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Biomedical subjects

H Persson

Publications and source records attributed to H Persson.

At least 127 records · Page 7Linked to original sources
PubMed1993

The impact of acute rejection episodes on long-term graft function and outcome in 1347 primary renal transplants treated by 3 cyclosporine regimens.

To characterize factors of importance for the occurrence of acute rejection as well as study the impact of these episodes on long-term renal survival and function, a total of 819 acute rejection episodes were studied in 951 primary cadaveric donor kidney recipients (CD) and in 396 primary living donor kidney recipients (LD). The patients were treated by three immunosuppressive schedules, namely, CsA given in a high dose, a medium dose, or a low dose. Additionally, all patients received PRED and patients in the low-dose group received AZA. The incidence of acute rejection was higher and occurred earlier after transplantation in the CsA medium dose and low dose groups than in the CsA high dose group (P < 0.05 and P < 0.01, respectively). Although the incidence of first acute rejection was similar in CD and LD patients, 59.1% vs. 60.6%, it was successfully reversed by antirejection treatment in a higher percentage in LD patients. The estimated graft half-life was shorter in patients who had acute rejection episodes than those who did not, 6.6 years vs. 12.5 years in CD patients (P < 0.0001). Renal function at 1-5 years after transplantation was stable, but significantly poorer in CD patients who had experienced acute rejection than in patients who had not, with the mean creatinine clearance rates in the ranges 45-47 vs. 54-60 ml/min in the other groups (P < 0.0001). In a stepwise Cox regression analysis in CD recipients, risk factors for acute rejection were CsA (low dose) treatment schedule, immunization as displayed by presence of panel-reactive antibodies and positive B cell cross-match, young recipient age, disease of diabetes mellitus, and HLA-DR mismatching. In LD recipients, the corresponding risk factors were treatment schedule, young recipient, HLA mismatching, and transplantation from parent to child. Thus, the study has demonstrated some factors of importance for acute rejection episodes in CsA-treated patients as well as showing the detrimental effect of these episodes on long-term graft survival and renal function. These results suggest that a primary aim of future treatment strategies should be to reduce the incidence of these episodes.

Adolescent↗
PubMed1993

Neurotrophin-4 is a target-derived neurotrophic factor for neurons of the trigeminal ganglion.

The cellular localization of mRNA for neurotrophin-4 (NT-4), a novel neurotrophic factor, in the developing whisker follicles and skin of the embryonic rat is demonstrated by in situ hybridization. Levels of NT-4 mRNA in the whisker pad decrease between embryonic day 13 (E13) and E20, correlating in time with the onset of naturally occurring neuronal death in the innervating trigeminal ganglion. In addition to NT-4, brain-derived neuotrophic factor (BDNF) mRNA is also shown to be expressed in the rat embryonic whisker follicles although in a different cellular localization, which combined with previous data on the expression of NGF and NT-3 mRNAs, shows that all four neurotrophins are expressed during development of this structure. NT-4 protein is shown to elicit neurite outgrowth from explanted embryonic trigeminal ganglia and to promote neuronal survival of dissociated trigeminal ganglion neurons when cultured during the phase of cell death. NT-4 and NT-3 mainly support different neuronal subpopulations, whereas some NT-4-responsive cells appear to respond also to NGF and BDNF. Analysis of mRNAs for members of the Trk family of neurotrophin receptors in neurons rescued by different neurotrophins demonstrates the presence of distinct neuronal subpopulations that respond to specific combinations of these factors. Based on these results we propose that NT-4, together with the other three neurotrophins, orchestrate the innervation of the different structures of the developing whisker pad by the trigeminal ganglion, acting as target-derived neurotrophic factors for different subpopulations of trigeminal ganglion neurons.

Animals↗
PubMed1993

Role and expression of neurotrophins and the trk family of tyrosine kinase receptors in neural growth and rescue after injury.

Molecular cloning of genes for the neurotrophin family and the identification of their high-affinity receptors have recently contributed to our understanding of neurotrophic interactions in the vertebrate nervous system. From their primary sites of synthesis, novel neuronal populations that may be sensitive to the neurotrophins have been identified. Protective roles for these factors following epileptic, ischemic, and hypoglycemic insults have been inferred. Documented neurotrophic actions on basal forebrain cholinergic neurons and mesencephalic dopaminergic neurons imply future clinical applications for the treatment of dementia of both Alzheimer's and Parkinson's disease. Studies on structure-function relationships of the neurotrophins hold promises for the development of specific receptor agonists and antagonists with possible basic science and clinical applications.

Animals↗
PubMed1992

Increased levels of trkB mRNA and trkB protein-like immunoreactivity in the injured rat and cat spinal cord.

Expression of neurotrophins and neurotrophin receptors was examined with in situ hybridization and immunohistochemical techniques 10 days to 6 weeks after ventral or dorsal funiculus spinal cord lesions in adult rats and cats, lesions that have previously been shown to allow axon regrowth. Strongly elevated levels of trkB mRNA were seen in the scar tissue formed in the white matter after both types of lesions. Only small increases were detected for nerve growth factor, brain-derived neurotrophic factor, neurotrophin 3, neurotrophin 4, trk, and trkC mRNA in response to the injuries. trkB protein-like immunoreactivity was increased in the regions that showed elevated levels of trkB mRNA. EM localized this immunoreactivity to neurons, astrocytes, and leptomeningeal cells. Neurofilament immunolabeling and axonal tracing demonstrated that nerve fibers in the scar tissue were concentrated to areas that showed strong trkB protein-like immunoreactivity. The findings implicate a role for neurotrophin receptors in axonal sprouting and glial reactions in the injured spinal cord.

Animals↗
PubMed1992

Regulatory elements and transcriptional regulation by testosterone and retinoic acid of the rat nerve growth factor receptor promoter.

The low-affinity nerve growth factor receptor (LNGFR) is a membrane-associated glycoprotein which is thought to participate in some of the biological activities of nerve growth factor (NGF). Expression of the LNGFR gene is known to be regulated both during development and in response to various agents in cell culture. However, molecular mechanisms responsible for the regulation have not been described. We report here an analysis of a 4.8-kb sequence from the 5'-flanking region of the rat LNGFR gene. Several regulatory elements were identified in this region by transfection of plasmid constructs containing sequences from LNGFR fused to a bacterial cat reporter gene. The proximal part of the promoter region (0.4-kb) was shown to be sufficient to support cat expression in all cell types used. A silencer element located between -1.5 kb and -1.8 kb from the start of translation, as well as an enhancer element in more upstream regions of the promoter, were identified in the phaeochromocytoma cell line, PC12, and in the Sertoli cell line, TM4, that express the LNGFR gene. Treatment of TM4 cells with retinoic acid (RA) increases the level of LNGFR mRNA twofold, while testosterone treatment results in a tenfold decrease. Regions of the promoter responsive to testosterone and RA in TM4 cells were found at -610 to -860 bp and -1840 to -4800 bp upstream from the translation start codon, respectively. A RA-responsive element active in PC12 cells is located between bp -610 to -860 from the start codon.

Animals↗
PubMed1992

Neuropeptide Y (NPY) synthesis in lymphoblasts and increased plasma NPY in pediatric B-cell precursor leukemia.

Neuropeptide Y (NPY), a regulatory peptide in both the central and peripheral nervous systems, has recently been found in neuroendocrine tumors as well as in the bone marrow of rat and certain autoimmune mice, but not in human bone marrow. To investigate a possible role for NPY in the human hematopoietic system, we have prospectively studied NPY-like immunoreactivity in plasma (P-NPY-LI) and NPY mRNA in bone marrow from children with acute leukemia. Northern blot showed high levels of NPY mRNA in bone marrow and peripheral lymphoblasts from children with B-cell precursor leukemia. In situ hybridization showed NPY mRNA in malignant B-cell precursor lymphoblasts. No NPY mRNA was detected in the bone marrow of children with T-cell leukemia. P-NPY-LI was higher (P less than .001) in 51 children with leukemia (200:50 to 385 pmol/L, median:interquartile range) compared to 51 age-matched healthy controls (37:20 to 52 pmol/L). P-NPY-LI was higher (P less than .001) in those with favorable clinical risk classification. Elevated P-NPY-LI, compared with the upper age-adjusted reference limit, was only found in children with B-cell precursor leukemia (31 of 40), whereas all children with B-cell, T-cell, or myeloid leukemia (n = 11) had normal P-NPY-LI (P less than .001). During the 2- to 46-month follow-up, children with elevated P-NPY-LI had better (P less than .001) outcome compared to those with normal P-NPY-LI (79.4% v 34.6% probability for event-free survival).

Antigens, Differentiation↗
PubMed1992

Widespread increase of nerve growth factor protein in the rat forebrain after kindling-induced seizures.

Nerve growth factor (NGF) protein levels were determined in various forebrain regions using a two-site immunoassay following kindling-induced seizures. In the dentate gyrus the NGF content was significantly elevated 7 days after the last seizure (to 152% of control). In the piriform and parietal cortices, maximal increases were seen at 12 h (to 261% of control) and at 24 h (to 169% of control), respectively, and the NGF content was then normalized at 7 days. The increased production of NGF might be a protective response or could be involved in plastic changes underlying kindling epileptogenesis.

Animals↗
PubMed1992

Stimulation of glutamate receptors increases expression of brain-derived neurotrophic factor mRNA in rat hippocampus.

The activation of neocortical glutamatergic neuronal afferents to the hippocampus as well as direct pharmacologic non-NMDA receptor activation within the hippocampus was shown to result in a dramatic increase in BDNF mRNA expression in granule cells of the dentate gyrus and throughout the pyramidal layer, especially in CA1. Less pronounced effects were also seen for NGF mRNA. These results indicate that expression of BDNF and NGF in the brain is regulated by neuronal activity and glutamate receptor stimulation. This opens up the possibility that the increased levels of these factors seen after excitotoxic brain damage may have a protective role during such brain damage.

Animals↗
PubMed1992

Amphetamine regulation of mesolimbic dopamine/cholecystokinin neurotransmission.

The effects of acute and repeated amphetamine administration on mesolimbic dopamine (DA) neurons was assessed by studying DA and cholecystokinin (CCK) release in the nucleus accumbens (Acc), as well as effects on mRNA genes regulating DA and CCK synthesis in ventral tegmental area (VTA) cells in rats. Amphetamine (1.5 mg/kg) markedly increased extracellular levels of DA in the medial Acc (assessed by in vivo microdialysis) in drug-naive animals, about twice the amount released in animals repeatedly administered the drug for the previous 7 days (twice daily). CCK overflow was found to mirror the DA responses in that the very transient elevation of CCK monitored in drug-naive animals was attenuated in those with prior amphetamine use. The attenuation of both DA and CCK overflow in the medial Acc was found to be associated with a decrease in the number of CCK mRNA-positive VTA neurons (assessed by in situ hybridization histochemistry). Although the number of cells expressing CCK mRNA were decreased, the gene expression in those positive CCK and tyrosine hydroxylase mRNA cells in the VTA was significantly increased. The CCK mRNA neurons in the VTA were positively identified as those projecting to the medial Acc by the local perfusion of Fluoro-gold retrograde tracer via microdialysis probes located in the Acc.

Amphetamine↗
PubMed1992

Disruption of the low affinity receptor-binding site in NGF allows neuronal survival and differentiation by binding to the trk gene product.

Nerve growth factor (NGF), like many other growth factors and hormones, binds to two different receptor molecules on responsive cells. The product of the proto-oncogene trk, p140trk, is a tyrosine kinase receptor that has been identified as a signal-transducing receptor for NGF, while the role of the low affinity NGF receptor, p75NGFR, in signal transduction is less clear. The crystal structure of NGF has recently been determined, although structures involved in receptor binding and biological activity are unknown. Here we show that Lys-32, Lys-34, and Lys-95 form a positively charged interface involved in binding to p75NGFR. Simultaneous modification of Lys-32 with either of the two other lysines resulted in loss of binding to p75NGFR. Despite the lack of binding to p75NGFR, these mutants retained binding to p140trk and biological activity, demonstrating a functional dissociation between the two NGF receptors.

Amino Acid Sequence↗
PubMed1992

Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial memory and enriched environment.

Enriched environment has been shown to enhance learning and memory and to induce morphological changes in the hippocampus. We report that rats housed in an enriched environment showed improved performance in the Morris water maze and decreased spontaneous motor activity. Exposure to behavioural tests increased expression of the mRNA that encodes brain-derived neurotrophic factor in the hippocampus. This was not seen when rats subjected to impoverished housing were tested suggesting that environmental history of the animal is of importance to induce expression of brain-derived neurotrophic factor in the hippocampus that may promote neuronal changes related to learning and memory.

Analysis of Variance↗
PubMed1992

Activation of basal forebrain cholinergic neurons differentially regulates brain-derived neurotrophic factor mRNA expression in different projection areas.

Afferent cholinergic pathways from the basal forebrain were activated by injections of the glutamate analog quisqualate either into the nucleus basalis or into the medial septal nucleus. Nucleus basalis injections had no effect on the expression of brain-derived neurotrophic factor (BDNF) mRNA in its neocortical projection areas as measured by in situ hybridization. In contrast, 7 h after an injection into the septum the level of BDNF mRNA increased 3- to 5-fold in the dentate gyrus, throughout CA1 to CA3 in the hippocampus and in the piriform cortex.

Afferent Pathways↗
PubMed1992

Widespread neuronal degeneration after ibotenic acid lesioning of cholinergic neurons in the nucleus basalis revealed by in situ hybridization.

In efforts to test the cholinergic hypothesis for Alzheimer's disease and to create an animal model for this disease, ibotenic acid has been used to lesion cholinergic neurons in the basal forebrain. In this study we have used in situ hybridization with oligonucleotide probes specific for mRNAs encoding choline acetyltransferase and glutamic acid decarboxylase, respectively, to study the effects of such a lesion. Our results show that lesion paradigms normally used to induce neuronal degeneration in nucleus basalis by ibotenic acid not only lesion the cholinergic neurons within this nucleus, but in addition, a major fraction of gamma-aminobutyric acid (GABA) neurons in nucleus basalis, substantia innominata, globus pallidus and ventral pallidum.

Animals↗