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Biomedical subjects

L Olson

Publications and source records attributed to L Olson.

At least 145 records · Page 8Linked to original sources
PubMed1996

Dieting in sixth grade predicts alcohol use in ninth grade.

Recent studies of community-based populations have shown that the comorbidity seen in clinical studies of individuals with eating disorders and substance abuse extends in a graded manner to subclinical levels of each dysfunction as well as to adolescent populations. We hypothesized that frequency of dieting in the sixth grade would predict later alcohol use in middle school students. Data from 1,905 participants in a middle school health promotion project were analyzed. We found a positive, graded relationship between the frequency of dieting in the sixth grade and the frequency of alcohol intake in the ninth grade. We also found that frequency of dieting in sixth grade was a more powerful predictor of future drinking than such parameters as others' approval of alcohol use, perceptions of peer use of alcohol, and personal feelings of shyness and self-satisfaction. Implications of these findings are discussed.

Adolescent↗
PubMed1996

Retinoid X receptor heterodimerization and developmental expression distinguish the orphan nuclear receptors NGFI-B, Nurr1, and Nor1.

NGFI-B, Nurr1, and Nor1 are three closely related orphan members of the steroid/thyroid hormone receptor superfamily. These receptors can bind to DNA as monomers and exhibit constitutive transcriptional activity. Moreover, two of the receptors, NGFI-B and Nurr1, have previously been shown to form heterodimers with the retinoid X receptor (RXR). Such heterodimers as well as complexes formed between RXR and the all-trans retinoic acid receptor bind to DNA response elements composed of direct repeats spaced by five nucleotides (DR5). However, whereas retinoic acid receptor can inhibit ligand-dependent RXR activation, NGFI-B and Nurr1 allow efficient RXR activation through DR5 elements and thus define a distinct pathway for vitamin A signaling. In this study we demonstrate that the most recently identified member of the subfamily, Nor1, shows similar monomer DNA-binding and constitutive transactivation properties as NGFI-B and Nurr1. In contrast, however, Nor1 is unable to promote RXR signaling due to its inability to form heterodimers with RXR. To begin to understand the physiological implications of these functional differences we used in situ hybridization to compare the distribution of Nor1, NGFI-B, and Nurr1 messenger RNAs during different developmental stages. The receptors are expressed in both distinct and overlapping patterns, predominantly in the central nervous system. Notably, Nurr1 is expressed in the prenatal ventral midbrain in a region that gives rise to dopaminergic neurons. Nor1 is also expressed during embryonic development, and all three receptors show a complex distribution in the postnatal brain. Furthermore, Nor1 colocalizes with NGFI-B in the adrenal glands and thymus, two tissues in which NGFI-B has been suggested to be functionally important. These data may indicate redundancy between members of the NGFI-B/Nurr1/Nor1 subfamily and could explain why no phenotypic disturbances have yet been found in mice in which the NGFI-B gene has been inactivated.

Animals↗
PubMed1996

Twelve years' experience with non-heart-beating cadaveric donors.

From 1983 to August 1995, the University of Miami Organ Procurement Organization evaluated 41 candidates for non-heart-beating cadaveric donation and determined that 34 patients met the criteria. All patients had irreversible brain injury incompatible with survival. All families gave permission for withdrawal of life support and for tissue and organ donation after cardiac arrest. Thirteen donors died in the operating room, and 9 died in the ICU or emergency department. Four of the 9 patients who died in the ICU had undergone femoral cannulation. The remaining 12 donors were brain-dead but had an unpredicted cardiac arrest before laparotomy. All kidneys were preserved by using machine pulsatile perfusion, and 21 kidneys were transported to other centers. Of the 35 transplanted kidneys, 26 (74%) had immediate function, 6 (17%) had delayed graft function, and 3 (9%) were not used for other reasons. Five of the six transplanted livers had immediate function.

Adolescent↗
PubMed1996

[Neurotrophic factors in the CNS. Increasing numbers of proteins with clinical potential].

The great Anders Jahre Prize, for 1995, for medical research, is to be shared by Professor Lars Olson, Stockholm, and Professor Anders Björklund, Lund. Lars Olson is one of the pioneers responsible for mapping the neural pathways of the brain. He has also systematically studied the mechanisms underlaying nerve cell growth and clucidated the growth factors involved. Our knowledge of the proteins necessary to neuron survival, nerve fibre growth, and the maintenance of synapses is increasing very rapidly. In a long-term perspective, this will open up new approaches to the treatment of a number of neuropathological diseases, eg, Parkinson's disease, and to the repair of nerve tissue, eg, after stroke.

Basal Ganglia Diseases↗
PubMed1996

A comparison of the effects of glial cell line-derived neurotrophic factor on spinal cord and cortex cerebri grafts.

Glial cell line-derived neurotrophic factor (GDNF) has trophic effects on developing dopamine neurons, enhances survival of embryonic motoneurons in vitro and prevents axotomy-induced motoneuron atrophy in vivo. Here we investigate effects of GDNF on grafts of cortex cerebri tissue from E18, P1 and P8 donors and on spinal cord tissue for P8 and adult animals transplanted to the anterior chamber of the eye of host rats. Grafts were treated with GDNF or cytochrome C on days 0, 5, 10, 15, 20 and 25 (total amounts 0.5 microgram GDNF/eye/injection). Spinal cord grafts from P8 donors treated with GDNF grew to sizes larger than controls, had higher numbers of neuron-like cells and showed increased areas of neurofilament immunoreactivity and decreased glial fibrillary acidic protein immunoreactivity. In contrast to the P8 spinal cord grafts, there were no such effects observed in adult spinal cord grafts or in E18, P1 or P8 cerebral cortex grafts. To determine if an endogenous source of GDNF might exert similar effects on spinal cord grafts, we transplanted spinal cord tissue from P1 together with pieces of developing kidney, known to express high levels of GDNF mRNA. Spinal cord cografted with kidney tissue grew to a slightly larger extent then controls. We conclude that GDNF exerts a powerful trophic effect on P8 spinal cord grafts, although GDNF appears unable to support survival of grafted adult spinal cord tissue. Grafts of cortex cerebri from several different stages of development were not affected.

Animals↗
PubMed1996

Case report: severe microcytosis associated with the anemia of chronic disease.

When microcytosis is present in patients with anemia of chronic disease, the mean corpuscular volume (MCV) rarely if ever falls below 70 fL. The lowest MCV previously reported is 67 fL. We describe a patient with anemia of chronic disease with severe microcytosis and an MCV of 61 fL. After correction of the chronic disorder, complete correction of the hematologic values occurred. In patients with a low total iron binding capacity, iron therapy should not be instituted without clearly establishing the presence of iron deficiency irrespective of the degree of microcytosis.

Anemia↗
PubMed1995

Brain-derived neurotrophic factor mRNA is expressed in the developing taste bud-bearing tongue papillae of rat.

Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are expressed in many areas of the nervous system and its target tissues. Using in situ hybridization we have investigated the possible presence of NGF mRNA and BDNF mRNA in the developing fungiform and circumvallate papillae of the rat tongue. BDNF mRNA is present in the epithelium of the developing fungiform papillae in E15, E16, and E17 rat embryos with peak concentration at E16. It starts to diminish after E17 and is almost absent at E21. There is a specific temporospatial change in the expression of BDNF mRNA in developing circumvallate papillae. It is expressed in the epithelium of the superior and posterior surfaces of the papillae at E15, E16, and E17. Already at E17 the BDNF mRNA labeling has started to decrease in the superior epithelium. At E19 and E21, BDNF mRNA is exclusively present in the epithelium of the inner and outer walls of the trench, surrounding the papilla at the posterior and lateral surfaces where the taste buds are located later in life. BDNF mRNA was also detected in the developing palatal taste buds. NGF mRNA was below detection level in the developing papillae. The highly localized expression of BDNF mRNA in areas where taste buds are to be formed suggests that BDNF may be one crucial factor in the formation of the epithelial innervation prior to taste bud formation. It might also participate in the formation and/or maintenance of the papillary and/or taste bud innervation apparatus. We conclude that the neurotrophin BDNF is expressed in early development of taste bud-bearing papillae in the rat tongue in a temporally and spatially controlled manner, presumably to act as a target-derived chemoattractant for the early nerve fibers.

Animals↗
PubMed1995

Retrograde axonal transport of glial cell line-derived neurotrophic factor in the adult nigrostriatal system suggests a trophic role in the adult.

The recently cloned, distant member of the transforming growth factor beta (TGF-beta) family, glial cell line-derived neurotrophic factor (GDNF), has potent trophic actions on fetal mesencephalic dopamine neurons. GDNF also has protective and restorative activity on adult mesencephalic dopaminergic neurons and potently protects motoneurons from axotomy-induced cell death. However, evidence for a role for endogenous GDNF as a target-derived trophic factor in adult midbrain dopaminergic circuits requires documentation of specific transport from the sites of synthesis in the target areas to the nerve cell bodies themselves. Here, we demonstrate that GDNF is retrogradely transported by mesencephalic dopamine neurons of the nigrostriatal pathway. The pattern of retrograde transport following intrastriatal injections indicates that there may be subpopulations of neurons that are GDNF responsive. Retrograde axonal transport of biologically active 125I-labeled GDNF was inhibited by an excess of unlabeled GDNF but not by an excess of cytochrome c. Specificity was further documented by demonstrating that another TGF-beta family member, TGF-beta 1, did not appear to affect retrograde transport. Retrograde transport was also demonstrated by immunohistochemistry by using intrastriatal injections of unlabeled GDNF. GDNF immunoreactivity was found specifically in dopamine nerve cell bodies of the substantia nigra pars compacta distributed in granules in the soma and proximal dendrites. Our data implicate a specific receptor-mediated uptake mechanism operating in the adult. Taken together, the present findings suggest that GDNF acts endogenously as a target-derived physiological survival/maintenance factor for dopaminergic neurons.

Animals↗
PubMed1995

Monitoring release of neurotrophic activity in the brains of awake rats.

Intracerebral microdialysis of awake rats was used to monitor the possible release of neurotrophic factors from brain cells in response to injury and excitation. Perfusates were tested with ganglia bioassays and enzyme immunoassay. Trophic activity was released after implantation of the microdialysis probe into the hippocampus but not into the striatum, as assessed by increased nerve fiber outgrowth from Remak's ganglion. Kainic acid treatment significantly increased the release of trophic activity from hippocampal sites. These findings suggest that the brain responds to mechanical injury as well as to certain excitatory stimuli by regional extracellular release of neurotrophic activity that is not identical to the actions of known neurotrophic factors.

Animals↗
PubMed1995

Allogeneic grafts of fetal dopamine neurons: immunological reactions following active and adoptive immunizations.

To define the importance of adoptive sensitization and duration of graft residence on transplant alloimmunization, behavioral and histochemical parameters were examined in unilaterally 6-OHDA-lesioned F344 rat hosts which received fetal ventral mesencephalic (VM) grafts from Wistar-Furth (WF) donors. In all animals which showed increased rotations after alloimmunization, increased numbers of T cell receptor (TcR) positive, CD8+ lymphocytes were detected in the grafts. In addition, an increased density of class I MHC antigens was seen in the graft and in the adjacent host brain. Lesser numbers of CD4+, CD11b+, and MHCII+ positive elements were also seen. Perivascular cuffing was often found in actively immunized animals. An increase in TcR+ and MHC class I+ elements was also seen in animals only adoptively immunized. The tyrosine hydroxylase positive graft area was also markedly reduced in actively immunized animals and the extent of reduction correlated with the number of cells used for immunization. These studies indicate that established allografts can evade rejection as long as host lymphocytes are not activated against graft alloantigens. In addition, increasing graft residence time in the host and adoptive immunization render the graft more susceptible to subsequent rejection.

Animals↗
PubMed1995

Neuronal and nonneuronal expression of neurotrophins and their receptors in sensory and sympathetic ganglia suggest new intercellular trophic interactions.

Nerve growth factor promotes the survival of populations of sensory and sympathetic neurons. Although ganglia have been used for classical assays of neurotrophin action, knowledge is incomplete regarding the spatial arrangements through which neurotrophins are delivered to responsive cells within the ganglia and their attached nerve trunks. Whereas populations of ganglionic neurons may be capable of responding to a particular neurotrophin in vitro, the spectrum of receptor components and neurotrophins expressed by the various neuronal and nonneuronal cells comprising the ganglia in adult rats remains to be elucidated in vivo. Brain-derived neurotrophic factor (BDNF) mRNA was expressed by a population of small to medium sized neurons in all sensory ganglia except in the mesencephalic nucleus of the trigeminal nerve. Interestingly, BDNF immunoreactivity was detected in a more widespread population of neurons of these ganglia, as well as in scattered satellite cells of both sensory and sympathetic ganglia. These nonneuronal cells also expressed mRNA encoding a truncated form of the BDNF receptor, trkBtrunc, and full-length transcripts of trkB appeared to be confined to neuronal populations. Several other components of neurotrophin receptors (low-affinity neurotrophin receptor, trk, and trkC) were prominently expressed by different populations of neuronal cells in sympathetic and sensory ganglia, but they were not detected in nonneuronal cells. Neither nerve growth factor nor neurotrophin-3 mRNAs were detected in these ganglia. Unexpectedly, BDNF and trkBtrunc expression was detected in oligodendrocytes myelinating the central processes of sensory neurons. Schwann cells did not express detectable quantities of either entity, thereby establishing a dramatic boundary delineated by neurotrophin/neurotrophin receptor expression that coincided with the interface between the oligodendroglia of the central nervous system (CNS) and Schwann cells of the peripheral nervous system (PNS). Localization of BDNF expression to an additional population of nonneuronal cells--satellite cells within sensory and sympathetic ganglia--suggest a more extensive role for neurotrophic factors than originally encompassed by the target-derived neurotrophic-factor-concept paradigm. These data support the hypothesis of a possible autocrine or paracrine trophic interaction between populations of neuronal and nonneuronal cells in the peripheral nervous system. BDNF expression in oligodendrocytes but not in Schwann cells at the CNS/PNS junction may provide an additional means of maintaining cell-appropriate connections in the nervous system.

Animals↗
PubMed1995

Glial cell line-derived neurotrophic factor stimulates fiber formation and survival in cultured neurons from peripheral autonomic ganglia.

Human recombinant glial cell line-derived neurotrophic factor (GDNF) was tested for its ability to stimulate fiber formation and neuron survival in primary cultures of peripheral ganglia dissected from the chicken embryo. GDNF, first characterized by its actions on central nervous system (CNS) neurons, had a marked stimulatory effect on fiber outgrowth in sympathetic and ciliary ganglia. Weaker responses were evoked in sensory spinal and nodose ganglia and in the ganglion of Remak. In addition, survival of neurons from the sympathetic and ciliary ganglia was stimulated by GDNF at 50 ng/ml. The effects were not mimicked by the distant but related protein transforming growth factor beta 1 (TGF beta 1). The profile of neurons stimulated by GDNF is also distinct from the patterns of stimulation shown by nerve growth factor (NGF), stimulating strongly sympathetic but not ciliary ganglia, and ciliary neurotrophic factor (CNTF), stimulating mainly the ciliary ganglion. Moreover, using in situ hybridization histochemistry, GDNF was demonstrated to be present in the pineal gland in the newborn rat, a target organ for sympathetic innervation. The present results suggest that GDNF is likely to act upon receptors present in several autonomic and sensory neuronal populations. GDNF may serve to support fiber outgrowth and cell survival in peripheral ganglia, adding yet one more trophic factor to the list of specific proteins controlling development and maintenance of the peripheral nervous system.

Animals↗
PubMed1995

Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo.

Glial-cell-line-derived neurotrophic factor (GDNF), a recently cloned new member of the transforming growth factor-beta superfamily, promotes survival of cultured fetal mesencephalic dopamine neurons and is expressed in the developing striatum. There have, however, been no reports about effects of GDNF in situ. We have used the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces parkinsonian symptoms in man, to determine whether GDNF might exert protective or regenerative effects in vivo in the adult nigrostriatal dopamine system in C57/B1 mice. GDNF injected over the substantia nigra or in striatum before MPTP potently protects the dopamine system, as shown by numbers of mesencephalic dopamine nerve cell bodies, dopamine nerve terminal densities and dopamine levels. When GDNF is given after MPTP, dopamine levels and fibre densities are significantly restored. In both cases, motor behaviour is increased above normal levels. We conclude that intracerebral GDNF administration exerts both protective and reparative effects on the nigrostriatal dopamine system, which may have implications for the development of new treatment strategies for Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

IGF-1 influences olfactory bulb maturation. Evidence from anti-IGF-1 antibody treatment of developing grafts in oculo.

Recent studies have indicated that both insulin-like growth factor-1 (IGF-1) and IGF-1 receptor mRNA are abundant in developing and adult olfactory bulbs, and that IGF-1 receptor mRNA is abundant in the prenatal cerebral cortex. To examine the potential role of IGF-1 in development of a central nervous system region rich in IGF-1 and its receptor (the olfactory bulb), as compared to one in which IGF-1 is less abundant (the cerebral cortex), tissue pieces of these two central nervous system areas from E15-E17 rat fetuses were transplanted into the anterior chamber of the eye of adult host rats. The transplants were treated with either a total of 300 ng truncated IGF-1, two different IGF-1 polyclonal antisera, two different non-immune sera, a total of 15 micrograms IGF binding protein-1, or vehicle alone. Treatments were administered by preincubation just prior to grafting and by 5 microliters injections into the anterior chamber on days 5, 10 and 15 postgrafting. Olfactory bulb grafts treated with either of the two IGF-1 antisera grew significantly larger than grafts receiving any other treatment. No enhancement of graft size was seen in E16-E17 parietal cortex grafts after IGF-1 antibody treatment. Immunohistochemical studies revealed no difference between the treatments with regard to glial fibrillary acidic protein-, tyrosine hydroxylase- or neurofilament-immunoreactivity within the olfactory bulb grafts. Since, in the olfactory bulb the presumed reduction of endogenous IGF-1 achieved by antibody treatment caused enhanced growth, we suggest that the presence of appropriate endogenous levels of IGF-1 in this area induces maturation. This mechanism is not operative in all brain areas since it was not seen in cortex cerebri grafts. Thus, endogenous IGF-1 appears to influence brain development in a regionally specific manner.

Animals↗
PubMed1995

A new surgical technique that allows proximodistal regeneration of 5-HT fibers after complete transection of the rat spinal cord.

Shortening of the spinal column has been regarded as one possible method to obtain cord-to-cord apposition after total transection of the spinal column. However, to further improve regenerative possibilities, the problems of inconstant bony fusion and cyst formations within the junctions must be resolved. Modifying the method of de Medinaceli on the rat thoracic spine, we attempted several fixation devices to achieve better interspinal fixation after spondylectomy and transection, including transpedicular miniscrews, wiring of the transverse processes, and wiring of the posterior spinal processes. A dynamic model, based on retracting and compressing the cut ends of the spinal cord by means of adjustable fixation devices to allow swelling and shrinking of the stumps was also attempted to better compensate pathophysiologic changes of the transected cord. The best regeneration, as indicated by regrowth of 5-HT fibers below the level of transection, was obtained following application of fibrin glue and compressive wiring of posterior spinal processes. In this group, the distance between proximal and distal GFAP-rich spinal cord tissue (gap consisting of GFAP-poor components such as cysts, phagocytic cells, and scar tissue) of the two spinal cord stumps was also the shortest. With better approximation, the numbers of regenerated 5-HT fibers improved remarkably, suggesting that this descending fiber system is able to bridge the transection under these conditions.

Animals↗
PubMed1995

Decrease of neurotrophin-3 mRNA in adult rat hippocampus after pilocarpine seizures.

Neurotrophins such as NT-3 are subject to complex regulation during epileptic seizures. Pilocarpine at a dose of 250 mg/kg induced either limbic seizures (LS) or limbic motor status epilepticus (LMSE) in adult rats. In situ hybridization signals for NT-3 mRNA declined moderately after LS and were nearly lost in LMSE at 3-4 h. Loss of NT-3 mRNA expression does not correlate with cell death and may reflect a functional down-regulation in certain hippocampal neurons.

Animals↗
PubMed1995

The effect of glial cell line-derived neurotrophic factor in fibrin glue on developing dopamine neurons.

Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-beta superfamily, promotes the survival, morphological differentiation, and high-affinity dopamine (DA) uptake of cultured nigral DA neurons. In order to test potential methodology for peptide delivery in vivo, GDNF-containing fibrin glue balls (8 micrograms/ball) were incorporated with pieces of fetal ventral mesencephalon (E15) and transplanted into the anterior chambers of sympathetically denervated adult rats. Five weeks after grafting, the numbers of TH-positive neurons and the nerve fiber density were significantly higher in the ventral mesencephalic grafts treated with GDNF-containing glue balls than in those treated with vehicle. In addition, the laminin and GFAP immunoreactivities were similar between the two groups. These data support the concept that GDNF is a potent trophic factor for DA neurons in vivo and suggest that fibrin glue may provide a unique and safe means to permit prolonged delivery of trophic molecules to CNS tissues.

Animals↗