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Biomedical subjects

L Olson

Publications and source records attributed to L Olson.

At least 235 records · Page 13Linked to original sources
PubMed1991

Functional innervation of spinal cord tissue by fetal neocortical grafts in oculo: an electrophysiological study.

The ability of fetal neocortex transplants, to functionally innervate maturated cervical spinal cord grafts in oculo, was investigated in rats. We found that a neocortex co-graft will grow and develop in contact with a spinal cord graft, and will generate a functional input to maturated spinal cord tissue which can be activated by electrical stimulation of the neocortex graft. Our data suggest that orthodromic stimulation of this pathway causes short latency, transient excitations of spinal graft neurons. These appear to be mediated by an excitatory amino acid receptor since the response was noncompetitively antagonized by kynurenic acid. Kynurenic acid also noncompetitively antagonized the excitatory effects of glutamate superfused over single spinal cord grafts. The mechanism of the excitation probably does not involve an NMDA (N-methyl-D-aspartate) receptor since APV (2-amino-5-phosphonovalerate) did not alter the spinal graft neuronal responses to neocortical co-graft stimulation. These data suggest that fetal neocortex can functionally innervate maturated cervical spinal cord in the in oculo graft preparation. The in oculo spinal cord graft model may thus provide a unique test system for studies of the influence of drugs and other manipulations that might alter cortico-spinal pathway development as well as influence reestablishment of neuronal pathways after spinal cord injury.

Action Potentials↗
PubMed1991

Effects of donor age on superior cervical ganglion transplants: evaluation of Falck-Hillarp histochemistry and immunocytochemistry.

The purpose of the present study was to investigate the viability, growth characteristics and neuropeptide expression of intraocular superior cervical ganglia (SCG) grafts from neonatal (1-3 d), mature (4-5 months) and aged (20-24 months) rats. In vivo measurements, Falck-Hillarp histochemistry using iris whole mounts to assess catecholamine fiber outgrowth and immunocytochemical localization of tyrosine hydroxylase (TH-), neuropeptide Y (NPY-), leu-enkephalin (ENK-) and calcitonin gene-related peptide (CGRP-) like immunoreactivity (LI) were used. Measurements indicated a marked decrease in volume during the first week after grafting and a more gradual decrease thereafter. This was most evident in newborn SCG. With prolonged survival time, the newborn ganglia demonstrated more varicose nerve terminals and increased catecholamine fiber outgrowth and arborization. Extensive and complex outgrowth of catecholamine fibers with varicose nerve terminals occurred more rapidly with mature and aged ganglia. In situ, all ganglion cell bodies and fibers demonstrated TH-LI. Localization of TH-LI after grafting indicated an increase in fiber density and a decrease in cell body density of 65%, 40% and 40% in newborn, mature and aged ganglia respectively. NPY-LI in cell bodies had a perinuclear fluorescence pattern consistent with localization in the Golgi apparatus. Grafting of newborn, mature and aged SCG resulted in a 20%, 20% and 35% decrease respectively of cell bodies containing NPY-LI. A concommitant increase in fiber diameter, fluorescence intensity and extent of arborization was observed. The characteristic distribution of ENK-LI in cell bodies and axons in mature and aged ganglia was not affected by grafting. However, there was a greater than 50% reduction in the number of cell bodies expressing ENK-LI. CGRP-LI, localized in fibers and axon terminals in SCG in situ, was not identified after grafting. In summary, we have demonstrated that SCG from all age groups form extensive fiber networks and continue neuropeptide expression after intraocular grafting. This was seen best in mature and aged donors and may suggest a role for SCG transplants in the replacement of monoaminergic neurons in the CNS.

Aging↗
PubMed1991

Acidic and basic fibroblast growth factors augment growth of fetal brain tissue grafts.

The fibroblast growth factor family of peptides (FGF's) are biological regulators which have a diverse array of activities. Among the biological responses reported are inductive effects during early embryogenesis, mitogenic activity on a variety of mesenchymally derived tissues, potent angiogenic activity and neurotrophic activity for both the peripheral and central nervous system. In vitro studies have been performed showing that the FGF's play a regulatory role in the survival and growth of neurons from several regions of the developing rat brain. By using the in vivo model of intraocular transplantation and repeated injections into the anterior chamber, we have been able to observe and follow the survival and growth of small, defined areas of central nervous system (CNS) under the influence of acidic (a) FGF or basic (b) FGF. Acidic FGF significantly enhanced growth of transplanted parietal cortex, embryonic day 17-20 [E17-20], hippocampus [E20] but not spinal cord [E14] when compared to the bovine serum albumin (BSA) vehicle alone. Parietal cortex grafts increased approximately 200% and the hippocampus grafts 100% when stimulated with aFGF. Basic FGF greatly enhanced the growth of intraocularly transplanted parietal cortex (E17-18), hippocampus (E16-17), and spinal cord (E14) by approximately 400%, 100% and 50% respectively when compared to the vehicle alone, and was thus significantly more potent than aFGF at the same concentration. Effects on all areas were seen using concentrations of aFGF down to 25 micrograms/ml and bFGF as low as 2.5 micrograms/ml. Histochemical and immunohistochemical studies carried out on cryostat sectioned grafts suggested either no change or normalization of markers for vascularization, glial and neuronal populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Short-term variability of ventricular arrhythmia and rapid assessment of drug efficacy.

Statistical criteria for suppression and aggravation of ventricular arrhythmia were defined by means of 50 short-term drug tests performed in 24 patients. Each patient's spontaneous variability (SV) was evaluated by linear regression analysis of hour-to-hour changes in ectopy during 24- to 48-hour Holter monitoring. The response to a single oral dose of disopyramide, 300 mg, flecainide, 200 mg, and propafenone, 450 mg, was measured during a trial lasting 4 hours. Lidocaine was administered intravenously in incremental doses of up to 4 mg/min and was evaluated over 3 hours. Threshold values of ventricular arrhythmia corresponding to 95% confidence limits were calculated from baseline recordings and were used to ascertain the likelihood of a true drug effect. The minimum decrease in hourly ectopy indicating arrhythmia suppression averaged 90.9%, while an increase of at least 947% was required for a proarrhythmic effect. When these efficacy criteria were applied, 16 of 50 short-term tests revealed no drug effect. In contrast, when a 70% threshold derived from studies of daily variability was employed, only 7 of 50 trials were negative. Thus individual determination of hourly arrhythmia variability yields more stringent criteria than extrapolation from day-to-day spontaneous variation.

Aged↗
PubMed1991

Functional enhancement of intrastriatal dopamine-containing grafts by the co-transplantation of sciatic nerve tissue in 6-hydroxydopamine-lesioned rats.

Peripheral nerve "bridges" demonstrate the ability to facilitate axonal growth and regenerate adult and fetal central nervous system tissue. The purpose of this study was to determine if co-grafted peripheral nerve tissue could enhance the ability of fetal dopamine (DA) cell transplants to reinnervate host striatum that had been denervated unilaterally. Male Fisher-344 rats were unilaterally lesioned with 6-hydroxydopamine to eliminate the nigrostriatal DA pathway. A total of 31 rats demonstrated a pattern of rotation indicative of a greater than 98% depletion in DA. Rats were kept as nongrafted controls (n = 6), grafted with sciatic nerve (PN) minces (n = 6), grafted with fetal ventral mesencephalon (VM; n = 10), or co-grafted with VM and PN minces (n = 9). All groups were then tested for changes in apomorphine-induced rotational behavior. The PN control group showed no significant differences in rotation when compared to pregrafting levels and to the lesioned nongrafted group. Both the VM-grafted group and the VM-PN co-grafted group showed significant (P less than 0.01, one-way ANOVA) decreases in rotations beginning at 1.5 weeks postgrafting. There was a progressive decrease in rotations up to 12 weeks, the last test point examined. Interestingly, the co-graft group revealed a significantly greater decrease in rotation (P less than 0.05) than the VM group beginning at 5 weeks and continuing out to the 12-week test point. Histological and immunocytochemical studies showed good survival of both PN and VM grafts. The augmented recovery could not be accounted for by increased DA cell survival or host brain DA reinnervation in the co-graft group. Taken together, these findings suggest that PN tissue enhances the ability of fetal VM grafts to reinnervate host brain.

Animals↗
PubMed1991

Ethical issues in brain-cell transplantation.

The ethical ramifications of intracranial transplantation are many. While the majority of ethical concerns have focused on the relationship of transplantation of fetal brain tissue to elective abortion, there are other significant issues relating to graft recipients (patients and their families) and to the allocation of public resources for clinical transplantation research. In this article, some of these latter problems will be considered first, followed by a discussion of the constraints derived from the abortion question that are placed on transplantation.

Aborted Fetus↗
PubMed1991

Combined lead acetate and disulfiram treatment-induced alterations of glial fibrillary acidic protein (GFA) immunoreactive astrocytes in brain smears.

Dithiocarbamates are known to form lipid-soluble complexes with lead and greatly increase brain lead levels. The present study was undertaken to investigate whether lead acetate, when administered together with disulfiram (Antabuse, metabolite of dithiocarbamate) during development, would induce morphological changes in brain astrocytes. Female Sprague-Dawley rats were given 0.25% lead acetate in the drinking water from day one of pregnancy and this treatment was continued after birth until the litters were 4 weeks old. In addition, some dams received disulfiram in a dose of 0.1 mmol/kg p.o. twice weekly and after parturition this dose was given s.c. directly to the offspring twice a week. Lead acetate and disulfiram treatments were discontinued at weaning and animals sacrificed 3 weeks later. Samples of parietal cortex, hippocampal formation and cerebellar cortex were dissected out and smeared onto glass-slides and astrocytes were visualized in toto using immunohistochemistry with antibodies against glial fibrillary acid protein (GFA), enabling morphometric analysis with a computerized image analyser. Animals treated with lead acetate showed a minor increase in the size of the GFA-immunoreactive astrocytes in parietal cortex smears, while animals treated with disulfiram showed no difference in size or form compared to controls. However, in combined lead acetate and disulfiram-treated animals a profound increase in astrocyte size and an increase in the number of processes of the individual GFA-immunoreactive astrocytes could be demonstrated in parietal cortex. No significant changes were noted in GFA-immunoreactive astrocytes of hippocampal smears following the different treatments, while GFA-immunoreactive astrocytes in cerebellar cortex smears were significantly smaller and had reduced number or processes following the combined lead acetate and disulfiram treatment compared to lead acetate treatment or controls. It is concluded that combined exposure to lead acetate and disulfiram during development induces regionally specific changes in GFA-immunoreactive astrocyte morphology. Furthermore, the present study demonstrates the usefulness of smear preparations combined with computerized image analysis to study the morphology of GFA-immunoreactive astrocytes as an index of toxic effects in CNS.

Animals↗
PubMed1991

Spatial distributions of cytoskeletal proteins and the nerve growth factor receptor in septal transplants in oculo: protection from abnormal immunoreactivity by hippocampal co-grafts.

Intraocular grafts of embryonic rat septum and co-grafts of septum plus hippocampus were studied with immunohistochemical markers after one and six months (short term) and 12 months (long term) of survival. Neurons in all the septal tissues expressed the epitope for the rat beta-nerve growth factor receptor in sections reacted with the monoclonal antibody 192-IgG. Stained fibers traversed the interface of the short and long term co-grafts and 192-IgG-positive processes were most prominent in the septum when combined with the hippocampal formation. In contrast, labeled processes were sparse and the perikarya of positive neurons appeared shrunken in the long term single septal transplants. Axon and dendrite profiles in the grafts were examined with antibodies that recognize the phosphorylated heavy neurofilament unit (RT97) and the high molecular weight microtubule-associated protein termed MAP 2, respectively. In the short term single and double grafts, characteristic arrays of RT97-positive processes defined the tissues and axonal tracts connecting the septum with the hippocampus. Typical immunostaining of the neuronal somas and the dendrite arbors were were outlined with the MAP 2 antibody. After one year in oculo, extensive changes in the patterns of axonal and dendritic immunoreactivity were noted in the isolated septal grafts. Abnormalities identified with the RT97 antibody included hypertrophied axons, short fragments of kinked axons and neurofilaments in the neuronal perikarya. The formation of circular "abnormal fiber aggregates" composed of densely packed abnormal and normal axonal processes were also distinctive in only the long term single septal transplants. In addition, a reduction in the density of dendrites and the presence of truncated arbors stained with the MAP 2 antibody suggested that regression of the dendrites had occurred. These spatial modifications in axonal and dendritic staining were not present in the septal portion of the combined preparations. In astrocytes, an increase in the antigenicity to glial fibrillary acidic protein paralleled the age of the transplant and was most extensive in the septal grafts. The results illustrate that intraocular co-grafts of hippocampus protect septal neurons and glial cells from abnormal changes in immunoreactivity to antibodies directed against cytoskeletal proteins and exemplify the long term supportive effects of the hippocampus on the morphology of septal neurons, including neurons that express the receptor for nerve growth factor.

Animals↗
PubMed1991

The nerve growth factor receptor gene is expressed in both neuronal and non-neuronal tissues in the human fetus.

In situ hybridization was used to study expression of beta-nerve growth factor receptor (NGF-R) mRNA in the early human fetus. In 8- to 12-week old fetuses, high labelling was found over motoneurons along the entire length of the lateral motor column. High levels of NGF-R mRNA were also seen over most developing nerve cell bodies in both the dorsomedial and ventrolateral part of the dorsal root ganglia. Lower, but clearly specific labelling was detected over a subpopulation of cells in Auerbach's plexus in the intestines. Evidence for a non-neuronal expression of NGF-R mRNA came from labelling over a subpopulation of cells in glomeruli of the kidney in a 12-week old human embryo. Myoblasts in skeletal muscle anlagen were labelled as well as cells along peripheral nerve. The widespread expression of NGF-R mRNA in the human fetus suggests that the NGF-R is important for development of a variety of different tissues of both neuronal and non-neuronal origin.

Fetus↗
PubMed1991

Effects of long-term treatment with methyl mercury on the developing rat brain.

Sprague-Dawley rats were exposed to low doses of methyl mercury (3.9 mg mercury/kg diet), via their dams during gestation and lactation and directly via their diet until sacrifice at 50 days postpartum, in order to study possible detrimental effects on CNS development. The methyl mercury exposure of the rats resulted in a brain concentration of 1.45 +/- 0.06 mg mercury/kg wet weight (mean +/- SEM). No general toxic effects were observed; body weight was not affected, brain weight was only slightly increased. No discernible general morphological alterations were seen in the brain as evaluated using cresyl violet histology. Furthermore, no effects on GFA-positive astrocytes in brain sections were observed and computerized morphometry of smeared astrocytes from frontal cortex, hippocampus, and cerebellum did not reveal any effects of the methyl mercury treatment. The noradrenaline (NA) and dopamine (DA) systems were also studied. In cerebellum the NA levels were increased (117% of controls, P = 0.008), whereas in other regions analyzed NA and DA levels were unchanged. Thus, long-term low-dosage exposure of methyl mercury in rats during development does not appear to exert any major effects on the morphological maturation of neurons and astrocytes. However, the results indicate that effects may occur in specific transmitter-identified systems, such as the NA input to cerebellum. The results therefore underline the need for detailed biochemical analyses to study the effects of long-term low-dosage exposure to neurotoxic compounds.

Animals↗
PubMed1991

Ankylosis of primary molars--a future periodontal threat to the first permanent molars?

Most infra-occluded and ankylosed primary molars with a permanent successor will exfoliate normally. Continuous supervision of occlusal development and radiographic control of normal root resorption have been recommended. The decreased height of the alveolar bone level at the site of the infra-occluded primary molar has been reported to normalize after the eruption of the permanent successor. However, opinions that infra-occlusion of primary molars entails a risk of future periodontal damage to the first permanent molars have been presented. The aim of this study was to perform a long-term follow-up of the alveolar bone level mesial to the first permanent molars after spontaneous exfoliation or necessary extraction of the infra-occluded second primary molars. The material consisted of 143 permanent molars adjacent to 119 infra-occluded primary molars and 24 normal contralateral primary molars in 68 individuals. The subjects were re-examined about 8 years after the exfoliation or extraction of the infra-occluded second primary molars. The subjects were examined both clinically and radiographically. Alveolar bone level mesial to the first permanent molars was measured in bite-wing radiographs. All but two permanent first molars showed a normal alveolar bone level mesially. In two first permanent molars where the primary molar was extracted, mesial approximal bone loss amounted to 4 and 3 mm, respectively, but no pocket formation was found. Infra-occlusion and ankylosis of primary molars does not constitute a general risk of future alveolar bone loss mesial to the first permanent molars. The general treatment recommendation to await normal exfoliation and eruption of successors remains valid.

Adolescent↗
PubMed1991

Factors affecting the ten-year outcome of human renal allografts. The effect of viral infections.

Long-term (10-year) results of kidney transplantation have been analyzed from this center with respect to several variables. In this report the influence of viral disease was added in studying the effect of cadaver versus living-related donor, recipient race, and compliance. Over all, 10-year actuarial patient and graft survival were 68% and 48%, respectively. Cytomegalovirus, hepatitis B and C, and HIV-1 were studied for their effects, and survival curves analyzed statistically. Although cadaver and living-related donor, recipient race, and compliance were 3 main variables influencing graft survival, these 4 viruses were not selective in their effects on any of them. Hepatitis B surface antigen positivity and hepatitis C antibody positivity did not influence overall mortality or graft survival. Only cytomegalovirus seronegative status was important (as opposed to seropositive status, which was not). Of seronegative patients only those receiving a kidney from a seropositive donor were adversely affected. The presence of HIV-1 antibody had an adverse effect on graft survival, but the question remains as to whether overall mortality in HIV seropositive patients is any worse than those receiving dialysis therapy.

Cadaver↗
PubMed1991

Craniomandibular function in juvenile chronic arthritis. A clinical and radiographic study.

Craniomandibular function was studied in 70 subjects with juvenile chronic arthritis (JCA). The subjects represented the total group of children and adolescents with the diagnosis JCA in a Swedish county. At examination, the median age of the subjects was 11.9 years and the median duration of the disease was 2.6 years. The most important finding of the study was the high prevalence (41%) of radiographic signs of temporomandibular joint (TMJ) pathology. Few subjects showed the typical craniofacial abnormalities associated with JCA, like mandibular micrognathia, facial asymmetries and open bite. Subjective symptoms of dysfunction were almost absent in subjects younger than seven years but were reported by 56% of the older subjects. TMJ sounds and pain on jaw movements were the most frequent symptoms reported. At the clinical examination, TMJ crepitations and restricted horizontal jaw movements were noted in 26% and 32% respectively. The high prevalence of TMJ involvement found in this study underlines the importance that dentists become part of the medical team responsible for the treatment of children and adolescents with JCA.

Adolescent↗
PubMed1990

[Nerve growth factor as a therapeutic agent: transplantation of brain tissue as a possible treatment of neurodegenerative disorders].

An account of experiments focused on the treatment of neurodegenerative disease by means of cell grafts, in which genetically modified cells that release abundant nerve growth factor are described, and their transplantation to the rat brain reported. The cells can survive in the rat brain and exert potent effects on cholinergic neurons both in the host cortex, basal forebrain and striatum, and in tissue grafts.

Animals↗
PubMed1990

Expression of beta-nerve growth factor receptor mRNA in Sertoli cells downregulated by testosterone.

Nerve growth factor (NGF) is synthesized in male germ cells. The NGF receptor (NGFR) mRNA was found in the Sertoli cells of rat testis. Hypophysectomy increased both NGFR mRNA in testis and the number of NGFR hybridizing cells in seminiferous tubules. This was suppressed by treatment with chorionic gonadotropin or testosterone, but not with follicle-stimulating hormone. The NGFR mRNA also increased after destruction of Leydig cells or blocking of the androgen receptor. This suggests that NGF produced by male germ cells regulates testicular function in an androgen-modulated fashion by mediating an interaction germ and Sertoli cells.

Animals↗
PubMed1990

Rescue of basal forebrain cholinergic neurons after implantation of genetically modified cells producing recombinant NGF.

Mouse 3T3 fibroblasts were genetically modified by transfection with a mammalian expression vector containing the rat beta-nerve growth factor (NGF) gene. The transfected cell line, designated 3E, contains several hundred copies of the rat NGF gene and secretes high levels of biologically active NGF. Pieces of collagen gel containing the NGF-secreting 3E cells were grafted to the brains of unilaterally fimbria-fornix-lesioned rats. Grafts of the genetically modified NGF-producing cells rescued axotomized basal forebrain cholinergic neurons and significantly reduced cholinergic cell death in the medial septum as compared with rats treated with grafts of the parental 3T3 cells. Grafted fibroblast cells were detected, and rescue effects were noted up to 6 weeks after grafting. Local effects of NGF secreted by grafted cells were also seen at the gel-brain border in the form of sprouting acetylcholinesterase immunoreactive host cortical fibers. We suggest that implantation of genetically modified cells producing NGF 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.

Acetylcholinesterase↗
PubMed1990

Regulation of beta-nerve growth factor expression by inflammatory mediators in hippocampal cultures.

Substances which regulate expression of nerve growth factor (NGF) were examined in embryonic rat hippocampal cultures containing both neurons and glial cells. Both cell types expressed NGF mRNA when cultivated in vitro. Lipopolysaccharide, an activator of macrophages, elicited a significant increase in NGF mRNA. Interleukin-1 beta evoked a similar increase in NGF mRNA which was accompanied by a rise in NGF protein. The Il-1-induced increase was partially blocked by indomethacin, suggesting that prostaglandins might mediate this effect. Treatment of the cultures directly with prostaglandin E2 resulted in elevated levels of both NGF mRNA and protein. Thus, agents which promote inflammatory activity appear to increase NGF expression. Moreover, a suppressor of inflammation, dexamethasone, decreased NGF expression. Our observations indicate that a variety of immunomodulators regulate NGF expression in the hippocampus.

Animals↗