortex, as revealed by radioactive in situ hybridization. Using nonradioactive in situ hybridization with digoxigenin-labelled riboprobes, combined with immunohistochemistry for glial fibrillary acidic protein we demonstrated that bFGF mRNA was exclusively increased in astrocytes at the probe insertion site. Using immunohistochemistry we also found that bFGF-like immunoreactivity was increased after implantation of the probe close to the lesion site, as shown by an increased number of bFGF immunoreactive nuclear glial profiles. These results provide evidence that the implantation of a microdialysis probe into the brain induces activation of bFGF gene expression in astrocytes associated with nuclear bFGF-like immunoreactivity. We conclude that lesion-induced effects have to be considered when evaluating microdialysis data, and that mechanical trauma to the brain will activate astroglial trophism, as seen from the increased density of astroglial profiles demonstrating bFGF mRNA and protein levels.

Animals↗
PubMed1994

Engineering cells to secrete growth factors.

The neutrotrophins stimulate survival and differentiation of a range of target neurons. A wealth of evidence suggests that central cholinergic neurons depend on nerve growth factor (NGF) for trophic support. Grafts of NGF-producing cells rescue axotomized basal forebrain cholinergic neurons and reduce cholinergic cell death in the medial septum. Skeletal muscle cells, immortalized from embryonic day 15 (E15) rat embryos for transplantation purposes, were transfected with a human NGF construct and individual clones tested for NGF production by a biological assay using embryonic sympathetic ganglia. Clone RM22 showed a consistent ability to produce human recombinant NGF in high concentration; RM22 cells were grafted to the rat brain, following fimbria-fornix lesions, in order to examine the influence of these cells on basal forebrain cholinergic neurons. The results suggest that implantation of genetically modified cells, engineered by the introduction of expression plasmids or viral constructs to produce NGF or other neurotrophins may have therapeutic applications in rescuing damaged central cholinergic neurons in senile dementia of the Alzheimer type as well as in providing trophic support for chromaffin tissue grafts in Parkinson's disease. Moreover, the use of genetically engineered cells may be used to study the effects of administering tailor-made neurotrophins with novel activity profiles.

Animals↗